The standardized residency training (SRT) program in China is an important link for continuing education and clinical work training for graduate students. The purpose of our study was to enable educators to maintain the effectiveness of hysteroscopy teaching techniques and make the standardized residency training students well experienced in surgery, thus demonstrating that higher efficiency of teaching can lead to better proficiency for surgery.  We generated resident-as-teacher teaching round and tutor guided hysteroscopic surgery as well as a questionnaire based on the mastery degree of the basic theoretical knowledge and operational skills of hysteroscopy among seven junior residents and five senior residents of the Obstetrics and Gynecology Department, including four attending gynecologic surgeons of a hysteroscopy teaching program. p < 0.05).  Senior residents felt confident to teach, while junior residents learned effectively through the teaching round. There were statistically significant differences in the whole operation time and the volume of distension fluid used between junior and senior residents  discussion dominated by the residents themselves and overall surgical skills of teaching and learning. Medical graduates are not fully trained physicians when they leave medical school, so it is very important to build a connection between theoretical learning in college and practical training in the hospital. The standardized residency training (SRT) program in China is an important link for continuing education and receiving system-based clinical work training for students who have completed basic theoretical courses in a medical college . It is dThe training process comprises standardized courses to facilitate the acquisition of the required skills. In Grade 1, basic skills will be trained, and in Grade 2 to 3, clinical skills and theoretical knowledge will be thoroughly studied and mastered. The residents should pass the theoretical and operating comprehensive examination before they graduate from the SRT program; then, they could become a specialist doctor. Currently, SRT is conducted in progress in most hospitals according to the Ministry of Health guidelines, while educators have long struggled with how best to act in teaching . We. We15]. t-test. Uterus position, postoperative vaginal bleeding, and pathology were performed by the Mann–Whitney test, and skewed data were compared using Fisher's exact test. All p values less than 0.05 were considered statistically significant, and all p values were two-sided.All enrolled attending resident physicians and doctors abstracted the medical records. Comparisons between groups of junior and senior residents in the patient age, year of menopause, whole operation time, the volume of distension fluid used in the HS operation, and the intrauterine depth were performed by the There is, in particular, unique challenges for trainees to follow a clear educational plan in advance in order to gain specific theoretical knowledge prior to performing a hysteroscopic surgical intervention through TR. In general, we talk about theoretical knowledge in TR which was taught by the teachers before the surgery. Different from the traditional mode, in this program, a 2-month teaching rounds (TR) program was managed by senior residents though the PBL pattern. Senior residents have attended similar TR courses when they were in their junior grade given by the teachers; thus, this time, it was their turn to act as leaders to hold the course. Each teaching round had a focus on meeting the demands of different development strategies for trainees so that they learn effectively. Residents analyzed the causes, symptoms, signs, ultrasound reports, lab data, diagnosis, and treatments that require further observation, which could help in hospitalization at the bedside . The teaObservation of the actual operation could be a powerful tool to develop teaching skills, and the standardization process consisted of a videotaped HS by an experienced teacher so that the trainees could follow the procedure. Video-based education has potential use in surgical education as trainees face significant barriers in their practice. The use of video settings offered sufficient opportunities to integrate theoretical and clinical understanding. Hysteroscopic two-dimensional image display system videos were commonly used for residents who were unfamiliar with hysteroscopy.Within one week after each TR, we arranged a test to observe if residents have grasped the content of the lesson and to evaluate the effect by different speakers. The teachers explained and reviewed the answers. As to junior residents, they got the mean score of 10.7 in the first test and 14.4 in the second test, and we observed that the more courses the residents attended, the higher scores they achieved among junior residents . Senior After the students had mastered theoretical knowledge related to hysteroscopy through TR, they tried to engage in the hysteroscopy practical training stage. We arranged suitable HS cases for residents to operate according to the European Gynecologic Endoscopy Association. The training in hysteroscopy surgery is divided into the following three levels: primary level, which is suitable for the junior and senior residents, mainly for the diagnosis and simple operation, such as intrauterine fixed-point biopsy, removal of an intrauterine device, and mild intrauterine adhesions . In ordeEducators were encouraged to teach trainees hands-on , cultivaThe directors try to avoid the occurrence of intraoperative complications, including controlling the surgery time to less than 1 h to minimize the occurrence of complications. In clinical observation, fluid overload caused by longer operation time means excessive use of fluid in patients in HS which usually results in the symptom of bloating as a result of the fact that the fluid in the uterine cavity enters the pelvis through the fallopian tube. In addition, in order to avoid serious complications following hysteroscopy such as air embolism or cutting excessive myometrial tissue, we should remove the air in the tube and control the pressure of the expansion valve and the flow rate of the perfusate as well as the cutting depth.p=0.90) (p=0.50) (p < 0.05) (p < 0.05) (p=0.84) (p=0.29) (p=0.49) (p=0.86) , the mean menopause age was 3.8 years (range = 0–26 years), and the mean intrauterine depth was 7.22 cm (range = 5–9.5 cm). In this patient population, 62 procedures (60.6%) were performed by involving junior resident trainees, and 50 procedures (39.4%) were performed by involving senior resident trainees. Patient characteristics were summarized in p=0.90)  and meno(p=0.50) . Since t < 0.05) . Junior  < 0.05) , mainly (p=0.84) , uterus (p=0.29) , postope(p=0.49) , and pat(p=0.86) . Only on(p=0.86) .The time of the TR courses when each resident participated in the gynecological ward was shown in When the HS program finished, we ranked a list of potential concerns through a questionnaire focusing on different attitudes and effects between TRs managed by the teachers and residents which concluded challenges to good clinical rounds and HS based on responses from the focus group discussions . All thehttp://www.acgme.org) is responsible for the management of training residents to acquire advanced skills in the aspect of patient care, medical knowledge, evidence-based practice, communication skills, and system-based practice [In the clinical teaching process, we were usually confused with the situation that although the teacher teaches the same contents, different students had different comprehension and master levels. Was this just because students had different degrees of ability or it also related to teaching methods? We thought it was the latter. The Accreditation Council for Graduate Medical Education (ACGME) (practice . Generalpractice . In our The use of clinical rounds, as an integral part of clinical teaching to help residents acquire essential skills of practicing medicine, is critically important. The father of modern medicine, William Osler, highly acknowledged bedside teaching in modern medicine: “To study the phenomena of disease without books is to sail an uncharted sea, while to study without patients is not to go to sea at all.” It was noted that “Twelve Tips to Improve Bedside Teaching,” which included preparation, priming of the patients, assignment of roles, the establishment of expectations, roadmap, the focus of the encounter, patients' notes, bedside teaching, role model, summary, feedback, and reflection, were conducive for residents skilled in basic operations . DiffereFurthermore, teaching by residents has demonstrable value since the students' affective domain cannot be ignored . ResidenChecking rounds is an assessment tool in surgery . Side byHowever, there were limitations in our study including small sample size, thereby limiting the statistical difference between groups. Additional studies are recommended to assess the efficiency of hysteroscopy teaching under faculty supervision during the basic surgical procedure. The residents should also be able to perform HS efficiently when they operate independently in the future. Larger studies are needed to further explore the potential links among on-round TR, acquisition of high-value operational principles by the trainee, and patient outcomes, and more medical teachers should take part in faculty development programs.Overall, surgical residents train and teach both in and outside of the operating room. It was noted that the higher the efficiency of teaching, the better the proficiency for surgery. It is important to improve the theoretical knowledge of resident physicians in the surgical department before the actual operation. This study acknowledges better characterization of the link between the use of TRs dominated by the residents themselves and tutor guided surgical skills. By adopting and promoting interprofessional collaborative practice model, the quality and effectiveness of bedside TR and HS guidance could be improved for the benefit of trainees and the instructor team as a whole.


Phthalates and bisphenol A, classified as endocrine disruptors, have weak estrogenic, anti-androgenic properties, and affect thyroid hormone regulation. The aim of this study on male rats was to compare the subacute toxic effects of low doses of single compounds (bis (2 –ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and bisphenol A (BPA)) with the effects of their mixture through different biochemical, hormonal, and hematological parameters. Rats were divided into five experimental groups: Control (corn oil), DEHP (50 mg/kg b.w./day), DBP (50 mg/kg b.w./day), BPA (25 mg/kg b.w./day), and MIX (50 mg/kg b.w./day DEHP + 50 mg/kg b.w/day DBP + 25 mg/kg b.w./day BPA). Animals were sacrificed after 28 days of oral treatment and blood was collected for further analysis. The results demonstrated that the mixture produced significant changes in lipid profile, liver-related biochemical parameters, and glucose level. Furthermore, the opposite effects of single substances on the thyroxine level have been shown in comparison with the mixture, as well as a more pronounced effect of the mixture on testosterone level. This study contributes to the body of knowledge on the toxicology of mixtures and gives one more evidence of the paramount importance of mixture toxicity studies, especially in assessing the endocrine disruptive effects of chemicals. HighlightsMore adverse effects induced by the mixture compared to the single substancesSignificant changes in lipid profile, liver-related biochemical parameters, and glucose levelOpposite effects of single substances on the thyroxine level in comparison with the mixtureMore pronounced effect of the mixture on testosterone levelMixture toxicity studies are of primary importance for endocrine disruptorsIn real-life scenarios, the general population experiences uncontrolled multi-chemicals low-dose exposure from many different sources ,2,3,4,5.Some of the already identified and well-established chemicals with endocrine-disrupting properties include organochlorine pesticides, polybrominated diphenyl ethers, polychlorinated biphenyls, toxic metals, as well as phthalates and bisphenol A ,21,22,23The current study will concentrate on the investigations of the combined effects of selected phthalates and bisphenol A. Phthalates have been used as softeners in PVC plastic and vehicles for fragrance in cosmetics , while bStudies on experimental animals have shown that phthalates and bisphenol A interfere with the endocrine system inducing developmental and reproductive toxicity ,32. ThesHaving in mind that phthalates and bisphenol A coexist in natural environments, their combined effects require further investigation . ReproduHowever, studies on the subacute toxicity of the mixture of DEHP, DBP, and BPA are, to the best of our knowledge, limited, if nonexistent, especially those considering the thyroid-disrupting effects. Therefore, the aim of this experimental study was to compare the effects of single compounds  with the effects of their mixture on different hematological, biochemical, and parameters of endocrine function in rats orally exposed to these chemicals for 28 days. Bis(2-ethylhexyl) phthalate , dibutyl phthalate  and bisphenol A  were used in this study. All reagents and chemicals were of analytical grade quality or higher purity. Phthalates and bisphenol A were dissolved in corn oil. Rattus norvegicus), weighing 150–200 g, were used for the experiment. Animals were housed under the standard controlled conditions (temperature (20–24 °C), light (12 h night: 12 h day), relative humidity of 35% to 60%. They were allowed free access to standard rat chow ) and tap water during the experiment. Animals were given seven days to acclimate to their new environment and experimental conditions. All experimental procedures were approved by the Ethical Committee on Animal Experimentation of the University of Belgrade, Faculty of Pharmacy .Male Wistar rats (n = 6): Control and four treated groups, of six animals each: (i) Control group (corn oil), (ii) DEHP (50 mg/kg b.w./day), (iii) DBP (50 mg/kg b.w./day), (iv) BPA (25 mg/kg b.w./day), (v) MIX (50 mg/kg b.w./day DEHP + 50 mg/kg b.w/day DBP + 25 mg/kg b.w./day BPA). Not more than six rats were used per group, in accordance with the 3Rs principle and good animal welfare. Body weights, as well as food and water consumption, were recorded daily and the dose administered each day was adjusted for the body weight. Treatment of all animals was performed by oral gavage 28 days. The doses selection was made according to the reported overall no-observed-adverse-effect level (NOAEL) for DBP (50 mg/kg b.w./day) [In this study, we have chosen to use only male rats having in mind all the evidence that both phthalates and bisphenol A are toxic to the male reproductive system ,49. Rats.w./day) . The dos.w./day)  and gluc.w./day) . Further.w./day)  for deve.w./day) . Oral ad.w./day) ,46.g for 30 min and frozen (−20 °C) for biochemical assays and serum hormone level analysis. One aliquot of blood, collected in heparin vacutainers, was used for the determination of hematological parameters. At the end of the experiment, final body weights and weight gain for all animals were calculated and recorded. Bodyweight gain was calculated by the following equation:On the 28th day rats were weighted and euthanized under light anesthesia, intraperitoneal ketamine (75 mg/kg b.w.)/xylazine (10 mg/kg b.w.) injection. Blood samples were collected by cardiac puncture after anesthetic administration. For biochemical and hormonal parameters, blood was collected in a centrifuge tube for serum separation. Serum was separated by centrifugation at 3000× In this equation, mf signifies final body weight, while mi signifies initial body weight. The organs were collected and weighed, and the relative organ weight was calculated by dividing organ weight with the final body weight.Hematological parameters were measured according to good laboratory practices by the MYTHIC 22 analyzer . Multi-angle polarized scatters separation was used for white blood cell and dual-angle optical analysis for platelets count. The following hematological parameters were examined: White blood cell count (WBC) with WBC differential count (neutrophils (NEU), eosinophils (EOS), lymphocytes (LYM), basophils (BAS), and monocytes (MON)), red blood cell count (RBC), hemoglobin concentration (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and platelet count (PLT).2+), inorganic phosphorus (PO43−), magnesium (Mg2+), and chloride (Cl−). In order to identify the cause of liver damage the AST/ALT (the De Ritis ratio) ratio was calculated. All biochemical assays were performed with commercial reagents and according to the good laboratory practices on the Cobas C311 analyzer . The measured biochemical parameters in rat serum included triglycerides (TG), cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), creatinine (CRE), uric acid (UA), total serum proteins (TP), albumin (ALB), direct bilirubin (DB), total bilirubin (TB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), serum iron, calcium  tests by Cobas E411 analyzer . The measured hormonal parameters in rat serum included triiodothyronine (T3), thyroxine (T4), and testosterone. All assays were performed with commercial reagents and according to the good laboratory practices. The statistical analyses were performed using GraphPad Prism 6 software . The normality of distribution for all parameters was tested using the Shapiro–Wilk method in all experimental groups. In the case of the normal distribution, a one-way analysis of variance (one-way ANOVA) was used to analyze the differences between the experimental groups. Fisher’s least significant difference (LSD) as a post-hoc test was performed. If the distribution was not normal, the non-parametric Kruskal–Wallis test was used for group differences along with the Dunn’s post-hoc test. A value of p < 0.05 was considered statistically significant.Bodyweight gain (BWG) and percentage difference of BWG in four selected time points during the experiment are presented in On the other hand, there was no significant difference in body weight gain between the MIX group compared to all the groups in which rats were receiving single substances for all presented time points.Food and water consumption of rats in the control and treated groups are given in A significant decrease in overall water consumption was noted in BPA and MIX group compared to the control, as well as in the first three time points . Water cOn the other hand, water consumption was significantly higher in the DEHP and DBP groups compared to the MIX in all four presented time points, except for the third week, after which there was no significant difference for the DBP group compared to the MIX. After both the first and the second week, water consumption was significantly higher in the BPA group compared to the MIX, but lower compared to the oil control. However, there was no significant difference between the BPA and MIX group after the third and fourth week. As for the overall water consumption, it was significantly higher in the DEHP and DBP groups compared with the MIX, while there was no significant difference between the BPA and MIX group. Relative organ weights are presented in Hematological parameters measured in the present study are presented in Serum biochemistry parameters after 28 days of exposure to the investigated substances and their mixture are presented in Liver-related serum biochemistry parameters are presented in In the MIX group, there was a significant elevation of the urea level compared to the control. Having in mind that there were no significant changes in this parameter in single substance groups, this could suggest the additive effect of the investigated substances. However, there was no significant difference between the urea level in the DEHP, DBP, and BPA groups compared to the MIX.A significant increase in the glucose level compared to the control was noted not only in the MIX, but in the DEHP and DBP groups as well. There was no significant difference in the glucose level in the BPA group compared to the control, but it was significantly lower when compared with the MIX group. Lipid profile parameters are presented in Hormone parameters measured in this study are presented in In the groups receiving single substances, the testosterone level was lower, but not significantly. Nevertheless, in the MIX group, a notable decrease in this parameter was observed compared to the control. However, there was no significant difference in testosterone levels between the groups receiving single substances in comparison with the MIX group. In this experimental study on rats, subacute toxic effects of single compounds  and their mixture were investigated through different biochemical, hormonal, and hematological parameters.in utero exposure to BPA, DEHP, and DBP can lead to obesity later in life, through various mechanisms, such as disturbances of the methylation process and changes in the histone structure which consequently affect gene expression in the case of phthalates [Although the given dose of BPA is considered the NOAEL for the effects on body weight, in this study, a decrease in body weight was shown in almost all presented time points, as well as for the overall body weight gain. In their study, Miao et al. (2008) stated that the ability of BPA to put the stress on rats resulting in a decrease in their weight by depressing the appetite and, thus, reducing the food intake . Howeverthalates  and altethalates . HoweverIt was noted that DEHP, DBP, and MIX groups caused a significant increase in the level of lymphocytes, while there was no significant difference in the BPA group compared to the control. This, along with the CRP level, significantly elevated in these groups as well, could be linked to the low-grade systemic inflammation caused by the investigated substances. This is in accordance with the results obtained in the study, in which rats were orally exposed to 0, 5, 50, and 500 mg/kg b.w./day DEHP for eight weeks. This study has demonstrated the increased inflammatory factors (IL-1β and TNF-α) and concluded that the inflammation may play a regulatory role in lipid metabolic disorders induced by DEHP . FurtherIn our study, thyroid function was investigated by measuring T3 and T4 serum content. A significant negative association was found in the DBP group for the T4 level, as well as in the BPA group. In a study on rats by Wu et al. (2017) the decrease in the T3 and T4 levels was demonstrated after five weeks of oral exposure to the same dose of DBP (50 mg/kg/day) . ConversIn our study, a decrement in the cholesterol level was observed in the DEHP, DBP, and MIX groups compared to the control, while the cholesterol level in BPA was significantly higher in comparison with the MIX group. Triglyceride concentration was significantly elevated in the DBP and BPA groups compared to the control. The hypo-cholesterol level may be explained by the possible impairment of the liver function, in the case of the DEHP group, in which the increase in the relative liver weight was observed, along with the increase in ALP activity compared to the control. The decrement in the cholesterol level might also be connected with the decrease in the T4 level and altered thyroid function present in the DBP group . FurtherAgents that cause peroxisome proliferation in the liver might also cause thyroid hyperactivity, and it is commonly assumed that the two actions are mechanistically linked . Kim at The present study has demonstrated a significant increase in the glucose level compared to the control in DEHP, DBP, and MIX groups, while the glucose level was significantly lower in the BPA group compared to the MIX. In support of our results, Srinivasan et al. (2011) showed the connection between DEHP 30-day rat oral exposure and the decrement of both testosterone and insulin levels at the dose 100 mg/kg, connecting the DEHP exposure to the higher glucose level in rat serum . ImpairmIn the present study, the serum testosterone level was measured as a marker of androgen activity. Our results have indicated a significant decrease in this parameter in comparison with the control only in the MIX group, while there was no significant difference upon the administration of single compounds  for 28 days, although a slightly decreasing trend can be observed. The more pronounced effect of the mixture on the testosterone level can be explained by the possible toxicokinetic interactions between the substances present in the mixture. These interactions were confirmed in an acute toxicity study on mice, which explored the influence of a single dose of DEHP injected subcutaneously  on the deposition of BPA received as a food supplement (50 μg/kg 14C–BPA). The results of this study indicated that DEHP increases the deposition of BPA in the epididymis of male mice compared to the control group . The effIn conclusion, this study demonstrated that a mixture of low doses of DEHP, DBP, and BPA produced significant changes in body weight gain, food, and water consumption, thyroid hormone and testosterone levels, lipid profile, liver-related biochemical parameters, and the glucose level. Some of these effects, especially those connected to endocrine disruption, were not observed in groups treated with single compounds. Overall, it could be concluded that the more pronounced effects observed at certain parameters with mixture exposure are due to the increased total exposure amount, suggesting the dose addition. The results of the study challenge the results of toxicity studies of single chemicals and further contribute to the understanding of the health effects posed by real-life exposure to chemical mixtures.


Leskea-type, and it also induces the development of proximal branch leaves that normally do not develop a lamina above the stem surface. This fact supports conclusions regarding the homology of the Leskea-type of paraphyllia with leaves.Moss paraphyllia, the trichome-like or foliose structures on moss stem surfaces, are usually treated as epidermal outgrowths. However, in some taxa of the moss families Leskeaceae, Neckeraceae, and Amblystegiaceae their distribution along the stem is consistently correlated with parts of the stem surface near branch primordia. In other moss families, Climaciaceae, Hylocomiaceae, and Pseudoleskeaceae the specific paraphyllia-generating epidermal layer produces paraphyllia evenly all along the stem. These results suggest that there are at least two different types of regulation of paraphyllia development; however, both of them may be involved in the morphogenesis of paraphyllia in some families, for example in the Thuidiaceae. Exogenous abscisic acid treatment consistently increases the number of paraphyllia of the  Mosses are small plants, and their morphology remains incompletely understood despite a long history of studies. Among the most controversially interpreted features are foliose and filamentose appendages on the stem surface in pleurocarpous mosses, commonly called paraphyllia and pseudoparaphyllia. An interest in their structure has been recently revived after molecular phylogenetic studies showed that many morphological characters used in “classical taxonomy” are enormously homoplasious and can no longer be used as key diagnostic characters. The classification of pleurocarpous mosses at family level is especially flawed, as sporophyte characters have been shown to be extremely plastic during the transition to epiphytism . ConversRhynchostegium (Brachytheciaceae) and Rhytidiadelphus (Hylocomiaceae). Ironically, the first world-wide comprehensive overview of pseudoparaphyllia by Paraphyllia are filamentose or narrowly lanceolate, rarely ovate, multicellular, branched or unbranched structures, densely or sparsely covering the stems or solitary , a term Alsia, Cratoneuron, Leptodon, and Leskea, “paraphyllia” are more abundant near branch primordia or situated, often in pairs, at the locations of undeveloped branch primordia. These authors concluded that in the studied taxa “paraphyllia” may be assumed to be pseudoparaphyllia that have escaped for a certain distance from the branch primordia. However, this suggestion did not meet with wide acceptance.Paraphyllia have attracted less attention, and the most detailed overview remains a publication by Hypnum cupressiforme Hedw. . The selection of ABA is based on preliminary studies with three phytohormones, cytokinin, auxin, and ABA, on the growth of ABA is an important compound in plants, involved in the regulation of plant growth, germination, stomatal movement, responses to abiotic stresses, as well as the stresses caused by viruses and bacteria . AlthougPhyscomitrella, confirming the similarity of its physiological responses to that in seed plants. For the morphogenetic role of ABA, however, Populus, thereby inducing bud dormancy (Physcomitrella patens (Hedw.) Bruch & Schimp. and showed that the molecular trafficking through them is rapid and reversibly restricted by abscisic acid. Thus a kind of release from dormancy may be better understood using deeper ABA studies. Branch primordia in the majority of pleurocarpous moss genera have a specific variant of dormancy: branch primordia start to develop, produce small-sized foliose protective structures covering the bud, and then revert to a dormant state but are promptly released from it in the case of damage to a stem apical cell. Although ABA was never considered for dormancy in mosses, its effect on structures associated with dormancy seems to merit being tested.The putative importance of ABA studies to the paraphyllia/pseudoparaphyllia problem can be related to its ability to promote seed dormancy in angiosperms  and to mdormancy . KitagawLeskea polycarpa was the main focus of the present study as its paraphyllia are the easiest to count. This is a widespread epiphytic moss, common on tree trunks in the temperate zone of the Northern Hemisphere. Its habitats periodically experience drought lasting from several days to several weeks. Intensive growth of Leskea polycarpa in the Moscow region starts in the second half of spring. As the species was the main subject of our ABA investigation, we undertook anatomical studies by sectioning to elucidate the sub-surface structure of its branch primordia.Leptodon (Neckeraceae) and Cratoneuron (Amblystegiaceae).Two other mosses studied for paraphyllia distribution along the stem and also for the effect of ABA were chosen from genera of different families: Cratoneuron, Palustriella), Climaciaceae , Leskeaceae (Leskea), Neckeraceae , Pseudoleskeaceae , Theliaceae (Thelia), Thuidiaceae .Genera from the following families known to have paraphyllia were re-studied with light microscopy to observe the distribution pattern of the paraphyllia: Amblystegiaceae  Spruce. The area of the stem was subdivided into three zones  were fixed in a 2.5% glutaraldehyde solution for 7 days, post-fixed in a 1% OsO4 water solution for 3 hours, washed in water. After washing, the material was dehydrated in an alcohol series , alcohol–acetone mixture (1:1), and acetone for 1 hour in each solution, soaked in an acetone–resin mixture series  for 12, 24 and 3 hours respectively, and embedded in epon-araldite resin as recommended by the manufacturer. The resin was polymerized at 60°C for 24 hours. Serial longitudinal, transverse, and oblique sections were cut 2 µm thick with glass knives, placed on glass slides without mounting medium, stained with 0.01% berberine or its combination with DAPI and scanned under a laser scanning confocal microscope Olympus FV-1000 based on Olympus BX61, using or combining 405 and 473 nm lasers. Z-stacks of several scans were usually obtained and are presented here.Anatomical studies were conducted with Two series of longitudinal sections and three series of transverse ones were made, and some interesting cases observed under the microscope were studied.The structure of branch primordia was studied for pleurocarpous species of several families, mainly for taxonomic purposes. In the present paper we illustrate the least known cases involving the complete reduction of proximal branch leaves, and their division to the base, causing them to appear to be compound.These studies involved light microscopy (LM), scanning electron microscopy (SEM), and laser scanning confocal microscopy (LSCM).LM analysis: paraphyllia were described with regard to their shape and structure, position, and arrangement on the stem, contrast being enhanced by fuchsine and picroindigocarmine staining.SEM analysis the shoots were fixed in a 4% glutaraldehyde solution for 7 days, incubated in a 1% OsO4 water solution for 6 hours, washed in water, dehydrated through an ascending alcohol–acetone series, dried at the critical point, and coated with gold. Prepared shoots were observed and photographed under a LEO430 scanning electron microscope . For some shoots SEM observations of gold-coated samples were performed with the SEM Jeol 6380, without additional preparation.For LSCM with similar staining by berberine or berberine/DAPI, without fixation. Combinations of lasers 405, 473, and 576 were used for maximally detailed pictures. Scan series  are presented here as Z-stacked images, or, in some cases, photo-galleries of parts of series.Living material was observed and photographed with Leskea polycarpa, Cratoneuron filicinum. Leptodon smithii, and Thuidium tamariscinum (Hedw.) Schimp., representatives of four different families. The selection depended on the position and number of paraphyllia which are readily countable. Thuidium tamariscinum has very dense and numerous paraphyllia on stem and primary branches, but on secondary branches their number is comparable with that in Leskea; thus only secondary branches were studied for this species. Species with very dense and interwoven paraphyllia, e.g., Hylocomium and Climacium were not studied, because it is almost impossible to count paraphyllia on their stems and branches, and paraphyllia are situated on all cells.Observations were conducted on Leskea polycarpa was placed in Petri dishes (diameter 9 cm) as ten tufts of ca. 2×2 cm, without separating plants into individuals. They were put on one layer of filter paper moistened with 5 ml of distilled water or an aqueous solution of ABA  at a concentration of 0.1 μmol, 0.04 μmol, 0.01 μmol, 0.002 μmol, hereafter referred to according to the amount applied in μmol as ABA-0.5, ABA-0,2, ABA-0.05, and ABA-0.01. Petri dishes were placed in a Sanyo Environmental Test Chamber MLR-352H: temperature + 7°С/+ 12°С (night/day), light period 10 hours, PPFD - 14 μmolm-2s-1 for 21 days.Leskea in vivo to exclude the possibility that the observed effect on paraphyllia depends on cultivation in the permanently humid condition of the Petri dish. ABA was applied directly to tufts of Leskea polycarpa growing in the park of the Tsitsin Main Botanical Garden in Moscow, on four trunks: two of Acer tataricum L., and one each of A. platanoides L. and Malus sylvestris Mill., at 1.5 m above the ground. Two tufts 5 x 5 cm of Leskea were moistened on each trunk: one with ABA-0.5 solution and one with distilled water. A soft painting brush was used for wetting moss turfs. All turfs were situated on the same eastern side of the trunk in similar conditions. The experiment was conducted in the period following 25 April 2017, i.e. when most epiphytic mosses had resumed growth in Moscow (in the rainy and warmer days after winter).In addition to the experiments in the test chamber, we explored the effect of ABA on After 21 days of cultivation, 50 shoots from each Petri dish were selected. All leaves were removed from the stems with thin tweezers. The stems were stained with fuchsine, placed on a glass slide, and covered by another glass slide, allowing observations from both sides of the stem. The stems were examined under the light microscope (Olympus-CX41) and photographed with a digital camera (Infinity 2-2). Stem diameter was measured, and the number of paraphyllia was counted from the images. The number of paraphyllia was calculated for one square millimeter of the stem surface. Cultivated plants, plants from the field, and herbarium materials were studied in the same way.The significance of the ABA effect was evaluated by the T-test in MS Excel  Schimp. which were used for this study, were collected from the park in the Tsitsin Botanical Garden in Moscow.Brachytheciaceae is known as a family in which the branch primordia lack leaves formed from the first and second branch merophytes, which therefore appear underdeveloped, forming no foliose structures above the stem surface . We haveLeptodon smithii, Cratoneuron filicinum, and Leskea polycarpa, species from three different families, show approximately the same pattern. Paraphyllia are most abundant near the branch primordium and along the route that the primordium passes in its ontogenetic history on the path from mother leaf N  Ochyra, P. decipiens (De Not.) Ochyra, Leskea gracilescens Hedw., L. obtusa Renauld & Cardot, and Hygroamblystegium varium (Hedw.) Mönk. , Hylocomiastrum, Hylocomium, Loeskeobryum, and Rhytidiopsis (Hylocomiaceae) , although sometimes they are very homogeneous . At the same time, their branches are less abundantly paraphyllose, and the concentration of paraphyllia near the branch bases is obvious  inhibited the increase in the numbers of paraphyllia by exogenous ABA  in Mniaceae; the differences of micronemata from macronemata  in this family were described by Climacium-type and micronemata is initiated from longitudinally oriented structures of modified and somewhat inflated epidermal cells: ridges in Climacium and Pleuroziopsis , plant fixation and embedding (US), anatomical study (US), microscopy , ABA experiments (TV), manuscript preparation .Russian Foundation for Basic Research 19-04-00976 and MBG Institutional research project 18-118021490111-5.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Background: Patients with glioblastoma have a poor prognosis. We want to develop and validate nomograms for predicting overall survival in patients with glioblastoma.Methods: Data of patients with glioblastoma diagnosed pathologically in the SEER database from 2007 to 2016 were collected by SEER*Stat software. After eliminating invalid and missing clinical information, 3,635 patients  were finally identified and randomly divided into the training group  and the verification group . Cox proportional risk regression model was used in the training group, the verification group and the total group to analyze the prognostic factors of patients in the training group, and then the nomogram was constructed. C-indexes and calibration curves were used to evaluate the predictive value of nomogram by internal (training group data) and external validation (verification group data).Results: Cox proportional risk regression model in the training group showed that age, year of diagnosis, laterality, radiation, chemotherapy were all influential factors for prognosis of patients with glioblastoma (P < 0.05) and were all used to construct nomogram as well. The internal and external validation results of nomogram showed that the C-index of the training group was 0.729 [95% CI was ], and the verification group was 0.734 [95% CI was ]. The calibration curves of both groups showed good consistency.Conclusions: The proposed nomogram resulted in accurate prognostic prediction for patients with glioblastoma. Glioma is the most common primary central nervous system malignancy in adults, with an annual incidence of 5.26 per 100,000 people  in the Whttps://seer.cancer.gov/) is from the National Cancer Institute (NCI). This database records in detail the demographic information, tumor site and morphology, diagnosis stage, treatment and prognosis of millions of patients with malignant tumors and carcinoma in situ in some states since 1973 (SEER database (surveillance epidemiology and end results) (nce 1973 –10. In t*Stat (version 8.3.4) to collect 128,554 cases of nervous system tumors diagnosed pathologically. Then Excel 2016 was used to perform data cleaning to eliminate invalid data and select patients with glioblastoma from 2009 to 2015  in the training group and the verification group, respectively, for internal and external validation. The higher the C-index is, the more accurate the prognosis is . In the This study included the following characteristics into the analysis: age, race, sex, year of diagnosis, degree of differentiation, laterality, primary site surgery, radiation sequence with surgery, reason no cancer-directed surgery, radiotherapy, chemotherapy, tumor size, cause-specific death classification, other cause of death classification, sequence number, NHIA , age at diagnosis, insurance, marital status at diagnosis .The results of the univariate analysis have been listed in rcorrp.cens package in Hmisc was used to calculate the C-index for measuring the performance of the nomogram. The C-index for OS prediction was 0.729 . Calibration curves of 1-, 3-, or 5-years survival rates show good agreement between nomogram predictions and actual observations , and calibration curves showed good agreement between nomogram-predicted probability and actual observations of 1-, 3-, or 5-years survival . In veriAccurate and effective prognosis assessment is of clinical significance for individualized treatment and follow-up treatment of patients with GBM. GBM is usually diagnosed in late stage  by MRI wTo construct the nomogram, independent predictors of OS in patients with GBM should be determined first. Univariate and multivariate Cox proportional risk regression models were used to determine independent prognostic factors for OS. Multivariate Cox regression proportional analysis showed that age, year of diagnosis, laterality, radiation, chemotherapy were independent prognostic factors for OS in patients with GBM.p < 0.001)  and found that the death rate of patients with GBM over 65 years old was more than seven times higher than that of patients under 65 years old, thus the prognosis of patients with GBM over 65 years old was much worse than that of patients with GBM under 65 years old . In our < 0.001) . Elderly< 0.001) –26. In a< 0.001) . All thoP < 0.001).For newly diagnosed glioblastoma, the most important treatment is the resection of the contrast-enhanced region on imaging, followed by radiotherapy and chemotherapy , 28. TheThe impact of tumor laterality on the prognosis of patients has not been fully investigated so far. Daniel et al. retrospectively analyzed 235 cases of patients with glioblastoma on surgical outcome, which were grouped for left—and right—sided GBM . The resBased on the above results, we propose the following suggestions for the treatment of patients with glioblastoma. Pay attention to the age of the patient, especially those aged 65 or older, because elderly people have a worse prognosis. Radiotherapy  and chemotherapy should be used, as they can significantly improve the prognosis of patients with glioblastoma. Increase attention to tumor laterality, it may also be a potential prognostic factor.However, our study has some limitations. Firstly, the SEER database does not include information about tumor markers, such as MGMT (O (6)-methylguanine-DNA methyltransferase) promoter methylation  and IDH In conclusion, nomogram integrates easily available factors and serves as an easy-to-use tool to assist patients with glioblastoma in risk assessment and clinical decision-making. The nomogram proposed in this study may objectively and accurately predict 1-, 3, and 5-year OS of patients with glioblastoma. Additional studies are needed to determine whether it is appropriate for the other patient group.https://seer.cancer.gov/.Publicly available datasets were analyzed in this study. This data can be found here: HLi and XZ performed the statistical analyses. XZ checked the statistical accuracy as an expert in statistics. HLi performed the literature search and wrote the first draft of the manuscript. HLi, LH, YH, HLu, and XZ revised and edited the final version of the manuscript. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Sebastes oculatus, has been determined for the first time. Assembled mitogenome was 16,767 bp in length, including 13 protein-coding genes, 22 transfer RNA and two ribosomal RNA genes as well as the non-coding region. The order and structure are the same as those of other Sebastes species. S. oculatus was sister to S. nigrocinctus and this clade is closely related with S. rubrivinctus, as well as support for previously published complete mitochondrial genome trees (Sandel et al. S. oculatus provides significant DNA molecular data for further identification and phylogenetic analysis within Scorpaenid.The mitogenome of rockfish,  Sebastes Cuvier, 1829 called rockfishes are one of the most diverse genera of marine fishes, and their genus contains more than 110 species . The voucher specimens are deposited in National Marine Biodiversity Institute of Korea (MABIK Lot no. 0009366-0009368). The genomic DNA was extracted from muscle tissue and mitogenome sequences were analysed in two ways: First, after COI gene was amplified through universal primers, primer sets designed from partial sequences of COI gene of S. oculatus and highly preservative gene regions for the Sebasetes species. Then, we conducted long-range PCR (LR-PCR) to amplify targeted genomic intervals and sequenced by the Sanger method. The sequences were assembled and annotated in comparison with previously reported mitogenome sequences of the Sebastes species  was 16,767 bp in length, which includes two ribosomal RNA (rRNA), 22 transfer RNA (tRNA), and 13 PCGs as well as the non-coding region. Most of the genes are encoded on the H strand, while nine genes  are encoded on the R-strand and their order and structure in the genome are identical to those of other Sebastes species (Kim and Lee The circular mitogenome of S. oculatus was clustered with the Sebastes species previously announced from the GenBank, with high bootstrap values of 100% (S. oculatus was sister to S. nigrocinctus and this clade is closely related with S. rubrivinctus, as well as support for previously published complete mitochondrial genome trees (Sandel et al. In NJ tree,  of 100% . S. ocul


Background: Scarce literature has yet to characterize the tactile discrimination capability as well as the underlying mechanism of tactile deficits in psychotic disorder. In particular, very little is known regarding the tactile perception acuity in schizophrenia.Methods: A total of 131 clinically stable patients with schizophrenia (SCZ) and 79 healthy control (HC) volunteers were enrolled in the study. All the participants were tested on a tactile stimulus device which could quantify the tactile discrimination capability with right index finger scanned over the angles via the passive finger-movement apparatus. The MATRICS Consensus Cognitive Battery (MCCB) was adapted to assess the neurocognition of the participants. Correlation analysis and multivariate linear regression analysis were performed to investigate the relationship between tactile perception performance and neurocognitive function.Results: It was discovered that there existed a significant deficits in the tactile passive perception acuity  in patients with schizophrenia compared with their healthy controls  = 11.458, P = 0.001,partial η2 = 0.053). The MCCB total score and its six domains were significantly lower in SCZ patients than those in HCs . In the SCZ group, the composite score of the MCCB  and domains of neurocognition including speed of processing , attention/vigilance , working memory , verbal learning , visual learning , and reasoning and problem solving  showed significant negative correlations with the tactile angle discrimination threshold. Multivariate linear regression analysis revealed that neurocognition impairment, especially the decline of working memory ,underpin the tactile perception discrimination deficits in patients with SCZ.Conclusion: To the best of our knowledge, this is the first study to unravel the deficits of tactile passive perception acuity and its underlying neurocognition basis in patients with SCZ. This finding adds novel evidence to the subtle variation in haptic discrimination skills in schizophrenia which contributes to a more comprehensive understanding of the sensory profiles of this disorder. Schizophrenia (SCZ) is a major psychiatric disorder characterized by a wide range of neurocognitive deficits , 2 and sTactile perception involves the complementary interaction of the bottom-up peripheral sensory process and top-down central cognitive mechanisms for detection and sensation of objects and discrimination and evaluation of their size, shapes, and surface characteristics , 18. It Studies with regard to somatosensory discrimination, such as discrimination between different textures, sizes, and shapes of objects; two-point tactile discrimination; stereognosis; and graphesthesia are scarce, reflecting a critical gap since the somatosensory system serves as an important foundation for many aspects of human development, including fine motor skills  and social and communication skills .Of strikTactile spatial discrimination is deemed as one of the main manual learning and memory skills in humans. Studies have demonstrated that abnormal somatosensory information processing contributes to the functional decline of tactile shape discrimination in patients with mild cognitive impairments and Alzheimer's disease . The somThis study enrolled 131 clinical stable patients with a diagnosis of schizophrenia or schizoaffective disorder  who wereper se, medical records, as well as the information provided by their caregivers, would be combined. Socio-demographic and clinical variables, including duration of the psychosis and current pharmacological treatment, were assessed. The dose of antipsychotics was converted to the chlorpromazine equivalent  Consensus Cognitive Battery (MCCB) , which dThe tactile angle discrimination apparatus via finger sensation was employed to detect the haptic perception acuity of the participants in the current study, as previously described , 52. Thet-test, and chi-squared test was used for categorical variables, such as sex. The duration of psychosis, antipsychotics, and the PANSS scale scores were described, and analysis of covariance was employed for the comparison of MCCB scores between groups, with sex and years of education as the covariates. A two-way of analysis of variance (ANOVA) was performed to investigate the differences in the tactile angle discrimination threshold between the two groups, with group (patient vs. control) as an inter-subject factor, sex  as a within-subject factor, and age and years of education as covariates. Moreover, partial correlation analysis and multiple linear regression were performed to analyze the relationship between neurocognition function and angle discrimination threshold. All statistical analyses were performed using SPSS for Windows version 20.0 . For all tests, significance was set at P-value < 0.05.Demographics of participants, including age and years of education, were compared using a Student's 2 = 6.975, P = 0.008). Moreover, schizophrenia patients had lower years of education than their healthy counterparts . No significant age difference was observed between groups . Both schizophrenia patients (CDSS: 2.95 ± 3. 72) and healthy controls (PHQ-9: 1.68 ± 2.68 vs. GAD-7: 1.50 ± 2.31) did not show notable affective symptoms. All the participants were right-handed. As for the neurocognition assessment, SCZ patients showed significant poorer performances in the domains of processing speed, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and the composite scores than did HCs  and 79 healthy controls (HCs) participants (the HC group) were included in the current study. There was a higher proportion of males in SCZ group than in HC group  = 11.458, P = 0.001, partial η2 = 0.053), but no significant main effect of sex  = 0.053, P = 0.818, partial η2 = 0.000) or group*sex interaction  = 1.676, P = 0.197, partial η2 = 0.008) was observed. Male (30.66 ± 20.09) and female (27.22 ± 16.77) SCZ patients exhibited poorer performances in angle discrimination threshold than male (18.85 ± 13.20) and female (22.70 ± 15.19) HCs, respectively, indicating deficits in the tactile perception acuity in SCZ patients.In our study, the results of the tactile perception trial reported by the participants were logistically transformed to the angle discrimination threshold via plotting a logistic curve function of the angular differences between the comparison and reference angles; the obtained angle discrimination threshold indicates the minimum angle size that participants could distinguish, and the smaller value of angle discrimination threshold indicates the better capability of tactile perception to distinguish the angle differences. Results of the tactile perception task performance are shown in r = −0.191, P = 0.031), attention/vigilance , working memory , verbal learning , visual learning , and reasoning and problem solving  showed significant negative correlations with the tactile angle discrimination threshold. In addition, the composite score of the MCCB  was negatively correlated with the angle discrimination threshold as well  and the angle discrimination threshold. Moreover, there was no relationships between clinical symptoms obtained using the PANSS positive , PANSS negative , PANSS general psychopathology , or PANSS total score  and tactile angle discrimination threshold. In the HC group, neurocognition domains of reasoning and problem solving were marginally negatively associated with the tactile angle discrimination threshold , and no correlation between the other domains of the MCCB or the MCCB total score and tactile angle discrimination threshold was observed   .2 = 0.098, P < 0.001; adjusted R2 = 0.090, P < 0.001), and the working memory had a significant negative predictive effect on the deficits in the angle discrimination threshold  in SCZ, while neither of the other six domains made a contribution to the model  in SCZ. The findings shed new light on the underlying characteristics of the somatosensory disorder in patients with SCZ.Our angle discrimination threshold paradigm with a pair of angles randomly presented to participants via passive touch without visual feedback includes the following possible procedures: (i) encoding the first angle, extracting the relevant parameter, and storing the parameter value in memory; (ii) encoding the second angle, extracting the relevant parameter, and comparing the second angle parameter with the memory of the first angle parameter; and (iii) making a decision based on the outcome of the comparison . Althougin utero to synaptic pruning in adolescence (Although the pathophysiology of SCZ remains to be determined, accumulating evidences have demonstrated elevated presynaptic dopamine function in the striatum  as well lescence , and thelescence ; some fulescence .Similar to neurons in the central nervous system, epithelial tissues, such as tactile corpuscles in the skin's dermal papillae that function in tactile sensation, derive from the ectoderm. It is presumable that tactile perception acuity deficits are associated with neurocognitive impairment caused by neurodevelopmental abnormality from phylogenetic and ontogenetic perspectives. Notably, the duration of disease and PANSS scores, which could partly reflect the severity of the disease, are not associated with the tactile perception acuity in SCZ, suggesting that subtle variations of haptic discrimination skills in SCZ are not linked to the course or severity of the disease, which in line with the previous studies showing that tactile perception disturbance precedes the onset of disease .ThereforThe present study has some strengths. To the best of our knowledge, few studies have focused on tactile perception acuity capability in SCZ, and this study is the first to investigate the tactile angle discrimination performance and its neurocognitive basis in SCZ. In addition, we used continuous measurements of angle discrimination thresholds to define tactile variations, which would otherwise be difficult to assess. Further, the sample size is sufficient for a behavioral paradigm study, further supporting the robustness of our findings. However, our study has some limitations. First, both visuo-spatial and somatic codes are involved in the tactile sensation , and theIn conclusion, this study found tactile perception acuity deficits and their association with neurocognitive impairment in schizophrenia patients. This finding adds novel evidence to the subtle variation in haptic discrimination skills in schizophrenia which contributes to a more comprehensive understanding of the sensory profiles of this disorder. Future studies examining basic perception processing capacities and their relevance to underlying genetic and molecular mechanisms are needed to determine whether the angle discrimination threshold could be used as a “trait” biomarker in SCZ for assistance in the diagnosis of diseases or the prediction of treatment efficacy and outcomes.Star950214@126.com.The datasets analyzed in this article are not publicly available. Requests to access the datasets should be directed to The studies involving human participants were reviewed and approved by Ethics Committee of Beijing Huilongguan Hospital. The patients/participants provided their written informed consent to participate in this study.DLiu executed the analyses, interpreted the data, and wrote the first draft of the manuscript. ST and TY conceived and designed the study, supervised the project, and gave important suggestions for the revision of the manuscript. HF undertook the statistical analyses. WZ, YW, and DLi collected the clinical data and aided with angle discrimination trail. JW provided important technical support. All authors contributed to and have approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In recent years, more and more attention has been paid to the role of skin microcirculation in the pathogenesis of psoriasis. The vascular network of the skin is mainly distributed in the dermis and the subcutaneous fat layer join. The microvessels are composed of terminal arterioles, arteriovenous capillaries, and postcapillary venules. Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of psoriasis by promoting angiogenesis. The purpose of this study is to evaluate the relationship between serum VEGF and psoriasis vulgaris.Embase, CENTRAL, PubMed, China Biology Medicine Database, China National Knowledge Database, Wan Fang Database, and Chong Qing VIP Database will be searched to collect case-control studies and cohort studies and evaluate the relationship between serum VEGF and psoriasis vulgaris. The search time limits will be from the establishment of the database to December 2020. Two researchers will independently screen the studies, extract data, and evaluate the risk of bias of the studies. The Meta-analysis will be carried out with the RevMan5.3 software. The quality of all included studies will be evaluated by the Newcastle-Ottawa scale.This study will evaluate the relationship between serum VEGF and the pathogenesis of psoriasis vulgaris.This study will provide a theoretical basis for the pathogenesis of psoriasis vulgaris.DOI 10.17605/OSF.IO/6DV8P The vascular network of the skin is mainly distributed in the dermis and the subcutaneous fat layer join. The microvessels are composed of terminal arterioles, arteriovenous capillaries, and postcapillary venules.,3Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of psoriasis by promoting angiogenesis.,5 Because of its complex pathogenesis, psoriasis can not be cured completely at present. The main purpose of treatment is to control and stabilize the disease, slow down the development process, reduce clinical symptoms such as erythema, scale, plaque thickening, and pruritus, reduce short-term and long-term adverse reactions, control psoriasis-related complications, and improve patients’ quality of life.The change of microcirculation is an important histopathological change in psoriasis, which results in structural and functional changes under the action of various pathogenic factors, resulting in the occurrence and maintenance of inflammatory reaction. The changes of microcirculation can be used as an effective index to evaluate the severity of the disease, the efficacy of drugs and the monitoring of the disease. The formation of skin blood vessels includes vasculogenesis and angiogenesis, and vasculogenesis is a key factor in the pathogenesis of psoriasis. VEGF is the mediator of pathological angiogenesis and is overexpressed in the skin of patients with psoriasis. VEGF not only promotes skin angiogenesis in patients with psoriasis, but also acts as an autocrine regulator of epidermal hyperplasia, driving psoriasis keratin imbalance and epidermal hyperplasia, thus forming a characteristic lesion of psoriasis.Psoriatic lesions are characterized by a high degree of changes in the vascular network, that is, a large number of dilated, tortuous, and highly permeable skin vessels. The secretion of a variety of angiogenic growth factors promotes the expansion of the vascular network of psoriatic skin cells. Angiogenesis in psoriasis is closely related to vascular endothelial activation, angiogenesis, inflammation, and skin lesions. The correlation study on the mechanism of angiogenesis in psoriasis vulgaris showed that the expression of VEGF in skin lesions and serum of patients with psoriasis vulgaris was significantly higher than that in normal controls, suggesting that VEGF may play an important role in angiogenesis and inflammation of psoriasis and can be used as an index to evaluate the severity of psoriasis vulgaris. Related studies also show that VEGF may be an important index to judge the activity of psoriasis vulgaris.,12,13Besides, VEGF promotes the formation of cell adhesion molecules in capillaries and increases vascular permeability, resulting in the migration of leukocytes to the skin of patients with psoriasis. This process leads to the increase of oxygen consumption and the activation of angiogenic transcription factors, which makes it difficult to heal the angiogenesis and inflammation of psoriasis repeatedly.2This protocol has been registered in the Open Science Framework. The system review will be submitted to peer-reviewed journals. This protocol will be based on the preferred reporting items for systematic reviews and meta-analysis protocols 2015 statement.2.12.1.1All case-control studies and cohort studies that evaluate the relationship between serum VEGF and psoriasis vulgaris.2.1.2Patients diagnosed with psoriasis vulgaris, regardless of nationality, race, gender, age, and course of the disease.2.1.3The levels of serum VEGF.2.1.4The expression levels of serum VEGF and its correlation with psoriasis vulgaris.2.2The exclusion criteria will be as follows: duplicate literature; literature with only abstracts but no full text; literature with incomplete data; studies involving animal experiments; patients who have taken steroids within the preceding two weeks and/or taken retinoids or topical steroids within the preceding week.2.3Embase, CENTRAL, PubMed, China Biology Medicine Database, China National Knowledge Database, Wan Fang Database, and Chong Qing VIP Database will be searched to collect case-control studies and cohort studies and evaluate the relationship between serum VEGF and psoriasis vulgaris. The search time limit will be from the establishment of the database to December 2020.2.4The keywords of the search will include ‘Vascular Endothelial Growth Factors’, ‘Vascular Endothelial Growth Factor’, ‘VEGF’, ‘Vascular Endothelial Growth Factor A’, ‘Vascular Endothelial Growth Factor B’, ‘Vascular Endothelial Growth Factor C’, ‘Vascular Endothelial Growth Factor D’; ‘psoriasis’, ‘psoriasis vulgaris’, ‘plaque psoriasis’, ‘guttate psoriasis’; ‘Case-Control Studies’, ‘Case-Control Study’, ‘Studies, Case-Control’, ‘Study, Case-Control’; ‘Cohort Studies’, ‘Cohort Study’, ‘Studies, Cohort’, ‘Study, Cohort’.2.5Two researchers will independently screen the studies, extract data, and perform crosschecks. Differences will be solved through discussion with a third researcher. The data extraction includes the first author, publication time, country, sample size, VEGF detection methods, the VEGF types, outcome measure (the expression levels of serum VEGF and its correlation with psoriasis vulgaris).2.6Meta-analysis will be performed with RevMan V.5.3 software. Standardized mean difference will be used for continuous variables, and the 95% CI will be given for each effect size.2.72 index. If the I2 < 50%, studies will not be considered heterogeneous, and the fixed-effects model will be used for meta-analysis. If the I2 > 50%, we will analyse the cause of the heterogeneity by using subgroup and sensitivity analysis, and the random-effects model will be used for meta-analysis.The studies’ heterogeneity will be assessed by using the I2.7.1If there is significant heterogeneity in the included studies, we will conduct subgroup analysis according to the study types, VEGF detection methods, and the VEGF types.2.7.2Sensitivity analysis will be conducted to check the stability of the outcome by rejecting low-quality studies.2.7.3The funnel plots will be used to assess publication bias.2.7.4,16 The NOS ranges between zero up to nine stars. It will evaluate the quality of each study from the following three aspects: the selection of the study groups, the comparability of the groups, the exposure of case-control studies, and the outcome of cohort studies. The total scores are categorized into three groups: very high risk of bias (0 to 3 NOS points), high risk of bias (4 to 6), and low risk of bias (7 to 9).The quality of the included study will be assessed by the Newcastle-Ottawa scale (NOS).3–20 but there are few systematic reviews to explore the relationship between serum VEGF and psoriasis vulgaris. In this study, we will systematically evaluate the relationship between serum VEGF and the pathogenesis of psoriasis vulgaris through a comprehensive search of the literature. The results of this study will summarize the latest evidence about the relationship between serum VEGF and psoriasis vulgaris. This study will not only provide useful evidence for patients and clinicians but also provide a theoretical basis for the pathogenesis of psoriasis vulgaris.Several previous clinical studies have reported the relationship between serum VEGF and psoriasis,However, this systematic review may have several limitations. First of all, the databases we searched are limited and do not represent all the studies. Secondly, we will include both case-control studies and cohort studies, which may result in substantial heterogeneity. Third, there are a variety of methods for the detection of serum VEGF, which will become a factor in heterogeneity. We hope that this systematic review and Meta analysis can provide reliable evidence for the association between serum VEGF and psoriasis vulgaris.Conceptualization: Juan Gong, Dongwei Qi.Investigation: Hua Yang, Xueyong Tang.Supervision: Juan Gong, Dongwei Qi.Writing – original draft: Hua Yang, Xueyong Tang.Writing – review & editing: Hua Yang, Dongwei Qi.


DES gene cause hereditary and sporadic myopathies and cardiomyopathies. A subgroup of human desminopathies comprises autosomal recessive cases resulting in the complete abolition of desmin protein. In these patients, who display a more severe phenotype than the autosomal dominant cases, it has been reported that some individuals also suffer from a myasthenic syndrome in addition to the classical occurrence of myopathy and cardiomyopathy. Since further studies on the NMJ pathology are hampered by the lack of available human striated muscle biopsy specimens, we exploited homozygous desmin knock-out mice which closely mirror the striated muscle pathology of human patients lacking desmin protein. Here, we report on the impact of the lack of desmin on the structure and function of NMJs and the transcription of genes coding for postsynaptic proteins. Desmin knock-out mice display a fragmentation of NMJs in soleus, but not in the extensor digitorum longus muscle. Moreover, soleus muscle fibers show larger NMJs. Further, transcription levels of acetylcholine receptor (AChR) genes are increased in muscles from desmin knock-out mice, especially of the AChRγ subunit, which is known as a marker of muscle fiber regeneration. Electrophysiological recordings depicted a pathological decrement of nerve-dependent endplate potentials and an increased rise time of the nerve-independent miniature endplate potentials. The latter appears related to the fragmentation of NMJs in desmin knockout mice. Our study highlights the essential role of desmin for the structural and functional integrity of mammalian NMJs.Desmin, the major intermediate filament (IF) protein in muscle cells, interlinks neighboring myofibrils and connects the whole myofibrillar apparatus to myonuclei, mitochondria, and the sarcolemma. However, desmin is also known to be enriched at postsynaptic membranes of neuromuscular junctions (NMJs). The pivotal role of the desmin IF cytoskeletal network is underscored by the fact that over 120 mutations of the human  Mutations of the human desmin gene on chromosome 2q35 cause a wide variety of hereditary and sporadic myopathies and cardiomyopathies .2 and 5% CO2 at room temperature  to the same solution. In some experiments, the effect of the toxin wore off after 1–2 h and contractions resumed in response to nerve stimulation. These preparations were then exposed a second time to the toxin. Two intracellular electrodes (resistance 10–15 MΩ) were inserted within 50 μm of the NMJs under visual inspection  and endplate currents (EPCs) could be recorded  for 1 h at room temperature. Stained bundles were washed three times 5 min in PBS and embedded in Mowiol.3D Imaging was essentially performed as previously described . Images were deconvolved and analyzed using different modules in AxioVision Software. The following parameters were determined for each NMJ: volume, surface, gray sum, gray mean, and the number of fragments. More than 100 NMJs were analyzed.RNA sequencing was performed on RNA extracted from the gastrocnemius muscle of 3-month-old wild-type and desmin knock-out mice and is available by GEO accession number GSE154573t-test, or as indicated by the figure legends, and provided as real P-values that are believed to be categorized for different significance levels, like, ***P < 0.001, **P < 0.01, or *P < 0.05.Data are presented as the mean values, and the error bars indicate ± SEM. The significance is calculated by unpaired, two-tailed First, we asked for phenotypical changes of desmin knock-out mice in comparison with controls. Based on patient data, we expect a loss of muscle grip strength in the desmin knock-out mice. This might be accompanied by an impact on the bodyweight of the mice. Moreover, since pathological disorders of the skeletal muscles are often observed being age-dependent, two age stages of the mice were examined, i.e., 3–4 and 7–8-month-old mice. The weight of the mice turned out to be reduced at both stages of age . The decMany perturbations of NMJs lead to structural disorders and are often represented by fragmentation of NMJs  and being aware that also the plantaris muscle contains a decent amount of slow fiber types .The datasets generated for this study are available by GEO accession number GSE154573 (The animal study was reviewed and approved by Animal protection officer, Sachgebiet Tierschutzangelegenheiten, FAU Erlangen-Nürnberg, AZ: I/39/EE006, TS-07/11.NE, FF, MS, CT, CC, RS, and SH designed and performed the experiments. NE, FF, CC, RS, and SH prepared figures and wrote the original draft. All authors performed review and editing of the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Backgroud: Pre-eclampsia (PE) is a common pregnancy-induced hypertension disease. Some case–control studies reported the association between vascular endothelial growth factor (VEGF) gene polymorphisms  and PE risk. However, these associations were inconsistent in several studies. Therefore, we conducted this meta-analysis to assess the role of VEGF gene polymorphisms in PE more precisely.Methods: Eligible studies were searched in PubMed, Embase, Web of Science and Chinese  and WanFang) databases. Statistical analyses were performed by Stata 12.0 software. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of the association. In addition, subgroup analyses, sensitive analyses and publication bias analyses were performed to further assess this meta-analysis.Results: In total, 21 studies were included in the meta-analysis covering 2018 cases and 2632 controls. There were significant associations between VEGF polymorphisms  and PE risk in the overall populations. In the subgroup analyses, we found that rs3025039 polymorphism was associated with the increased risk of PE among Chinese. As for rs2010963 polymorphism, a significant association was observed in subgroup of Caucasian.Conclusion: The present study suggested that the two VEGF gene polymorphisms  are associated with increased risk of PE in different ethnic groups, which means that the targets may be useful genetic markers for early prediction of PE. Pre-eclampsia (PE), a common pregnancy disease diagnosed by hypertension and proteinuria, occurs in approximately 2–8% of pregnancies ,2. PE isin utero [The vascular endothelial growth factor (VEGF) gene, located on chromosome 6p21.3, is a key regulator of angiogenesis and vascular function. Therefore, VEGF is vital for the formation of trophoblasts, embryonic vasculature and maternal and foetal blood cells in utero . Abnormain utero ,9.The associations between polymorphisms of the VEGF gene and PE have been extensively studied . HoweverThis meta‐analysis was conducted in accordance with the guidance of the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement . The PRIThe inclusion criteria were as follows: (i) studies which estimated the associations between VEGF rs2010963 or rs3025039 and the susceptibility to PE; (ii) case–control studies or cohort studies of PE; (iii) patients must be clinically diagnosed for PE (blood pressure ≥ 140/90 mmHg on two measurements with ≥1+ proteinuria or 300 mg/24 h after the 20th week of pregnancy); (iv) reported the allele frequencies of both cases and controls for different genotypes; (v) genotype distribution in the control group confirmed by Hardy–Weinberg equilibrium (HWE). The exclusion criteria of the meta-analysis were: (i) non-human studies, meta-analysis, comments, letters, reviews, mechanism studies or studies without controls, (ii) studies with overlapping or incomplete data. When overlapped population between studies was identified, only the newest or most complete article was included in the analysis. According to the corresponding criteria, two independent authors screened the articles.Data were extracted by two authors independently from each study. The following information was collected: first author, publication year, participants’ country, ethnicity , sample size, study design (case–control or cohort), genotyping method, alleles and genotype frequency distribution in cases and controls, and the major conclusion of the study. When incomplete or apparent conflicting data were found in the article, we made an attempt to contact authors. Inconsistencies in data interpretation were resolved with discussion. The Newcastle–Ottawa Quality Assessment Scale (NOS) was employed to evaluate the methodological quality of the identified articles, and scores ranging from 0 (the worst) to 9 (the best) were assigned based on the quality of the studies. The studies with no less than 5 stars were considered to be of high quality.P<0.05). Stata 12.0 was used to perform quantitative meta-analysis. The association was estimated with four models: Allele comparison model, Dominant model, Recessive model and Homozygote model. The four models of the data analysis were conducted by the random-effects model to prevent exaggerated results. The association between the VEGF rs3025039 or rs2010963 and PE risk was assessed by the raw odds ratios (ORs) with 95% confidence intervals (CIs). The Student’s t test was used to determine the significance of the crude OR, and P<0.05 was considered statistically significant. In addition, heterogeneity assumption among the included researches was evaluated by the Chi-square and 2I, which was regarded to be statistically significant if P<0.10. And 2I values of 25, 50 and 75% were nominally assigned as low, moderate and high estimates. To insure that any single study did not cause an obvious influence to the whole effects, sensitivity analysis was performed to estimate the validity and stability of the study. In addition, to further analyze the source of the heterogeneity and the specific association between the VEGF polymorphism and PE, studies were also divided into several subgroups on the basis of the country, the ethnicity of the related population and the genotyping method. Egger’s test was performed to estimate the potential publication bias.First, deviation from HWE in the distribution of allele frequencies was estimated again by the chi-square test  and others were acceptable. An analysis of 1148 cases and 1388 controls for rs2010963 showed the C allele in allele comparison model, CC and CG genotype in the recessive model and CC genotype in the homozygous model increased the risk of PE significantly , the Dominant model showed low heterogeneity (2I < 0.001%), the Recessive model showed high heterogeneity (2I = 71.6%) and the Homozygote model showed moderate heterogeneity (2I = 32.3%). However, no significant association was found in the Korea’s subgroup and other countries’ subgroup, and relatively high heterogeneity was observed in the almost all models of the two subgroups except in Dominant and Homozygote model of other countries’ subgroup, which indicated the differences of population countries were not the major cause of the heterogeneity for rs3025039 in this meta-analysis. Then, we performed an ethnic restriction including Xanthoderm, Caucasian and Indo-European hybrid for further subgroup analysis in rs3025039. No significant association was observed in the any model, and the heterogeneity of various models in different subgroups showed no significant reduction. Next, subgroup analysis was performed in rs3025039 according to the genotyping methods including MassARRAY system, Sequencing, PCR-RFLP and Snapshot. A significantly increased risk was found in the Sequencing and PCR-RFLP subgroup, but a protective effect was found in the MassARRAY system subgroup with Allele comparison model and Snapshot subgroup with Recessive model. The heterogeneity of all the subgroup in the four models were relatively low, which indicated that the genotyping methods might be the major source of the heterogeneity.The subgroup analyses were carried out due to the heterogeneity of result and biases of the different subgroups. The results of subgroup analyses were shown in P=0.046; Homozygote model: OR = 1.461, P=0.039), and other subgroups showed no obvious difference. Moreover, the heterogeneity of allele comparison model and homozygote model in Caucasian subgroup was low . However, the difference between the overall heterogeneity and subgroup heterogeneity was not apparent, illustrating that the ethnicity was not the important cause of heterogeneity in the meta-analysis. Regarding the genotyping methods subgroups, we divided into three groups: Sequencing, PCR-RFLP and other methods, owing to the duplicating number of the genotyping methods. The result of the Sequencing subgroup showed a statistically significant in Allele comparison model and Homozygote model with indistinctive heterogeneity . Besides, heterogeneity of the Sequencing and PCR-RFLP subgroups in all models was not significant (2I < 0.1%), while heterogeneity of other methods subgroups was higher. The results suggested that the source of the heterogeneity might be the genotyping methods, consistent with the conclusion above.For rs2010963, we performed the subgroup analysis based on ethnicity and genotyping methods, because the overlapping countries were limited. The subgroups of ethnicity were divided as the same as the subgroups of rs3025039. A significant association was observed in the Caucasian subgroup with both Allele comparison model and Homozygote model , Amosco et al. (2016), Salimi et al. (2015), Silva et al. (2014), Zhang Honghui et al. (2014), Procopciuc et al. (2014), Atis et al. (2012), Chen Baoli et al. (2011), Liu Shifang (2010)); second, multiple subgroups were divided to be analyzed; thereby a more adequate statistical power was gained in our study. Similar to the published researches, we found significant associations between the two VEGF gene polymorphisms  and PE, suggesting VEGF gene variants in rs3025039 and rs2010963 loci might be involved in the development of PE. Our results provide evidence of a significantly increased risk about rs3025039 polymorphisms for PE with the four models. Compared with the previous meta-analyses, a significantly increased risk for PE was observed in rs2010963 polymorphisms with less heterogeneity except for the Dominant model. In the stratified analysis by ethnicity and countries for rs3025039, a significantly increased risk of pre-eclampsia was observed in studies conducted among Chinese population. As for subgroup analyses of ethnicity in rs2010963, a statistically association was found in the Allele comparison and the Homozygote models of Caucasian.2I < 40%, P>0.10), where the results of the PCR-RFLP and Sequencing were consistent with the total result , but different from the result of the other genotyping methods. Similarly, the heterogeneity of the three subgroups covering PCR-RFLP and Sequencing and other methods was different for rs2010963 polymorphism. The heterogeneity of the PCR-RFLP and Sequencing subgroup was quite low , whereas the heterogeneity of the other methods subgroup was extensive (2I > 40%). The reason could be that studies in each subgroup are relatively few or different genotyping methods may influence the genotyping result. This observation is similar to previous studies, in which differences in genotyping methods might contribute to heterogeneity [In addition, the heterogeneity could be accounted for by the subgroup analysis of genotyping methods. For rs3025039 polymorphism, the subgroup analyses of four genotyping methods including MassARRAY system, Sequencing, PCR-RFLP and Snapshot all showed low levels of heterogeneity , which may limit the statistical power. Third, the recruitment criteria of patients and controls varied in different studies. Finally, gene–gene or gene–environment interactions were not considered in the present study—such as age, smoking, alcohol status and mental state—which may have influenced the associations between VEGF gene polymorphisms and PE risk. Nevertheless, this meta-analysis improves our understanding of the associations between two polymorphisms of VEGF gene and the risk of PE.In conclusion, the two VEGF gene polymorphisms are associated with an increased risk of pre-eclampsia in different ethnic groups, respectively. A large number of and high-quality studies are required to establish more precise evidence and minimize the bias in meta-analysis.Click here for additional data file.


Background: It was difficult to distinguish the cartilage thinning of an entire knee joint and to track the evolution of cartilage morphology alongside ages in the general population, which was of great significance for studying osteoarthritis until big imaging data and artificial intelligence are fused. The purposes of our study are (1) to explore the cartilage thickness in anatomical regions of the knee joint among a large collection of healthy knees, and (2) to investigate the relationship between the thinning pattern of the cartilages and the increasing ages.Methods: In this retrospective study, 2,481 healthy knees  were recruited. With magnetic resonance images of knees acquired on a 3-T superconducting scanner, we automatically and precisely segmented the cartilage via deep learning and calculated the cartilage thickness in 14 anatomical regions. The thickness readings were compared using ANOVA by considering the factors of age, sex, and side. We further tracked the relationship between the thinning pattern of the cartilage thickness and the increasing ages by regression analysis.Results: The cartilage thickness was always thicker in the femur than corresponding regions in the tibia (p < 0.05). Regression analysis suggested cartilage thinning alongside ages in all regions (p < 0.05) except for medial and lateral anterior tibia in both females and males (p > 0.05). The thinning speed of men was faster than women in medial anterior and lateral anterior femur, yet slower in the medial patella (p < 0.05).Conclusion: We established the calculation method of cartilage thickness using big data and deep learning. We demonstrated that cartilage thickness differed across individual regions in the knee joint. Cartilage thinning alongside ages was identified, and the thinning pattern was consistent in the tibia while inconsistent in patellar and femoral between sexes. These findings provide a potential reference to detect cartilage anomaly. Osteoarthritis (OA) is a chronic, disabling joint disease with a total incidence of 15% in populations . OA causTherefore, it is necessary to systematically analyze structural changes of knee cartilage by magnetic resonance (MR) imaging to better understand the development of OA and to focus on early detection and disease prevention. Previous studies reported cartilage/meniscus segmentation and quantification , evaluatConcerning the necessity to examine the critical role of articular cartilage in the whole knee joint, we conducted a comprehensive and in-depth big data study to track the thickness changes of knee cartilage in this work. Specifically, we quantified the cartilage morphology by automatic image segmentation powered by deep learning and standardize the knee cartilage thickness among a large Chinese population of healthy knees. We aim to compare the cartilage thickness among different age groups and associate the thickness readings with 14 individual ROIs in the knee joint according to the whole-organ magnetic resonance imaging score (WORMS) . In thisThis research project was approved by the institutional review board, Tongren Hospital, Shanghai Jiao Tong University School of Medicine. Subjects were retrospectively selected from the hospital database with both plain films and MR images from January 2018 to March 2019. Images of the knees were acquired on a 3-T superconducting MR scanner  with an eight-channel knee coil . The knee flexion angle was kept naturally bent, and a dedicated holder was used to reduce motion artifacts at the time of acquisition. The MR protocol included four sequences : (1) sagTo facilitate region-based analysis of cartilage thickness, the knee MR image was divided into 14 structural ROIs, including anterior (A), central (C), and posterior (P) regions of the medial (M)/lateral (L) femur (F), tibia (T), and patella (P), with exemplar delineation in A neural network was used to segment knee joint from MR images automatically. Similar to Norman et al. , we chosDSC = 2|A∩B|/(|A|+|B|), where A and B were the reference segmentation  and automatic segmentation, respectively, whereas the operator |·| counts the number of elements in the set. The value of DSC ranges from 0 to 1, and the higher value indicates better segmentation performance. We used 27 subjects (570 slices) for training and 20 subjects (471 slices) for testing. The segmentation DSCs of femoral cartilage, tibial cartilage, and patellar cartilage were 0.87 ± 0.01, 0.82 ± 0.01, and 0.76 ± 0.04, respectively, which were comparable with manual labeling  was used to evaluate the accuracy of segmentation. DSC was calculated with ling see . The repling see .With the development and degeneration of normal human cartilage, the cartilage thickness at different regions of the knee joint changes gradually. On the basis of the automatic segmentation results described earlier, we could calculate the cartilage thickness  followinNext, we used an atlas with predefined ROIs to complete the segmentation of individual regions per subject. The atlas was labeled to delineate all 14 ROIs. By deforming the atlas to align with each subject image via one-by-one registration, we acquired ROIs for all collected images. Then, for each subject MR image, we calculated the cartilage thickness and derived the average measure for each region . The carCartilage thickness of different regions, ages, sexes, and sides were compared using ANOVA pairwise comparisons method Tukey. Tukey's method is used in ANOVA to create confidence intervals for all pairwise differences between factor level means while controlling the family error rate to a level specified. An alpha level of 0.05 was set for statistical significance, and all tests were two-tailed. In the Tukey simultaneous test results, the 95% simultaneous confidence level implies that all the confidence intervals contain the true differences. If an interval does not contain zero, the corresponding means are significantly different.p-value lower than 0.05 indicates that this difference is statistically significant. In other words, we could conclude that sex/laterality affects the relationship between input and output. The consistent (or inconsistent) change with age implies no significant (or significant) difference between sexes/lateralities. The analyses mentioned earlier were performed in Minitab Version 19.1, and the figures were drawn in Python 3.7.Regression analysis of cartilage thickness changes in 14 regions with sex/laterality was performed with a fit regression model. We created a categorical condition variable, i.e., sex/laterality. Then, we included the interaction term for input × condition, i.e., age × sex/laterality. We fit the regression model with input (continuous independent variable), condition (main effect), and input × condition (interaction effect). The coefficient of age × sex/laterality represents the difference between the coefficient for males and females. The p < 0.05 in all above tests}. In the femur particularly, the cartilage thickness in the non-load-bearing areas  was greater than the load-bearing C areas (FMC and FLC) and P areas (FMP and FLP) . On the contrary, for the tibia, the C areas of TMC and TLC led in the thickness measuring, compared with A and P areas .The average thickness of each ROI over all subjects was plotted in p < 0.05 in all tests mentioned earlier). The largest margin for the sex-related cartilage thickness occurred in FLA (0.27 ± 0.01), contrary to the smallest difference in TMP (0.04 ± 0.01).For each ROI, the thickness reading was further separated into male and female sexes and was compared in p < 0.05 in tests mentioned earlier). In all TL regions, the same findings were revealed . However, no significant difference between the left and right sides was detected in TMA, TMC, and the patella (p > 0.05).The thickness measured in p > 0.05), whereas others became thinner. Meanwhile, considering the inconsistent six regions, the cartilage thickness in FMP increased slightly alongside age for women  and in other ROIs decreased temporally . The thinning speed in the FMA area was faster in men than in women  and, in contrast, slower for men in the PM area . Additionally, the cartilage degenerated in the ROIs of FMC, FLA, and FLP for men , whereas women's changes were not statistically significant .For each ROI, the regression model of the cartilage thickness with respect to ages was derived for both men and women. The models for all 14 ROIs are shown in p > 0.05 for all age × laterality coefficients except for FMC). Among the consistent regions, the cartilage thickness in the TMA and TLA regions did not change significantly with age , FMP increased with age , and others degenerated . That is, both knees tended to degenerate in a synchronized manner.Further, the regression models were fitted for the left and right knees and compared with the entire population in We used the deep learning method to automatically segment the cartilage and calculated the cartilage thickness in 14 individual regions of the whole knee joint. For the first time, we specified the characteristics of cartilage thickness across 14 nonoverlapping ROIs of the knee joint and tracked their thinning alongside aging, which provided a standardized reference to reveal the pathogenesis of knee OA potentially. From our findings, male cartilage thickness was greater than female in all age groups across the knee joint. Furthermore, the thinning was inconsistent from PM and all femoral ROIs except for FLC between men and women. Age and sex do play a role in cartilage thinning despite the diversity in men and women. Differences in cartilage thickness may further suggest varying risks of developing knee OA between women and men , 23.So far, only one study using deep learning to assess the thickness of femoral cartilage has been reported . ParticuOur study filled the vacancy with increasing ages in a relatively younger population (mean age: 36 years), comparing our results with another large population-based cross-sectional study, i.e., Framingham OA study investigating knee MR imaging in the middle-aged and elderly population (mean age: 62 years) –27. The Based on the regression analysis of men and women, we found that the cartilage thickness in the FMP region of bilateral knees of women increased with age. Previous studies , 29 alsoGiven the regression results of left and right knees, we found that the cartilage thinning pattern was always consistent except for FMC only. Moreover, previous studies , 32 alsoThere existed several limitations in our study. Firstly, our sample size was skewed to a certain extent, resulting in the relatively young age distribution . Secondly, our segmentation protocol did not include high-resolution three-dimensional imaging, and we would further use the three-dimensional sequences of the knee joint to improve our segmentation model in the following research. Thirdly, because the assessment was blindly performed by two practicing board-certified musculoskeletal radiologists without identification and health information of patients, we did not assess more information such as body mass index and medical history such as common chronic diseases. Finally, we did not accomplish follow-up exams in this cohort to obtain and compare its cartilage information to make more accurate predictions, which would be a potential direction for future research.In conclusion, prevalent cartilage thickness differences existed across individual regions in the knee joint, by considering the factors of age, sex, and side, with respect to a large population of 2,481 subjects and their 3-T MR images. Cartilage thinning alongside ages was identified for both men and women. The thinning pattern was consistent in the tibia while partially inconsistent from patellar and femoral cartilages between women and men. The findings earlier may provide references to detect cartilage anomaly.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Ethics Committee of Shanghai Sixth People's Hospital. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.KX and QW: computer programming and manuscript editing. WY and HZ: guarantors of integrity of entire study and study concepts/study design. LS and KX: statistical analysis and experimental studies. LS and JH: data acquisition or data analysis/interpretation. LS, JZ, YX, JG, and YH: literature research and manuscript revision. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.