Obesity has been reported to be associated with frailty and coronary artery disease (CAD).  The present study aimed to investigate the role of the seven traditional obesity parameters body mass index (BMI), waist-height ratio (WHtR), waist-hip ratio (WHR), body adiposity index (BAI), body shape index (BSI), waist circumference (WC), and hip circumference (HC) in the prediction of frailty among CAD patients undergoing cardiac catheterization. Setting. Three main hospitals were located at the northern and middle regions of Jordan. Participants. 220 hospitalized patients undergoing cardiac catheterization were recruited. Measurements. The traditional obesity parameters were measured using an anthropometric tape and weight scale and frailty was measured using the Tilburg Frailty Indicator (TFI). Data were analyzed using bivariate Pearson's correlation and forward linear regression analysis.  A secondary data analysis was conducted. p < 0.05). The model of the seven predictors explained 32.4% of the variance in frailty (p = 0.02).  Total cholesterol, HC, triglycerides, age, random blood sugar, and WC had significant positive associations with and were predictors of frailty ( The incidence of frailty can be predicted by the increase in total cholesterol, HC, triglycerides, age, random blood sugar, and WC. The results of this study may help healthcare providers, including nurses, to identify the factors that could lead to frailty among CAD patients undergoing cardiac catheterization. Obesity is conceptually described as the excessive accumulation of fatty tissue across the human body, predisposing patients to several health risks . The WorObesity is considered a strong contributing factor for the progression of frailty . FrailtySeveral factors have been reported to be associated with the incidence of frailty. As compared to younger people, older people have a higher tendency to become frail, which may be due to their increased risks of having chronic diseases like diabetes mellitus, hypertension, and dyslipidemia . FurtherThus, obesity was revealed as one of the major risk factors for coronary artery diseases (CADs) among patients undergoing cardiac catheterization. Frailty might be coexistent with frailty among those risky patients. Thus, the detection of frailty among patients with CADs undergoing cardiac catheterization should be based on holistic approach, using not merely one instrument, but the traditional obesity parameters as well as health and biomarkers might provide a better scope of frailty. Therefore, this study aimed to investigate the role of the seven traditional obesity parameters BMI, waist-height ratio (WHtR), waist-hip ratio (WHR), body adiposity index (BAI), body shape index (BSI), WC, and hip circumference (HC) as well as health and biomarkers in predicting frailty among CAD patients undergoing cardiac catheterization.A secondary data analysis was adopted from an original study . The aimG power with the following settings: F test as family test and linear hierarchical multiple regression with effect size 0.15, alpha error probability of 0.05, power of 0.8, and number of predictors of 25. To account for any possible dropouts, an additional 25% of the required sample size was added, and a total of 220 participants were recruited using convenience sampling.The study participants were recruited from two major referral hospitals in the middle and north regions of Jordan. Data were collected from the participating patients before they underwent cardiac catheterization. Data collection took place in the hospital wards, including medical wards, coronary care units, intensive care units, and emergency departments, before the patients were transferred to the catheterization laboratories. The required sample size was calculated as 172 patients using The inclusion criteria included being a Jordanian male or female aged 18 years or over and being a hospitalized patient undergoing either elective or urgent cardiac catheterization. Meanwhile, the exclusion criteria included being a patient with severe organ disease, such as severe liver disease and renal failure, being pregnant, having undergone coronary artery bypass graft surgery, having an autoimmune disease, being an immunosuppressed patient who has undergone organ transplant, and being a cancer patient.The independent variables, which included the obesity parameters and the basic data , were recorded by well-trained registered nurses. These nurses had completed three training sessions of one hour each, delivered by the primary researcher. The data were collected at the admission assessment before cardiac catheterization using a flexible anthropometric tape for WC and HC, and a rigid anthropometric tape for height and weight. Participants were recruited during the period from March 18, 2021, to July 18, 2021.Data pertaining to the participants' sociodemographic and health characteristics were collected from the patients themselves or from their medical files. These characteristics included age, gender, education, marital status, income, employment, smoking status, blood pressure, and daily activity based on the number of daily steps. Serology tests were also collected, including low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride, high-sensitivity C-reactive protein (HS-CRP), random blood sugar (RBS), and hemoglobin A1c (HbA1c).Anxiety and depression levels were analyzed as continuous variables (score from 1 to 21) and measured using a psychometric tool. The Hospitalized Anxiety and Depression Scale (HADS), developed by Zigmond and colleagues , is a tom) 〗 ^ 1.5–18) was used to calculate BAI.As with regard to the traditional obesity parameter measurements, weight was measured to the nearest 0.1 kg using a rigid measurement device and with the participants wearing their hospital gowns. Waist circumference was measured at the midpoint between the lowest rib margin and the level of the anterior superior iliac crest, using a flexible anthropometric tape and with measurements rounded to the nearest 0.1 cm. Hip circumference measurements were taken at the greatest protrusion of the gluteal muscles and also rounded to the nearest 0.1 cm. Waist hip ratio was calculated as WC/HC, and WHtR as WC/height. The formula (WC (cm))/(〖BMI〗 ^ 2/3) × (〖Height (m)〗 ^ 0.5) was used to calculate BSI, and the formula (weight (kg))/〖height (m)〗 ^ 2) was used to calculate BMI. The formula (HC (cm))/〖height (r) values have been reported for the physical (−0.71), psychological (r = −0.68), social (r = −0.40), and environmental (r = 0.54) domains  [Frailty was measured using the Tilburg Frailty Indicator (TFI) prior to the patients undergoing cardiac catheterization. The TFI is a 15-item self-report questionnaire used to measure frailty . The TFIdomains) . Furtherdomains) .An acceptable Cronbach's alpha value (0.771)  has beenT test was used for variables with two categories, such as gender, and “ANOVA test” was used for variables with more than two categories, such as employment status, marital status, and educational level. Forward linear regression was employed to assess the ability of the obesity parameters and sociodemographic and health variables to predict frailty. The Statistical Package for the Social Sciences software version 25 (SPSS) was used to analyze the study data. A significance level of 0.05 was used in the current study.Means and standard deviations were used to describe the continuous variables, such as age, and frequencies and percentages were used to describe the categorical variables, such as gender. Bivariate Pearson's correlation was employed to assess the correlation (strength of relationship between variables) between the obesity parameters, socio-demographic and health variables, and frailty. After obtaining institutional review board approval from Jordan University of Science and Technology and approval from the selected hospitals, consent forms were obtained from the participants prior to their participation. These forms outlined the participants' rights to withdraw from the study at any time without consequences, in addition to the intended benefits and risks of participation. The principal researcher and trained research assistants explained the study's purpose, procedures, intended benefits, and potential risks to all of the participants. The participants were provided with time to read the consent forms and ask any questions about the study prior to them deciding whether to participate in the study.The average age of the participants was 49.9 years (SD ± 11.7), with ages ranging between 24 and 90 years. Around two-thirds (73.2%) of the participants were male, and the majority of the participants (62.3%) were married. As for the employment status, approximately half of the participants (49.1%) were employed. Further, 38.2% of the participants were nonsmokers, while the rest (61.8%) were smokers. Around two-thirds (72.7%) of the participants had anxiety, and around half (45.5%) had depression see .Correlations (Pearson's correlation) between the traditional obesity parameters and frailty were built in order to assess the relationships between these parameters. Frailty was found to have significant positive weak correlations with weight, WC, HC, and BAI, as shown in p < 0.001), while model (7), which had seven predictors, explained 32.4% of the variance (p=0.02). Model (7) illustrated that increased total cholesterol by 7.1 mg/dl (β (0.288)∗ SD (24.7)), increased HC by 8.3 cm (β (0.62)∗ SD (13.4)), increased age by 8.3 years (β (0.245)∗ SD (11.4)), increased triglycerides by 8.6 mg/dl (β (0.25)∗ SD(34.3), increased RBS by 4.9 mg/dl (β (0.214)∗ SD(23)), or increased WC by 4.4 cm (β (0.329)∗ SD(13.3)) increased frailty by 1 score (p < 0.05). However, increased HDL by 0.7 mg/dl (β (0.146)∗ SD (4.8)) decreases frailty by 1 score (p=0.02).To test the relationship between the model of obesity parameters, health variables, and sociodemographic variables and frailty, statistical analysis was carried out using a forward regression analysis as shown in The relationships between frailty and its possible predictors  were investigated. It was concluded that there were strong and moderate relationships between frailty and its possible predictors among CAD patients undergoing cardiac catheterization.Our study found that the increase in age could increase susceptibility to becoming frail, which is consistent with the findings of previous studies. Casals and colleagues , MatsuokAs for the relationships between health variables and frailty, this study found that total cholesterol, triglycerides, RBS, and HDL were significantly and positively associated with frailty. Casals and colleagues  found thThis study found that participants with hypertension II (≥169/≥100 mmHg) had a higher tendency to be frail than did participants with normal blood pressure (100–129 to 60–89 mmHsg). In accordance with our study results, Liu and colleagues  and Vetr2, or WC > 88 cm) is positively associated with frailty. They justified their results by pointing out that in older adults, height is decreased and abdominal girth is increased, which could result from the weakening of muscle and increase in the fat composition of the older body.The present study findings indicated that frailty had significant positive associations with HC and WC among CAD patients undergoing cardiac catheterization. Similarly, Zaslavsky and colleagues  found thThis study addressed numerous significant traditional obesity parameters and health and biomarkers that might assist healthcare providers, including physicians and nurses, in detecting patients with CADs who are at higher risk for frailty while undergoing cardiac catheterization. This might provide a better scope of frailty and tailor the appropriate interventions to those risky patients on a timely manner. Similarly to this implication, a previous study indicated that future studies of frailty should address the significance of health-function indicators in detecting elderly patients who at higher risk for frailty, and in turn, planning effective healthcare .The results of the current study should be used cautiously due to numerous limitations. This study should be replicated with different populations, particularly with variant level of cardiovascular risk profile and metabolic syndrome, which might provide inconsistent findings pertaining to frailty. Moreover, in this study, the traditional cardiovascular risk factors and other risk factors contributed to frailty for 32% in the established model. Consequently, there are numerous factors that might negatively affect the health status of those risky patients, and which in turn, further investigations are needed to address these factors.The predictors of frailty were total cholesterol, HC, triglycerides, age, random blood sugar, WC, and HDL. Participants educated to primary school level had a higher tendency to be frail than did illiterate participants. Further, hypertension II participants (≥169/≥100 mmHg) had a higher tendency to be frail than did participants with normal blood pressure (100–129/60–89 mmHg). The findings of this study could help healthcare providers, including nurses, to identify the factors that could lead to frailty among CAD patients undergoing cardiac catheterization.


Salmonella enterica serovar Enteritidis (S. Enteritidis), we focused on the common response of cecal microbiota to an inflammatory state in respect of transcriptome and microbiome. The inoculation of S. Enteritidis improved the microbial diversity and promoted the microbiota evolution in our infection model. Correlation analysis between bacteria and inflammation-related genes showed that some intestinal microorganisms were “inflammophile” and thrived in an inflamed environment. The global function of cecal microbiome was to maintain the homeostasis likely by the up-regulation of microbial metabolism pathway in bacitracin, putrescine, and flavonoids production, although the bacitracin may affect the symbiotic bacteria Enterococcus. The action of S. Enteritidis had close relationships with multiple inflammation-related genes, including the genes PTAFR, LY96, and ACOD1 which proteins are related to the binding and tolerance of LPS, and the genes IL-18, IL-18R1 and IL-18RAP which products can form a functional complex and transmit IL-18 pro-inflammatory signal. Additionally, the infection of S. Enteritidis aroused the transcription of EXFABP, which protein has a potential to sequestrate the siderophore and might cause the decline of Escherichia-Shigella and Enterococcus. S. Enteritidis can escape from the sequestrating through the salmochelin, another kind of siderophore which cannot be recognized by EXFABP. Probably by this way, S. Enteritidis competed with the symbiotic bacteria and edged out the niches. Our research can help to understand the interplay between host, pathogen, and symbiotic bacteria.By combining the experiments of reciprocal crosses of chicken infected with  Animal gastrointestinal tracts are highly populated with a diverse array of microorganisms that share a symbiotic relationship with their hosts and contribute to the overall health and disease state of the intestinal tract . MicrobiSalmonella enterica is a kind of facultative intracellular pathogens , which is most frequently associated with diarrheal disease in humans but can colonize chicken intestine with little clinical symptoms  with ad libitum access to water and antibiotic-free feed. The strain of S. Enteritidis (CVCC3377) was purchased from China Veterinary Culture Collection Center . After rejuvenation with nutrient broth , the bacterial solution was centrifuged at 4,000 rpm for 5 min and suspended again with sterilized PBS to 1.0 × 108 cfu/ml. At 2-day old, the birds of treatment group were orally inoculated with 0.3 ml S. Enteritidis, and the birds of control group were mock inoculated with the same volume of PBS. At 3 days post-inoculation (dpi), 9 to 12 birds in each group were sacrificed. The cecal contents and cecum tissues were collected aseptically for 16S rRNA gene sequencing and RNA sequencing, respectively. The experimental procedure was repeated on another crossbreed. Thus four groups were generated as Cross Control , Cross Treatment , Reverse-cross Control , and Reverse-cross Treatment . The animal experiment was approved by the Laboratory Animal Management and Use Committee of Shandong Agricultural University (Permit Number: SDAUA-2018-058). We strove to reduce the suffering of animals.As described previously , the chiS. Enteritidis infection between two inbred lines  according to manufacturer’s protocols. The final DNA concentration and purification were determined by NanoDrop 2000 , and DNA quality was checked by 1% agarose gel electrophoresis. The V3-V4 region of the bacteria 16S rRNA gene was amplified by PCR using the following primer pair: 338F, ACTCCTACGGGAGGCAGCAG, and 806R, GGACTACHVGGGTWTCTAAT. PCR reactions were performed in 20 μl mixture containing 4 μl 5 × FastPfu Buffer, 2 μl 2.5 mM dNTPs, 0.8 μl 5 μM each primer, 0.4 μl FastPfu Polymerase and 10 ng template DNA under the following cycling conditions: 3 min at 95°C followed by 27 cycles of 30 s at 95°C, 30 s at 55°C and 45 s at 72°C, and a final 10 min at 72°C. The pooled products were paired-end sequenced (2 × 300) on the Illumina MiSeq platform  according to standard protocols.Raw fastq files were demultiplexed, quality-filtered by Trimmomatic and merged by FLASH with the following criteria: (i) The reads were truncated at any site receiving an average quality score < 20 over a 50 bp sliding window. (ii) Primers were exactly matched allowing 2 nucleotide mismatching, and reads containing ambiguous bases were removed. (iii) Sequences whose overlap longer than 10 bp were merged according to their overlap sequence. Operational taxonomic units (OTUs) were clustered with 99% similarity cut-off using UPARSE and chimeric sequences were identified and removed using UCHIME. The taxonomy of each 16S rRNA gene sequence was analyzed by RDP Classifier algorithm against the Silva138 16S rRNA database using confidence threshold of 70%. 16S rRNA gene sequencing and the preliminary analysis were completed in Majorbio Biotech Co., Ltd. .t test and so on, which details were recorded in the results. Most of them were run on the OEBiotech CloudWe performed the analyses of DESeq2, BugBase, PICRUSt1, Wilcoxon rank-sum test, Studen’s The transcriptome data and the microbiome data were deposited in National Genomics Data CenterS. Enteritidis (OTU607) was detected in treatment groups (CT and RT) but not in the control groups , which were clustered into 943 OTUs  includinn = 20) and MT (n = 20), respectively. Analysis on OTU level showed that the richness estimate with Sobs , but the latter had a tendency of increase. At the same time, the evenness estimate with Shannoneven . Under the co-action of richness and evenness, the diversity estimate of MT with Shannon . It should be noted that the diversity analysis within each crossbreed had the similar result  and the treatment groups (CT and RT) into MC  while Proteobacteria decreased from 32.80 to 23.64% (p = 0.044).The Firmicutes and Proteobacteria phyla were dominant in the cecal microbiota of 5-day-old chickens regardless of whether d or not . Comparep = 0.044) and its Escherichia-Shigella genus , though its two other genera Salmonella  and Klebsiella  had an increase compared to control.Further analysis on family  and genuS. Enteritidis inoculation  and NK4A136 group , Sellimonas  and Blautia . A norank genus of Ruminococcaceae family was increased significantly  though the overall increase of this family was not marked (p = 0.239). Erysipelotrichaceae family was almost composed of Clostridium innocuum group, which increased markedly after inoculation . It is worth noting that, contrary to the overall up-regulation of Firmicutes phylum, Enterococcaceae family and its only Enterococcus genus decreased notably after inoculation .For Firmicutes phylum, the Lachnospiraceae family had the largest increase after p < 0.05), but the facultative anaerobes, the bacteria containing mobile elements, and the potential pathogen were increased (p < 0.05). As S. Enteritidis only contributed about 1% of the proportion, we deduced that the phenotypic differences were derived from cecal microbiota rather than S. Enteritidis alone.To explore the influence of microbiota change on phenotype, we used the BugBase tool to predict the phenotypes . After ip < 0.05, Student’s t test), including D-Arginine and D-ornithine metabolism , Flavonoid biosynthesis , Flavone and flavonol biosynthesis , Steroid hormone biosynthesis , N-Glycan biosynthesis , Atrazine degradation , Other glycan degradation , Biosynthesis of siderophore group nonribosomal peptides , and Fluorobenzoate degradation .In addition, we used the PICRUSt1 tool to predict the functions of cecal microbiota. Among the 125 metabolic pathways on level three , 9 pathwp < 0.1 (Student’s t-test between MC and MT) in category 1 were decreased after inoculation, including OTU825 (Escherichia-Shigella), OTU275 (Enterococcus), OTU669 (an unclassified of Lachnospiraceae), and OTU668 (an unclassified of Lachnospiraceae), while all the OTUs with p < 0.1 in category 2 were increased after inoculation, including OTU607 , OTU269 (Negativibacillus), OTU150 (Flavonifractor), OTU896 (Clostridium innocuum group), OTU949 (a norank of Ruminococcaceae), OTU868 (an unclassified of Lachnospiraceae), and OTU886 (an unclassified of Lachnospiraceae). We inferred that the microbes in category 2 were more adaptable to the inflamed cecal environment than the ones in category 1.The host’s genes can not affect intestinal bacteria directly, but there must be some indirect relationships between them, especially for the inflammation-related genes. As the 12 transcriptomic samples were overlapped with the microbiomic samples, we constructed the correlation analysis with the most abundant 50 OTUs and the 30 genes enriched in inflammatory response term . The resS. Enteritidis (OTU607) was correlated positively with genes PTAFR, EXFABP, IL18, IL18R1, IL18RAP, PSTPIP1, TLR2A, LY96, CCL4, BCL6, TLR15, CCR2, ACOD1, and THEMIS2 (p < 0.05). By retriving the functions of these genes in NCBI, we found that the proteins encoded by PTAFR, LY96, and ACOD1 are related to the binding and tolerance of lipopolysaccyaride (LPS); the products of IL-18, IL-18R1 and IL-18RAP can form a functional complex and transmit IL-18 pro-inflammatory signal, which is capable of stimulating interferon gamma production [the gene IFNG was increased by 18.06 times (Padj = 3.33E-06) at mRNA level in our RNA-seq data], and of regulating both T helper (Th) 1 and Th2 responses. Importantly, EXFABP [increased by 14.19 times (Padj = 5.43E-09) in our RNA-seq data and 14.62 times  in RT-qPCR data compared to control] encodes a conserved domain (NCBI: cd19439), which is bacteriostatic and tightly binds the 2,3-catechol-type ferric siderophores associated with enteric bacteria and Gram-positive bacilli. These data indicated that the host’s inflammatory response was closely related to the S. Enteritidis infection.Additionally, we found S. Enteritidis treatment compared to control. It is suggested that the inoculation of S. Enteritidis, a non-host specific pathogen, can phenotypically promote the evolution of chicken microbiota from single species to a complex community at newly hatching period. This might be due to the inflammation and the environmental changes, which broke the original ecological balance and induced some low-abundance species to proliferate.Bacterial colonization of the intestinal tract begins after birth or hatching, or earlier . In chicS. Enteritidis inoculation. This discrepancy may be caused by many factors including bacterial strains and concentration, chicken breeds and age, etc. For example, Our result at this point is contrary to previous studies , which rS. Enteritidis. Another important metabolic pathway is the Biosynthesis of siderophore group (KEGG: ko01053). Some bacteria including Escherichia coli . There are two key products derived from this module, bacitracin and putrescine. Bacitracin is a natural polypeptide antibiotic and interferes with the peptidoglycan synthesis of Gram-positive microorganisms . Putreschia coli  possess Microorganisms have evolved the ability to thrive in host gastrointestinal tract, including in states of inflammation . AccordiSalmonella can entry into epithelial cells via a type III secretion system, which is present and conserved in all Salmonella serotypes tested . The marked decrease of Enterobacteriaceae family and Enterococcaceae family (Bacilli class) let us image that triction . Additioerophore , which mS. Enteritidis, the response of cecal microbiota was diverse. Some bacteria such as Salmonella, Negativibacillus, Flavonifractor, and Clostridium innocuum group had a preference for inflammation and outgrew other bacteria. The action of S. Enteritidis had close relationships with multiple inflammation-related genes, such as PTAFR, LY96, ACOD1, IL-18, IL-18R1 and IL-18RAP. Additionally, the challenge of S. Enteritidis aroused the transcription of EXFABP, which protein can sequestrate the siderophore secreted by enteric bacteria and Gram-positive bacilli, such as Escherichia-Shigella and Enterococcus. S. Enteritidis can escape from the sequestrating through the particular salmochelin, another kind of siderophore which cannot be recognized by EXFABP. We assumed that, probably by this way, S. Enteritidis competed with its relatives and other symbiotic bacteria, and profited from others’ misfortune.In an inflammatory state induced by The data presented in the study are deposited in National Genomics Data Center, accession number CRA005292 and CRA004605.The animal study was reviewed and approved by Laboratory Animal Management and Use Committee of Shandong Agricultural University.LiL and XL planned and designed the research and experiments. GH, XM, YZ, and LeL undertook the animal trial and the processing of samples. GH and YP performed the experiments and analyzed the data. GH, LiL, and XL wrote the paper. All authors contributed to the article and approved the submitted version.This work was supported by National Natural Science Foundation of China (31601980 and 31872343), National Key Research and Development Program of China (2021YFD1300102), Shandong Modern Agricultural Industry and Technology System (SDAIT-11-02), and Shandong Provincial Natural Science Foundation (ZR2018MC026).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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Diabetes mellitus (DM) increases the risk of morbidity and mortality after liver resection. Albuminuria is associated with a higher risk for all-cause and cardiovascular mortality. This study evaluated albuminuria as a predictor of the outcome of living donor liver transplantation (LDLT) in patients with pre-existing DM.This retrospective study involved 103 type II diabetic patients with end-stage liver disease who received LDLT. Preoperative spot urine albumin: creatinine ratio was used to determine the degree of albuminuria. The primary outcome measure was the impact of urinary albumin excretion on the 3-year mortality rate after LDLT in this diabetic cohort.Hepatitis C virus infection was the main cause of cirrhosis. Albuminuria was detected in 41 patients (39.8%); 15 had macroalbuminuria, while 26 had microalbuminuria. Patients with microalbuminuria were significantly older than those with macroalbuminuria and normal albumin in urine. After 3 years, twenty-four patients (23.3%) died within 3 years after LT. Myocardial infarction was the leading cause of death (25%). Albuminuria was an independent factor affecting 3-year mortality with an odds ratio of 5.17 (95% CI: 1.86–14.35).Diabetes mellitus (DM) increases the risk of morbidity and mortality after liver resection.Albuminuria is associated with a higher risk for all-cause and cardiovascular mortality.Preoperative albuminuria is a significant predictor of mortality within 3 years after LDLT in diabetic patients.Preoperative albuminuria is an independent factor affecting mortality within 3 years after LDLT in type II diabetic patients. Myocardial infarction was the leading cause of death in 25% of cases, followed by hepatocellular carcinoma recurrence, sepsis, and graft failure. In Egypt, 13 centres perform living donor liver transplantation (LDLT). By June 2014, 2,406 procedures were done. The main indication was cirrhosis post-hepatitis-C viral infection [Type II diabetes mellitus (T2DM) is frequently detected in patients with severe liver diseases, including cirrhosis and hepatocellular carcinoma (HCC) ,6 that mThis study aimed to evaluate albuminuria as an early marker for renal dysfunction in patients with pre-existing T2DM for predicting the outcome of LDLT.This retrospective analysis was performed from May 2005 to June 2012. All type II diabetic patients with end-stage liver disease who received LDLT were enrolled. Patients <18 years of age, having a previous liver transplant, with non-diabetic causes of albuminuria, and those with elevated serum creatinine above 1.2 and 1.4 mg for females and males, respectively, and/or end-stage renal disease were excluded. The study protocol adhered to the ethical guidelines of the 1975 Declaration of Helsinki. The local ethical committee of Cairo University Hospitals approved the protocol and patients’ consent was waived due to the retrospective nature of the study.All patients’ medical records were reviewed to extract the following data: demographic information, aetiology of primary liver disease, clinical and laboratory parameters, graft–recipient weight ratio, donor age and degree of steatosis, duration of hospital and ICU stay, and outcome within 3 years.The severity of liver disease was assessed by Child-Pugh points  and modeDetermination of micro- and macro-albuminuria was based on preoperative spot urine albumin creatinine ratio (uACR) measurements. Data from early morning urine samples were used. Normoalbuminuria was defined as uACR ≤2.5 mg/mmol for males and ≤3.5 mg/mmol for females. Microalbuminuria was defined as uACR >2.5–30 mg/mmol for males and >3.5–30 mg/mmol for females. Macroalbuminuria was defined as uACR >30 mg/mmol . eGFR waThe primary outcome measure was the impact of urinary albumin excretion on the 3-year mortality rate after LDLT in this type II diabetic cohort.t-test or Mann–Whitney test. Comparison between three groups was made using ANOVA test, or Kruskal–Wallis test followed by the appropriate post hoc test. Odds ratio (OR) with its 95% confidence interval (CI) were used for risk estimation. A p-value <.05 was considered significant.Statistical analysis was done using IBM© SPSS© Statistics version 23 . Numerical data were expressed as mean and standard deviation or median and range as appropriate. Qualitative data were expressed as frequency and percentage. Chi-square test was used to examine the relation between qualitative variables. For quantitative data, comparison between two groups was made using independent sample p = .014) and had comparable age with the microalbuminuria group (p = .234). Microalbuminuria and no albuminuria groups were comparable in recipient age (p = .443). Otherwise, there was no significant difference between the three groups in all demographic, clinical, and laboratory characteristics of the patients ; 15 had macroalbuminuria, while 26 had microalbuminuria. patients .p = .039). On multivariate analysis, albuminuria was the only independent factor affecting 3-year mortality  died, and myocardial infarction was the leading cause of death (25%) . Albuminortality .p = .021) and had lower BMI (p = .019) and shorter duration of DM (p = .028). Seventeen patients (70.8%) of those who died within 3 years had albuminuria. Albuminuria was an independent factor affecting 3-year mortality with an OR of 5.17 (95% CI: 1.86–14.35).This study found that preoperative detection of albuminuria was significantly associated with mortality within 3 years after LDLT in type II diabetic patients. Myocardial infarction was the leading cause of death in 25% of cases, followed by HCC recurrence, sepsis, and graft failure.In Egypt, T2DM is a rapidly growing health problem affecting about 15.6% of adults. It is the primary cause of end-stage renal disease in Egypt . In thisIn patients with end-stage liver disease, DM positively correlates with disease severity ,22. ManyIn terms of LT, pre-transplant DM is an important predictor of post-transplant DM and metabolic syndrome ,27. The The effect of pre-existing DM on survival after LT has been previously investigated with controversial results. Some studies did not find an association between DM before LT and survival after LT . On the Albuminuria was demonstrated as a predictor of mortality in diabetic patients of Asian and Caucasian populations ,37. It wMoreover, even with low concentrations, albuminuria has been recognized as a critical cardio-renal risk marker . AlbuminThe current work found that preoperative albuminuria was significantly associated with mortality post LDLT. Previous studies have tried to investigate the effect of albuminuria on LT. Pan and colleagues found that the presence of proteinuria ahead of LT is a negative predictor for in-hospital survival. In addition, they reported that the existence of proteinuria after LT was an early prognostic factor of the short-term outcome. Based on these findings, repeated surveying of proteinuria in the preoperative and postoperative periods was advocated .Moreover, Amygdalos and his colleagues studied 390 LT recipients and demonstrated that preoperative proteinuria is a reliable tool to predict mortality in LT recipients .The present study has some limitations. The retrospective nature of the study was the main limitation of the present study. However, the relatively large number of the study sample and the reasonably acceptable follow-up period are points of strength that can support the findings. Another limitation was the heterogenous causes of liver disease that indicated LT. However, to our knowledge, only a few studies addressed the impact of urinary albumin excretion in diabetic patients, especially after LDLT. Therefore, this article adds momentum to the literature regarding this unique topic. Furthermore, it is sensible to say that this work may point to nongraft potential contributing factors that may affect prognosis after LT and may provide novel horizons in terms of this aspect. This can make it an attractive goal for therapeutic approaches to focus on detecting albuminuria to improve the outcome after LT. Most importantly, given the statistical results, the study underlines that urinary albumin excretion has a substantial impact on mortality after LT.In summary, pre-existing albuminuria in diabetic patients subjected to LDLT is a significant predictor of mortality within 3 years. In this series, myocardial infarction was the leading cause of death in 25% of cases, followed by HCC recurrence, sepsis, and graft failure. Although albuminuria is an early marker of renal disease, it is—more notably—a significant predictor of all-cause and cardiovascular mortality and LT.


Parabens (PBs) are used as preservatives to extend the shelf life of various foodstuffs, and pharmaceutical and cosmetic preparations. In this work, the membrane barrier passage potential of a subset of seven parabens, i.e., methyl-, ethyl-, propyl- isopropyl, butyl, isobutyl, and benzyl paraben, along with their parent compound, p-hydroxy benzoic acid, were studied. Thus, the Franz cell diffusion (FDC) method, biomimetic liquid chromatography (BLC), and in silico prediction were performed to evaluate the soundness of both describing their permeation through the skin. While BLC allowed the achievement of a full scale of affinity for membrane phospholipids of the PBs under research, the permeation of parabens through Franz diffusion cells having a carbon chain > ethyl could not be measured in a fully aqueous medium, i.e., permeation enhancer-free conditions. Our results support that BLC and in silico prediction alone can occasionally be misleading in the permeability potential assessment of these preservatives, emphasizing the need for a multi-technique and integrated experimental approach. Parabens (PBs) are a group of C-4 esterified molecules of hydroxybenzoic acid (pHBA) with a broad antimicrobial and antifungal spectrum, commonly used since the 1920s . PBs havPBs act by altering mitochondria and membrane transport, with their long-chain ester group showing higher antimicrobial properties. Moreover, the longer-chained PBs, such as Butyl 4-hydroxybenzoate (BuP) and Propyl 4-hydroxybenzoate (PrP), show higher endocrine disruptive properties than short-chain analogs, such as Methyl 4-hydroxybenzoate (MP) ,10. In rMoreover, PBs can affect reproduction by altering fertility and reproductive functions in male rodents after repetitive oral exposure by causing epigenetic hypermethylation of sperm DNA, which may impact transcription regulation and be transmitted to the offspring . AlthougImmobilized artificial membrane stationary phases consist of phosphatidylcholine (PC) analogs covalently bound to silica, aiming to mimic biological cell membranes closely. The degree of affinity between analytes and the IAM stationary phases is regarded as phospholipophilicity and indicated by the logarithm of coefficient of analytical retention achieved at or extrapolated to 100% aqueous conditions (log kw IAM). Indeed, previous studies by our research team demonstrated a good correlation between data obtained with traditional in vitro methods  and those achieved with this analytical technique ,26, whic−1) to their detection, and a sound linear relationship (r2 > 0.9256) was found between the instrument response and the applied concentration values spanning in the range 0.052–0.886 µg mL−1 , which is significantly higher than that of EP (maximum flux of 2.35 ± 0.71 µg/cm2/h). Thus, PBs with a shorter alkyl chain present higher permeation, MP > EP, and show that the skin permeation degree of PBs can be considered moderate, according to the definition of Marzulli et al. [MP and pHBA exhibited a maximum passage through the porcine skin within 30 min from the beginning of the experiment, while EP passage was realized within 120 min. Furthermore, as shown in i et al. . ConversOver the years, in vitro Franz diffusion experiments have evolved into one of the most important methods for researching transdermal absorption . However2 = 0.898) was found between log kwIAM values determined on the IAM.PC.MG and IAM.PC.DD2 stationary phases, as can be seen in A good relationship (rhttps://nova.disfarm.unimi.it/vegaol/logkwiam.htm (accessed on 27 June 2022) able to predict the phospholipophilicity of any molecule included in the PubChem collection [® software  compared to those for the PBs able to cross the skin in our experimental conditions.In the llection . Table 4® software. Indeed, pHBA is the only acidic analyte of the dataset. According to the pH piston hypothesis formulated by Avdeef [®, a good relationship is observed if pHBA is left out , models based on diffusion mechanisms, or a combination of both [® contradict the experimental permeation data. Indeed, according to the in silico data, the Kp values would be rather similar for the whole dataset, and there is only a slight difference in permeation rate starting from MP up to the higher chain analog. Instead, in our FDC experiment, only three compounds could cross the pig skin membrane.Similar to SwissADME of both . Mathema of both ,37,38,39We should highlight that membrane crossing is a complex phenomenon where multiple passage pathways that cannot be necessarily accounted for by either in silico or IAM methods can occur. The routes of permeation of the molecules across the skin includes the transcellular route where the molecule encounters the low lipid regions in the cytoplasm of the corneocytes; the intercellular route of dense lipids and fatty acids featuring both hydrophilic and lipophilic regions, making this route very resistant to permeation; and the shunt pathway or appendageal route with diffusion into the sweat gland, hair follicles, and sebaceous gland . Indeed,Our FDC data substantiate that the permeation potential of the target preservatives could also be affected by solubility, which decreases at increasing chain length, and so, the absolute amount exposed to the membrane for PBs with chain length > propyl is fairly inferior to that of other PBs . The exc-Decreasing the polarity of the medium and increasing the relative solubility of our target preservatives, and-Disrupting the packing of lipids into biological membranes and increasing their leakiness.For these reasons, most of these excipients can act as enhancers to increase skin barrier permeability. Indeed, in the Caon et al. study , PBs areLipophilicity is a driving force of the transmigration of xenobiotics through the membrane, but the presence of other active/excipients can reduce surface tension, minimizing its impact on the overall permeation.For this reason, the surrogate models such as in silico prediction and BLC should only be used as preliminary screening tools for chemicals to be followed by diffusion studies exploiting natural skin model, as these can fail in the estimation of molecule’s permeation.−1 at 25 °C . Phosphate buffered saline (PBS) was freshly made in-house by adding disodium hydrogen phosphate and sodium chloride , and potassium chloride (Sigma Aldrich), by diluting with Milli-Q water to 1 L. The pH (7.00) was determined by a pH meter. Acetonitrile (ACN) and methanol (MeOH) were HPLC grade and purchased from Sigma Aldrich .Methyl 4-hydroxybenzoate (MP), Ethyl 4-hydroxybenzoate (EP), Propyl 4-hydroxybenzoate (PrP), and Butyl 4-hydroxybenzoate (BuP) were purchased from Merck & Co. . Isopropyl 4-hydroxybenzoate (iPrP) was purchased from Fluorochem , Benzyl 4-hydroxybenzoate (BzP) was purchased from Sigma Aldrich , and Isobutyl 4-hydroxybenzoate (iBuP) and 4-Hydroxybenzoic acid (pHBA) were purchased from J&K Scientific . The purity of all PBs was equal to or higher than 98%. Milli-Q water was produced in-house, and its conductivity was 0.055 μS cmFor the ex vivo skin penetration studies, the Organization for Economic Co-operation and Development (OECD) guideline recommends pig ear skin as a suitable skin surrogate to mimic human percutaneous penetration . The ski® VT 310® , and only the skin samples with TEWL values < 10 g/m2/h were used in this study. Subcutaneous fat was removed, and skin samples were kept at room temperature and hydrated in saline solution (0.9% NaCl) for 5 min. Then, skin specimens were put on a filter paper  and cut into pieces before assembly in the Franz Diffusion Cell (FDC).The integrity of the skin area used for the permeation experiment was examined by measuring non-invasive trans-epidermal water loss (TEWL) using an In-vitro Tewameter2 and receptor volume of 5.0 mL [Skin absorption tests were performed using Franz-type vertical static diffusion cells  with an effective diffusion area of 0.6 cmf 5.0 mL . The totf 5.0 mL . The don−1. Data acquisition and integration were accomplished by Cromatoplus 2011 software . Methanol injections were made every five runs to assess that no carryover occurred.PBs’ quantification was obtained by the regression equation obtained from standard curves prepared on the same day and performed in concentration levels according to the solubility of each PB to achieve a concentration close to saturated solution. Analytical methods were set up ad hoc to analyze chemicals of interest in the receptor’s fluids. Analyses were performed at room temperature (22 ± 2 °C). HPLC , equipped with an ultraviolet (UV)–visible detector (Shimadzu Model SPD10 AV) set at λ 254 nm, was used. The stainless-steel column was a reversed-phase Supelco Ascentis C18  with a Supelguard Ascentis C18 guard column . All mobile phases were vacuum filtered through 0.45 μm nylon membranes . Overall analyses were conducted at 0.5 mL min® 3 software . On both columns, employed eluents were 0.1 M phosphate buffer at pH 5.0 and acetonitrile at various percentages with a flow rate of 1.0 mL min−1. All samples were dissolved in acetonitrile (ca. 10−4 M), and chromatographic analyses were carried out at 22 ± 2 °C. The two different IAM stationary phases differ from each other in the end-capping of residual amino groups of the silica-propylamine core, which support C10 and C3 alkyl chains being end-capped by both decanoic and propionic anhydrides (IAM.PC.DD2), while IAM.PC.MG supports hydroxy groups being end-capped by methyl glycolate. IAM parameters performed on both stationary phases have already been found to be strongly interrelated, as assessed in our previous studies [v/v), were employed. All kw IAM values average at least three individual measurements, and the final values are reported as decimal logarithms.Phospholipophilicity was experimentally determined using two IAM analytical columns, i.e., IAM.PC.MG  and IAM.PC.DD2 , both from Regis Chemical Company . The analyses on the IAM.PC.MG were conducted on a LC-20 AD VP , equipped with an ultraviolet (UV)–visible detector (Shimadzu Model SPD10 AV) set at λ = 254 nm. For the determinations on the IAM.PC.DD2, an alliance HPLC system  with 2690/2695 separation module, 2996 PDA detector, 717 plus autosampler, and 2487 dual λ absorbance detector, was used at 254 nm wavelength instead. The methods were set, and chromatograms were recorded by Waters Empower studies ,28,31. T studies . Since a2*h). The permeability coefficient (Kp (cm/h)) was determined from J and the drug concentration in the donor phase (Cd (µg/cm3)):The skin permeability was calculated as follows: PBs flux (J) was calculated from the quantity of each PB, which permeated through the membrane, divided by the insert membrane surface and the time duration (µg/cm® engine (freely accessible at http://www.swissadme.ch (accessed on 27 June 2022) was used, based on a linear model adapted from Potts and Guy, who found that Kp linearly correlated with molecular size and lipophilicity [For in silico determination of log Kp, the SwissADMEhilicity .® Excel® of Office 365. All data sets are shown as the mean ± standard deviation (SD), with statistically significant differences determined by a t-test with probability (p) values < 0.05.Calculations were made using MicrosoftWe studied the affinity of PBs for biomembranes, which plays a crucial role in their membrane barrier passage that strongly affects their toxicokinetic. The study of the permeation of PBs in a formulation vehicle was not in the scope of this work, as whichever experimental design would have never mirrored the plethora of cosmetic and pharmaceutical formulations in which PBs can be found. The actual issue of PBs’ toxicity is their occurrence, even at low regulated doses, in many consumer goods of large consumption that can create continuous and multiple sources of exposure for humans and generate a chronic toxicity issue.Our results demonstrate that caution is required when using in silico and chromatographic data, with the aim of surrogating in vitro permeation values. Indeed, IAM data reflect the affinity of compounds for phospholipids, but not necessarily their permeation through complex barrier. In silico data are based on the application of mathematical models that are often based in full or in part on molecular lipophilicity. However, their performance can unfortunately be substandard when passage is modulated by other features.


MAPT and AP2M1, were identified by the mediation center algorithm, 34 miRNAs with obvious prognosis were identified by the cox regression model, and 16 key circRNAs were selected by the database. To develop competitive endogenous RNA (ceRNA) networks, hub circRNAs and mRNAs were used. Finally, GO analysis and clinical data verification of key genes were carried out. We discovered that a down-regulated circRNA (has_circ_002048) caused the increased expression of numerous miRNAs, which further inhibited the expression of a critical mRNA (AP2M1), leading to Alzheimer’s disease pathology. The findings of this work contribute to a better understanding of the circRNA-miRNA-mRNA regulating processes in Alzheimer’s disease. Furthermore, the ncRNAs found here might become novel biomarkers and potential targets for the development of Alzheimer’s drugs.Alzheimer’s disease (AD) is a progressive neurological disease that worsens with time. The hallmark illnesses include extracellular senile plaques caused by β-amyloid protein deposition, neurofibrillary tangles caused by tau protein hyperphosphorylation, and neuronal loss accompanying glial cell hyperplasia. Noncoding RNAs are substantially implicated in related pathophysiology, according to mounting data. However, the function of these ncRNAs is mainly unclear. Circular RNAs (circRNAs) include many miRNA-binding sites , which operate as miRNA sponges or competing endogenous RNAs (ceRNAs). The purpose of this study was to look at the role of circular RNAs (circRNAs) and microRNAs (miRNAs) in Alzheimer’s disease (AD) as possible biomarkers. The Gene Expression Omnibus (GEO) database was used to obtain an expression profile of Alzheimer’s disease patients . Through preliminary data deletion, 163 genes with significant differences, 156 miRNAs with significant differences, and 153 circRNAs with significant differences were identified. Then, 10 key genes, led by  Alzheimer’s disease (AD) is a chronic neurological illness that worsens with time. Extracellular senile plaques created by β-amyloid protein deposition, neurofibrillary tangles formed by tau protein hyperphosphorylation, and neuronal loss with glial cell hyperplasia are the hallmark diseases. Despite substantial progress in identifying disease-related molecular and cellular processes over the last decade, the molecular mechanisms underlying the pathogenesis of AD remain largely unclear , and none of the existing pharmaceutical therapies for AD can stop or reduce its progression . As a result, further research into the underlying disease processes is urgently needed to better understand AD and aid in the development of viable therapy options. Now, a comprehensive body of evidence shows that non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) and round RNAs (circRNAs), are being highlighted for involvement in pathophysiology associated with the promotion.Non-coding RNA (NC) has no protein-coding activities but is an important regulator of many cellular processes . MicroRNE2A (UBE2A), and also showed that circRNAs are involved in the regulation of circulating miRNA genes in AD. Zhang et al., Found that the circRNA-associated ceRNA network in the mouse cerebral cortex is affected by mouse aging  sponges. miRNA is also involved in gene expression regulation , proteinse aging . The undHere, we established a regulatory network of ncRNAs and mRNAs by integrating circRNAs, and mRNAs, and competing with them for co-binding miRNAs, in an attempt to gain a deeper understanding of the potential functions of the circRNA-miRNA-mRNA network in AD. These findings will help to better understand the underlying pathogenesis of AD and explore new potential biomarkers for the diagnosis and treatment of AD.https://www.ncbi.nlm.nih.gov/geo/browse/). This database generated a total of 340 datasets on human Alzheimer’s disease. Three gene expression patterns  were selected after careful examination. GSE5281 were among them based on the GPL570 (Affymetrix Human Genome U133 Plus 2.0 Array) platform, GSE97760 and GSE122063 were constructed on the Agilent GPL16699 platform . All of the data were freely available online and the fact that these databases come from different platforms, different brain regions, different age groups, and different genders make it easier for us to identify genes that are generally significantly different. GSE5281Expression profile included 161 different age samples of 74 people without disease and 84 people with Alzheimer’s disease . The data came from six different areas of the brain . The GSE97760 database analyzed the blood RNA of female patients with advanced AD and matched healthy controls, including 10 age-matched female healthy controls (age 72.1 ± 13.1 years) and 9 advanced AD patients (age 79.3 ± 12.3 years). GSE122063 includes 56 disease (AD) and 44 non demented controls (controls) from various age stages (60–91). AD gene expression profiles were obtained from frontal and temporal cortices of autopsy hemispheres collected from the University of Michigan, United States (All gene expression data sets used in this research were collected from the GEO database. (d States . Download States . We atted States . For GSEd States .https://www.ncbi.nlm.nih.gov/geo/geo2r/), and adjusted p-values and |logFC| were calculated. For the gene expression profiles of GSE5281 and GSE97760, Log2-FoldChange (FC)|>1.0 and an adjusted p-value <0.05 were used as cutoff criteria, and the adjusted p < 0.05 and |logFC|>0.5 the gene expression profiles of GSE122063 were treated as DEGs. Differential miRNAs were screened and selected from GSE150693 by the ‘limma’ package in the ‘R' language based on the criteria of p < 0.05 and FC > 1. Differential circRNAs were first screened in GSE161435 based on the criteria of p < 0.05 and FC > 1.5.Data were processed using DEG’s GEO2R online analysis tool (https://david.ncifcrf.gov/). For KEGG pathway analysis, p ≤ 0.01 and count≥4 were considered sufficient and analysis results were visualized using the online analysis tool Sangerbox (http://vip.sangerbox.com/home.html). To better analyze the function of the DEGs gene, in this study, biological processes (BP), cellular components (CC) molecular functions (MF), and molecular functions (MF) are annotated, analyzed, and visualized using R language “cluster profile”, “GGploT2 “and” enrichPlot “packages.The KEGG database is widely used and stores large amounts of data on genomes, biological pathways, diseases, and medicines. GO analysis is a common method for large-scale functional enrichment studies; gene functions can be divided into the biological process (BP), cellular component (CC), and molecular function (MF). KEGG pathway enrichment analysis of DEGs in this study was performed using the Database Annotation, Visualization, and Integrated Discovery (DAVID) tool (http://string-db.org/) is designed to analyze the PPI information. To evaluate the potential PPI relationship, the DEGs identified previously were mapped to the STRING database. The PPI pairs were extracted with a combined score = 0.4. Subsequently, the PPI network was visualized by Cytoscape3.9 software (http://www.cytoscape.org/).To better search for proteins related to Tau protein, the algorithm Between Centrality was adopted in this study to find the important nodes  database (nt nodes  and 2. CThe formula can be standardized to obtain (2), where the denominator represents the number of paths between two points in the figure, that is, the number of all paths.p < 0.05 and FC > 1 criterion, a total of 156 miRNAs were identified from GSE150693, 141 of which were upregulated and 15 downregulated. Then in this study, to integrate survival time, AD transformation status, and 35 feature data, we used the ‘R' software package ‘survival’ and assessed the prognostic significance of these features in 197 samples by the cox method. Overall prognosis difference was significant .Through the ‘R' language ‘limma’ package, based on p < 0.05 and FC > 1.5, difference circRNA was preliminarily screened in GSE161435, including 18 upregulated and 87 downregulated circRNA. Then we selected 16 important circRNAs from the ENCORE database.Then based on the criteria of KM-Pvalue<0.01, the Top 34 miRNA with the most obvious prognosis were selected as research objects. According to criteria We used ENCORE to predict circRNA and mRNA target miRNAs. The ceRNA network was constructed using Cytoscape, based on the function of circRNA, miRNA, and mRNA sponge.http://software.broadinstitute.org/gsea/index.jsp) website for the GSEA software (version 3.0). The specimens were divided into highly expressed groups (>=50%) and low expression groups (<50%) according to the expression level of genes, and obtained from Molecular Signatures The Database  to download a subset of“c3.mir.v7.4.symbols.gmt”.To evaluate related pathways and molecular mechanisms, based on gene expression profile and phenotype grouping, the minimum gene set was 5, the maximum gene set was 5,000, 1,000 resampling, p-value of <0.05, and an FDR of <0.25 were considered statistically significant. To verify the binding relationship of miRNAs to target genes by GSEA.For Gene Set Enrichment Analysis (GSEA), we obtained data from GSEA  were chosen for analysis. Based on the criteria of |logFC|>1 and adjusted diagram, , and theSalmonella infection, Epithelial cell signaling in Helicobacter pylori infection, MAPK signaling pathway, and Synaptic vesicle cycle, neuron projection cytoplasm.Enrichment analyses of KEGG pathway enrichment and GO functional enrichment analysis of DEGs by DEGs was performed using DAVID And R package “cluster profile” , 2. GO tPPI network construction and core gene screening Prediction of protein interactions between DEGs using the STRING database. A total of 119 nodes and 78 edges are involved in filtering through the PPI network . In the MAPT were the most outstanding gene with a score = 1820, followed by encoded as a subunit of the heterotetrameric coat assembly protein complex2 (AP2) , encodes a component of vacuolar ATPase (V-ATPase) . SNCA (Synuclein Alpha) is a Protein Coding gene. It may serve to integrate presynaptic signaling and membrane trafficking , the Catalytic subunit of the peripheral V1 complex of vacuolar ATPase (V-ATPase) , And the clinical information is verified in the database GSE1297. The top 10 hub genes are shown in The results showed that encodes of the microtubule-associated protein tau  compete for the same miRNA response elements to affect one another. Furthermore, We intersected the selected miRNAs with 34 miRNAs in the GSE150693 database to identify common miRNAs and establish key circRNA-miRNA pairs. Through the screen out of the ENCORI database, only 10 of the 16 circRNAs were eligible, and the miRNAs that bound to them were predicted . The resAlzheimer’s disease (AD), the most common neurodegenerative disorder, is a progressive neurologic disorder with insidious onset and is the primary cause of dementia. In AD, two hallmarks are intracellular neurofibrillary tangles of hyperphosphorylated tau and accumulation of beta-amyloid plaques. . β-amyloAP2M1 is mainly enriched in ion channel binding and inner cytocapsula. They may have a potential link with AD , and Huntington’s disease (HD)  . The synase (HD) . It has le cycle .UBE2A) defective in the expression of epidermal growth factor receptors (EGFR), thereby affecting the pathology of AD . The researchers also found a potential regulatory role of circRNA/ceRNA in Alzheimer’s disease in the cGMP-PKG signaling pathway  are also bound to hsa_circ_002048. The transformation curves of the three ADs are shown in AP2M1 . The basachinery .AP2M1 is a core component of the clathrin-mediated endocytosis machinery.A growing number of studies have demonstrated the potential impact of AP2M1 on neurodegenerative disease. LRK2-dependent phosphorylation of AP2M1 mediated dopaminergic neurodegeneration in a Drosophila model of PD . In earlier studies, it was found that in LC3-mediated autophagy (LANDO), the lack of LANDO in the Bone marrow chamber or specifically in microglia, typical autophagy is altered and can trigger inflammation, which is associated with β-amyloid deposition and tau hyperphosphorylation . Among them, AP2M1 and MAPT are co-expressed and some known experimentally determined interactions , which may limit the expression of


FKBP5) gene (androgen target gene) are associated with an association for PCOS and hyperandrogenism.Polycystic ovary syndrome (PCOS) is a common endocrine disorder in premenopausal women, whose etiology remains uncertain, although it is known to be highly heterogeneous and genetically complex. PCOS often presents with hyperandrogenism symptoms. The present study aimed to determine whether polymorphisms in the FK-506 binding protein 5  in the The genotype frequencies for the rs1360780 and rs3800373 SNPs differed significantly between the PCOS cases and healthy controls  and p = 0.029, OR is 1.59 (1.03–2.45) respectively under co-dominant model). Moreover, the genotype frequencies and genetic model analysis for the SNPs rs1360780, rs9470080, rs9296158, rs1043805 and rs7757037 differed significantly between the hyperandrogenism and non-hyperandrogenism groups of PCOS patients. The TT genotype of rs1360780, the TT genotype of rs9470080, the TT genotype of rs1043805 or the GG genotype of rs7705037 (ORs are 2.13 (1.03–4.39), 1.81 (1.03–3.17), 2.94 (1.32–6.53) and 1.72 (1.04–2.84) respectively) were correlated with androgen level of PCOS patients.FKBP5 gene polymorphisms are associated with PCOS generally (rs1360780 and rs3800373) and with the hyperandrogenism subtype specifically .Our study showed that The online version contains supplementary material available at 10.1186/s12920-022-01301-0. Polycystic ovary syndrome (PCOS) is an endocrine disorder which afflicts females of reproductive age . While tIL1B), prostaglandin-endoperoxide synthase 2 (PTGS2)), as well as granule cells(GCs) in the inflammatory environment of PCOS patients, have been linked to hyperandrogenism [PCOS is considered to be a chronic inflammatory disease , and mulrogenism –9. Hyperrogenism . The incrogenism , 12. Androgenism ; these hrogenism . Moreoverogenism .LHCGR (rs2293275) in PCOS showed strong correlations with body-mass index (BMI), waist to hip ratio, insulin resistance, luteinizing hormone, and LH/FSH ratio [INSR gene and the development of PCOS. Additionally, a T/C polymorphism was also reported among the Chinese population in the CYP17A gene: affected females having the CC genotype had increased testosterone levels compared to individuals harboring the TC and TT genotypes. Additional genes with PCOS-associations include the androgen receptor (AR) gene, the sex hormone-binding globulin (SHBG) gene, and the insulin-like factor 3 (INSL3) gene [PCOS has a strong genetic component . Some SNSH ratio . MoreoveL3) gene .FKBP5 encodes the FK-506 binding protein 5 (a co-chaperone of a heat shock protein (Hsp90)) [FKBP5 gene, and a study showed that FKBP5 expression is regulated by an interaction between the AR and this enhancer; specifically, AR selectively recruits cAMP response element-binding protein to this enhancer [FKBP5 is highly expressed in muscle and adipose tissue, and human FKBP5 is associated with type 2 diabetes(T2D) and with markers for both insulin resistance and obesity [FKBP5 and androgens in the context of PCOS etiology. The objective of the present case–control study was to investigate potential associations between single nucleotide polymorphisms of FKBP5 and PCOS pathogenesis and symptoms.(Hsp90)) , which ienhancer . Moreove obesity , 24. GivAll patients in this study gave their informed written consent; the protocol for this study was reviewed and approved by the Institutional Review Board of Reproductive Medicine of Shandong University .A total of 1558 women from the Reproductive Hospital affiliated with Shandong University were included in the present case–control study. Among them, 775 women had PCOS, while the other 783 were healthy control subjects, whose blood and other samples have been kept in the sample bank of the Affiliated Reproductive Hospital of Shandong University for research. The patients with PCOS and the healthy control subjects were diagnosed based on the presence of two out of three criteria of proposed by the Rotterdam European Society for Human Reproduction and Embryology (ESHRE)/American Society for Reproductive Medicine (ASRM)-sponsored PCOS Consensus Workshop Group; patients with PCOS were included if they met at least two of the following three criteria: (1) chronic oligoovulation and/or anovulation; (2) clinical or biochemical hyperandrogenism; and (3) polycystic ovaries on ultrasound, ≥ 12 ovary follicles measuring 2–9 mm in diameter in one or both ovaries, or ovarian volume > 10 mL . Other eControls were gathered primarily from healthy women who presented with regular menstrual cycles, excluding hyperandrogenism and PCOS. Clinical parameters of the patients with PCOS and the healthy control subjects are shown in Table 2). Peripheral blood samples were collected on days 2–5 of a spontaneous cycle or after withdrawal of bleeding from the subjects in a fasting state. Measurement with a chemiluminescent analyzer  was done for the following hormones: follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T). Blood samples, which were collected with EDTA as an anticoagulant and stored at − 80 °C, were prepared for genomic DNA extraction.The patients with PCOS and the healthy control subjects were diagnosed and examined at the Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, China. Weight and height were measured using standard protocols with calibrated instruments. Body mass index (BMI) was calculated as weight (kg) divided by height squared ; the clinical characteristics of groups are shown in Table FKBP5 and PCOS pathogenesis and symptoms, for the total 54,836 variants in the FKBP5 gene, we chose 13 SNPs. Selected criteria: functional region SNP were selected, including promoter, exon and 3′ UTR of gene, by SNP Function Prediction (https://snpinfo.niehs.nih.gov/) [https://www.internationalgenome.org/), setting up cutoff MAF > 0.05. Among them, the SNPs rs2817035 and rs4713902 of the FKBP5 gene were reported as linked to risk for coronary artery disease [FKBP5 gene [FKBP5   to evalu disease . A study disease . ConsideBP5 gene , we focuFKBP5 gene were genotyped using the MassARRAY RS1000 platform  according to the standard protocol. The genotyping primers were designed using MassARRAY Assay Design 3.1 Software (Sequenom) and were synthesized by Biomiao Biological Technology Company . Sequencing was performed on a MassARRAY Compact System (Sequenom), and the genotype data were analyzed using MassARRAY TYPER Analyzer Software version 4.0 (Sequenom).The genomic DNA of every subject was extracted from peripheral blood using DNA Blood Mini Kits . Thirteen SNPs in the http://bioinfo.iconcologia.net/snpstats/start.htm): the log-additive model (+/+ vs. −/−), the dominant model (+/+ plus +/− vs. −/−), the recessive model (+/+ vs. +/− plus −/−), the co-dominant model (+/+ vs. +/− vs. −/−), and the overdominant model (+/+ plus −/− vs. +/−). Considering that the outcome variables are dichotomous , the log-additive model was performed. The genetic model was assessed using the Akaike information criteria (AIC) and the Bayesian information criteria (BIC); the model with the lowest values was considered to have the best fit. Genotype differences and other statistical analyses, including chi-square tests, independent t tests, and logistic regression analysis, were performed using SPSS software version 20.0 . Data are expressed as means ± SD. Categorical data are expressed as frequencies or percentages. Associations with a two-tailed p value < 0.05 were considered statistically significant.Tests of Hardy–Weinberg equilibrium and linkage disequilibrium analysis were performed using HaploView software. The analysis of the association between clinical characteristics and genotypes was performed with independent sample t tests. The allele frequencies and genotype frequencies of the 13 SNPs were tested with chi-square tests, and were adjusted using logistic regression analysis . The genPrior to the case-control study, we confirmed that all of the genotyped SNPs agreed with Hardy-Weinberg equilibrium, thus ensuring that our sampling is representative of a truly large population , call rate > 95%,). The distribution of the genotypes and allelic frequencies of the 13 SNPs were analyzed with chi-square tests, and we investigated the 13 SNPs of the samples from PCOS and control groups in five genetic models: the log-additive model, the dominant model, the recessive model, the co-dominant model, and the overdominant model.Significant differences were detected for two SNPs: rs1360780 and rs3800373 , 40.3% 315/775), and 4.7% (37/775) in the PCOS patients, versus 56% (432/783), 36.3% (280/783), and 4.7% (59/783) in the healthy controls, with significant differences under the co-dominant genetic model . In the recessive genetic model, the frequencies of genotype AA and CA  in PCOS patients and healthy control also showed a significant difference . Regarding allele frequencies, no significant differences were found for any of the 13SNPs between the PCOS group and the control group (p > 0.05)  and non-hyperandrogenism (NHA) subtypes. Clinical or biochemical hyperandrogenism was defined on the basis of hirsutism  or elevated circulating total testosterone ≥ 60 ng/dl. Our study analyzed 588 HA and 187 NHA PCOS patients. The allele frequencies and genotype frequencies of the 13 SNPs were tested, and the genotype frequency of the 13 SNPs was analyzed with five genetic models Table .Table 4GUsing the log-additive model, significant differences were found for all five SNPs: rs1360780 (OR is 1.35(1.02–1.77), p = 0.036), rs9470080(OR is 1.33(1.03–1.71), p = 0.028), rs9296158(OR is 1.33(1.03–1.72), p = 0.031), rs1043805(OR is 1.37(1.03–1.83), p = 0.034) and rs7757037(OR is 1.32(1.04–1.69), p = 0.023). Under the codominant genetic model, the proportions of each genotype are shown on the Table Under a dominant genetic model, analysis of rs9296158 showed that the frequencies of GG and GA + AA were 47% (276/587) and 53% (311/587), and 38.5% (72/187) and 61.5% (115/187) in the HA PCOS patients and in the NHA PCOS patients, respectively. Notably, the genotypes carrying A alleles (G/A-A/A) were more strongly associated with NHA  and p-value of 0.041 under the dominant model). For rs7757037, the frequencies of AA and GA + GG were 38.3% (225/587) and 61.7% (362/587) in the HA PCOS patients, and 29.9% (56/187), and 70% (131/187) in the NHA PCOS patients. The genotypes carrying G alleles (G/A-G/G) were more strongly associated with NHA under the dominant genetic model (OR is 1.45 (1.02–2.07), p = 0.036, AIC = 855.5, BIC = 864.8). Under a recessive genetic model, analysis of rs1043805 showed that the frequencies of AA + TA and TT were 97.6% (572/586) and 14%(14/586), and 93.6%(175/187) and 6.4% (12/187) in the HA PCOS patients and in the NHA PCOS patients, respectively, OR is 2.80 (1.27–6.17) and p value is 0.01.In addition, the genotype frequencies and genetic model analysis of each SNP between the insulin resistance(IR) group and the control group were conducted, while no significant differences were found for any of the 13SNPs between the two group (P > 0.05)  SNPs rs2968909 and rs4409904 were associated with lower odds of PCOS [INSR), for which the CC genotype showed a higher frequency in PCOS women than in controls [sorbin and SH3-domain-containing-1 (SORBS1), which encodes a protein known to function in both insulin resistance and glucose uptake [Cytochrome P450 Family 11 Subfamily A Member 1 (CYP11A1) gene in affected siblings with hyperandrogenism and PCOS related traits was predicted by studying 37 candidate genes [In recent years, a large number of studies have shown that genetic factors play a role in the etiology of PCOS , 32, 33, of PCOS . Among t of PCOS , 36, an controls . Additioe uptake . Additiote genes .FKBP5, which is known to function as an androgen receptor. While hyperandrogenism is understood as a common clinical feature in PCOS patients, the specific contributions of androgens and related events in PCOS and PCOS-related complications are not yet clear [FKBP5 gene. The frequencies of TT genotype of rs1360780, the TT genotype of rs9470080, the TT genotype of rs1043805 or the GG genotype of rs7705037 were significantly higher in the NHA PCOS group than that in the HA PCOS group. Regarding genetic model analysis, the AA genotype frequency of the HA group is higher than that in the HA group in the dominant model for rs7757037, and for rs9296158, the GG genotype showed the same trend in the dominant model. While for rs9470080, the frequency of the TT genotype in NHA is higher than that in the HA group. Previous reports have proposed that the effects of androgens on cell activities in PCOS may relate to apoptosis, autophagy, mitochondrial dysfunction, and/or endoplasmic reticulum stress in granule cells and oocytes [Whereas these two previous studies linked PCOS to SNPs in genes related to glucose metabolism and insulin resistance, we focused on et clear . Unlike  oocytes . Excessi oocytes . Particu oocytes .FKBP5 is associated with endocrine disorders, which are highly consistent with the symptoms of PCOS. FKBP5 is involved in the regulation of glucose homeostasis through its regulation of AKT2 signaling [FKBP5 gene may be linked to the susceptibility to develop insulin resistance and dyslipidemia [FKBP5 functions in responses to steroids, and FKBP5 is strongly transcriptionally activated by androgens, glucocorticoids, and progestins [FKBP5 gene have been associated with differences in glucocorticoid sensitivity; notably many of the clinically linked SNPs localize close to (or overlap with) regions that encompass steroid-regulated enhancers [FKBP5 and could thereby influence the complex regulatory loops of steroid signaling [FKBP5 intronic methylation and the risk of cardiovascular disease in T2D patients [ignaling . Reportsipidemia . FKBP5 fogestins ; Severalnhancers . The polignaling . Also, apatients .FKBP5 polymorphisms includes association of rs1360780 with increased protein levels [FKBP5 levels promotes inflammation by activating the master immune regulator NF-κB [FKBP5 because of its function as an androgen receptor gene, our study showed FKBP5 gene polymorphisms are associated with PCOS generally  and with the hyperandrogenism subtype specifically , among which rs3800373 and rs1043805 belong to 3’ UTR variant of FKBP5 gene. There may be FKBP5 variants exhibiting yet to be discovered interaction effects with PCOS. Since this is the first study investigating the role of FKBP5 single nuclear polymorphism in PCOS it is not possible to compare our results with the data in literature. While in a discovery cohort, FKBP4 (a kind of androgen receptor gene) SNPs rs2968909 and rs4409904 were associated with lower odds of PCOS [Possible functional significance of n levels  and diffn levels  due to ior NF-κB . We paid of PCOS .FKBP5 SNPs and PTSD reported that the rs9470080 TT genotype carriers had a higher risk of developing high co-occurring PTSD and depression symptoms than the C allele carriers [FKBP5 SNP rs1360780 had an increased susceptibility to stress-related disorders [FKBP5 SNP rs9470080 and the TT genotype of rs1360780 was significantly higher in PCOS NHA group than PCOS HA group, and the TT of rs1043805, the GG of rs7757037 showed the same tendency. We mentioned above the SNPs of FKBP4 rs2968909 and rs4409904 were associated with lower odds of PCOS [Another study which focused on the relationship between carriers . A previ of PCOS . As noteIn another study , more coFKBP5 and PCOS need to be confirmed in a larger sample size that includes multiple ethnic groups. Second, the functional significance of the SNPs remains unknown and molecular mechanisms regarding FKBP5 in the pathophysiology of PCOS should be examined in future studies.There are some limitations to this case–control study that bear mention. First, the participants were all Han Chinese women, so there was very little variation in genetic background. Genetic factors that influence the pathogenesis of PCOS are known to differ by ethnic group , 48, so FKBP5 gene and PCOS. On the basis of the available evidence, we conclude that the SNPs, rs1360780, rs3800373, rs9470080, rs9296158, rs1043805, and rs7757037 in the FKBP5 gene are strongly associated with PCOS among Han Chinese women. These SNPs we detected should be useful in future investigations of HA in PCOS, and especially for supporting clinical diagnosis of PCOS as informed by genetic testing. The major limitation of our study was the small number of the studied sample. Further studies in humans and potentially some functional studies will be required to validate the predictive value of these SNPs as potential biomarkers and to elucidate the effects of FKBP5 on PCOS development and clinical outcomes.Our study covered a relatively large cohort of Chinese women with PCOS and represents the first study providing data about the FKBP5 gene is a potential association gene for PCOS, with some SNP genotypes associated with PCOS generally and with the hyperandrogenism subtype specifically. On the basis of the available evidence, we conclude that the SNPs, rs1360780, rs3800373, rs9470080, rs9296158, rs1043805, and rs7757037 in the FKBP5 gene are strongly associated with PCOS among Han Chinese women. Assuming the further validation including functional significance and molecular mechanisms of the SNPs and other evidence appears, we indicate that the SNPs we detected will be useful in future investigations of HA in PCOS, especially for supporting clinical diagnosis of PCOS as informed by genetic testing.Our study showed that the Additional file1. Table S1: Allele frequencies of FKBP5 SNPs in the PCOS patients and in healthy controls.Additional file2.Table S2: Genotype frequencies and genetic model analysis of FKBP5 SNPs in the IR group and the control group.


To analyze the risk factors for osteochondral fracture (OCF) of first-time acute patellar dislocation (APD) through measurements of patellofemoral anatomy in adolescents.  In this prospective study, all patients were divided into two groups according to whether OCF was detected on magnetic resonance imaging (MRI): Group A (associated with OCF) and Group B (without OCF). Patellofemoral anatomy was evaluated with four aspects including trochlear/patellar dysplasia, patella location, patellofemoral matching, and morphologic classification. On MRI scans, trochlear facet asymmetry ratio (TFAR), lateral trochlear inclination (LTI), sulcus angle (SA), trochlear depth (TD), and patellar depth (PD) were measured to assess trochlear/patellar dysplasia. Insall–Salvati index (ISI), Caton–Deschamps index (CDI), Blackburne–Peel index (BPI), lateral patellofemoral angle (LPFA), patellar tilt angle (PTA), and lateral patellar displacement (LPD) were measured to show the location of patella. Patellofemoral matching was analyzed through the measurements of patellofemoral congruence angle (PFCA), patellofemoral index (PFI), and patellotrochlear index (PTI). vs. 2.10 ± 0.44) and PTI (0.28 ± 0.05 vs. 0.22 ± 0.07) were significantly higher in Group B than Group A (P < 0.05). There were no significant differences in other quantitative outcomes of the two groups (P > 0.05). The distribution of Dejour/Wiberg classification was statistically similar between the two groups (P > 0.05).  A total of ninety-four adolescents from 49 boys and 45 girls  with first-time APD were recruited and included in Group A (65) and Group B (29). The PFI (2.62 ± 0.51  Adolescent patients with first-time APD complicating OCF have closer morphologic features of patellofemoral dysplasia and patella location when compared to adolescents without OCF. Abnormal patellofemoral matching increases the risk of OCF after first-time APD in adolescents. Acute patellar dislocation (APD) is a clinically common injury, especially in adolescents . Recent Magnetic resonance imaging (MRI) is an irreplaceable diagnostic examination in delineating the structural features of soft tissues for knee joint . PathoanThe purpose of this study was to analyze potential anatomic risk factors leading to first-time APD complicating OCF in adolescent populations. We hypothesized that our study findings could reveal some classic anatomic parameters that might relate to OCF. It could also provide better understanding of injury mechanism and theoretical guidance for accurate diagnosis.This retrospective study included consecutive patients with first-time APD who had undergone hospitalization from 2011 through 2020 and was approved by the required institutional review boards of level-I trauma centers (No. TSEY-LL-L20220013). All patients were divided into two groups according to the diagnosis of OCF: Group A (first-time APD children with OCF) and Group B (without OCF).The inclusion criteria for this study were defined as follows: ① age 18 years or younger; ② first-time APD was diagnosed based on MRI ; and ③ pThe MRI was performed on a GE 1.5 Tesla magnet. The sequences were obtained as follows: sagittal T1-weighted image (T1WI) views were achieved by using a spin echo sequence system, while sagittal T2-weighted image (T2WI) views were obtained by a fast spin echo sequence system. Slice thickness was 3 mm with 1 mm gap, and sequence parameters were repetition time (TR) of 1892 ms/echo time (TE) of 10.1 ms for T1WI and TR of 2700 ms /TE of 123 ms for T2WI.All imaging data were identified from the picture archiving and communication system (PACS). The MRI scans were evaluated for all cases, and the anatomic parameters were measured blindly by two trained orthopedists who specialized in pediatric sports medicine. To minimize errors, the mean value of measurements for each parameter was recorded.Trochlear facet asymmetry ratio (TFAR), lateral trochlear inclination (LTI), sulcus angle (SA), trochlear depth (TD), and patellar depth (PD) were measured to assess trochlear or patellar dysplasia on axial knee MRI –15.Patellar height  was assessed by using the Insall–Salvati index (ISI), Caton–Deschamps index (CDI), and Blackburne–Peel index (BPI) on sagittal knee MRI at the midsagittal slice –18. PatePatellofemoral congruence angle (PFCA), patellofemoral index (PFI), and patellotrochlear index (PTI) were measured to assess the matching of patellofemoral joint , 23.The morphology of dysplastic trochlea and patella were evaluated by Dejour classification and Wiberg classification , 25, rest-test or Mann–Whitney U test was used for the comparison of continuous variables. Differences in categorical variables were compared using the chi-square test or Fisher's exact test. A P value of <0.05 was considered as statistically significant.All statistical data in our study were analyzed with SPSS 25.0 software . Continuous variables were used to analyze and presented as mean ± standard deviation. According to whether the variables conformed to a normal distribution, the independent P > 0.05).One ninety-four (49 boys and 45 girls) MRI scans were reviewed, with a mean age of 15 years . Sixty-five adolescents were allocated into Group A (associated OCF), and twenty-nine adolescents were allocated into Group B (without OCF). Patient demographics of two groups are summarized, as shown in P < 0.05). There was no statistically significant difference between TFAR, LTI, SA, TD, PD, ISI, CDI, BPI, LPFA, PTA, LPD, and PFCA of the two groups (P > 0.05). No significant differences were observed in the distribution of Dejour and Wiberg classification between the two groups (P > 0.05), as shown in All measured results of anatomic parameters for trochlear/patellar dysplasia, patella location, and patellofemoral matching are provided in Tables 2APD is a common spontaneous knee injury and tends to occur in adolescent active population , 26. It The patella has a physiological tendency to slide laterally when the knee keeps flexion over enough angles . The innThe static strength of inhibition mainly originated from patellofemoral bony structure . Over the past years, many scholars –32 reporWe evaluated the position of the patella in our study population, recording anatomic parameters on both sagittal and axial views. For sagittal views, patella alta was regarded as a risk factor for lateral patellar instability, and the incidence of patella alta in first-time APD was approximately 25% . In thisIn this study, the results of measurements showed that PFI and PTI of Group B were significantly higher than those in Group A. PFI and PTI not only predisposed to patellofemoral joint instability but also contributed to OCF risk. In brief, we found that abnormal patellofemoral matching may increase risk of OCF after first-time APD. Uimonen et al. , studyinThe strengths of this study included the comprehensive anatomical measurements, and common injury pattern of OCF after APD was analyzed. Furthermore, measuring results for adolescents were conducted by two trained observers, which effectually improved the reliability of the measurements. The current study had some limitations. First, the sample size was small. Some patients with no or insufficient MRI were not included, which might have limited the generalizability of the study results. Second, all results were measured after dislocation and relocation, leading to the direction and distance of the displaced patella being changed, which could cause inevitable errors for a part of parameters. Third, the occurrence of OCF was a multifactorial consequence. More anatomical factors, such as soft tissue factors, could be evaluated under a further study.In conclusion, first-time APD with OCF remains a common injury pattern in adolescent patients. The adolescents with or without OCF have closer trochlear/patellar dysplastic morphology and patella location. Patellofemoral matched malformation may contribute to the risk of OCF in this injury pattern.


To compare patient-reported outcomes (PROMs) following surgery for degenerative cervical myelopathy (DCM) among patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) versus those without rheumatic diseases.Data were obtained from the Norwegian Registry for Spine Surgery. The primary outcome was change in the Neck Disability Index (NDI) at 1 year. Secondary endpoints included the European Myelopathy Score (EMS), quality of life (EuroQoL-5D [EQ-5D]), numeric rating scales (NRS) for headache, neck pain, and arm pain, and complications.P = .372), EQ-5D , NRS neck pain , NRS arm pain , and NRS headache .Among 905 participants operated between 2012 and 2018, 35 had RA or AS. There were significant improvements in all PROMs at 1 year and no statistically significant difference between the cohorts in mean change in NDI (− 0.64, 95% CI − 8.1 to 6.8, Our study adds to the limited available evidence that surgical treatment cannot only arrest further progression of myelopathy but also improve functional status, neurological outcomes, and quality of life in patients with rheumatic disease. Degenerative cervical myelopathy (DCM) is the most common cause of spinal cord impairment and can cause neurological symptoms including gait disturbances, imbalance, loss of dexterity, poor coordination, pain and stiffness in the neck, pain and numbness in limbs, and autonomic alterations that may cause bowel, urinary, and sexual problems , 16. DCMAlthough there is growing evidence that decompressive surgery can halt disease progression and is associated with meaningful improvement in function, pain, and quality of life , 5, 8, tThe aim of this study was to compare the effectiveness and safety of surgery for DCM in patients with RA or AS versus patients without rheumatic disease based on PROMs 1 year after surgery.The Regional Committee for Medical Research Ethics approved the study (2016/840), and all participants provided written informed consent. This study was part of the first author’s master thesis at the Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.Patients were identified through the Norwegian Registry for Spine Surgery (NORspine), a comprehensive nationwide registry for quality control and research. NORspine provides prospectively collected data on patients undergoing surgery for degenerative spinal disorders, and more than 80% of all cervical spine surgeries are included [The primary outcome was change in the Neck Disability Index (NDI) at 1 year . The NDISecondary outcome measures were changes in DCM severity assessed by the European Myelopathy Score (EMS) , 21, numBaseline data were collected on admission for surgery where the patients completed a self-administered questionnaire. Using a standard registration form, surgeons recorded data on diagnosis, comorbidity, American Society of Anesthesiologists (ASA) grade, image findings, and surgical procedure. NORspine distributed self-administered questionnaires to the patients by mail 3 and 12 months after surgery.P ≤ 0.05. Changes in EMS, NDI, EQ-5D, and NRS were compared with paired sample T-test. Missing data were handled with mixed linear model analyses [Statistical analyses were performed with SPSS version 26 (IBM) and software R version 3.6.3. For statistical comparison tests, we defined the significance level as analyses . Becausen = 25) or AS (n = 10). In total, 697 (77%) participants provided PROMs at 3 months and/or 1 year, with no statistically significant differences between the two cohorts . Baseline characteristics are presented in Table P = 0.025).Among 905 patients included in this study, 35 (4%) were diagnosed with either RA (r AS n = 0. In totP < 0.001). Patients with RA or AS reported a higher NDI score before surgery (46.7 vs 34.5 points), but there was no statistically significant difference in mean change between the cohorts at 1 year in the complete case analysis . Patients with RA or AS experienced a significantly larger improvement in the mixed model analysis . The change in NDI exceeded the MCIC of 7.5 points for both cohorts.PROMs are presented in Table P = 0.168), neck pain NRS , arm pain NRS , and headache NRS . In the mixed model analysis, patients with RA or AS experienced statistically significant larger improvement in EQ-5D compared to those without rheumatic disease . Patients with RA or AS had lower EMS scores at both baseline and at 1 year compared to patients without rheumatic disease. Improvement in EMS was larger in patients with RA or AS compared to those without. The change in EQ-5D for the total study population represents a moderate clinical change with an effect size of 0.51.There were significant improvements in all PROMs at 1 year for both cohorts. Complete case analyses showed no statistically significant difference between the cohorts in mean change in EQ-5D .Patients’ perceived benefit of surgery assessed by the GPE is presented in Fig. Details of surgical treatment and complications are presented in Table Although patients with RA or AS had more complications, they experienced improvements in their conditions after surgery for DCM that were similar to those of the patients without rheumatic disease. Our study adds to the limited available evidence that surgical treatment cannot only arrest further progression of myelopathy but also improve functional status, neurological outcomes, and quality of life in patients with rheumatic disease .Patients with RA or AS reported higher disability and more severe myelopathy before surgery. Possible explanations include delay in diagnosis, disability due to the rheumatic disease itself, differences in disease progression and pathology, additional comorbidity, and a higher threshold for surgery in patients with RA or AS. In our study, the proportion of patients with symptoms exceeding 1 year was similar for both cohorts. A posterior surgical approach and instrumented fusion were more common in patients with RA or AS, suggestive of more pronounced DCM and multilevel involvement. A recent trial showed similar outcomes following anterior and posterior surgical approaches, but with higher complication rates for the former mainly due to more postoperative dysphagia and dysphonia . There hTimely diagnosis of rheumatic disease and adequate medical treatment are likely to reduce the risk of developing DCM requiring surgery; however, the cases that need surgery are becoming more complex . While cLack of verification of RA and AS diagnoses according to validated disease criteria by a rheumatologist is an important limitation. The two cohorts of patients were unequal relative to the number of participants, and as perhaps expected were not balanced for all baseline and treatment factors. Furthermore, the pathophysiology of DCM in patients with rheumatic disease is likely to differ from those without. Loss to follow-up is a concern. However, a previous study from NORspine showed no difference in outcomes between responders and non-responders . NORspinPatients with RA or AS experienced similar improvement following surgery for DCM compared to patients without rheumatic disease at the expense of more complications. Surgical treatment cannot only arrest further progression of DCM in patients with RA or AS, but also improve functional status, neurological outcomes, and quality of life.