The rangelands of Crete island (Greece) are typical Mediterranean habitats under high risk of degradation due to long-term grazing and harsh climatic conditions. We explored the effect of abiotic  and biotic factors  on the floristic composition and diversity of selected lowland  and highland  rangelands. In each rangeland, the ground cover was measured, and the floristic composition was calculated in terms of five functional groups: grasses, legumes, forbs, phrygana, and shrubs. The aridity index, species turnover, species richness, Shannon entropy, and Gini–Simpson index (with the latter two converted to the effective number of species) were calculated. Our results reveal that highlands are characterized by the highest aridity index (wetter conditions). Lowland rangelands, compared to highland, exhibited a higher percentage contribution of grasses, legumes, and forbs, while species turnover decreased along the altitudinal gradient. The Shannon entropy index was correlated (a) positively with Gini–Simpson and mean annual temperature and (b) negatively with mean annual precipitation, aridity index, and altitude. Moreover, the Gini–Simpson index correlated positively with mean annual temperature and negatively with altitude. Our results could help to understand the effects of grazing on rangeland dynamics and sustainability in semi-arid regions in the context of climatic change. Arid and semi-arid rangelands occupy approximately 40% of the Earth’s land surface and influence the livelihood and well-being of one-fifth of the world’s human population ,2. More Despite their high importance, most of the non-marketed services of these rangelands and their economic value have often been neglected ,9. MoreoIt is well demonstrated that rangelands are maintained by grazing. However, they can be severely affected by the high intensity of the latter, climate change, soil quality, nutrient depletion, fire, habitat fragmentation, as well as human activities ,7,14. InAlthough it is known that the richness of vascular plant species decreases with an increase in altitude ,26,27, tTo assess the impact of grazing on vegetation, the effect of precipitation on species diversity should be thoroughly studied and considered . Both loThere is a list of methods employed to study diversity, which is a multi-dimensional phenomenon . The simThirty-five percent of the Greek land, and more specifically 37–50% of the land in Crete, is characterized as critically susceptible to desertification due to the combination of a warming climate with low precipitation and intensified human activities ,59. To t(a)Do patterns of species diversity indices and composition differ among rangelands exposed to different grazing intensities?(b)Do these differences vary among rangelands with different altitudes and climatic conditions?The current study aimed to investigate the effect of abiotic  and biotic factors (long-term grazing) on the floristic composition and diversity of lowland and highland rangelands on the island of Crete, Greece, which are typical Mediterranean habitats at high risk of degradation. We aimed to answer the following questions:The current study indicates that the existing high grazing pressure, in combination with climatic conditions, could result in rangeland degradation on Crete island.Diverse climatic conditions prevail among the four studied rangelands . At FaisdM) classifies the type of climate in relation to water availability, and it is a crucial environmental factor affecting the growth of natural vegetation. In the present study, IdM was negatively correlated with mean air temperature and positively with altitude and precipitation  in forage production in both fenced plots and grazed sites and for FUP (p < 0.001), but only for forage production in grazed sites. The forage production in fenced plots ranged from 189.2 ± 24.2 to 116.5 ± 7.3 g m−2, while in grazed from 128.9 ± 4.8 to 15.8 ± 1.4 g m−2. The lowland rangelands had higher forage production in relation to the highland. This is in agreement with Bhandari and Zhang [p < 0.001) only for FUP. The FUP was 84.4–87.1% at Nida, 74.1–76.1% at Vroulidia, 74–75% at Pyrathi, and 15–17% at Faistos for 2014 and 2015, respectively  in vegetation cover among the studied rangelands. The vegetation cover recorded in Nida and Vroulidia scored the lowest values, 52% to 66% and 64% to 70%, for 2014 and 2015, respectively, in comparison to the lowland sites of Pyrathi (78–90%) and Faistos (92–99%). The low vegetation cover and the high FUP at Nida and Vroulidia are likely the results of overgrazing, as the number of transhumant small ruminants, and, consequently, the grazing pressure is immoderate in the Psiloritis mountain [It is known that the cover of vegetation is a health indicator of the rangelands. Our data analysis revealed significant differences . On the contrary, there was a significant interaction between rangeland and functional groups (p < 0.001) (p < 0.05) higher percentage contribution of grasses, legumes, and forbs (p < 0.05) higher percentage in the highlands compared to the lowlands, while phrygana [p < 0.05) higher at Nida compared to Vroulidia, while the opposite trend was detected for forbs in highlands for both experimental years (p < 0.05) in the Faistos rangeland compared to Pyrathi  . Overallnd forbs . On the phrygana ,75 had sal years . As othe Pyrathi . On the On Crete island, as elsewhere in Greece, farmers traditionally improve grassland productivity  and qualA drop in species turnover is observed between pairs of lowland to highland rangelands . SpeciesDiversity in terms of abundance (ENS Shannon entropy) was lower than species richness, while diversity in terms of dominance (ENS Gini–Simpson index) was lower than the Shannon entropy for both years of the study . This reHeavy grazing (high FUP) may result in high-level species replacement . Plants According to the Pearson correlation coefficient, the Shannon entropy index was positively correlated with the Gini–Simpson and mean annual temperature and negatively with mean annual precipitation and altitude, while the Gini–Simpson index correlated negatively with altitude . AccordiThe research was conducted during 2014–2015 on the island of Crete, the southernmost part of Greece. The selected experimental sites were two lowland rangelands of Heraklion prefecture: Faistos (F)  155 m a.s.l. and Pyrathi (P)  355 m a.s.l., and two in the highlands of Psiloritis mountain (Rethymnon prefecture): Vroulidia (V)  1100 m a.s.l. and Nida (N)  1530 m a.s.l. that have been subjected to grazing .The livestock farming system was introduced on the island about 8000 years ago, and animal husbandry has been used by humans to transform natural ecosystems to produce more grazing material and, therefore, more animal products for their own consumption and survival. Through these processes, the extensive forests of the island were turned into rangelands, while the abandoned fields due to grazing could not be reforested. Uncontrolled and random, both spatially and temporally, grazing is the rule on the island. In lowlands, e.g., Faistos, in recent years, a change in land-use has been observed with farming replacing pastoralism, so there is low grazing intensity in the area. On the other hand, the lowlands of Pyrathi are heavily grazed all year round by sheep and goat flocks. Concerningly, the highlands of Vroulidia are grazed all year by sheep and goats, while Nida, from April to October, by transhumant small ruminant flocks. The highlands are characterized by a long history of small ruminant overgrazing .www.en.climate-data.org, 12 December 2021). The daily climatic data  for the two lowland rangelands   b,c were s  a from thi is the population frequency of the ith species. The Gini–Simpson index (HGS) was converted by the transformationThe vegetation (ground) cover was measured at the end of the growing season according to the line and point method . Three ei=1spi2),57,105. i=1spi2),107.dM) was calculated following the formula in Equation (2) below [http://chelsa-climate.org/, 2 February 2022), which is a global climate database covering the period 1979 to 2013.For every studied rangeland, the aridity index  below :IdM = P/The species turnover was calculated as the gain and loss of species between altitudes following the formula in Equation (3) below : β(H) = ectively .2 were fenced to be protected from grazing. The above-ground herbage production was collected by clipping three 0.5 × 0.5 m quadrats in each fenced plot . In the same period into grazed rangelands (sites), the remaining above-ground biomass after grazing was collected by clipping in three similar quadrats in each transect , in May 2014–2015. Consequently, grazing intensity was expressed by FUP. The difference among herbage yields of fenced (UG) and grazed sites (G) was used to calculate FUP from the formula of Equation (4) below [In order to estimate the forage utilization percentage (FUP) in the spring of 2012 in each of the four rangeland’s three plots, 9 m4) below :FUP= [. The Paleontological statistics software package for education and data analysis (Past) was used to calculate the diversity indices.The Generalized Linear Model (GLM), assuming a normal distribution, was used to assess whether the altitude of each rangeland, functional group, and year were significant predictors of ground cover and floristic composition. Before analysis, the data were converted to ln + 1 to meet assumptions of normality (tested with the Kolmogorov–Smirnov test) and homogeneity of variances (Levene’s test). Estimated marginal means for all the above factors were calculated with pairwise contrasts, and LSD adjustment was applied for the multiple comparisons (α = 0.05). The data in the figures and tables depict values before the transformation. Pearson correlation was used to explore links among R, SE, GS, IThe Mediterranean basin includes a wide range of vegetation, climatic, and edaphic conditions that have been shaped by natural selection under the pressure of a distinct climate and human activities. Our results demonstrate the strong relationship between diversity and temperature and agree with the fact that vegetation diversification is strongly related to the climatic gradient and is more related to temperature than precipitation. Moreover, this research could help to understand how grazing intensity and climatic conditions interactively influence rangelands dynamics in semi-arid regions and monitor the livestock management and decision making in these areas.


Exploring the risk factors of conjunctival squamous cell carcinoma (CSCC) and establishing a prognostic model. T-test. The risk factors of CSCC were explored by COX multivariate analysis, and the corresponding prognostic model was established as a result.  Information on patients with CSCC was extracted from the SEER database, conducting a retrospective study. 650 patients with CSCC were finally included in the model. Descriptive analysis was performed by Chi-square test and P < 0.05. The new model had C index and area under curve ROC (AUC) value greater than 0.7. Calibration curve, Net Reclassification Index (NRI), Integrated Discrimination Improvement (IDI), and Decision Curve Analysis (DCA) indicate the new model has better predictive performance than the American Joint Committee on Cancer (AJCC-TNM).  The all-cause mortality rate of CSCC was 38.3%, and the risk factors were age (HR = 1.077), sex (HR = 0.691), grade (HR = 7.857), laterality (HR = 1.403), N (HR = 7.195), M (HR = 0.217), and surgery (HR = 1.618), all  Compared with the clinical guidance of AJCC (TNM) for patients with CSCC, the established model exhibits good performance and can provide guidance for clinical decision-making. Squamous cell carcinoma is a malignant tumor that easily occurs in various epithelial tissues. The ocular surface  is one of the tissues prone to squamous cell carcinoma. It most frequently occurs at the corneoscleral limbus and exposed areas of bulbar conjunctiva. The conjunctiva is composed of nonkeratinized epithelial composition, including stratified squamous epithelium and stratified columnar, and is scattered with goblet cells . The marCSCC is the terminal stage of a series of diseases called ocular surface squamous cell tumors . This ilThe American Joint Committee on Cancer  recently reviewed the classification of conjunctival squamous tumors. The clinical staging for carcinoma of the conjunctiva is based on tumor size with T as carcinoma in situ; T1 and T2 as tumor less than and more than 5 mm with breach in continuity of basement membrane, respectively; T3 as tumor invasion into adjacent tissues (excluding orbit); T4 as tumor invasion into surrounding tissues including orbit. . AJCC  and establish the corresponding prognostic model as a reference for clinical decision-making. The database is open to scholars free of charge, and we have obtained access to the data with the account number 11215-Nov2020.Data were obtained from the SEER database, one of the most representative large-scale tumor registration databases in North America that records information about the morbidity and mortality of millions of patients with cancer in some states and counties of the United States. This is a retrospective study, and patient consent for the data obtained from the SEER database was not necessary because no information that can be used to identify individual patients was extracted . This reN = 520) were randomly divided into the training cohort, and 20% (N = 130 cases) were divided into testing cohort. First, a descriptive analysis was performed on the data. Continuous variables were described by median quarterback interval values, categorical variables were expressed as percentages, and P values were obtained by T-test and Chi-square test. The training set was used in COX survival analysis to obtain the different variables of HR and further analyze the effect of different variables on patient survival outcomes. All variables influencing the final outcome of CSCC were incorporated into the model to establish its nomogram to predict the patient survival rates at 3, 5, and 8 years and compare the newly established model with the TNM model. C index and the area under the ROC curve (AUC) were applied to judge the discrimination of the model [http://www.microsoft.com) and R . A bilateral probability value of P < 0.05 indicated statistical significance. The research flow chart is shown in Among the patients, 80% . Age was a risk factor, that is, prognosis worsens with age (P < 0.001). The female gender is a protective factor. The risk for women was 0.691 times that for men (P = 0.046). The number of grade IV tumors was 7.857 times higher than that of grade I (P = 0.01). The prognosis of tumors in the left eye was not as good as that in the right eye. N2 had 7.195 times the risk of N1 (P = 0.011), and M0 had 0.217 times the risk of MX (P = 0.044). The number of patients without surgery and missing records was 1,618 times greater than the number of patients undergoing surgery. Once conjunctival squamous cell carcinoma is diagnosed, especially when the tumor tissue in the early stage is limited and has not invaded into adjacent tissues, surgical resection should be selected as soon as possible. So far, surgery is still considered as a protective treatment measure for patients, which also provides tissue for diagnosis.The results of COX multivariate analysis are in According to the results of the COX multicause analysis, a nomogram was created for the seven variables that influence the prognostic outcome of CSCC: age, sex, grade, laterality, N, M, and surgery. After modeling, the C index was calculated for the new model and the TNM model. The training set C index of the new model was 0.744, while the test set was 0.716. This result demonstrated that the model had a high level of discrimination. On the contrary, the C index of the training set of the TNM model was 0.554, while the test set was 0.504. Therefore, this model does not show a good degree of discrimination, which is similar to a previous study . These rThe AUC values of the new model and TNM were also computed. As shown in P < 0.001). The statistical results of NRI and IDI in A calibration curve was utilized to check the calibration performance of the model. As shown in CSCC is the most common tumor of the conjunctival epithelium that is associated with the risk of permanent visual impairment. What is more, it has the ability to relapse, metastasize, and cause death . It is tThe AJCC (TNM) treatment guidelines for conjunctival cancer have been deemed inaccurate, which is in agreement with the findings of this study. The TNM model was utilized as the primary indicator to predict the long- and short-term survival of patients with CSCC. However, the survival rate effect is extremely poor, the C index and AUC values are extremely low, and no good degree of discrimination has been achieved. The proposed model shows outstanding discrimination (C index and AUC), calibration , model improvement (NRI and IDI), and clinical decision benefit (DCA) performance.α2b, and 5-fluorouracil have been highly recognized and accepted, and drug treatment has grown popular. [According to the established nomogram, age is a high-risk factor. CSCC is more common in areas where the eyes are exposed to the sun, such as the sun-damaged conjunctiva of the limbus. Therefore, UV rays may be the principal cause of CSCC , 27. Witpopular. . An initpopular. . AccordiSix risk factors, namely, age, sex, grade, laterality, N, M, and surgery were explored and integrated into a model to establish a nomogram, which was then verified through multiple perspectives of discrimination, calibration, improvement, and clinical decision-making benefits. The model was proven to be trustworthy and accurate in its predictions. Compared with the current AJCC (TNM) that fails to provide high-quality guidance in the treatment and prognosis of CSCC (limited to patients), the proposed model may accurately estimate the survival rate of patients with CSCC through patient information. This is the first study to establish a prognostic nomogram for CSCC, this tool allows clinicians to provide effective guidance during decision-making.This is a retrospective study, and there will inevitably be biases. Our data comes from the SEER database, and the promotion of conclusions is limited. Owing to the limited public information provided by the database and the lack of laboratory data, only a few factors were included in this study. Regardless, this research is meaningful and can provide a reliable reference for clinicians and patients.


Protein malnutrition is a well-described complication of peritoneal dialysis (PD), a standard mode of treatment for end-stage renal disease (ESRD), and contributes to morbidity, treatment failure, and mortality. To assess the usefulness of WeChat-based education for ensuring optimal protein intake through the consumption of egg white protein, 140 young and middle-aged patients undergoing PD are assigned to either the intervention group or the control group. The results show that reinforcing comprehensive PD education using WeChat can improve nutritional parameters, clinical parameters, and quality of life. Peritoneal dialysis (PD) is a common renal replacement therapy (RRT). Several young and middle-aged patients with end-stage renal disease (ESRD) chooses PD as the first choice of RRT in China, as it is simple and be performed at home. However, because of the loss of albumin and absorption of glucose from the dialysate, PD patients always have a poor appetite. Along with the effect of uremic toxins, poor appetite reduces the protein-energy intake, which is strongly associated with malnutrition, low serum albumin, and microinflammation , 2. ProtIn China, WeChat, a comprehensive, large-scale, instant, and free network social media platform, is widely used among young individuals, including those receiving PD for life-sustaining RRT. WeChat can be used to send a vast amount of data through text messages, image sharing, voice communication, and video consultation. Several clinical studies have used WeChat as a tool for conducting educational health interventions , 10. HerThe rest of this paper is organized as follows: Health education for patients with ESRD treated with PD is an integral component of management that contributes significantly to successful treatment outcomes. Patients learning to perform self-care at home must learn not only technical details about the PD procedures and the dialysis modality but also new nutritional strategies that are intended to prevent nutritional complications that are all too common in PD patients and contribute to significant morbidity and mortality. PEW, peritonitis, and inadequate dialysis are dreaded complications for PD patients that contribute significantly to poor quality of life, treatment-related morbidity, and illness-related mortality.The conventional Chinese health education for patients learning PD is initiated in the classroom at the dialysis center and is reinforced through telephone conversations and written materials that are provided to patients regularly (every 1–3 months). This educational strategy has obvious limitations. It is intended to provide life-sustaining knowledge to patients with ESRD, which is accomplished for most patients. However, the education provide consists of a large body of information over a short period, usually 1-2 weeks, and for the most part, it is not reinforced except in cases of treatment-related complications. The standard education does not specifically address the patient's adaptation to chronic illness and the behavioral changes needed to perform PD in the home setting. For many patients, the routine procedure of PD is daunting, and the nutritional requirements are difficult to achieve because the food requirements are so different from the usual Chinese diet. The current Chinese diet is composed of a variety of foods with insufficient high biological value protein, making the traditional culturally derived diet inadequate for the successful management of PD. The current diet with inadequate protein content is heavily influenced by culture, education, and economics, and this is not easy to change. Consequently, PEW is a direct consequence of inadequate DPI and has been associated with adverse clinical outcomes such as chronic inflammation, insufficient dialysis, infection, and accelerated rates of cardiovascular disease.It has been shown that single and episodic approaches to patient education are not adequate to bring about sustainable behavior change and adherence . TherefoThe PD nurse sent the pattern of optimal protein intake every 2 weeks and a pattern of comprehensive knowledge about PD every 4 weeks. Similarly, patients sent feedback on their dietary material pictures to the WeChat platform every month under the supervision of medical staff to record the accurate diet of every patient. Nurses command and give prizes to patients who are provided correct feedback on dietary material, point out mistakes of dietary material, and urge the patients who do not send or sent wrong dietary material pictures so that patients follow the physician's dietary recommendation. Furthermore, the problems that patients face in the process of PD are sent to the WeChat group without the limitation of time and location. PD physicians and nurses responded timely. Consequently, both medical staff and patients obtained effective and real information and communicate with each other conveniently. On the other hand, patients who achieve the standard of the recommended diet served as a good model for other patients in the WeChat group. Hence, an increasing number of patients followed the example of the recommended diet, and the intervention is more effectively implemented to attain optimal satisfaction. The results of this study revealed that although the two groups are recommended the same diet, the levels of DPI, EWPI, HBVPI, H/D, and E/H are much higher in IG than in CG. In addition, the dietary adherence rate is better in IG than in CG, while there is no statistical difference in calorie intake in both groups. Therefore, patients in IG are better at incorporating the recommended diet than those in CG because of the use of the comprehensive WeChat-based PD education module.Kt/V, Ccr, and RRF are improved in patients in IG than those in CG. The outcome of better dialysis adequacy and residual renal function in the IG can be explained by the improved serum albumin level and nutrition status [This dietary intervention takes a particular position on the management of chronic kidney disease (CKD) and its complications. It is a cost-effective treatment and one of the main therapies with evidence of improving serum albumin and prognosis for dialysis patients , 15. Then status , 17. Then status , 19. Henn status . Egg whin status , 22. Morn status . Our datE/H) after adjustment for confounders. This finding facilitates a better understanding of the contribution of egg white-based protein intake to the increase in serum albumin. In our study, in the IG, E/H in IG arrived at 18.43%, (approximately 19%) at 6 months and further reached 22.34% (exceeding 19%) at 12 months. In the CG, E/H is 9.8% and 10.19%, respectively, at 6 and 12 months, being significantly lower than those of IG. Consequently, the level of serum albumin in IG is higher than in CG, and the result provides more evidence that egg white-based optimal protein intake could improve the level of serum albumin. However, in this study, the upper limit of the EWPI ratio for improving serum albumin is not confirmed. This may be attributed to the small sample size and the short duration of the study, and further research is needed to explore this possibility.Numerous studies have shown the following findings: RRF can influence nutritional status and serum albumin in patients on dialysis, RRF is an independent factor affecting the hemoglobin level in PD patients, and low serum albumin in patients on dialysis is a predictor of anemia indicating unresponsiveness to conventional treatment for anemia . AnotherThe young and middle-aged PD patients are rather weak in social and family function, as they had ESRD, which makes patients prone to depression and psychological disorders. The study applies WeChat on smartphones to educate patients on optimal egg white-based protein intake diet in PD, troubleshoot problems, and provide follow-up information. Furthermore, the optimal dietary intervention is integrated with the mental and material motivation that helps patients gain respect and appreciation from others. Motivation may help meet patients' mental needs, foster a positive atmosphere for management, arouse patients' initiative concerning physiology, and increase adherence. Therefore, it can stimulate initiative, improve self-confidence, break psychological barriers, and effectively improve treatment compliance. Additionally, the increased communication with medical staff during the whole intervention process enables young and middle-aged PD patients to gain more health knowledge and support, which enhances their confidence in overcoming the disease. Consequently, the present study shows that the incidence of peritonitis, rehospitalization rate, and scores of KDTA and SF-36 that represent the quality of life in PD patients are much better in the IG than those in the CG.There are some limitations to the present study. Firstly, it is a single-center, combined prospective and retrospective study with relatively small sample size. Secondly, the patients in the IG are selected randomly, but only half of the patients in the CG can be randomized, necessitating the use of secondary control data to obtain adequate cases for comparison. Furthermore, although all patients are advised to obtain eggs from the supermarket to ensure uniformity, we could not confirm that this happened in all cases. Patients are trained to weigh food, and all food data are self-reported, which could have led to response bias. Nevertheless, this study has several strengths. To the best of our knowledge, the present study is the first to explore the effect of egg white-based optimal protein intake for PD patients. The unique health education platform for young and middle-aged PD patients is designed. Moreover, atleast, this preliminary study points out the associations between serum albumin levels and the ratio of EWPI to HBVPI. Nevertheless, these data can be considered preliminary and additional studies with a larger sample size, and a longer period of observation should be performed to confirm these findings.In total, 115 consecutive new patients with PD between January 2015 and October 2017 are assigned to either the WeChat intervention group (IG) or the classroom control group (CG). We are not successful in the randomization because WeChat is so popular in China that many patients refused to be assigned to the CG. We modify the study to account for the difficulty by adding secondary data of 35 patients as a retrospective CG to the 35 prospectively assigned WeChat CGs from January 2014 to January 2015. Nephrologists and PD nurses followed up with the patients for 12 months after recruitment. Data of clinical and laboratory parameters are collected by a research assistant every 3 months. Informed written consent is obtained from all the participants. α-ketoacidosis supplements at a dose of 5 g/day and are instructed to take 2–4 egg whites per day along with their usual diet. Egg white, which has a very low phosphate-to-protein ratio, is added to help the patients reach the KDIGO dietary recommendations.All patients in both groups received conventional classroom education at the hospital, and any additional patient education is also delivered in the hospital classroom setting. All patients received classroom dietary education emphasizing the need for adequate protein intake. The target DPI of ≥0.8 g/kg, of which at least 50% would be of a high biological value, is the basic recommendation. Chinese PD patients find it challenging to achieve the KDIGO target of 1.2–1.4 g/kg of DPI . In addiPatients in the conventional education (CE) are received conventional education only, which means physicians and nurses performed routine healthy education through telephone calls or oral and sent health text reading materials every 1–3 months.α-ketoacid, and the optimal protein intake is defined as a daily protein intake (DPI) ≥0.8 g/kg·d and at least 50% of the dietary protein should be of a high biological value, through foods such as egg, milk, and lean meat; (2) foods with a low phosphorus-protein ratio (1.2 mg/g) and well-tolerated, 2–4 egg whites, are strongly recommended per day; (3) using of electronic scales to weigh food and record 3-day diary (including 1 working day and 1 weekend); (4) requiring execution of dialysis prescription, operation of dialysate exchange, catheter nursing, self-management, and arrange follow-up time.The conventional education material includes the following aspects: (1) the intake of optimal dietary protein with α-ketoacid supplement, and they are instructed to supplement their usual diet with 2–4 egg whites per day. The IG, in addition, received a comprehensive PD education module with a strong emphasis on achieving the target intake through 2–4 egg whites daily via WeChat. In addition, the WeChat module provides information on choosing foods with high biological protein content. The comprehensive WeChat platform-based PD education module is carried out by two nephrologists and two PD nurses. The physicians develop the working rules and strategy and regularly summarized and supervised the management of the module. Furthermore, the physicians also design a pattern for this educational intervention module in the form of an easy-to-understand visual image with minimal text forma: (1) the pattern of optimal protein intake is made according to the content of optimal DPI mentioned in conventional education. It also contained visual images of 2–4 egg white intake and the cooking method. This pattern is conveniently sent to the WeChat platform every 2 weeks; (2) the pattern of comprehensive knowledge of PD, such as prevention of peritonitis and self-management, is shared every 4 weeks. The nurses act as the manager to establish the WeChat group and trained the patients who are unfamiliar with the use of WeChat to send or receive messages, voices, images, and videos. In addition, nurses sent the patterns and made group announcements to everyone on WeChat according to the working rules and strategy. At the same time, the patients sent feedback on their dietary intake as pictures through WeChat every month. Then, nurses commended the patients who sent correct feedback on dietary materials and gave prizes. Simultaneously, nurses pointed out mistakes in the dietary pattern so that the patients can correct and send the feedback again and the nurses also urge the patients who do not send the dietary pattern. Furthermore, nurses release follow-up information promptly as planned; (3) patients state the problems that they encounter during PD treatment on the WeChat platform and obtained a response from physicians or nurses within 24 hours in the form of messages, voices, and images. Patients in the IG have received the same basic conventional education, dietary instructions for a DPI of 0.8 g/kg per day, and 5 g/day of α-ketoacid. Biochemical indices and dialysis adequacy data are collected at the initial visit, 6 months, and 12 months. Biochemical indices including hemoglobin, serum creatinine, urea nitrogen, serum albumin, and serum lipids are examined by using an automatic chemistry analyzer. In addition, the serum intact parathyroid hormone (iPTH) is tested by isotopic chemiluminescence. The 24-hour urine and dialysate samples are collected to perform the peritoneal equilibration test. Weekly urea clearance (Kt/V), creatinine clearance (Ccr), and normalizing protein catabolic rate (PCR) are calculated using standard methods. Residual renal function (RRF) is estimated using the average renal clearance of urea and creatinine. Data on the incidence of peritonitis, rehospitalization rate, and dietary adherence are recorded during the study. The dietary adherence is calculated using the following formula: the number of patients achieving the recommended dietary protein/total number in the group. Lastly, the feedback rate equaled the actual number of feedback , which is recorded only in the IG.Demographic data are collected at baseline, which included age, gender, body mass index (BMI), diabetes, phosphate binders, and Based on the 3-day diet diary, DPI, egg white protein intake (EWPI), high biological value protein intake (HBVPI), the ratio of HBVPI to DPI (H/D), the ratio of EWPI to HBVPI (E/H), and daily energy intake (DEI) are calculated using the software . All patients received conventional glucose-based PD solutions . Total energy intake (TEI) = DEI + calories from dialysate sources , 27. BotThe Kidney Disease Quality of Life-short form (KDQOL-SF version 1.3) questionnaire has been validated for use as a disease-specific measure of the quality of life for dialysis patients and combines the kidney disease-specific instrument  with the generic SF-36 instrument . KDTA has 11 domains with 43 kidney disease-targeted items, including symptoms, effects,and burden of kidney disease, work status, cognitive function, quality of social interaction, sexual function, sleep, social support, dialysis staff encouragement, and patient satisfaction. The SF-36 has 8 domains with 36 generic core items, which are physical function, physical role, pain, general health, emotional wellbeing, social function, energy, and fatigue. The score ranges from zero to 100 with higher scores representing the better-perceived quality of life.In total, 140 patients are enrolled in this study, with 70 in each group. However, 113 patients (59 patients in the IG and 54 in the CG) completed the 12-month follow-up; 11 (15.71%) dropped out from the IG, and 16 (22.86%) dropped out from the CG . No diffH/D, and E/H than the CG, and an interaction effect is also observed (P < 0.05). Additionally, this significant difference is maintained at 12 months (P < 0.05). No significant difference in DEI and TEI is noted (P > 0.05). In Both the IG and CG show improvements over time. Thus, the value of dietary protein intake is better in the IG, as shown in P = 0.025) and maintains this significant difference at 12 months (P = 0.004), and an interaction effect is also observed (P = 0.049). The IG also has a significantly higher Ccr, Kt/V, and PCR and lower triglyceride levels than the CG (P < 0.05) at 12 months, but not at 6 months. There is no significant between-group difference in the RRF over time. However, an interaction effect is present (P = 0.0112), indicating that the IG had a better time-based value of RRF than the CG. No difference in other parameters is observed between groups, as shown in Kt/V is weekly urea clearance, Ccr is weekly creatinine clearance, and RRF is residual renal function.The IG has better value serum albumin levels than the CG at 6 months  is related to serum albumin levels, and an inflection point K is calculated, as shown in Univariate analysis suggested that serum albumin levels are nonlinearly and positively correlated with E/H, H/D, EWPI, HBVPI, and RRF. Moreover, they show a linear and positive correlation between hemoglobin and PCR, and a negative correlation with the presence of diabetes. Threshold effect analysis shows that P = 0.005). A segmented regression model is set up with adjustment for confounders such as H/D, EWPI, HBVPI, RRF, hemoglobin, PCR, and diabetes as follows:The models are tested using a likelihood ratio test , P = 0.944; 6.2 < E/H < 19, β6.2–19 = 0.144, 95% CI (−0.03 to 0.317), P = 0.106; and E/H ≥ 19, β19 = 0.221, 95% CI (0.024–0.419), P = 0.029. This suggests that serum albumin levels may increase significantly when E/H becomes greater than 19%.The results are as follows: P = 0.047). P < 0.05). Furthermore, the IG received the pattern of optimal protein intake 26 times, and feedback dietary material pictures are to be provided 12 times per patient, resulting in a total number of 708 times. The actual feedback from dietary material pictures is obtained 603 times, and the rate of feedback is 85.15%. Finally, the IG had better KDTA and SF-36 scores than the CG (P < 0.05). In At the end of the study, there is one episode of peritoneal infection for every 0.169 patient-years in the IG, whereas it is 0.333 patient-years in the CG (This paper uses a comprehensive WeChat platform-based PD education module with a strong emphasis on egg white-based optimal protein intake in addition to conventional education to perform an intensive health education intervention to augment DPI in patients undergoing PD in China. The IG, which receives the WeChat comprehensive education program, not only improves DPI and serum albumin but also robust improvement in clinical outcomes and quality of life, suggesting that the education program engaged the patients and enabled them to participate more in their care to improve dialysis outcomes. Additionally, this study identified an association between serum albumin levels and the ratio of EWPI to HBVPI. A ratio greater than 19% is determined to be the threshold needed to obtain an increase in serum albumin levels. Reinforcing comprehensive PD education using WeChat helps patients, including those with ESRD, improve nutritional parameters, clinical parameters, and quality of life. Education through social media represents a new opportunity for improving prognosis in ESRD patients with PD.


Background and Objectives: Odontogenic infections (OI) represent a frequent cause of dental and maxillo-facial interventions, mostly due to late presentations or misdiagnosed complications. It is believed that the intensity of the immunoinflammatory response in OI is the main prognostic factor. Therefore, in this research, it was pursued to determine if the combination of C-reactive protein (CRP) and Neutrophil to Lymphocyte Ratio (NLR) (CRP-NLR) may serve as potential severity predictors in patients with odontogenic infections. Materials and Methods: A retrospective analysis on 108 patients hospitalized for odontogenic infections was conducted at the Department of Maxillofacial Surgery. Depending on the symptom severity scale, patients hospitalized with OI were divided into two equal groups based on infection severity (SS). Results: Patients with severe OI from Group B were associated more frequently with diabetes mellitus and smoking more often than those with a lower severity from Group A. In Group A, abscesses of odontogenic origin accounted for 70.4% of hospitalizations, while in Group B, abscesses and cellulitis were associated in 55.6% of cases . The disease outcomes were more severe in Group B patients, where 22.2% of them developed sepsis, compared to 7.4% of Group A patients . However, there was no significant difference in mortality rates. The SS and systemic immune inflammation index (SII) scores of Group B patients were substantially higher than Group A patients , respectively, 2312.4 vs. 696.3 for the SII score . All biomarker scores, including the CRP-NLR relationship, were considerably higher in Group B patients, with a median score of 341.4 vs. 79.0 in Group B . The CRP-NLR association determined a 7.28-fold increased risk of severe OI. The receiver operating curve (ROC) analysis of CRP-NLR yielded an area under curve (AUC) value of 0.889, with high sensitivity (79.6%) and high specificity (85.1%), for predicting a severe odontogenic infection using biomarkers measured at hospital admission . Conclusions: Therefore, it can be concluded that CRP-NLR is a reliable and affordable biomarker for determining the severity of odontogenic infections that may be included in other prognostic models for dental infections. Overall, the incidence of severe odontogenic infections is believed to be declining for a variety of reasons, including the availability of antimicrobials, innovations in healthcare delivery, and overall improvement in oral hygiene, leading to a decrease in mortality ,2. InfecIt is crucial while treating patients with odontogenic infections to identify those that pose a high likelihood of developing serious consequences. These results may influence judgments on the dosage and effectiveness of therapy for some complicated cases. The strength of the immunoinflammatory response is believed to be a main prognostic factor . Using fConsequently, the white blood cell count (WBC) is a well-researched predictor of inflammation  with a hInstead, the NLR score, computed as the ratio between the neutrophil and lymphocyte counts detected in peripheral blood, is a valid indicator for detecting inflammatory status, bacteremia, and sepsis ,21. BecaNeutrophil to lymphocyte ratio (NLR) and C-reactive protein (CRP) levels are typically elevated in patients that develop abnormal inflammatory responses. To our knowledge, no studies have investigated so far the relationship between NLR and CRP with the severity of odontogenic infections. Therefore, it is believed that combining these two inflammatory scores would result in a more accurate disease-severity score, while the null hypothesis states that NLR-CRP association is an insignificant predictor of OI severity. In our investigation, we predicted that by combining the fast-rising characteristics of CRP with the high sensitivity of NLR for inflammation, it would be possible to obtain a measure with the capacity to predict the severity of odontogenic infections with great accuracy.The study was designed as a retrospective cohort of patients admitted for odontogenic infections to the Maxillofacial Surgery Department of City Emergency Hospital Timisoara (SCMUT), affiliated with the Victor Babes University of Medicine and Pharmacy from Timisoara between January 2017 to April 2022. These data were collected from digital and paper records only with the patient’s agreement and the ethical approval obtained from the Ethics Committee of SCMUT with the approval number I-27098 from 14 October 2022.Patients above the age of eighteen were enrolled in the research. Infections of odontogenic origin were examined for inclusion according to the international classification of diseases (ICD-10) disease classification . PatientA convenience sampling method was employed to calculate the appropriate sample size. Considering the incidence of OI in the general population ranges between 0.05% and 0.1% ,34, the Demographic data and the patient’s medical history were collected. The hospital information system obtained the patients’ discharge reports, clinical evaluations, laboratory values, and imaging tests. Furthermore, routine blood samples, white blood cell count (WBC), hemogram indexes such as neutrophil and lymphocyte count, Neutrophil to Lymphocyte Ratio (NLR), and platelet count were evaluated. The variables considered for analysis comprised demographic data: age, gender, and place of origin, clinical presentation features , odontalgia , mandibular pain , dysfunctional disturbances of the masticatory system ), edema, signs of obstruction , and signs of systemic infection  [p-values, and correlation coefficient “r” of the laboratory values were calculated using the statistical analysis software MedCalc . Variables were compared between group A and group B, including the laboratory tests mentioned above related to the Severity Score (SS) of odontogenic infections. The Mann−Whitney U test was applied to compare non-normally distributed means, while Student’s t-test was used to compare normally-distributed data. Chi-square and Fischer’s exact tests were applied to verify a possible difference between the two groups regarding variables described as proportionate values. Logistic regression analysis was applied to determine the association between CRP and NLR. The hazard ratio and adjusted odds ratios were determined for the assessment of CRP and NLR as predictors for infection severity (represented by SS score severity). The area under the curve (AUC) was plotted for CRP and NLR to determine their accuracy in predicting the severity of odontogenic infections. A p-value < 0.05 was considered statistically significant when comparing the study variables.Data were obtained electronically and deidentified. Mean values and standard deviations (SD), p-value = 0.150). However, the place of origin was significantly different between the study groups, with patients with more severe infections coming more frequently from rural regions . Additionally, patients with severe OI were more often affected by diabetes mellitus , and smoking was more common in Group B compared to the group with lower severity infections .In total, 544 patients diagnosed clinically and radiologically with odontogenic infections were admitted and hospitalized at the Maxillofacial Surgery Department, SCMUT, Romania, between January 2017 and April 2022. Only 108 patients met the inclusion criteria and were enrolled in the study, as described in p-value < 0.001), as seen in p-value = 0.030), and four patients with severe OI were admitted to the ICU. However, mortality was not significantly different between the study groups . The median duration of hospitalization was significantly longer in patients from Group B, compared to Group A , in correlation with a higher frequency of severe complications in Group B .Regarding the infection type in OI admitted to the hospital, 70.4% of them were abscesses in the lower infection cohort (Group A), while in Group B, 55.6% of infections were associations of abscesses and cellulitis . A severe trismus score was observed in 27 (50.0%) of patients from Group B, compared to only 9.3% in Group A . Similar observations were noticed in the dysphagia score and fascial space score, where a statistically significantly higher prevalence of high severity was found in Group B patients. The prevalence of patients with odontogenic infections who were admitted with dehydration and significant comorbidities was significantly higher in Group B .The symptom severity evaluation presented in p-value < 0.001), respectively, 2312.4 in Group B compared to 696.3 in Group A . All tested biomarker scores were significantly higher in Group B patients, including the CRP-NLR association, with a median score of 341.4, compared with 79.0 in Group B .p-value < 0.001), high CRP levels with a 6.65 higher likelihood of severe OI, and lastly, the CRP-NLR association being responsible for a 7.28 higher risk (95% CI = 4.83–10.16). The ROC analysis of CRP-NLR resulted in a 0.889 AUC value , with high sensitivity (79.6%) and high specificity (85.1%) for predicting a severe odontogenic infection using these biomarkers measured at hospital admission (The logistic regression analysis presented in dmission .The decision-making process in medicine incorporates clinical and laboratory considerations. Detecting an increase in acute phase reactants may assist the diagnostic interpretation of clinical symptoms in circumstances when an infection is suspected. In our investigation, CRP-NLR, which consists of CRP level at admission and NLR level at admission, was shown to have a more accurate ability to predict the severity of odontogenic infection. Initially, it was shown that a high CRP-NLR was substantially and strongly connected with high severity levels in odontogenic infection. Then, we examined the connection between CRP-NLR levels and WBC levels at admission in both severity groups and discovered that CRP-NLR had a greater predictive capability.A better understanding of the inflammatory cascade has led to new discoveries and the identification of many mediators that, in combination with clinical symptoms, might serve as valuable infection indicators . Bagul eDynamic changes in NLR, on the other hand, predate the clinical condition by several hours and may alert doctors to an ongoing pathogenic process. Despite these benefits, NLR as a biomarker for assessing the progression of odontogenic infection has limited use. A recent meta-analysis  revealedIn addition, NLR may be used as a predictor for surgical treatment in submandibular abscesses  and as aAccording to several research, despite the increase in frequency, the patient features have remained basically unchanged . The majOur research has some important limitations and restrictions. To begin, the study was a single-center investigation of patients who had been admitted to the medical facility for odontogenic infections. Second, because of the retrospective design, we had to rely on the data from medical records; as a result, statistical analysis was susceptible to the risk of being inaccurate due to human error. Additionally, the retrospective study design impacts our results, as the research depends on the accuracy of both patient information tracking and the digital transcription of data from paper records. Limited by the retrospective design of our study, we could not perform a dynamic profile analysis of CRP and NLR, which may offer more helpful information. Other limitations are represented by country-specific features, since all patients were from Romania, and the oral hygiene can influence the severity of odontogenic infections. To provide more evidence in support of our results, further prospective research should be carried out.This research aimed to determine whether there is a significant correlation between increased levels of inflammatory serum markers, as measured by the NLR and CRP, and the severity of odontogenic infections, as measured by the Symptom Severity score. The connection between these markers was discovered as an accurate predictor of OI severity. Thus, it can be concluded that CRP-NLR is a reliable and inexpensive biomarker to provide the severity of odontogenic infections that can be incorporated into other prognostic models to help determine the severity of odontogenic infections. Medical practitioners and their dental teams should be instructed to use the NLR-CRP score for the early identification and prognosis of severe odontogenic infections, hence potentially improving disease treatment choices.


Drug-resistant tuberculosis remains a serious public health problem worldwide, particularly in developing countries, including China. This study determined treatment outcomes among a cohort in Guangzhou, China, and identified factors associated with them.We initiated a retrospective study using drug-resistant TB data in Guangzhou from 2016 to 2020, managed by Guangzhou Chest Hospital. A competing risk model was used to identify the factors associated with treatment failure and death, as well as loss to follow-up (LTFU).A total of 809 patients were included in the study, of which 281 were under treatment. Of the remaining 528 who had clear treatment outcomes, the number and proportion of treatment success, treatment failure, death, and LTFU were 314 (59.5%), 14 (2.7%), 32 (6.0%), and 168 (31.8%), respectively. Being older and having cavities involving the upper lungs were risk factors for treatment failure and death, while non-Guangzhou household registration and interprovincial mobility were risk factors associated with LTFU.Treatment failure and death were significantly associated with cavitation in the lungs, and LTFU was significantly associated with household registration and geographical mobility. Early identification of factors associated with different treatment outcomes is extremely important for policymakers, health experts, and researchers to implement appropriate strategies and measures to treat and manage the TB-infected population in China. Mycobacterium tuberculosis (MTB), which mainly leads to lung infections but can also infect other organs. Drug-resistant TB is the result of the development of drug resistance by MTB and continues to be a public health threat (Tuberculosis (TB) is a chronic infectious disease caused by h threat . In 2019h threat .The directly observed treatment and short-course chemotherapy (DOTS) strategy, the main treatment strategy for TB and drug-resistant TB, has been gradually rolled out globally since 1997. It was reported that the reproduction number of TB in mainland China dropped from 1.7885 to 1.0741 after DOT realized its full coverage in mainland China  patients . Viboon We did a retrospective study with data obtained from Guangzhou Chest Hospital, Guangdong Province, China. Guangzhou Chest Hospital is the only specialized chest hospital in Guangzhou, the capital city of Guangdong Province, with a registered resident population of 9.85 million in 2020 . MeanwhiWe included all the patients with drug-resistant TB (defined as resistance to at least one anti-tuberculosis drug) in Guangzhou from 1 January 2016 to 31 December 2020. Based on that, patients were excluded from this study if they were (1) those who did not accept treatment; or (2) those whose dates of diagnosis were later than the dates ending their treatment due to a registration error .Suspected patients with TB would take bacteriological tests (sputum smear or culture) and be diagnosed according to the diagnostic criteria for TB (WS 288-2017) issued by the National Health Commission of China . Based oBacteriologically confirmed drug-resistant patients with TB would be hospitalized at Guangzhou Chest Hospital for at least 2 weeks while receiving DOTS by trained medical personnel. After that, they received outpatient treatment. All patients are treated individually, based on standardized therapies developed by WHO. During the whole process of anti-TB treatment, each patient was assigned to a designated hospital for management. Patients were managed by a trained family member or supervisor from the local community and returned to the hospital once a month for medication refills as well as adherence and progress evaluation. At the same time, staff also provide health education to patients to keep them in good adherence.Patient information, including socio-demographic characteristics such as age, gender, occupation, household, and mobility, and clinical characteristics, such as treatment outcomes, previous TB treatment history, duration of treatment, commodities, image data, and DST results, were obtained from the internet-based TB Management Information System in the Tuberculosis Control Institute of Guangzhou and from medical records, image system as well as the testing system. In China, household registration records people's names, addresses, and other basic information for providing fast services for public life, group production, social services, and government administration. Information on household registration and mobility could be obtained directly from patients' medical records. In our study, the resistance pattern was categorized as mono/poly drug-resistant, MDR, and XDR. Mono drug-resistant is defined as resistance to only one of the first-line drugs ; poly drug-resistant is defined as resistance to two or more of the first-line drugs, but not both isoniazid and rifampicin; MDR is defined as resistance to two or more of the first-line drugs and at least both isoniazid and rifampicin; and XDR is defined as MDR plus resistance to a fluoroquinolone and an injectable agent. TB treatment history was defined as patients who have ever received anti-TB treatment, no matter what and how many drugs they have taken. The cavity was categorized as none, with cavities but not involving the upper lungs, and with cavities involving the upper lungs  according to references and clinicians' experience .Study definitions were completely consistent with WHO guidelines, as follows: treatment outcomes were classified as treatment failure, cured, treatment completed, LTFU, death, and under treatment. Treatment failure is defined as a patient with TB whose treatment was terminated or need for permanent regimen change of at least two anti-TB drugs because of the lack of conversion by the end of the intensive phase, or bacteriological reversion in the continuation phase after conversion to negative, or evidence of additional acquired resistance to fluoroquinolones or second-line injectable drugs, or adverse drug reactions (ADRs); cured is defined as a TB patient whose treatment was completed as recommended by the national policy without evidence of failure and three or more consecutive cultures taken at least 30 days apart are negative after the intensive phase; treatment completed is defined as a patient with TB whose treatment was completed as recommended by the national policy but no record of meeting the definition for cured; death is defined as a patient with TB who dies for any reason during the course of treatment; LTFU is defined as a patient with TB whose treatment was interrupted for 2 consecutive months or more; under treatment, which is equivalent to not evaluated, indicated that none of the foregoing outcomes had occurred at the end of observation .The dependent variables in this study, namely, treatment outcomes, were divided into two groups: (1) treatment success if patients were cured or completed the treatment and (2) unfavorable outcomes if the patients were dead, treatment failure, or LTFU (whichever occurred first). Furthermore, unfavorable treatment outcomes were divided into two groups recursively: (2a) LTFU if the patients were “lost” during the treatment; and (2b) poor treatment outcomes if the patients died or had an outcome of treatment failure.Continuous variables were described using the mean and standard deviation if they were normally distributed, otherwise the median and interquartile range would be utilized. The classification variables are described using frequency and percentage. The cumulative incidence function (CIF) was used to estimate the cumulative incidence rate of various events . The Fine and Gray models were used to determine the influential factors associated with treatment outcomes.The time to treatment outcome is the period from when a patient is diagnosed as drug-resistant to when treatment outcome occurs. In our analysis, both successful treatment outcomes  and under treatment  were defined as censored. In our study, we focused on two different events based on the competing risk framework. Event one was the occurrence of poor treatment outcomes , and event two was the occurrence of LTFU. In the analysis of poor treatment outcomes, we considered LTFU as a competing risk . Similarly, in the analysis of LTFU, death was considered a competing risk. Due to the existence of competing risks, we used the Fine and Gray subdistribution model based on CIF, which can directly estimate the effects of the factors associated with the event of interest in the presence of competing risks.P-value < 0.10 and age  were included in the multivariate analysis. We also included hypertension, diabetes, and resistance pattern as confounders that needed to adjust no matter if they are statistically significant or not. Factors with P < 0.05 in multivariate analysis were considered statistically significant. Then, a sensitivity analysis using the 500 data generated by multiple imputations was run based on the assumption that missing values were missing at random. The covariates used to impute missing variables were all the complete variables except the dependent variables. We adopted the multivariate model established by complete case analysis to analyze these datasets, and we got different estimates of the same covariates. Finally, according to Rubin's Rule, we pooled these results.For all the complete cases, univariate analysis was performed for the two events individually. As a result, factors whose Data recording was done with Microsoft Excel 2016, and analyses were fulfilled using R 4.0.2 with the package “cmprsk.”A total of 809 patients with drug-resistant TB were included in the study from 1 January 2016 to 31 December 2020. IQR: 31–57) and 62 years old (IQR: 56–71.5) in the dead patient group.As shown in In the group of treatment failure and death, the proportion of those with cavities involving the upper lungs was 64.3% (9/14) and 71.9 (23/31) and their diabetes prevalence was a little higher than others, accounting for 28.6% (4/14) and 31.3 (10/32), respectively. Besides, it seems that there were not many differences in the prevalence of viral hepatitis and hypertension as well as the proportion of those receiving TB treatment previously among treatment success, treatment failure, death, and LTFU. Of all the 809 patients, the proportion of MDR is the highest, accounting for 72.2% (584/809), followed by mono/poly drug-resistant and XDR, accounting for 17.6% (142/809) and 5.0% (40/809), respectively.There were missing values in diabetes, smoking, drinking, viral hepatitis, hypertension, resistance pattern, and cavities. The one with the highest missing rate was the resistance pattern, at 5.2% (43/809).The cumulative incidence of poor treatment outcomes (event one) among all patients at months 6, 12, and 24 were 2.3, 4.7, and 8.3%, respectively . At montP-value of 0.071, the actual lower limit of 95% CI of age was 0.999, making it very close to statistically significant  . In the nificant .Sensitivity analyses showed that after multiple imputations, the results for events one and two were almost identical to those of the complete data analysis, except that age  was a risk factor and MDR  was a protective factor for LTFU after multiple imputations.Unlike previous studies focusing on a comprehensive unfavorable outcome, which is the composite event of treatment failure, death, and LTFU, this study focused on the outcome of treatment failure and death, as well as the LTFU separately by using a competing risk model. In our study, the proportion of LTFU was 31.8%, slightly higher than that of 29% in the TB report 2020 of WHO and 27% in a study of Hunan province, China, in 2017 . The proMycobacterium tuberculosis in cavities is more resistant to drugs. In our study, cavities involving the upper lungs were found to be a risk factor. The cavity is a risk factor for inducing resistance and leading to treatment failure, yet considering its location at the same time is the highlight of this study. Bowness et al. .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.


Serum pepsinogens are serological biomarkers of gastric atrophy, and the latter is a risk factor for esophageal squamous cell carcinoma (ESCC). However, the association of serum pepsinogens with ESCC risk remains unclear. This systematic review and meta-analysis aimed to assess the relationship between serum pepsinogen I (PGI) and pepsinogen I: pepsinogen II ratio (PGR) and ESCC risk.PubMed, Embase, and Web of Science were searched for articles on the effect of serum PGI and PGR on ESCC risk, published up to the end of February 2022. Meta-analysis with a random-effect model was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs).I2 = 60.2%, P = 0.028) rather than in serum PGI . In stratified analysis by study quality, the significant risk effect on ESCC was remained for PGI  and PGR  when only the studies with high quality were pooled.Five case–control studies and three prospective studies were included. In comparison with the high categories, the low categories of serum PGI  and PGR  were associated with an increased risk of ESCC, although a substantial heterogeneity was observed in serum PGR (Based on the available studies, although limited in number, this systematic review along with meta-analysis suggests that low serum PGI and low PGR may be related to an increased risk of ESCC. This present study provides evidence for using serum pepsinogen biomarkers in predicting ESCC. More delicate well-designed cohort studies with high study quality are needed, and dose–response analysis should be performed. Esophageal cancer is one of the most common malignant tumors worldwide. It ranks seventh in cancer incidence and sixth in cancer mortality worldwide , 2. EsopEarly detection, early diagnosis, and early treatment can improve the patient’s condition and thereafter increase the survival of patients. Invasive and costly endoscopy and biopsy for histopathology are the gold standard for diagnosis of esophageal cancer . HoweverTwo previous meta-analyses , 26 examTherefore, this systematic review and meta-analysis aimed to assess the association of ESCC risk with serum PGI and PGR by pooling the existing evidence.This systematic review and meta-analysis was conducted by following the PRISMA statement . The twoA systematic literature search for studies published in PubMed, Embase, and Web of Science was conducted up to the end of February 2022 for original studies in humans on the association between serum pepsinogens and ESCC, with no language restriction. The following search strategy was adopted:  AND . Reference and citation tracking was also conducted to retrieve potential studies. A more detailed search strategy is shown in Eligible studies met the following criteria: study design of the case–control study or cohort study, ESCC cases were diagnosed by histological examination, the association of serum pepsinogens with ESCC incidence was examined, and the relative risk (RR) or odds ratios (ORs) and their 95% confidence interval (CIs) were reported or could be calculated. Cross-sectional studies, comments, editorials, animal studies, and abstracts were excluded. For multiple reports of the same biomarker from the same research population, only the most recent or informative report was included.The quality of included studies was evaluated using the Newcastle–Ottawa Scale (NOS) , 31. ThiThe following information was collected from each included study, including first author, year of publication, country where the study was performed, study design, follow-up period for cohort studies, period when subjects were recruited for case–control studies, number of cases and total individuals for cohort studies, number of cases and controls for case–control studies, median or mean of age, male proportion, serum pepsinogen biomarkers and boundary point, risk estimates and their 95% CIs, and the covariates. The cutoff points for serum PGI and PGR varied in different studies. When the results for several cutoff points were provided in a study, we selected those which were more consistent with the cutoff points in other studies, that is, PGI <25 to ≤ 70 μg/l and PGR≤ 2 to ≤3.I2 ≥ 50% and P ≤ 0.1); otherwise, the fixed-effect model was adopted , and two studies were found from reference tracking. A total of 1,549 studies were left after duplicate removal. Of 42 studies for further full-text reviewing after the abstract screening, 34 studies were excluded for the reason of unavailable outcomes of interest, inappropriate exposure, conference abstract, review, and studies in the same population. Finally, eight studies –24 were I2 = 46.4%, P-heterogeneity = 0.070). The Egger’s test (P = 0.156) and the funnel plot  and Europe   rather than with low quality .As shown in I2 statistic was 60.2% and the P value for Q-test was 0.028, suggesting a marginal heterogeneity. The Egger’s test (P = 0.812) and the funnel plot  or three studies with case–control design were pooled .For six studies that assessed the association between serum PGR and risk of ESCC, the pooled OR (95% CI) was 1.70  when comparing the low with high level Table 2.In the present study, we found that both low level of serum PGI and low level of serum PGR were associated with an increased risk of ESCC.Smoking and drinking were two risk factors for ESCC; hence, we conducted a subgroup analysis based on whether these two risk factors were adjusted. Two studies [one cohort study  and one For PGI, the subgroup analysis by region found that the association was stronger in European than in Asian, suggesting the geographical or ethnic variation. This was consistent with the finding by Islami et al. . When stHelicobacter pylori infection was associated with a higher risk of ESCC, and gastric atrophy may be an intermediate step in the pathway from Helicobacter pylori infection to ESCC. However, since most studies did not provide information on the combined stratification of Helicobacter pylori and serum PGI or PGR, we cannot examine it directly in the present meta-analysis.Gastric atrophy has been associated with ESCC, but its causal relevance has been questioned. It was suggested that gastric atrophy might be related to ESCC because of bacterial overgrowth and N-nitrosation reactions caused by the reduced gastric acid production during gastric atrophy or duodenal reflux –39. SomeThere are some advantages in this study. Firstly, as many eligible studies as possible were included in this study. Secondly, several subgroup analyses were conducted to identify potential sources of heterogeneity. Several limitations also existed. Firstly, substantial heterogeneity was observed among included studies. This heterogeneity may be due to various factors, such as diversity in the population characteristics, serum pepsinogen detection methods, and study design. Secondly, there is no consensus on the best cutoff point for serum pepsinogen biomarkers. Dichotomous comparisons may not be the most efficient use of data in estimating the association between gastric atrophy and ESCC risk. These comparisons may be misleading, because any cutoff point will put people with considerably different risks into the same category. Therefore, it is urgent to conduct the delicate well-designed longitude studies and dose–response analyses.In summary, this systematic review with meta-analysis, although based on a limited number of studies, suggested that both low level of serum PGI and low level of serum PGR were related to an increased risk of ESCC, respectively. This present study provides evidence for using serum pepsinogen biomarkers in predicting ESCC. More delicate well-designed cohort studies with high study quality are needed and dose–response analyses should be performed.Publicly available datasets were analyzed in this study. The data are available by contacting the corresponding author or extracting from originally published research.XL and WZ conceived and designed this study. Z-XY and L-BY researched the literature. Z-XY and PH performed the statistical analysis. Z-XY and PX drafted the manuscript. XL, XX, YL, WZ, and L-BY edited and reviewed the manuscript. All authors contributed to the article and approved the submitted version.This study was supported by the National Key R&D Program of China (No. 2018YFE0208000), the Guangdong Basic and Applied Basic Research Foundation (No. 2019A1515011599), and the Science and Technology Program of Guangzhou City (No. 202102080404). The funders had no role in the design, analysis, or writing of this manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.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.


The purpose of this study was to explore the application of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) image radiomics in the identification of spine multiple myeloma (MM) and bone metastasis (BM), and whether this method could improve the classification diagnosis performance compared with traditional methods.This retrospective study collected a total of 184 lesions from 131 patients between January 2017 and January 2021. All images were visually evaluated independently by two physicians with 20 years of experience through the double-blind method, while the maximum standardized uptake value (SUVmax) of each lesion was recorded. A total of 279 radiomics features were extracted from the region of interest (ROI) of CT and PET images of each lesion separately by manual method. After the reliability test, the least absolute shrinkage and selection operator (LASSO) regression and 10-fold cross-validation were used to perform dimensionality reduction and screening of features. Two classification models of CT and PET were derived from CT images and PET images, respectively and constructed using the multivariate logistic regression algorithm. In addition, the ComModel was constructed by combining the PET model and the conventional parameter SUVmax. The performance of the three classification diagnostic models, as well as the human experts and SUVmax, were evaluated and compared, respectively.P = 0.01 and P = 0.001; Validation: P = 0.018 and P = 0.033), and no statistical difference was observed between the CT model and human experts .A total of 8 and 10 features were selected from CT and PET images for the construction of radiomics models, respectively. Satisfactory performance of the three radiomics models was achieved in both the training and the validation groups . Moreover, the PET model and ComModel showed significant improvement in diagnostic performance between the two groups compared to the human expert (Training: The radiomics model constructed based on 18F-FDG PET/CT images achieved satisfactory diagnostic performance for the classification of MM and bone metastases. In addition, the radiomics model showed significant improvement in diagnostic performance compared to human experts and PET conventional parameter SUVmax. Multiple myeloma (MM) was a malignant clonal cell tumor that originated from bone marrow plasma cells. MM extensively invades bone marrow, bones, and extramedullary organs, leading to prime syndromes such as bone pain, anemia, infection, fractures, and kidney damage . Bone mePrevious studies had considered serologic markers such as serum creatinine, serum globulin, and serum alkaline phosphatase as crucial information for differentiating MM from BM. However, some patients with light chain secretory, low, and non-secretory myeloma may have low or normal levels of these serologic markers, and such examinations were often used for preliminary screening , 6. 18F-Radiomics converted texture, intensity, density, and other features extracted from medical images into mineable high-dimensional data through automated or semi-automated methods, which could be used as a non-invasive assessment of spatial heterogeneity of tumors and facilitate personalized patient treatment , 14. TheThe purpose of this study was to explore the feasibility of radiomics based on 18F-FDG PET/CT images in the identification of MM and BM and whether it could improve the diagnostic performance of these two diseases.Participants between January 2017 and January 2021 were enrolled in this study according to the following inclusion criteria: (1) The diagnosis of MM meets the standards of the International Myeloma Working Group ; (2) BM All the image acquisition procedures in this study were completed in the PET/CT(Philips Ingenuity TF). The radioactive tracer 18F-FDG was automatically synthesized by the cyclotron  and the 18F-FDG chemical synthesis module , and the radioactive tracer purity was guaranteed to be >95%. The patient fasted for at least 6 h before the examination, and the glucose level lower than 11.1 mmol/L was ensured by routine measurement of the blood samples before the PET/CT examination. Patients were injected with 18F-FDG(5.55 MBq/kg) intravenously in a quiet state and were placed in a room with dim light for 40–60 min, and then underwent PET/CT after emptying the bladder. The scanning process includes a low-dose CT scan and PET scan from the top of the skull to the upper thigh. CT acquisition parameters were as follows: tube current tube voltage was automatically generated according to the positioning image, tube rotation time: 0.35 s, output voltage: 70–140 KV, output current: 20–450 mA, layer thickness: 0.7 mm, reconstruction time: 40 frames/s, reconstruction matrix: 512 × 512, number of detector rows: 64, pitch: 0.15–1.5. After standardizing all parameters of the patient's PET/CT images, the window width and window level of the CT images were set to 350 and 50, respectively, and the PET data were reconstructed by attenuation correction and iterative method , and then transmitted to the MedEx workstation together with the CT images for fusion imaging. The maximum standardized uptake value (SUVmax) was automatically generated by the workstation based on the information of the subject's weight, injection dose, and time. The region of interest (ROI) was outlined along with the extent of the lesion at the level where the concentration of the radioactive tracer was most obvious, and the workstation automatically calculates the SUVmax.Considering that detailed pathological examination was not available in all patients, we determined the diagnosis of the lesions on the basis of pathological biopsy, imaging follow-up, and clinical course of the disease. Independent visual analysis of lesions was evaluated by two physicians (TAJ and JY) with 20 years of diagnostic experience using the double-blind method, physicians were not informed of the patient's clinical information and pathology but were told that the lesion was either MM or BM. The weighted kappa analysis was used to determine the interobserver agreement. Kappa coefficients of 0–0.20, 0.21–0.40, 0.41–0.60, 0.61–0.80, and 0.81–1 were considered to be slight, fair, moderate, good, and almost perfect agreement, respectively .Segmentation of the lesions was also performed by double-blind methods with physicians who had 10 years of experience (CMY and ZJN) in diagnostic work. All features were extracted in MaZda software, which has been proven in previous studies for radiomics, and all radiomics features extracted were in accordance with Image Biomarker Standardization Initiative (IBSI) standards , 25. TheTo ensure the stability and reproducibility of the extracted features, a reliability test was performed. Another physician with 10 years of diagnostic experience repeated the outlining of the above ROI by randomly selecting 30 lesions. The reliability of the ROI outlined by the two physicians was assessed by the class correlation coefficient. Class correlation coefficients greater than 0.75 for radiomic features were considered to have good stability and reproducibility and were used for subsequent feature screening and model construction.Before the feature screening, the normalization of the features was performed by the Z-score method, which aims to avoid the training of the model with too small weights, causing numerical instability, and to improve the comparability of the data, while enabling the parameter optimization to converge at a faster rate. After the reliability test, the training group was subjected to the least absolute shrinkage and selection operator (LASSO) regression for further data selection. LASSO regression was performed by fitting a generalized linear model with variable selection and complexity adjustment regularization. The filtering features were validated by 10-fold cross-validation based on the bias minimization criterion. Finally, for the final selected non-zero features, a classification model was built by multivariate logistic regression. CT models and PET models were constructed based on the final selected features . In order to better evaluate the performance of radiomics, a combined model (ComModel) was constructed by adding the PET conventional parameter SUVmax combined with PET radiomics features.P < 0.05 was considered to be statistically different. In addition, calibration curves and Brier scores were used to evaluate the predictive ability and goodness of fit of the classification models to observe the agreement between the actual and predicted probabilities of the models. Decision curve analysis (DCA) was used to visualize and evaluate the clinical net benefit and clinical utility of the classification prediction model by the graphical presentation.The performance of all classification diagnostic models was evaluated by comparing the area under the receiver operating characteristic (ROC) curve (AUC), accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV), while 95% CI of AUC were calculated. The DeLong test was used to compare the diagnostic effects between the models, and t-test or Mann—Whitney U-test was used to compare continuous variables with normal or non-normal distribution in the MM and BM groups. Categorical variables between the two groups were assessed using the chi-square test or Fisher test and weighted Kappa statistics were used to assess interobserver agreement. The processing of features screen, model construction, and comparison of the diagnostic performance of the models were performed in R software (version 4.1.1) and Python (version 3.8.1). IBM SPSS (version 21.0) and MedCalc software (version 20.0) were used for other clinical data analysis and ROC curve plotting. Probability values of P < 0.05 were considered statistically significant.Independent samples n = 10; stage II: n = 19; stage III: n = 16. The primary tumor of patients diagnosed with BM were as follows: lung cancer: n = 24; breast cancer: n = 17; prostate cancer: n = 14; pancreatic cancer: n = 4; kidney cancer: n = 3; ureteral cancer: n = 3; stomach cancer: n = 3; thyroid cancer: n = 3; liver cancer: n = 2; bladder cancer: n = 2; colon cancer: n = 2; parotid cancer: n = 2; gallbladder cancer: n = 2: fallopian tube cancer: n = 2; uroepithelial cancer: n = 1; esophagus cancer: n = 1; cervical cancer: n = 1. A total of 184 lesions were obtained and randomly divided into training and validation groups according to the ratio of 7:3 .According to the inclusion and exclusion criteria, a total of 131 patients were enrolled, including 86 patients who were diagnosed with bone metastases (BM), and the remaining 45 patients were confirmed as MM. The statistics and comparison of basic information of the patients were shown in P = 0.013 and P = 0.024, respectively), while the PET model did not show a statistical difference in the DeLong test although it had a higher diagnostic performance compared to the CT model (P = 0.131). In the validation group, the ComModel  and the PET model  achieved similar diagnostic performance and outperformed the CT model , and the DeLong test suggested no statistical difference between the three models .After reliability testing and excluding features with ICC coefficients less than 0.75, 223 and 234 radiomics features were extracted from CT and PET in the training group, respectively. Then, 10 and 8 texture features were obtained from CT and PET after LASSO regression and 10-fold cross-validation, respectively. The LASSO regression screening process was described in detail in k-value for the interobserver agreement was 0.832, which indicates a relatively reliable agreement. In the training and validation groups, the AUC values of human experts for the classification and diagnosis performance of MM and BM were 0.835 (CI95%:0.760–0.895) and 0.840 (CI95%:0.717–0.925), respectively. while the AUC values of SUVmax between the two groups were 0.802 (CI95%:0.723–0.867) and 0.810 (CI95%:0.681–0.903), respectively. Both the ComModel and the PET model showed significant differences in the classification diagnosis of MM and BM compared to human experts in both the training  and validation groups . The CT model was not statistically different between the two groups compared to the human experts . The ComModel and the PET model also showed great superiority compared to SUVmax between the two groups . No statistical difference was observed that the human expert compared to SUVmax between the two groups (P = 0.036 and P = 0.732). The classification diagnostic performance of all models was described and illustrated in Human experts' classification diagnostic of lesions was estimated by the kappa coefficient, and in this study, the weighted According to the calibration curves, all the radiomics models were closer to the ideal curve, implying a good categorical diagnostic performance. In addition, the ComModel had a better fitness compared to the PET and CT models because of the smaller Brier scores , the calibration curve was shown in Both myeloma and metastases were common malignant lesions of the spine. When patients only present with lumbar pain and no previous history of tumor, the clinical symptoms and imaging manifestations of both were similar. However, the treatment and prognosis of them were significantly different. Although bone biopsy was the gold standard for identifying benign and malignant lesions, there were limitations in clinical diagnosis due to its invasive examination. Radiomics provided a non-invasive assessment of the lesion and its microenvironment and allow quantification of the spatial heterogeneity of the lesion, which allows identification and evaluates the prognosis. In this study, we constructed and validated a radiomics model based on 18F-FDG PET-CT images and achieved excellent performance in classifying and diagnosing BM and MM. Furthermore, the radiomics model showed unique superiority and clinical utility compared to human experts as well as PET conventional parameter SUVmax. This will play a decisive role as a non-invasive and easy-to-use method in the diagnosis, staging, and re-staging of diseases and even in the selection of treatment strategies for diseases.Previous studies had pointed out that the traditional imaging features of bone destruction in myeloma involved a series of small focal-like, worm-like, and broad bone destruction, especially for the imaging features such as chisel-like changes in the skull and broad bone destruction in the ribs were specific , 28. In Maximum standardized uptake value as the conventional parameter of PET/CT was used in past studies to determine the treatment sensitivity and prognostic value of malignant lymphoma in the early and intermediate stages , 31. On Radiomics could transcend subjective visual assessment to provide an objective evaluation of lesion and tissue heterogeneity, which served as a new tool to provide valuable information about the microenvironment of lesions that cannot be observed by the human eyes. PET/CT radiomics was demonstrated several times in past studies to play an essential role in the diagnosis and prognosis of diseases and performing assessment of therapeutic efficacy. In our research, the radiomics models constructed based on PET/CT images had high diagnostic efficacy in discriminating MM and BM not only in the training group, with AUC values of 0.909, 0.949, and 0.973 for the CT model, PET model, and ComModel, respectively, but also in the validation group, with AUC values of 0.897, 0.929, and 0.948 for the CT model, PET model, and ComModel, respectively. In addition, the diagnostic performance and clinical utility of the radiomics model were superior to those of the human expert and SUVmax, with incremental value for differential and diagnostic purposes, especially the PET and COM models. It should note that a proportion of patients incorrectly staged by human experts (10.9%) and SUVmax (23.9%) were correctly diagnosed by our radiomics model, indicating that the radiomics model could complement the current staging scheme. More importantly, our findings suggest that the PET model had a higher value than conventional CT radiomics in discriminating MM from BM. Although there was no statistical difference in the Delong test, the AUC, Accuracy, Sensitivity, and Specificity of the PET model were significantly improved compared with the CT model. This may be due to the fact that PET images represent radioactive tracer uptake and metabolic information of the lesion. At the same time, PET/CT radiomics reflected the quantification of tumor uptake heterogeneity and earlier detection of lesions compared to conventional imaging, which brings additional value for lesion and tissue specificity identification.Our results show that Perc.01% and Vertl_RLNonUni were the most representative features in identifying MM and BM, as they appeared in both CT and PET models. The radiomics parameter Perc.01% derived from HSLM reflected the brightness value of the area where it was located and the number of pixels, which further confirmed the excellent performance of the radiomic model since these parameters were closely related to bone density in CT images and radioactive tracer uptake in PET images, as well as to the osteoporosis exhibited by patients with myeloma . The radOur findings were highly reproducible because we applied rigorous subject screening and reliability testing of lesion segmentation during the study. The LASSO regression algorithm has been applied and validated many times in the past to have good utility in screening the feature parameters. Our radiomics model has been validated by methods such as the Calibration curve and DCA curve, and has good fitness and is very close to the ideal curve. It was worth noting that we performed the outline of ROI in 2D mode rather than 3D mode, and the radiomic features generated by different mode outlines may be different. Still, past studies had demonstrated that the models constructed in 2D or 3D mode achieved similar classification diagnostic performance . In thisThere were still exist some limitations in our study. First, as a single-center study, this study may be biased in terms of patient selection, and thus, the results may hardly represent generalizable findings. In addition, there was a lack of external validation data from the multicenter association. Therefore, all aspects still need to be adjusted and optimized before applying to the clinic. Second, retrospective studies may have selection bias related to study data collection. Third, not all patients enrolled had pathological findings, and we combined pathological findings and follow-up results to determine the classification of lesions under strict adherence to inclusion and exclusion criteria.The radiomics model constructed based on 18F-FDG PET/CT images achieved satisfactory diagnostic performance for the classification of MM and bone metastases. In addition, the radiomics model showed a significant improvement in diagnostic performance compared to human experts and PET conventional parameter SUVmax. This non-invasive method could be used as a complement to traditional diagnostic methods. Furthermore, it had the potential to help clinicians physicians to develop individualized treatment plans, avoid adverse risks, and improve treatment outcomes.The original contributions presented in the study are included in the article/Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent from the patients/participants their next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.ZJ and JY contributed to the conception and design of the study. FZ and YIW carried out data statistics and analysis. ZJ wrote the manuscript. JY revised the manuscript. All authors read and approved the final manuscript.This study was supported by the Nature Science Foundation of Liaoning Province of China (No. 2019-ZD-0620).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.