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Xiao Liu,1,&ast; Kun-He Lin,1,&ast; Yue-Hua Li,2 Jun-Nan Jiang,3 Zheng-Dong Zhong,1 Ying-Bei Xiong,1 Jin Zhou,1 Li Xiang1,4 1School of Medicine and Health Management, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Wuhan Center for Tuberculosis Control and Prevention, Wuhan Pulmonary Hospital, Wuhan, People’s Republic of China; 3School of Public Administration, Zhongnan University of Economics and Law, Wuhan, People’s Republic of China; 4HUST Base of National Institute of Healthcare Security, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Xiang, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Email xllyf@hust.edu.cnBackground: Drug-resistant tuberculosis (DR-TB) is an increasingly serious global issue. DR-TB has a lower success rate and more severe interruption of treatment than ordinary tuberculosis. Incomplete treatment not only reduces recovery rate in DR-TB patients but also increases the spread of DR-TB. Optimizing medical security policies for DR-TB can reduce the economic burden of patients and can thereby improve treatment success rate.Methods: Patients with DR-TB who were registered in Wuhan Center for Tuberculosis Control and Prevention from January 2016 to December 2019 were selected as research subjects. General descriptive statistical analysis methods were used in analyzing patients’ treatment outcomes and medical security compensation rate. The binary logistic regression was used in analyzing the impacts of medical security level on treatment outcomes of DR-TB.Results: A total of 409 DR-TB patients were included in the study, and the refusal rate was 12.47%. The treatment success rate was only 37.09% for patients who started treatment and had treatment outcomes. The total out-of-pocket expenses (OOPs) per capita for DR-TB patients were 13,005.61 Chinese yuan. The outpatient effective compensation ratio (ECR) of DR-TB patients was only 51.04%. The outpatient ECR of DR-TB with subsidies of public health projects (SPHPs) were nearly 80% higher than those without SPHP. high outpatient ECR helped optimize treatment outcomes (P < 0.001, OR = 1.038). The inpatient ECR had no effect on patients’ treatment outcomes (P = 0.158, OR = 0.986).Conclusion: Many DR-TB patients did not receive complete treatment. The key breakthrough point in improving DR-TB treatment outcomes is to optimize the outpatient medical insurance compensation policy. Including the costs of DR-TB in expenses for severe diseases in outpatient care is recommended, and financial investment should be appropriately increased to ensure the high coverage ratio of subsidies for public health projects.Keywords: drug-resistant tuberculosis, medical security, treatment outcomes

Herein, a label-free single-molecule electrical sensor was first proposed for the ultrasensitive and selective detection of iodide ions in human urine. Single-molecule conductance measurements in different halogen ion solutions via scanning tunneling microscopy break junction (STM-BJ) clearly revealed that I - ions strongly affect the stability and displacement distance (Δ z ) distribution of molecular junctions. Theoretical calculations prove that the specific adsorption of I - ions modifies the surface properties and weakens the molecular adsorption. Furthermore, the average conductance peak area versus the logarithm of the I - ion concentration has a very good linear relationship in the range of 5 × 10 -6 to 5 × 10 -10 M, with a correlation coefficient of 0.99. This quantitative analysis remains valid in the presence of interfering ions of SO 4 2- , ClO 4 - , Br - , and Cl - as well as interfering molecules of ascorbic acid, uric acid, dopamine, and cysteine. A cross-comparison of the human urine detection results of this single-molecule electrical sensor with those of the clinical method of As 3+ -Ce 4+ catalytic spectrophotometry revealed an average difference of 0.9%, which decreased the detection time of 2 h with the traditional method to approximately 15 min. This work proves the promising practical potential of the single-molecule electrical technique for relevant clinical analysis.

Based on structural elucidation of natural and hydrolyzed glycans, the general glycans profiling of D. officinale were unequivocally established for the first time as follows: The results indicated that the structure of D. officinale glycans with low degree of polymerization (DP ≤ 22) was linear α-D-1,4-glucan, whereas the structure of glycans with high degree of polymerization (DP > 24) was linear acetylated 1,4-glucomannan. The content of acetyl groups and mannose to glucose (M/G) ratio increased with the degree of polymerization of D. officinale glycans. In addition, this study showed that natural D. officinale glycans protected pancreatic β-cell damage induced by glucotoxicity through the extracellular signal-regulated kinase (ERK)1/2 pathway., Competing Interests: Declaration of competing interest The author declares no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

By analyzing the of genetic testing data of patients with renal polycystic kidney disease and their relatives, this study aims to identify unreported novel gene mutation sites associated with autosomal dominant polycystic kidney disease (ADPKD). Structural prediction software was employed to investigate protein structural changes before and after mutations, explore genotype-phenotype correlations, and enrich the ADPKD gene database. In this single-center retrospective study, patients with multiple renal cysts diagnosed from January 2019 to February 2023 at the Zhong Da Hospital Southeast University were included. Genetic and clinical data of patients and their families were collected. Unreported novel gene mutation sites associated with ADPKD were identified. The AlphaFold v2.3.1 software was used to predict protein structures. Changes in protein structure before and after mutations were compared to explore genotype-phenotype correlations and enrich the ADPKD gene database. Twelve mutated genes associated with renal cysts were detected in 52 families. Nineteen novel gene mutation sites associated with ADPKD were identified, including 17 mutations in the PKD1 gene (one splicing mutation, seven frameshift mutations, four nonsense mutations, one whole-codon insertion, and four missense mutations); one ALG9 missense mutation; and one chromosomal structural variation. Truncating mutations in the PKD1 gene were correlated with a more severe clinical phenotype, while non-truncating mutations were associated with greater clinical heterogeneity. Numerous novel gene mutation sites associated with ADPKD remain unreported. Therefore, it is essential to analyze the pathogenicity of these novel mutation sites, establish genotype-phenotype correlations, and enrich the ADPKD gene database.

The liver fluke disease caused by Clonorchis sinensis is one of the most serious food-borne parasitic diseases in China. Many freshwater fish and shrimps can be infected with C. sinensis metacercariae as the second intermediate hosts in endemic regions. Owing to the lack of infected humans and the good administration of pet dogs and cats in cities of non-endemic regions, few fish are expected to be infected with C. sinensis metacercariae in urban lakes. To determine the infection of C. sinensis metacercariae in freshwater fish and shrimps in urban lakes, a total of 18 fish species and one shrimp species were investigated in the East Lake of Wuhan City. Metacercariae were isolated by artificial digestive juice and identified using morphology and rDNA-ITS2 sequences. Five species of fish, Pseudorasbora parva , Ctenogobius giurinus , Squalidus argentatus , Hemiculter leuciclus , and Rhodeus spp., were infected with C. sinensis metacercariae. The overall prevalence of C. sinensis was 32.5%. The highest prevalence was found in P. parva with 57.9%, while S. argentatus exhibited the highest mean abundance (13.9). Apart from the C. sinensis metacercariae, four species of other trematode metacercariae were also identified across twelve fish species in total. Owing to the consumption of undercooked fish and feeding cats with small fish caught by anglers, there is a potential risk that the small fish infected with C. sinensis metacercariae may act as an infection source to spread liver fluke. Given the complete life cycle of C. sinensis , stray cats and rats were inferred to act as the important final hosts of C. sinensis in urban lakes in non-endemic areas.

Objective: To compare physical activity and its influencing factors in patients with chronic obstructive pulmonary disease (COPD) between China and the United Kingdom. Methods: We analyzed baseline data from China Kadoorie Biobank and the United Kingdom Biobank among COPD patients who were diagnosed with a one-second rate (FEV 1 /FVC) less than 70%. Physical activity level was calculated as metabolic equivalent (MET) and divided into three levels: low, medium, and high, according to tertiles stratified by gender and age. Multiple logistic regression was used to estimate OR s and 95% CI s for COPD and Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade about physical activity level, and subgroup analysis was conducted. Results: A total of 506 073 Chinese adults and 231 884 British adults were included. After adjusting for potential confounders, COPD was associated with lower physical activity levels in both Chinese and British COPD patients, with OR (95% CI ) of 1.07(1.03-1.10) and 1.03(1.01-1.06) compared with non COPD patients, respectively. The GOLD grade was inversely correlated with physical activity level, particularly in a dose-response manner in the CKB population (trend test P <0.001). The negative relationship was stronger among the elderly, people with less education and lower economic status, and those with a smoking or chronic disease history. Chinese rural COPD patients were at high risk of decline of physical activity. Conclusions: Physical activity is inversely related to COPD, with a dose-response connection to GOLD grade. Therefore, physical activity maintenance and improvement should be encouraged and promoted in COPD patients, especially in high-risk groups.

Objective: To evaluate the level of psychological distress among Chinese children and adolescents and analyze its lifestyle influencing factors. Methods: Data were obtained from the 2019 Chinese National Survey on Students' Constitution and Health. A lotal of 120 285 Han Chinese children and adolescents aged 9-18 years with complete information on the psychological distress scale and lifestyle factors were selected, including 58 432 boys and 61 853 girls. The Kessler Psychological Distress Scale (K10) measured psychological distress, and lifestyles such as physical activity, sedentary behavior, diet, and sleep were also investigated. K10 scores of different genders were compared using the t -test, and the levels of psychological distress were compared using the χ 2 test. Logistic regression was used to analyze lifestyle risk factors associated with high psychological distress, and multiple linear regression was used to find the relationship between K10 scores and lifestyle scores. Results: The average K10 score for Han Chinese children and adolescents aged 9-18 years was 21.25±7.35, with girls (21.43±7.35) scoring higher than boys (21.06±7.36), the difference was statistically significant ( t =8.72, P <0.001). The rate of high psychological distress was 29.81%, with girls (31.08%) reporting higher rates than boys (28.46%), the difference was statistically significant ( χ 2 =98.54, P <0.001). 56.10% of children and adolescents have unhealthy lifestyles, with girls (58.77%) reporting higher rates than boys (53.27%), the difference was statistically significant ( χ 2 =368.53, P <0.001). Except for insufficient outdoor activities for girls ( P =0.128), lifestyles such as insufficient physical activity, insufficient muscle-and-bone exercises, long screen time, not eating breakfast, eggs and dairy products every day, drinking sugary beverages once or more per day, and not having enough sleep are all risk factors for high psychological distress (all P <0.001). For every additional healthy lifestyle score, the K10 score decreased by 0.98 [ β =-0.98 (95% CI : -1.01- -0.95)] points ( P <0.001). K10 scores in each region negatively correlate with lifestyle scores (all P <0.001). Among them, the K10 score in the eastern region showed the slightest decrease as the lifestyle score increased, while the western region showed the most decrease. Conclusions: The prevalence of psychological distress and unhealthy lifestyle in Chinese children and adolescents are high and interrelated. Compared those with healthy lifestyles, children and adolescents with unhealthy lifestyles are at greater risk of high psychological distress. Therefore, promoting healthy lifestyles for children and adolescents may be one of the important ways to improve their mental health.

Objective: To analyze the association between exposure to ambient PM 2.5 and its components [sulfate (SO 4 2- ), nitrate (NO 3 - ), ammonium (NH 4 + ), organic matter (OM), and black carbon (BC)] and psychological distress among school children and adolescents aged 9 to 18 years in China. Methods: Based on data from the 2019 Chinese National Survey on Students' Constitution and Health, 130 808 children and adolescents aged 9 to 18 years were included. Scoring and determination of higher psychological distress were based on the Kessler Psychological Distress Scale (K10), and annual average exposure data for air pollution were matched by survey location and time. We used a restricted cubic spline approach based on logistic regression to fit the associations between PM 2.5 , SO 4 2- , NO 3 - , NH 4 + , organic matter, black carbon concentrations, and psychological distress. Logistic regression models were used to analyse different age, gender, BMI and physical activity subgroups to estimate the association between exposure to high levels of pollution and high levels of psychological distress in different subgroups. Results: The proportion of children and adolescents with high levels of psychological distress in China was 30.4%, with girls being higher than boys at 31.6% and 29.1%, respectively ( P <0.05). A non-linear positive association existed between exposure to PM 2.5 , SO 4 2- , NO 3 - and organic matter concentrations and higher psychological distress. As PM 2.5 , NO 3 - , NH 4 + , organic matter, and black carbon concentrations continued to rise, the increase in the risk of higher psychological distress slowed, while SO 4 2- showed little change in the OR of psychological distress at lower concentrations but continued to rise at higher concentrations. PM 2.5 and its components were statistically associated with psychological distress in the physically inactive group but not in the physically active group. The association between high levels of pollutants and high psychological distress was stronger among students aged 9 to 12 years compared with students aged 13 to 15 years and 16 to 18 years. Conclusions: The ambient pollutant PM 2.5 and its components are associated with psychological distress in children and adolescents aged 9 to 18 years in China. High pollutant exposure is a risk factor for high psychological distress among physically inactive children and adolescents, and there are age differences in the association between PM 2.5 and components and psychological distress.

Objective: To analyze the association between the occurrence of spermarche and menarche and psychological distress among Chinese Han children and adolescents aged 9 to 18 years. Methods: Data were drawn from the 2019 Chinese National Survey on Students' Constitution and Health, and a total of 54 438 boys aged 11 to 18 years and 76 376 girls aged 9 to 18 years with psychological distress, spermarche/menarche records were included in the final analysis. The occurrence of spermarche/menarche was recorded by physicians, and psychological distress was classified according to the Kessler Psychological Distress Scale scores. The chi-square test was used to compare the difference between groups in the occurrence of spermarche/menarche, and the multinomial logistic regression model and stratification analysis was established to analyze the association between psychological distress and spermarche/menarche. Results: The incidence of spermarche/menarche in 2019 ranged from 6.3% to 96.5% for eight age groups of Chinese boys and 2.8% to 99.0% for ten age groups of girls. The rates of high psychological distress among boys and girls were 32.5% and 32.7%. Among boys aged 11 to 18 years, the rate of high psychological distress increased with age, with a trend test P <0.001, and the difference in the rate of high psychological distress between those who had and had not had their spermarche was not statistically significant in all age groups. Among girls aged 9 to 18 years, the rate of high psychological distress increased with age, with a trend P <0.001; the rate of high psychological distress was higher in the group with menarche at age 10 and 12 than in the group without menarche (all P <0.05). High psychological distress was positively correlated with spermarche among boys aged 13-15 years living in urban areas and hight level economic development areas ( OR =1.11, 95% CI : 1.02-1.21; OR =1.18, 95% CI : 1.06-1.32). Overall, high psychological distress was positively correlated with menarche in girls aged 9-12 and 13-15 years ( OR =1.33, 95% CI : 1.25-1.42; OR =1.22, 95% CI : 1.07-1.39). High psychological distress was positively correlated with menarche among girls aged 9-12 years living in different regions except for the Northeast region, in areas with different levels of economic development, and in urban and rural areas, in girls aged 13-15 years living in urban, central, and western regions, and in girls aged 16-18 years residing in the central region. Conclusions: This study found an association between the occurrence of spermarche/menarche and psychological distress among Chinese Han children and adolescents aged 9 to 18 years in 2019, which was particularly significant among girls aged 9 to 12 years and boys aged 13 to 15 years living in areas with higher levels of socioeconomic development.

Objective: To describe the status of physical fitness of children and adolescents aged 13-18 years in China in 2019 and analyze its association with psychological distress. Methods: Data were drawn from the 2019 Chinese National Survey on Students' Constitution and Health, and 90 633 Han children and adolescents aged 13-18 years were included. Physical fitness was evaluated by "National Students Constitutional Health Standards" (2014 revised edition). Psychological distress was classified according to the scores of the Kessler Psychological Distress Scale: ≤19, 20-24, 25-29, and ≥30 scores indicated no, mild, moderate, and severe psychological distress, respectively, with moderate and severe psychological distress collectively referred to as high psychological distress. The χ 2 test was used to compare the distribution differences between boys and girls, the Cochran-Armitage test was used to analyze the trend, and the multinomial logistic regression in the mixed effect model was established to analyze the association between physical fitness and psychological distress. Results: In 2019, the unqualified rate of physical fitness among children and adolescents aged 13-18 years in China was 17.2%, and the prevalence of excellent and good physical fitness was 18.2%, which was lower among boys (15.9%) than girls (20.5%) with a statistically significant difference ( P <0.05). The excellent and good physical fitness rate showed a significantly decreasing trend with age (trend test P <0.05). The rate of high psychological distress among children and adolescents aged 13-18 years in China in 2019 was 39.3%, with boys (37.0%) having a lower prevalence than girls (41.6%), supported by a statistically significant difference ( P <0.05), and a decreasing trend with the degree of physical fitness was observed both in boys and girls (trend test P <0.05). The multinomial logistic regression model showed that the prevalence of moderate ( OR =0.83, 95% CI : 0.79-0.88, P <0.001) and severe ( OR =0.81, 95% CI : 0.77-0.86, P <0.001) psychological distress were both lower in children and adolescents with excellent and good physical fitness. Conclusion: The status of physical fitness and psychological distress of Chinese children and adolescents aged 13-18 in 2019 was not optimistic, with physical fitness showing a significantly negative association with psychological distress.

Objective: To describe the prevalence of psychological distress and to analyze its influencing factors among Chinese children and adolescents aged 9-18 years in 2019. Methods: Data was from the 2019 Chinese National Survey on Students' Constitution and Health, and 148 892 children and adolescents were included. Psychological distress was measured using the Kessler Psychological Distress Scale (K10): scores ≤19 were defined as no psychological distress, scores between 20-24 were defined as mild psychological distress, scores between 25-29 were defined as moderate psychological distress, and scores ≥30 were defined as severe psychological distress (moderate to severe psychological distress were defined as high psychological distress). The ANOVA, t test, and χ 2 test were used to compare the differences in K10 scores and high psychological distress rates among children and adolescents with different characteristics. The ANOVA and trend χ 2 test were used to analyze the trends. Modified-Poisson regression models were used to determine influencing factors of high psychological distress. Results: The K10 scores for Chinese children and adolescents aged 9-18 years in 2019 was 21.5±9.2, and their rate of high psychological distress was 31.6%. The rates of high psychological distress among children and adolescents aged 9-12, 13-15, and 16-18 years were 22.3%, 35.9%, and 38.8%. K10 scores and rates of high psychological distress showed an increasing trend as age increased (trends test all P <0.001). K10 scores and rates of high psychological distress were higher among children and adolescents who were older, female, rural, in areas with medium to low GDP per capita level, and with lower parental education (all P <0.001). Multifactorial modified-Poisson regression analysis showed that children and adolescents aged 13-15 years, 16-18 years, female, rural, and in areas with low to moderate GDP per capita level were at higher risk of high psychological distress (all P <0.05), with a OR (95% CI ) of 1.55 (1.52-1.58), 1.66 (1.63-1.69), 1.07 (1.05-1.09), 1.02 (1.01-1.04), 1.10 (1.07-1.12). Children and adolescents in areas with medium to high GDP per capita level, whose father had a secondary or high school degree, whose father had a college degree or above, whose mother had a secondary or high school degree, and whose mother had a college degree or above were at lower risk of high psychological distress (all P <0.05), with a OR (95% CI ) of 0.96 (0.94-0.98), 0.92 (0.90-0.93), 0.84 (0.82-0.86), 0.95 (0.93-0.97), 0.86 (0.83-0.88). Conclusions: The prevalence of psychological distress was high among Chinese children and adolescents aged 9-18 years in 2019, which is a vital problem. Mental health interventions need to be implemented among children and adolescents that were older, girls, rural, live in areas with lower economic levels, and whose parents have a lower education level.

Objective: To analyze the association between overweight and obesity, psychological distress, and the influence of physical exercise among Chinese children and adolescents. Methods: The study used data from the 2019 Chinese National Survey on Students' Constitution and Health. A total of 95 280 Han Chinese children and adolescents aged 13 to 18 years were included in the study based on complete information on overweight and obesity, psychological distress assessment, and physical exercise variables. The Kessler Psychological Distress Scale was used to measure their psychological distress, with scores above 25 indicating high psychological distress. The BMI group of the adolescents was evaluated according to the Chinese standard "WS/T 586-2018 Screening for Overweight and Obesity in School-age Children and Adolescents", including underweight, normal weight, overweight, and obesity. The individual's BMI Z-score (BMIZ) was evaluated using the WHO standard and divided into ten groups based on the population percentile distribution. The survey collected the subjects' average daily physical exercise time and divided them into two groups: less than 1 hour and greater than or equal to 1 hour. Logistic regression analysis was used to analyze the relationship between overweight and obesity and high psychological distress among children and adolescents and the differences in association between different physical exercise groups. Results: The detection rates of overweight and obesity among Han Chinese children and adolescents aged 13 to 18 years in 2019 were 14.5%, and 7.6%, respectively. The rate of high psychological distress was 37.6%, and the rate of average daily physical exercise time exceeding 1 hour was 17.1%. Using the population with a BMIZ P 10 below as a reference, the association strength between high psychological distress and the population gradually increased, with an OR (95% CI ) value of 1.08 (1.02-1.14), 1.09 (1.02-1.14), 1.10 (1.03-1.16), and 1.16 (1.09-1.23) for BMIZ in the P 60 -, P 70 -, P 80 -, > P 90 groups. Compared to normal weight, both overweight and obesity were positively associated with high psychological distress in children and adolescents, with obesity showing a more significant correlation, while underweight was negatively associated with high psychological distress. The detection rates of high psychological distress in normal weight, underweight, overweight, and obese groups were 37.6%, 37.0%, 38.2%, and 38.7%, respectively, with an OR (95% CI ) value of 0.93 (0.88-0.98) for the underweight group and 1.05 (1.01-1.10) and 1.13 (1.07-1.19) for the overweight and obese groups, respectively. The positive correlation between BMIZ, overweight, and obesity with high psychological distress was significant only in adolescents who exercised less than 1 hour per day on average. Conclusions: Chinese children and adolescents face the problem of obesity and high psychological distress, with a positive correlation between these two problems. Physical activity may moderate the association between obesity and psychological distress in children and adolescents. Adequate physical exercise may offset the potential high psychological distress caused by obesity in children and adolescents. Thus, strengthening physical exercise among children and adolescents reduces the risks of both obesity and psychological health problems effectively.

Objective: To analyze the association between different growth patterns and metabolic syndrome in children and adolescents aged 7 to 17 years, and to provide suggestions for the prevention and control of metabolic syndrome in Chinese children and adolescents., Methods: Data were collected from the research project "Development and Application of Technology and Related Standards for Prevention and Control of Major Diseases among Students" of public health industry in 2012. This project is a cross-sectional study design. A total of 65 347 students from 93 primary and secondary schools in 7 provinces including Guangdong were selected by stratified cluster random sampling method. Given the budget, 25% of the students were randomly selected to collect blood samples. In this study, 10 176 primary and middle school students aged 7 to 17 years with complete physical measurements and blood biochemical indicators were selected as research objects. Chi-square test was used to compare the distribution differences of growth patterns under different demographic characteristics. Birth weight, waist circumference and blood biochemical indexes were expressed in the form of mean ± standard deviation, and the differences among different groups were compared by variance analysis. Binary Logistic regression model was used to analyze the relationship between different growth patterns and metabolic syndrome in children and adolescents aged 7 to 17 years., Results: The prevalence of metabolic syndrome in children and adolescents was 6.56%, 7.18% in boys and 5.97% in girls. The risk of metabolic syndrome was higher in the catch-down growth group than in the normal growth group ( OR =1.417, 95% CI : 1.19-1.69), and lower in the catch-up growth group( OR =0.66, 95% CI : 0.53-0.82). After adjusting for gender, age and so on, the risk of developing metabolic syndrome in the catch-down growth group was higher than that in the normal growth group ( OR =1.25, 95% CI : 1.02-1.52), but there was no significant difference between the catch-up growth group and the normal growth group ( OR =0.79, 95% CI : 0.62-1.01). Stratified analysis showed that the association between different growth patterns and metabolic syndrome was statistically significant in the 7-12 years group, urban population, and Han Chinese student population., Conclusion: There is a correlation between different growth patterns and metabolic syndrome in children and adolescents. The risk of developing metabolic syndrome in children and adolescents with catch-down growth is higher than that in the normal growth group, which suggests that attention should be paid to the growth and development of children and adolescents, timely correction of delayed growth and prevention of adverse health outcomes.

Objective: To investigate the status of depression and social anxiety in children and adolescents, and to analyze the association between body fat distribution and depression, social anxiety in children and adolescents., Methods: A total of 1 412 children aged 7 to 18 years in Beijing were included by stratified cluster random sampling method. Body fat distribution, including total body fat percentage (total BF%), Android BF%, Gynoid BF% and Android-to-Gynoid fat ratio (AOI), were obtained by dual-energy X-ray absorption method. Depression and social anxiety were evaluated by Children Depression Inventory and Social Anxiety Scale for Children. Multivariate linear regression and restricted cubic spline analysis were used to estimate the linear and non-linear correlation between body fat distribution and depression and social anxiety., Results: 13.1% and 31.1% of the children and adolescents had depressive symptoms and social anxiety symptoms respectively, and the detection rate of depression and social anxiety in the boys and young groups was significantly lower than those in the girls and old groups. There was no significant linear correlation between total BF%, Android BF%, Gynoid BF%, AOI and depression and social anxiety in the children and adolescents. However, total BF% and Gynoid BF% had significant nonlinear correlation with depression, showing an inverted U-shaped curve relationship with the tangent points of 26.8% and 30.9%, respectively. In terms of the nonlinear association of total BF%, Android BF%, Gynoid BF% and AOI with depression and social anxiety, the change trends of the boys and girls, low age group and high age group were consistent. The overall anxiety risk HR of body fat distribution in the boys was significantly higher than that in the girls, and the risk HR of depression and social anxiety were significantly higher in the high age group than those in the low age group., Conclusion: There was no significant linear correlation between body fat distribution and depression and social anxiety in children and adolescents. Total BF% and depression showed an inverted U-shaped curve, mainly manifested in Gynoid BF%, and this trend was consistent in different genders and different age groups. Maintaining children and adolescents' body fat distribution at an appropriate level is the future direction of the prevention and control of depression and social anxiety in children and adolescents.

Objectives: To describe the ultrasonographic appearance of congenital anaplastic astrocytoma, so as to provide diagnostic clues for it. An updated review of the literature was also carried out., Results: There was a case of fetal anaplastic astrocytoma detected by ultrasound at 37 + 1 weeks of gestation. It showed that a hypoechoic mass was located in the left hemisphere with a relatively clear margin and subtle color flows. Prenatal magnetic resonance imaging (MRI) which was taken subsequently confirmed the result of ultrasound. Intratumoral hemorrhage was observed in later follow-up and further confirmed by histological examination. The fetus was delivered vaginally at 39 + 6 weeks. The infant died 2 h after delivery due to respiration failure. The histological examination confirmed an anaplastic astrocytoma., Conclusions: Congenital anaplastic astrocytoma commonly detected by ultrasound has a relatively better perinatal prognosis, especially compared with glioblastoma. Prenatal ultrasonography diagnosis accurately is of critical importance. The anaplastic astrocytoma should be considered in cases in which fetal images reveal a heterogeneous echogenic mass in the brain, especially in the presence of intratumoral hemorrhage, subtle color flow, and relatively clear margin.

With the solvothermal reactions of flexible tetracarboxylic acid ligand with the Cd(II) and Ca(II) ions, we acquired a new heterometallic coordination polymer formulated as {[Cd 2 Ca 2 (L) 2 (DMF) 2 (H 2 O) 7 ]·(DMF)·2(H 2 O)} n ( 1 , H 4 L is 5-(bis(4-carboxybenzyl)amino)isophthalic acid, DMF is N,N'-Dimethylformamide). Furthermore, the solids of 1 shows ligand-centered luminescence at room temperature. It not only evaluated the treatment and nursing application value on acute cerebral infarction, but also explored the related mechanism. Above of all, ELISA assay measured the content of the MMP-9 released into the cerebrospinal fluid, and the real time RT-PCR was implemented and the NF-κB activation in the brain tissue was measured., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Objective: To retrospectively analyze the serological, virological, biochemical, liver histological status and clinical outcomes in HBeAg-negative chronic hepatitis B (CHB) patients with low HBV viral load, and to explore the necessity of antiviral therapy for these patients. Methods: A total of 99 HBeAg-negative CHB patients with HBV DNA level < 4 lg copies/ml who performed liver biopsy at the baseline were enrolled from the follow-up cohort. Among them, 23 cases received the second liver biopsy during follow-up. The relationships among the degree of inflammation and fibrosis of liver tissues, the status of HBsAg and HBcAg, age, gender, family history, HBV DNA load, serological markers and other indicators were analyzed. The pathological differences between two liver biopsy examinations were compared. The effect of nucleos(t)ide analogues (NAs) treatment on patient's clinical outcomes were analyzed. For multivariate analysis, a binary logistic regression model was performed. Log-rank test was used to compare the cumulative incidence of hepatocellular carcinoma (HCC) in NAs-treated and non-NA streated patients. Results: Baseline liver histology status showed that 58.6% (58/99) patients had obvious liver tissue damage in their baseline liver tissue pathology (G≥2 and /or S≥2). Univariate logistic regression analysis showed that a liver cirrhosis (LC) family history, a HBsAg-positive family history, baseline alanine aminotransferase and aspartate aminotransferase levels were positively correlated factors for liver tissue damage. Multivariate logistic regression analysis showed that a LC family history was the main risk factor for liver tissue damage. Twenty-three cases had received a second liver biopsy after an interval of 4.5 years. In 10 untreated cases, the second liver biopsy results showed the rate of obvious liver tissue damage (G≥2 and/ or S≥2) increased from 50.0% to 90.0%. In the other 13 cases who received NAs treatment, the second liver biopsy showed improvement in liver histology, and the rate of obvious liver tissue damage decreased from 61.5% to 46.2%. The 5-year HCC cumulative incidence in non-NAs-treated patients was significantly higher than that of in NAs-treated patients (17.7% vs . 3.8%, P = 0.046). Conclusion: For most HBeAg-negative CHB patients with low viral load, liver tissue pathology result suggests that it meets the indications for antiviral therapy, especially in patients with a LC familial history. Without antiviral therapy, liver tissue damage for these patients will progressively worse with the high incidence of HCC. Therefore, it is suggested that antiviral therapy should be started as soon as possible for the HBeAg-negative CHB patients with low viral load regardless of the alanine aminotransferase level, especially in patients over 30 years-old with a LC or HCC family history.

Objective: To retrospectively analyze the risk factors for the development of liver cancer in patients with hepatitis B-related liver cirrhosis (LC) treated and fully managed with long-term nucleos(t)ide analogues (NAs). Methods: The study subjects were derived from the follow-up cohort of chronic hepatitis B and liver cirrhosis who received antiviral therapy in the Department of Infectious Diseases of the First Affiliated Hospital of Guangxi Medical University from February 2004 to September 2019. LC patients who met the inclusion criteria were enrolled. The life-table method was used to calculate the incidence of liver cancer. Multivariable Cox regression model was used to analyze the risk factors that may affect the development of liver cancer in patients with LC. A subgroup analysis was conducted in liver cirrhotic patients who developed liver cancer to evaluate the effectiveness of antiviral treatment compliance. The (2) test was used for rate comparison. Results: The median follow-up time of 198 LC cases treated with NAs was 6.0 years (1.0-15.3 years). By the end of the visit: (1) 16.2% (32/198) of LC patients had developed liver cancer, and the cumulative incidence of liver cancer in 1, 3, 5, 7, and 9 years were 0, 8.9%, 14.3%, 18.6%, and 23.4%, respectively, with an average annual incidence of 3.1%. Among the 32 cases with liver cancer, 68.7% had developed small liver cancer (22/32). (2) Univariate Cox model analysis showed that the development of liver cancer was related to four factors, i.e., the presence or absence of LC nodules, whether the baseline was first-line medication, the family history of liver cancer, and patient compliance. The results of multivariate Cox model analysis showed that poor patient compliance and baseline non-first-line medication were risk factors for liver cancer. (3) The results of log-rank test subgroup analysis showed that the 5-year cumulative incidence of liver cancer in patients with hardened nodules was significantly higher than that of patients without hardened nodules (21.7% vs. 11.5%, P = 0.029). The 5-year cumulative incidence of liver cancer in patients with non-first-line drugs was significantly higher than that of patients with first-line drugs (22.0% vs.8.2%, P = 0.003). The 5-year cumulative incidence of liver cancer in patients with poor compliance was significantly higher than that of patients with good compliance (21.3% vs. 12.7%, P = 0.014). The 5-year cumulative incidence of liver cancer in patients with a family history of liver cancer was significantly higher than that of patients without a family history of liver cancer (22.3% vs. 8.1%, P = 0.006). (4) Compared with patients with poor compliance, patients with good compliance had higher HBV DNA negative serconversion rate (98.7% vs. 87.8%, P = 0.005), and a lower virological breakthrough rate (12.1% vs. 29.3%, P = 0.007). Conclusion: The long-term NAs antiviral therapy can reduce the risk of liver cancer, but it cannot completely prevent the development of liver cancer, especially in patients with a family history of liver cancer and baseline hardened nodules (high risk of liver cancer). Furthermore, the complete management can improve patient compliance, ensure the efficacy of antiviral therapy, and reduce the risk of liver cancer development, so to achieve secondary prevention of liver cancer, i.e., early detection, diagnosis and treatment.

Gastric cancer is the most prominent form of malignancy in China, and the high mortality associated with it is mostly due to peritoneal metastasis. We have previously elucidated that the RNA-binding protein poly r(C) binding protein 1 (PCBP1) and miR-3978 function as repressors of peritoneal metastasis, partially by downregulation of six-transmembrane epithelial antigen of the prostate 1 (STEAP1). We now show that STEAP1 is regulated at the level of cap-dependent translation initiation by phosphorylated eIF4E. Chemically inhibiting phosphorylation of eIF4E or genetic ablation of phosphorylated eIF4E inhibit translational upregulation of STEAP1 in the peritoneal metastasis mimicking cell line MKN45 in comparison to the normal mesothelial cell line HMrSV5. Thus phosphorylation of eIF4E is required for peritoneal metastasis of gastric cancer via translational control of STEAP1 . Chemical inhibitors targeting phosphorylation of eIF4E or its interaction with the translation initiation complex thus might prove effective in treating patients with peritoneal metastasis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Tuberculosis (TB) is still a major public health problem in China. To scale up TB control, an innovative programme entitled the 'China-Gates Foundation Collaboration on TB Control in China was initiated in 2009. During the second phase of the project, a policy of increased reimbursement rates under the New Cooperative Medical Scheme (NCMS) was implemented. In this paper, we aim to explore how this reform affects the financial burden on TB patients through comparison with baseline data., Methods: In two cross-sectional surveys, quantitative data were collected before (January 2010 to December 2012) and after (April 2014 to June 2015) the intervention in the existing NCMS routine data system. Information on all 313 TB inpatients, among which 117 inpatients in the project was collected. Qualitative data collection included 11 focus group discussions. Three main indicators, non-reimbursable expenses rate (NER), effective reimbursement rate (ERR), and out-of-pocket payment (OOP) as a percentage of per capita household income, were used to measure the impact of intervention by comprising post-intervention data with baseline data. The quantitative data were analysed by descriptive analysis and non-parametric tests (Mann-Whitney U test) using SPSS 22.0, and qualitative data were subjected to thematic framework analysis using Nvivo10., Results: The nominal reimbursement rates for inpatient care were no less than 80% for services within the package. Total inpatient expenses greatly increased, with an average growth rate of 11.3%. For all TB inpatients, the ERR for inpatient care increased from 52 to 66%. Compared with inpatients outside the project, for inpatients covered by the new policy, the ERR was higher (78%), and OOP showed a sharper decline. In addition, their financial burden decreased significantly., Conclusions: Although the nominal reimbursement rates for inpatient care of TB patients greatly increased under the new reimbursement policy, inpatient OOP expenditure was still a major financial problem for patients. Limited diagnosis and treatment options in county general hospitals and inadequate implementation of the new policy resulted in higher inpatient expenditures and limited reimbursement. Comprehensive control models are needed to effectively decrease the financial burden on all TB patients.

Objective: The aim of this study was to investigate whether lnc00908 could affect the proliferative and migratory behaviors of ovarian cancer (OC) cells by regulating microRNA-495-5p, thus participating in the development of OC., Patients and Methods: Quantitative Real Time-Polymerase Chain Reaction (QRT-PCR) was used to detect the expression levels of lnc00908 and microRNA-495-5p in OC tissues and normal ovarian tissues, as well as OC cell lines. The regulatory effects of lnc00908 and microRNA-495-5p on the proliferative and migration abilities of OC cells were detected by cell counting kit-8 (CCK-8) and transwell assay, respectively. The binding relationship between microRNA-495-5p and ANXA3, as well as miR-495-5p and lnc00908, was examined by luciferase reporter gene assay. Gain-of-function experiments were conducted to verify whether lnc00908 could affect the proliferative and migratory behaviors of OC cells by regulating microRNA-495-5p., Results: Lnc00908 was highly expressed in OC tissues, and its expression was positively correlated with tumor stage. Overexpression of lnc00908 markedly promoted the proliferative and migratory abilities of SKOV3 and OVCAR cells. Luciferase reporter gene assay showed that lnc00908 could bind to microRNA-495-5p. However, microRNA-495-5p was significantly downregulated in OC tissues. Overexpression of microRNA-495-5p reversed the enhanced abilities of proliferation and migration in SKOV3 and OVCAR3 cells by lnc00908 overexpression. ANXA3 was a target gene of microRNA-495-5p. Moreover, overexpression of ANXA3 attenuated the inhibitory effect of miR-495-5p on the proliferative and migratory behaviors of SKOV3 and OVCAR3 cells., Conclusions: We found that the high expression of lnc00908 can promote the proliferation and migration abilities of OC cells through sponging microRNA-495-5p to regulate ANXA3 expression.

Nickel-containing wastewater is a serious hazard to water environment, so that it is a burning issue to find an efficient and environment-friendly adsorbent. The conventional biochar could not effectively adsorb nickel (Ni(II)), so our study focuses on exploring the adsorption of chemically modified biochar to Ni(II). In this study, the biochar derived from waste peanut shell was modified by KMnO 4 and KOH (MBC). And a series of experiment were carried out to evaluate the sorption ability and explore adsorption mechanism of modified biochar to Ni(II). The results showed the adsorption ability of MBC to Ni(II) reached 87.15 mg g -1 . And the reaction process was spontaneous and endothermic chemisorption. Meanwhile, the analysis of FTIR and XPS visually revealed that the amine groups in the modified biochar could form NH 2 Ni with Ni(II) by complexation, while the hydroxyl could form nickel hydroxide and complexed nickel oxide by co-precipitation and complexation. This research showed this novel MBC is a promising adsorbent and has a fantastic prospect in the application of nickel-containing wastewater., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Modified biochar has attracted wide attention due to its advantageous adsorption performance. However, the influence of modification process of biochar on adsorption capacity was seldom studied. In this study, biochar derived from corn stalks was modified through two kinds of modification processes: pre-pyrolysis (MBCpre) and post-pyrolysis (MBCpost) modification with citric acid, sodium hydroxide, ferric chloride, respectively. The results showed that the biochar modified by ferric chloride (MBC) provided better adsorption capacity for Cr(VI), and the pre-pyrolysis offered more favorable adsorption capacity for biochar than post-pyrolysis. By means of instrumental analysis, it was found that MBCpre owned highly dispersed Fe 3 O 4 particles and larger surface area, which could be the critical role for enhancing the adsorption capacity of MBCpre. Meanwhile, MBCpost appeared more protonated oxygen-rich functional groups(C=O, -OH, etc.) and adsorbed Cr(VI) by electrostatic attraction and complexation. This study will offer a novel idea for the treatment of chromium-containing wastewater by selecting the modification processes of biochar. Graphical abstract.

Objective: Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA. Methods: Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA < 200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 ( n = 153) or 96 weeks ( n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281. Results: At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg < 1 500 IU/mL and week 24 HBsAg < 200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss. Conclusion: Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

In China, majority of the mortality in gastric cancer are associated with peritoneal metastasis. Since most gastric tumors are metastatic at initial diagnosis, the treatment of gastric cancer is limited to radical resection. Therefore, it is imperative to identify diagnostic and prognostic biomarkers. From 2014 to 2015, 20 patients were enrolled in the study. To search translationally upregulated genes in the context of epithelial to mesenchymal transition (EMT), polysome profiling was performed. The MTT, migration, and invasion assay were conducted to determine cell proliferation, migration, and invasion ability respectively. Experiments of gain and loss of function were performed using the overexpression plasmid, siRNA, and shRNA. Xenograft assay was established using nude mice to explore the role of targets translationally upregulated gene in vivo . Polysome profiling defined the landscape of translationally regulated gene products with differential expression between non-metastatic and metastatic cohorts. Six-transmembrane epithelial antigen of the prostate 1 ( STEAP1 ) was found to be the most translationally upregulated gene product in either experimental groups. STEAP1 was found to be required for cell proliferation, in vitro migration and invasion, and in vivo tumorigenesis. RNAi-mediated silencing of STEAP1 potentiated chemosensitivity of the MKN45 cells to docetaxel treatment, highlighting the importance of STEAP1 as a novel biomarker in gastric cancer patients with peritoneal metastasis. STEAP1 is thus induced translationally and its expression promotes proliferation, migration, invasiveness, and tumorigenicity of gastric cancer. STEAP1 can be a potent candidate for designing of targeted therapy.

Low bone mineral density (BMD) is a risk factor of osteoporotic fracture (OF). Peripheral blood monocytes (PBM) can differentiate into osteoclasts to resorb bone. It was known that PBM-expressed Anxa2 protein is associated with BMD, and extracellular Anxa2 protein promotes osteoclastogenesis. This study aimed to test 1) whether Anxa2 protein level in PBM differs significantly between subjects with OF and without fracture history (NF); 2) whether Anxa2 level in plasma is associated with BMD; 3) how Anxa2 protein at various concentrations would affect osteoblastic activity in vitro. All the study subjects were Chinese Han elderly. Firstly, Anxa2 protein in PBM was identified and quantitated by LC-MS/MS and compared between 45 OF cases and 42 healthy controls. Secondly, plasma Anxa2 protein level was quantitated by ELISA and compared between unrelated subjects with extremely low vs. high hip BMD (0.63±0.10 vs. 1.05±0.10 g/cm2, n = 75). Furthermore, in vitro functional assay was utilized to test the effects of extracellular Anxa2 protein on osteoblastic growth. We found that Anxa2 protein expression in PBM was significantly up-regulated in OF vs. NF subjects (fold change [FC)] = 1.16, P<0.05). Plasma Anxa2 protein concentration (range: 31.69-227.35ng/ml) was significantly elevated in low vs. high BMD subjects (84.85 vs. 66.15ng/ml, FC = 1.28, P<0.05). Cellular dynamical monitoring demonstrated that the general shape of dose-response relationship is the inverse U-shaped curve. Specifically, lower dose of Anxa2 protein may promote osteoblast growth and the optimal concentration for osteoblastic growth was around 50ng/ml, but even higher concentration could attenuate hFOB1.19 osteoprogenitor cell growth. We concluded that Anxa2 protein could attenuate osteoblast growth and be associated with hip BMD and OF in Chinese elderly.

BACKGROUND The aim of this study was to investigate the effects of negative pressure therapy in the regeneration of the rabbit sciatic nerve using vacuum assisted closure (VAC). MATERIAL AND METHODS Thirty male New Zealand white rabbits underwent surgical injury of the sciatic nerve, followed by negative pressure therapy using vacuum assisted closure (VAC), in three treatment groups: Group A: 0 kPa; Group B: -20 kPa; Group C: -40 kPa. At 12 weeks following surgery, the following factors were studied: motor nerve conduction velocity (MNCV); the number of myelinated nerve fibers; the wet weight of the gastrocnemius muscle. Gastrocnemius muscle and sciatic nerve tissue samples were studied for the expression of S100, and brain-derived neurotrophic factor (BDNF) using Western blot. RESULTS At 12 weeks following VAC treatment, the MNCV, number of myelinated nerve fibers, and wet weight of the gastrocnemius muscle showed significant differences between the groups (p<0.05), in the following order: Group B >Group A >Group C. The sciatic nerve at 12 weeks following VAC in Group B and Group C showed a significant increase in expression of S100 and BDNF when compared with Group A; no significant differences were detected between Group B and Group C results from Western blot at 12 weeks. CONCLUSIONS The findings of this study, using negative pressure therapy in VAC in a rabbit model of sciatic nerve damage, have shown that moderate negative pressure was beneficial, but high values did not benefit sciatic nerve repair.

The expression of legumain which has been shown overexpressed in patients with metastatic gastric cancer is positively correlated to both disease progression and outcome, and negatively correlated to microRNA (miR)-3978 expression. The RNA-binding protein, poly r(C) binding protein 1 (PCBP1) was the most downregulated protein in the metastatic tissue specimens. Quantitative real-time PCR showed that PCBP1 expression is transcriptionally downregulated in peritoneal metastasis tissues. RNA immunoprecipitation experiments showed that PCBP1 and miR-3978 are sequestered in normal peritoneal tissue, but the complex is disrupted following metastatic progression. PCBP1 expression mimicked miR-3978 expression across gastric cancer patients. Finally, replenishment of PCBP1 or miR-3978 expression in the peritoneal metastasis cell line MKN45 decreased legumain protein expression and chemosensitized the cells to treatment with docetaxel. However, replenishment of one and concomitant depletion of the other failed to induce chemosensitivity to docetaxel. Replenishment of miR-3978 also resulted in induction of PCBP1 protein expression, potentially indicating that miR-3978 expression might downregulate a negative regulator targeting PCBP1. Our current study reveals PCBP1 as an additional biomarker in peritoneal metastasis. PCBP1 and miR-3978 expression were correlated and suggests a potential interplay of differential miRNA biogenesis and RNA binding protein during metastatic progression.

Osteosarcoma is suggested to be caused by genetic and molecular alterations that disrupt osteoblast differentiation. Recent studies have reported that transmembrane protein 119 (TMEM119) contributes to osteoblast differentiation and bone development. However, the level of TMEM119 expression and its roles in osteosarcoma have not yet been elucidated. In the present study, TMEM119 mRNA and protein expression was found to be up-regulated in osteosarcoma compared with normal bone cyst tissues. The level of TMEM119 protein expression was strongly associated with tumor size, clinical stage, distant metastasis and overall survival time. Moreover, gene set enrichment analysis (GSEA) of the Gene Expression Omnibus (GEO) GSE42352 dataset revealed TMEM119 expression in osteosarcoma tissues to be positively correlated with cell cycle, apoptosis, metastasis and TGF-β signaling. We then knocked down TMEM119 expression in U2OS and MG63 cells using small interfering RNA, which revealed that downregulation of TMEM119 could inhibit the proliferation of osteosarcoma cells by inducing cell cycle arrest in G0/G1 phase and apoptosis. We also found that TMEM119 knockdown significantly inhibited cell migration and invasion, and decreased the expression of TGF-β pathway-related factors (BMP2, BMP7 and TGF-β). TGF-β application rescued the inhibitory effects of TMEM119 knockdown on osteosarcoma cell migration and invasion. Further in vitro experiments with a TGF-β inhibitor (SB431542) or BMP inhibitor (dorsomorphin) suggested that TMEM119 significantly promotes cell migration and invasion, partly through TGF-β/BMP signaling. In conclusion, our data support the notion that TMEM119 contributes to the proliferation, migration and invasion of osteosarcoma cells, and functions as an oncogene in osteosarcoma.

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in infected hepatocytes is the main cause of off-therapy viral rebound. The half-life of cccDNA is only 33-50 days, so the conversion of newly synthesized rcDNA to cccDNA in the nucleus is essential for the maintenance of cccDNA pool in infected hepatocytes. Though not directly targeting the existing cccDNA, current nucleos(t)ide analogues (NAs) may exhaust the cccDNA reservoir by blocking the rcDNA formation. Indeed, a prolonged consolidation therapy post loss of serum HBV DNA can achieve sustained remission and thus safe drug discontinuation in a small proportion of chronic hepatitis B (CHB) patients. In recent studies, we and others have demonstrated that it is the serum HBV RNA that reflects the cccDNA activity in infected hepatocytes, particularly among the patients on NAs. Here we suggest that instead of measuring serum HBV DNA only, simultaneous measurement of both viral DNA and RNA would improve the accuracy to reflect the cccDNA activity; therefore, the virological response should be redefined as consistent loss (less than the lower limit of detection) of both serum HBV DNA and RNA, which indicates the safety of drug discontinuation. Accumulating evidence has suggested that for the CHB patients with lower serum HBsAg, switch-to or add-on pegylated interferon (Peg-IFN) treatment would result in loss of serum HBsAg in a relatively large proportion of CHB patients. Since serum HBV RNA is an ideal biomarker to reflect the intrahepatic cccDNA activity, for the patients with a serum HBsAg level lower than 1 500 IU/ml after long-term NAs treatment, the serum HBV RNA should be measured. If serum HBV RNA is detected, peg-IFN should be added on; if serum HBV RNA is not detected, NAs treatment should be switched to peg-IFN treatment. We believe the therapy based on serum HBV RNA would make the functional cure of CHB (serum HBsAg loss or even conversion to anti-HBs) more efficient.

Gastric cancer incidence and mortality are among the highest in China, with majority of the mortality related to peritoneal metastasis of gastric cancer. Treatment is limited to radical resection, which is impeded by incidence of metastasis at time of initial diagnosis, thus making it imperative to identify diagnostic and prognostic biomarkers. Legumain, a lysosomal cysteine endopeptidase of the asparaginyl endopeptidase family, has been shown to be overexpressed in patients with metastatic gastric cancer disease and its expression was positively correlated to both disease progression and outcome. However, the mechanism of legumain expression is currently unknown. Legumain overexpression was found to occur at the level of post transcriptional gene regulation. In situ prediction algorithms identified legumain as a putative target of miR-3978. MiR-3978 was significantly decreased in peritoneal metastatic tissue specimens and in MKN45 cells that mimic peritoneal metastasis features. Reporter assays using LGMN (encoding legumain) 3' untranslated region (UTR) showed that miR-3978 interacted with the wild-type but not miR-3978-seed mutant. Ectopic expression of miR-3978 mimic in the MKN45 cell line significantly decreased proliferation and suppressed in vitro migration and invasion. The miR-3978 mimic inhibited gastric carcinoma and metastatic progression in a mice model by regulating legumain protein expression. Inverse correlation of LGMN mRNA and miR-3978 levels in 20 gastric patients at different stages of metastatic disease confirmed the same. Cumulatively, our results indicate that loss of miR-3978 leads to increased expression of legumain, which indicates that miR-3978might be a biomarker for peritoneal metastasis in patients with gastric cancer.

Aim: To investigate clinical outcomes of chronic hepatitis B (CHB) and liver cirrhosis (LC) patients under whole-course management with lamivudine (LAM)., Methods: This was a retrospective-prospective cohort study based on two nonrandom cohorts of Chinese patients (LAM group and history control group). Two hundred thirty-eight patients with LAM treatment for at least 12 mo under whole-course management were included in the LAM group. The management measures included regular follow-up and timely adjustment of the therapeutic regimen according to drug-resistance and relapse. Two hundred thirty-eight patients with CHB or LC without any antiviral treatment and with follow-up over 12 mo were included in the history control group. The LAM and control group patients were 1:1 matched by propensity score method to ensure both patients were similar in general datum, sex, age, E antigen, and diagnosis. The incidence rates of endpoint events [LC, hepatocellular carcinoma (HCC), and death] were compared between the LAM and control groups., Results: Hepatitis B virus-DNA < 1000 copies per mL rate and rate of alanine transaminase < 1.3 of the upper normal limit in LAM and control groups were 89.1% vs 18.5% (P < 0.05) and 89.8% vs 31.1% (P < 0.05), respectively. Viral breakthrough occurred in 77 patients (32.4%); the one-, three-, and five-year cumulative rates were 6.8%, 33.1%, and 41.3%, respectively. In total, 44.5% (106/238) of patients had once stopped LAM, and 63 (59.4%) of them developed virologic relapse; the relapse rate of patients with and without reaching Asian Pacific Association for the Study of the Liver endpoint criteria were 52.4% and 69.8%, respectively. Six CHB patients in the LAM group developed LC compared to 47 patients in the control group; the three-, and five-year cumulative rates of CHB at baseline of LAM were lower than those of the control group: 0.7% vs 12.0% and 1.8% vs 23.8% (P < 0.01), respectively. The incidence of HCC in CHB at baseline of LAM was lower than that of the control group; the three-, and five-year cumulative rates were 0% vs 3.2% and 1.1% vs 3.2% (P = 0.05), respectively. The incidence of HCC in LC at baseline of LAM was lower than that of the control group: 9.8% (5/51) vs 25.0% (12/48), and the three-, and five-year cumulative rates were 4.5% vs 20.7% and 8.1% vs 37.5% (P < 0.01), respectively. The mortality rate in the LAM group was lower than the control group., Conclusion: Standardized long-term LAM treatment in combination with comprehensive management can reduce the incidence rates of LC and HCC as well as hepatitis B virus-related deaths.

Objective: To investigate the relationship between relapse and the levels of the residual amount of HBV DNA in serum at cessation in chronic hepatitis B patients meeting 2008 Asian Pacific Association for the Study of the Liver (APASL) nucleos(t)ide analogs (NAs) cessation criteria., Methods: A total of 72 chronic hepatitis B patients who took NAs and had reached 2008 APASL cessation criteria entered the study. Patients were followed up for 6 months or longer after antiviral therapy was stopped. Serum HBV DNA level at cessation was detected by a highly sensitive polymerase chain reaction assay with detection limitation of 2 IU/mL., Results: Of all the 72 patients, 42 patients (65.3%) relapsed after NA cessation. The detectable rate of the trace amount of HBV DNA at cessation was 41.7% by highly sensitive polymerase chain reaction reagents. The detectable rate of patients with consolidation treatment duration of <18 months was higher than that with consolidation duration of ≥18 months (47.5% vs. 15.4%, P=0.034), and the detectable rate of patients with HBeAg seroconversion within 6 months of treatment was lower than that of ≥6 months (25.0% vs. 61.5%, P=0.036). The residual amount of HBV DNA and detectable rate at cessation showed significant differences between relapsed and nonrelapsed patients (130.4±420.90 vs 44.6±155.16 IU/mL, P=0.004; 55.3% vs. 16.0%, P=0.001). The cutoff value predicting relapse was 2.24 IU/mL, with a sensitivity of 0.553 and specificity of 0.840., Conclusions: Residual amount of HBV DNA in serum at NA cessation is associated with HBV relapse. The cutoff value predicting relapse was 2.24 IU/mL, with a sensitivity of 0.553 and specificity of 0.840.

Objective: To examine the change in proinflammatory cytokines in the pathologic processes of endometriosis in mice., Design: A dynamic study on a murine model of endometriosis., Setting: Medical school., Animal(s): Female BALB/c mice., Intervention(s): Endometriosis was induced by injecting endometrial fragments of syngenic mice into the peritoneal cavity of model mice; in control group, phosphate-buffered saline instead of fragments was injected. The peritoneal fluid and the endometriotic lesions were harvested 1 to 21 days after the induction., Main Outcome Measure(s): The endometriotic lesions were weighed, the gene and protein levels of some proinflammatory cytokines, including interleukin 1beta, tumor necrosis factor alpha, vascular endothelial growth factor, and monocyte chemoattractant protein 1, were determined by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively., Result(s): The levels of these cytokines reached the first peak on the first day and no endometriotic lesions were found. The lesions began to appear on the second day, presenting red color during the initial 6 days, and then they turned dark-red, brown, or bluish. The adhesion took place on the 9th day, and all the lesions evolved into white or transparent cysts on the 15th day. Corresponding to these changes, the second and the third peaks were identified during the 3rd-6th day and the 12th-15th day, respectively., Conclusion(s): The change pattern of cytokines over time might bear some relationship with the development and progression of the endometriosis., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the clinical value in predicting the prognosis of chronic severe hepatitis between the Child-Turcotte-Pugh (CTP) score and the model for end-stage liver disease (MELD) score., Methods: Fifty-five cases with chronic severe hepatitis were scored by CTP and MELD score systems based on their biochemical and coagulation parameters, and related signs within 24 hours after their admission. The termination date of observation was the 90th day after their admission. The actual survival time were recorded. The comparison scores of CTP/MELD were conducted respectively and compared between the survival group and death group, among different clinical stages of chronic severe hepatitis. The correlation of CTP/MELD score with the clinical stages was analyzed respectively. The survival time, mortality and survival rate were compared respectively among the groups classified by CTP/MELD score according to Kaplan-Meier (K-M) survival curve., Results: The CTP score and the MELD score in death group were higher than those in survival group (both P<0.01). The CTP and MELD scores in the advanced stage group were also higher than those in the early and middle stage (both P<0.01). The correlation of the MELD score with the stage was higher (r(s) =0.689,P<0.01) than that of the CTP score (r(s)=0.428, P<0.01). The survival time of patients with CTP<12 scores, was longer than with CTP>or=12 scores, and their survival rate was also higher(both P<0.01). When the MELD score lowered, survival time was longer, and survival rate was higher. The survival time, mortality and survival rate showed significant difference among the groups classified by MELD score (or=40 points, all P<0.01)., Conclusion: The parameters employed in MELD score system are more, Objective: and easy to achieve, the score range for patients classification is wider and more practical, and the correlation with the clinical stage is higher than CTP score system, suggesting the MELD score system is better in predicting the prognosis of patients with chronic severe hepatitis than the CTP score system.