[Clinical analysis of adverse reactions in patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis treated with delamanid-containing regimen].

Objective: To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB). Methods: The prospective multicenter study was conducted from June 2020 to June 2023. A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females, aged 39.6(19.0-68.0) years. Patients were treated with chemotherapy regimens containing delamanid. Patients were closely supervised during treatment of medication, and all adverse reactions occurring during treatment were monitored and recorded. The clinical characteristics of adverse reactions were evaluated by descriptive analysis. Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation (QT corrected with Fridericia's formula). Results: Of the 608 patients enrolled in this study, 325 patients (53.5%) reported 710 adverse events within 24 weeks of treatment. The top 6 most common complications were hematological abnormalities (143 patients, 23.5%), QT prolongation (114 patients, 18.8%), liver toxicity (85 patients, 14.0%), gastrointestinal reaction (41 patients, 6.7%), peripheral neuropathy (25 patients, 4.1%) and mental disorders (21 patients, 3.5%). The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication. Serious adverse reactions occurred in 21 patients (3.5%). There were 7 patients (1.2%) with mental disorders, including 2 patients (0.3%) with severe mental disorders. Conclusions: The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good, and the incidence of adverse reactions was similar to that reported in foreign studies. This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas, suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing delamanid that may cause QT interval prolongation.

[Application of ureteral access sheath in the operation of middle and lower ureteral calculi in patients with massive benign prostatic hyperplasia].

Objective: To examine the effectiveness and safety of application of the ureteral access sheath in the treatment of middle or lower ureteral calculi in patients with large-volume benign prostatic hyperplasia above grade Ⅲ, which is expected to avoid the simultaneous or staged treatment of benign prostatic hyperplasia via eliminate the difficult angle and resistance of ureteroscopy caused by severe prostatic hyperplasia. Methods: From April 2018 to December 2020, the clinical data of 27 patients with massive benign prostatic hyperplasia above grade Ⅲ and middle and lower ureteral calculi treated with indwelling ureteral access sheath plus ureteroscopy holmium laser lithotripsy at Department of Urology, Zhejiang Quhua Hospital were retrospectively analyzed and followed up. All the patients were male, aged (69.7±12.8) years (range: 55 to 87 years). Prostate volume measured by transrectal ultrasound was (94.8±16.2) cm3 (range: 85 to 186 cm3). The ureteral access sheath was indwelled in advance, and then the semirigid ureteroscopy was introduced through the working channel of the sheath. Holmium laser lithotripsy was performed, and intraoperative and postoperative complications were recorded. Urinary abdominal plain X-ray or CT urography were performed at 1-and 2-month postopaerative to evaluate the residual stones and clinical efficacy. Results: The ureteral access sheath was placed and holmium laser lithotripsy under a semirigid ureteroscopy was performed successfully in all the 27 patients. In 2 patients, a second session of auxiliary procedure was required due to the large load of preoperative stones and residual stones after surgery, among whom 1 patient received extracorporeal shock wave lithotripsy and 1 patient underwent extracorporeal shock wave lithotripsy plus ureteroscopic lithotripsy. The stone free rate at 1-and 2-month postoperative were 92.6% (25/27) and 100% (27/27), respectively. There were no severe complications such as ureteral avulsion and perforation, perirenal hematoma, septic shock, severe hematuria, urinary retention, iatrogenic ureteral stricture occurred during and after the surgery. The ureteral calculus was wrapped by polyps heavily in 1 patient, he was diagnosed as ureteral stenosis 1 month postoperative, receiving laparoscopic resection of ureteral stricture plus anastomosis 3 months postoperative. Conclusions: In the operations of middle and lower ureteral calculi in patients with large-volume prostatic hyperplasia above grade Ⅲ, the ureteral access sheath can be placed first to effectively eliminate the difficult angle and resistance of ureteroscopy caused by severe prostatic hyperplasia, and then semirigid ureteroscopic lithotripsy can be safely performed. It could avoid the treatment of benign prostatic hyperplasia at the same time or by stages.

Relationship between viral load, infection-to-delivery interval and mother-to-child transfer of anti-SARS-CoV-2 antibodies.

OBJECTIVE: To investigate the association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and infection-to-delivery interval with maternal and cord serum concentrations of anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies and transplacental transfer ratio in pregnant women with active or recovered SARS-CoV-2 infection. METHODS: This was a prospective case series of consecutive pregnant women with laboratory-confirmed SARS-CoV-2 infection between 27 March 2020 and 24 January 2021. We collected information regarding deep throat saliva or nasopharyngeal swab (NPS) reverse transcription polymerase chain reaction (RT-PCR) test results, serial cycle threshold (Ct) values at and after diagnosis, demographic, clinical and outcome data, and neonatal NPS RT-PCR results. Qualitative and quantitative analysis of IgG and immunoglobulin M (IgM) antibodies against SARS-CoV-2 was performed in maternal and cord blood serum samples obtained at delivery. Correlation of maternal Ct values, infection-to-delivery interval, infection duration and viral load area under the curve (AUC) with gestational age (GA) at diagnosis, maternal and cord serum IgG concentrations and transplacental transfer ratio of IgG were evaluated using Pearson's correlation. RESULTS: Twenty pregnant women who consented to participate and who had delivered their babies by 31 January 2021 were included in the study, comprising 14 who had recovered from coronavirus disease 2019 (COVID-19) and six with active infection at delivery. The median GA at clinical manifestation was 32.7 (range, 11.9-39.4) weeks. The median infection-to-delivery interval and infection duration were 41.5 (range, 2-187) days and 10.0 (range, 1-48) days, respectively. The median GA at delivery was 39.1 (range, 32.4-40.7) weeks and the median seroconversion interval was 14 (range, 1-19) days. Of 13 neonates born to seropositive mothers with recovered infection at delivery, 12 tested positive for anti-SARS-CoV-2 IgG. All neonatal NPS samples were negative for SARS-CoV-2 and all cord sera tested negative for IgM. The median transplacental transfer ratio of IgG was 1.3 (interquartile range, 0.9-1.6). There was a negative correlation between infection-to-delivery interval and anti-SARS-CoV-2 IgG concentrations in maternal (r = -0.6693, P = 0.0087) and cord (r = -0.6554, P = 0.0068) serum and a positive correlation between IgG concentration in maternal serum and viral load AUC (r = 0.5109, P = 0.0310). A negative correlation was observed between transfer ratio and viral load AUC (r = -0.4757, P = 0.0409). CONCLUSIONS: In pregnant women who have recovered from COVID-19, anti-SARS-CoV-2 IgG concentrations at delivery increased with increasing viral load during infection and decreased with increasing infection-to-delivery interval. The median transplacental transfer ratio of IgG was 1.3 and it decreased with increasing viral load during infection. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Long Noncoding RNAs CUPID1 and CUPID2 Mediate Breast Cancer Risk at 11q13 by Modulating the Response to DNA Damage.

Breast cancer risk is strongly associated with an intergenic region on 11q13. We have previously shown that the strongest risk-associated SNPs fall within a distal enhancer that regulates CCND1. Here, we report that, in addition to regulating CCND1, this enhancer regulates two estrogen-regulated long noncoding RNAs, CUPID1 and CUPID2. We provide evidence that the risk-associated SNPs are associated with reduced chromatin looping between the enhancer and the CUPID1 and CUPID2 bidirectional promoter. We further show that CUPID1 and CUPID2 are predominantly expressed in hormone-receptor-positive breast tumors and play a role in modulating pathway choice for the repair of double-strand breaks. These data reveal a mechanism for the involvement of this region in breast cancer.

[Evaluation of potential renal acid load for estimating the health effects of drinking water].

There is a lack of a reliable comprehensive evaluation indicator to access the health effects of drinking water. In recent years, scholars established an indicator to evaluate the comprehensive effect of drinking water on the body's acid-base balance. This indicator came from the potential renal acid load (PRAL) of food and named the potential renal acid load of drinking water. It included several typical anions and cations which are widely found in drinking water. This article reviewed the application, advantages, and disadvantages of PRAL in accessing the effect of drinking water on body acidbase metabolism.

[The relationship between soluble silicate acid in drinking water and food and human health].

Silicon was once considered a biologically inert element, but recent research has shown its value for human health.Soluble silicic acid is the available form of silicon in human body. This paper reviews the absorption, distribution and metabolic characteristics of dietary soluble silicic acid in human body, as well as its relationship with human health.Available data show that it has lots of supporting evidences that dietary soluble silicic acid can prevent osteoporosis, maintain vascular health, improve the symptoms of Alzheimer's disease and multiple sclerosis.Its unique crosslinking ability and antagonism to toxic aluminum play a crucial role. In the early stage of human life, there is a strong demand for silicon, and the level of silicon in the aged is generally reduced, suggesting that pregnant women and old people should pay attention to the intake of soluble silicic acid. It is suggested to strengthen the basic and applied research on dietary soluble silicic acid,and gradually establish the relevant nutrition and hygiene standards.

[Meta-analysis of asthma prevalence of children aged 0-14 in surveillance cities of China].

Objective: To understand the prevalence of asthma and its variation over time in children aged 0-14 years in China. Methods: The studies on the prevalence of asthma in children in China were systematically retrieved from China National Knowledge Infrastructure (CNKI), WanFang Data, China Science and Technology Journal Database (VIP) and PubMed databases. The search time was up to June 2019, and the study site was located in the asthma surveillance cities. Random effect model was used to calculate the combined prevalence of asthma and its 95% confidence interval (CI). The subgroup analysis was conducted by period, sex and region. All analyses were performed by using Stata 15.1 and R Studio software. Results: Among 2 624 articles, 67 met the eligibility criteria, and the survey time was from 1989 to 2015. A total of 1 661 076 children were involved and 40 737 asthma cases were confirmed from 26 provinces, municipalities and autonomous regions. The prevalence of asthma varied greatly among different studies, ranging from 0.5% to 9.82%. Meta-analysis showed that the combined prevalence of asthma in Chinese children aged 0-14 was 2.6% (95%CI: 2.1%-3.1%), about 3.2% (95%CI: 2.6%-3.8%) for boys and 1.9% (95%CI: 1.6%-2.3%) for girls. The subgroup analysis showed a significant variation of the prevalence over different years, genders and regions (P<0.05). The prevalence of asthma in boys was consistently higher than that of girls. The overall prevalence of asthma showed an upward trend. Before 2010, the prevalence of asthma in the eastern region was higher than that in the central and western regions. The prevalence of asthma across regions showed a significant change and the prevalence of asthma in the central region was significantly higher than that in the eastern and western regions from 2010 to 2015 (P<0.05). Conclusion: The asthma prevalence of children aged 0-14 in China is generally increasing, and the prevalence rate of boys is higher than that of girls. The prevalence rate in the central region is significantly higher than that in the eastern region from 2010 to 2015, suggesting that those regions should strengthen the early prevention and intervention of asthma and implement a sex-specific information dissemination strategy.

[Using text mining to identify gap in acquired immunodeficiency syndrome related information dissemination between the official channel delivery and the needs of adolescents].

Objective: The study intends to identify gap in HIV/AIDS awareness dissemination between the official channel delivery and the needs of adolescents. Methods: We crawled all the HIV/AIDS queries from "Baidu zhidao" till June 11st, 2018. "Baidu zhidao" inquiry and information form official public service announcement (abbreviated for "official delivery" hereafter) were the data source for comparative analysis. We categorized the text data into four kinds, "prevention", "testing and treatment", "symptoms and infection" and "legalization and policies" according to official categorization. Word segmentation was used for text mining and word frequency statistics, as well word cloud was used for word frequency visualization (all based on a comparison after removing the useless words). Results: Of the official delivery, the proportion of prevention category accounted for 32.3% (n=162) (ranks 1st), and the proportion of legalization and policies category was 14.1% (n=71). While among the "Baidu zhidao" inquiry information, the proportion of testing and treatment category accounted for 51.7% (n=51 264), and the proportion of prevention category accounted for 11.4% (n=11 272). The frequencies of same terms/ repeated terms of two channels accounted for 60% (59.3%-63.9%) of each category among the official delivery, of which, the proportion of interest terms comparatively less and more diverse in "Baidu zhidao" inquiries. The proportion of the terms frequency of each category was about 45% in "prevention, testing and treatment", 34.3% (n=14 781) in "symptoms and infection" and 17.0% (n=5 744) in "legalization and policies", respectively. Conclusion: A big gap was identified between the available official source and inquiries' term, especially word frequency discrepancy between "legalization and policies" and "prevention" categories. It underscore the necessity for the official channel to address the needs and interests of adolescents in the future.

[Sex difference in height growth and blood pressure change among Beijing school-age children and adolescents: a ten-year longitudinal study].

Objective: To explore sex difference in height growth and blood pressure (BP) change among Beijing school-age children and adolescents. Methods: Using physical examination data of 70 769 school-age children and adolescents from primary to high school during 2009-2018 in Shunyi District, a longitudinal dataset was formed with completed anthropometrical measurements of height and blood pressure (BP) after individual information linkage. Age-specific height, BP, growth rate of height and BP as well BP growth rate based on age at peak height velocity (PHA) were calculated. Linear mixed-effects model was used to identify sex disparity in the growth rates of height and BP. Results: Height and BP increased with age in both boys and girls, and the mean height and BP of boys were always higher than those of girls, except age group from 10 to 11 years. Sex disparity existed in growth rates of height and BP (P<0.001), which was demonstrated by the interaction item of"sex x age"in linear mixed-effects model. The PHA of boys was 12 years old, which was 2 years later than that of girls, about 10 years old. The curves of BP growth rate with age showed double peaks in both boys and girls. Boys reached the peak BP velocity at 13 years old, 3 years lagging behind that of girls who reached the peak at 10 years old. However, the peak of height and BP velocity of boys were higher than that of girls. The change of BP was highly synchronized in time with the increase of height, after adjusting for the growth rate of height by PHA. BP velocity increased with age before onset of puberty till PHA and then declined. Conclusion: Sex disparity in height growth and BP change among school-age children and adolescents is persistent and significant and the change of BP is highly synchronized in time with the increase of height.

[Association of blood pressure and left ventricular mass in children from the PROC cohort study].

Objective: To explore the association between blood pressure (BP) and the left ventricular mass (LVM) in children aged 6-8 years. Methods: The participants were from the community-based census-like design child cohort on sensitization, puberty, obesity and cardiovascular risk (PROC) conducted in six public non-boarding primary schools in Shunyi District, Beijing. Repeated three measurements on anthropometrical, M-mode and 2-dimensional (2D) echocardiographic imaging (2D/M ECHO) and blood biochemical assay, and BP measurements were carried out at baseline and follow-up from October 2018 to June 2019. A total of 1 659 children who had repeated BP measurements and cardiac structure information were included in this study. The average value of last two measurements of BP was determined as BP value for analysis. Formula recommended by Devereux was used to calculate the mass of left ventricle. Robust linear regression models were used to explore the association between BP and LVM in different groups. Results: The average age of all patients was (7.10±0.29) years old, including 832 boys (50.15%). Of all, 83.54% (1 386/1 659) were grouped as normal BP with average LVM (58.54±13.33) g, and 16.46% (273/1 659) as elevated BP group with LVM (63.84±15.78) g (P<0.001). The LVM of the normal BP group was lower than elevated BP group in overall participants, boys and girls (P<0.005). Univariate analysis showed that systolic BP was associated with LVM in overall, boys and girls (P<0.001) respectively. While diastolic BP was associated with LVM in overall and girls (P<0.03). Multivariable analysis indicated that the associations between systolic BP and LVM were observed in overall, boys and girls (P<0.05) with the ß (95%CI)=0.14 (0.08, 0.21), 0.18 (0.08, 0.27) and 0.12 (0.03, 0.22), respectively. However, the associations of diastolic BP and LVM were not significant. Conclusion: Systolic BP is highly associated with LVM and elevated BP could increase the LVM in children. Boys with elevated BP present a larger LVM and might indicate higher risk of left ventricular hypertrophy in adulthood.

[Association between trunk fat index and carotid intima-media thickness among children aged 6-8 years old in Beijing].

Objective: The study is to explore the association between trunk fat index (TFI) and carotid intima-media thickness (cIMT) among children aged 6-8 years old in Shunyi District, Beijing. Methods: The participants were enrolled from the child cohort on sensitization, puberty, obesity and cardiovascular risk (PROC) conducted in Shunyi District, Beijing from October 2018 to June 2019. The PROC used a community-based census-like design, and all eligible first-grade children from six public non-boarding primary schools in urban area were approached. Finally, a total of 1 503 children with written informed consent from parents and had complete data of TFI and cIMT were included for the present study. Sequential baseline surveys including anthropometric measurements, laboratory testing and ultrasonography measurement were conducted to collect the data on height, weight, body composition, blood pressure, serum lipids and cIMT. Linear regression was used to determine the predictors of cIMT, receiver operating characteristic (ROC) curve analysis was used to determine the cut-off value of TFI to identify children with high cIMT, and analysis of covariance was used to evaluate the post-consistency classification of cIMT by TFI. Results: The age of 1 503 participants was (6.7±0.3) years, and 752 boys accounted for 50.0%. The average cIMT was (0.358±0.024) and (0.355±0.023) mm, and the M (P25, P75) of TFI was 0.70 (0.22, 1.78) and 0.74 (0.23, 1.52) kg/m2 for boys and girls, respectively. The detection rates for boys and girls of high cIMT were 2.1% and 3.3%, respectively. Linear regression analysis showed that height, systolic blood pressure (SBP), diastolic blood pressure (DBP), TFI were positively correlated with cIMT in boys (P values<0.05). And height, SBP, triglyceride (TG), TFI were positively correlated with cIMT, and high-density lipoprotein cholesterol (HDL-C) was negatively correlated with cIMT in girls (P values<0.05). ROC curve analysis indicated that the best cut-off values for TFI to identify children with high cIMT were 1.78 and 1.14 kg/m2, at P75 and P66 for boys and girls, respectively. After grouped with the cut-off value of TFI and adjusted for age, height, SBP, DBP, TG, HDL-C, multivariable covariance analysis showed a consistent cut-off of inter-group cIMT mean by TFI groups (P values<0.005). Conclusion: TFI is associated with cIMT, which underscore its application potential in identifying early vascular structural damage.

The joint impact of smoking plus alcohol drinking on treatment of pulmonary tuberculosis.

Tuberculosis, smoking, and alcohol drinking are major public health and social issues worldwide. We investigated the joint effect of smoking plus alcohol drinking on TB treatment. Retrospective study was conducted among TB patients in 49 units from eight provinces in China. All patients enrolled were classified into four groups according to their smoking and/or alcohol status. Current smokers plus drinkers belonged to group 1; ex-smokers plus ex-drinkers were in group 2; current smokers and ex-drinkers, current smokers and never drinkers, ex-smokers and current drinkers, ex-smokers and never drinkers, never smokers and current drinkers, and never smokers and ex-drinkers belonged to group 3; while the never smokers plus never drinkers were in group 4. We used a chi-square test to compare adverse drug reaction, lesions absorption and cavities of lung, sputum culture at the end of the second month, and treatment outcomes among the four groups. Among the 1256 participants enrolled in the study, 6.1% (76/1256) were current smokers plus drinkers; 25.9% (325/1256) were ex-smokers plus drinkers; 29.1% (366/1256) were current/never/ex-smokers and/or drinkers, and 38.9% (489/1256) were never smokers plus drinkers, respectively. Compared to the never smokers and drinkers, smoker plus drinker TB patients were more likely to experience adverse drug reaction (x2 = 8.480, P = 0.037), less proportion of lesions absorption in lungs (x2 = 10.330, P = 0.016), lower proportion of culture conversion (x2 = 18.83, P = 0.04), and more unfavorable outcomes. Smoking plus alcohol drinking adversely affect response against TB treatment, which increase adverse drug reactions, sputum culture-positive rate at the end of the second month, and failure rate of pulmonary tuberculosis patients.

[Effect of alcohol drinking on sputum conversion at the end of second month and outcome of smear-positive pulmonary tuberculosis patients].

Objective: To explore the effect of alcohol drinking on sputum culture conversion at the end of second month and outcome of smear-positive pulmonary tuberculosis (PTB) patients. Methods: Total 2 067 patients aged 18 years and above diagnosed and treated from 2008 to 2011 in 49 TB institutions from 8 provinces, antonomous regions and municipalities were enrolled, according to tuberculosis situation and regional distribution in China. Those patients were divided into three groups according to alcohol drinking, including never alcohol drinker group, ever-alcohol drinker group and current alcohol drinker group, respectively. Chi-square test was used to compare the following variables among the three groups: adverse action, lesions absorption, cavity size, sputum-culture results at the end of the 2(nd) month of treatment, and treatment outcome. Multivariate Logistic regression was used to explore that whether alcohol drinking was risk factor of poor treatment effect. Results: Among the 2 067 smear-positive PTB patients, never drinkers, ex-drinkers and current drinkers account for 55.2% (1 140/2 067), 36.5% (755/2 067), 8.3% (172/2 067), respectively. Among patients of never drinkers, ex-drinkers and current drinkers groups, sputum-culture conversion rate at the end of the 2(nd) month of treatment were 86.1%, 81.3% and 83.0%, respectively (χ(2)=6.782, P=0.033); the difference in treatment outcome was significant (χ(2)=13.620, P=0.034). Treatment success rate were 83.9%, 81.1% and 79.7%, respectively; failure rate was 6.4%, 10.3% and 9.9%, respectively, and fatality rate were 2.1%, 2.3% and 4.1%, respectively. Multivariate Logistic regression analysis showed that non-sputum conversion of the end of 2(nd) month and fatality rate of ex-drinkers were 1.431 and 1.668 times higher than never drinkers, respectively; non-sputum conversion of the end of 2(nd) month of current drinkers was 1.256 times higher than never drinkers. Conclusion: Alcohol drinking affects the treatment effectiveness of tuberculosis, which increased risk of culture-positive rate of the end of 2(nd) month and fatality rate.

[The blood lead level and its relationship with behavior in school-age children from rural areas of Chongqing].

Objective: To explore the blood lead level and its relationship with behavior in school-age children from rural areas of Chongqing. Methods: A total of 697 students from grades 3 to 6 in the fall semester of 2014 from 14 rural townships in one district of Chongqing was selected by using the random cluster sampling method. Blood were sampled to analyze the lead level. Neurobehavioral tests were performed to determine their personal cognitive and memory ability. Questionnaires and physical examinations were administered to obtain the information of confounding factors. All students were divided into Q1-Q4 groups according to the quartile of their blood lead level. The relationship between the blood lead level and behavior was analyzed by multivariate logistic regression model and restricted spline regression model. Results: The mean age of 697 students was (10.07±1.36) years old, and the median (interquartile range) of their blood lead level was 44.31 (35.42) µg/L. Multivariate logistic regression model showed that after adjusting for age, gender, body mass index and maternal culture level, compared with Q1 group, the OR (95%CI) values of high digit symbol substitution test (DSST) scores and high overall memory quotient (MQ) scores in Q3 group were 1.65 (1.01-2.70) and 2.10 (1.21-3.62), and the OR (95%CI) value of high long term memory (LTM) scores in Q4 group was 0.53 (0.31-0.92). The results of the restricted spline regression model showed that the dose-response curves between the blood lead level and MQ/LTM test scores were both parabolic (P<0.05). Conclusion: The blood lead level of school-age children from rural areas of Chongqing is the same as that from other areas of China, but slightly higher than that from other areas of Chongqing. Children with higher blood lead level have poor long-term memory ability.

Metformin reduces the relapse rate of tuberculosis patients with diabetes mellitus: experiences from 3-year follow-up.

The role of metformin (MET) on treatment effect of diabetic tuberculosis (TB) patients has not been studied in China. Thus, we conducted a retrospective study to investigate whether MET exhibited more efficacy in combination with anti-TB regimens for diabetic TB patients. All patients recruited came from five tuberculosis control and prevention institutes from July 2009 to July 2016 and completed 3 years of follow-up. We used chi-square test or Fisher's exact test to evaluate the demographic characteristics and the frequency of clinical outcome between MET and non-MET group. A total of 58 TB patients with diabetes mellitus (DM), of these 27.6% (16/58) patients in the MET group and 72.4% (42/58) patients in the non-MET group, there was no significant difference in blood glucose level between MET and non-MET group (P = 0.494), in addition, there was a higher proportion of treatment success (93.8 vs. 71.4%) and culture conversions by the end of 2 months (87.5 vs. 71.4%) among MET group; the relapse rates of patients in MET and non-MET group were 6.3% (1/16) and 35.7% (15/42) through a 3-year follow-up (P = 0.045). Our data revealed that the use of MET as a combination drug with existing regimen improved the success rate of anti-TB treatment and reduced the relapse rate in TB patients with DM.

[The effectiveness of individualized treatment regimen on smear-positive retreatment pulmonary tuberculosis with mono- and poly-drug resistance].

Objective: To analyze and evaluate the effectiveness of individualized treatment regimen in the therapy of smear-positive retreatment pulmonary tuberculosis with mono-and poly-drug resistance, and therefor to provide information on how to develop rational individualized regimen for retreatment tuberculosis cases with drug resistance. Methods: This was a multi-centered, prospective cohort study. Totally 254 cases of sputum positive tuberculosis with previous treatment history during the period from July 1, 2009 to August 30, 2016 were included in the analysis. All the cases were randomly divided into 3 groups and received therapy after randomization into treatment groups. After 3 months, cases with multidrug resistant tuberculosis, extensively drug-resistant tuberculosis, non-tuberculosis mycobacterial infection and those with smear-positive but culture-negative tuberculosis were excluded according to result of sputum culture and drug susceptibility test (DST). In treatment group A (individualized treatment group), 86 cases with an average age of (42.1±13.7) years for men and (38.5±12.8) years for women, were treated with individualized regimen, which allowed drug replacement on the basis of standard regimen (2SHRZE/6HRE) according to DST result. Treatment duration was recalculated after drug replacement and the total length should be 12 months or more. If the DST result did not show drug resistance, the patients would continue the 8 months' standard treatment. In treatment group B (intensified retreatment regimen group), 86 cases with an average age of (43.2±14.2) years for man and (37.9±14.1) years for women, received intensified retreatment regimen (2HL(2)EZS/2HL(2)EZS(3)/4HL(2)E). The dose for H was 0.3 g/d for patients with body weight <50 kg, and 0.4~0.5 g/d for higher body weight (≥50 kg); The doses for L(2,)E and Z were 0.6 g, 2/w; 0.75, 1/d and 0.5g, 3/d. In treatment group C (standard treatment group), 82 cases with an average of (42.5±11.9) years for man and (38.6±12.8) years for women, were treated with standardized regimen recommended by national tuberculosis program (2HREZS/6HRE). In both group B and C, the total treatment duration was 8 months and the drugs were not replaced for mono-and poly-drug resistance. Treatment outcomes of the 3 groups were analyzed, the status of drug replacement in group A was analyzed, and the adjustment of dose of H and R according to patients' body weight was observed. SPSS 19.0 was used for data analysis. Results: The treatment cure rates for group A, B and C were 73.3%(63/86), 76.7%(66/86) and 50%(41/82), and the treatment success rates were 80.2%(69/86), 84.9%(73/86) and 62.2%(51/82) respectively. Treatment failure was 8.1%(7/86), 4.7%(4/86) and 19.5%(16/82) in 3 groups. There were significant differences in the above indicators for group A and B in comparison with group C(χ(2)=13.127, P=0.001). However, there was no difference observed between group A and B(χ(2)=0.646, P=0.422). In group A, tuberculosis specialized hospitals using regular doses for R was only 38.7%(12/31). After 3 years' follow-up, no-relapse-success for group A was 66.7% (10/15). Conclusions: Inappropriate individualized treatment would increase treatment failure for retreatment tuberculosis. Higher doses of H and R and prolonged extensive therapy phase could contribute to increased treatment success.

[Relationship between the weight of hospitalized patients with pulmonary tuberculosis and the oral dose of isoniazid].

Objective: To study the relationship between the weight change trend of initial treatment patients with pulmonary tuberculosis and the dose change trend of isoniazid, and therefore to analyze the appropriate dose of isoniazid. Methods: Data of initial treatment inpatients with pulmonary tuberculosis from May 1955 to December 2012 were retrospectively analyzed. Elderly patients with pulmonary tuberculosis, patients with drug-resistant tuberculosis, extrapulmonary tuberculosis and those with complications were excluded from the study. The time period was separated as 20th century 1950s to 1960s, 1970s, 1980s, 1990s, 21th century 2000s and 2010s. Samples were selected in each year and month between 1950s to 1960s and 1970s. After 1980s, samples of 1 year were taken from each 5 years. The sex, age and weight for every patient were collected, as well as the dose of isoniazid of every inpatient on a day in therapeutic regimen. Meanwhile, the weight change trend of the patients in different ages and the dose change trend of isoniazid were compared. The total number of cases was 1 398, with 924 males and 474 females, averaging (36.7±14.4) years old. Results: The weight of the patients increased when it was compared between that in 1950s to 1960s, 1970s or 1980s and that in 2000s, with a increasing weight of 3 kg, 3.5 kg and 3 kg respectively. The difference showed statistical significance (P<0.003). The difference was also significant when the weight in 70s was compared with that in 2010s (P=0.002). The therapeutic dose of isoniazid remained invariable regardless of the weight change. At 1990s, 2000s and 2010s, the dose of isoniazid per kilogram of body weight would reduce to 0.005 4 g, 0.005 2 g and 0.0054 g relative to patients' weight increase, and the difference was statistically significant (P<0.001). Conclusions: The weight of pulmonary tuberculosis inpatients increased in recent 60 years. The weight has a close relation with the dose of isoniazid. A fixed dose of isoniazid (0.3 g/d) regardless of the weight change could result in low blood drug concentration . To avoid tolerance of isoniazid and increase the cure rates of pulmonary tuberculosis, the dosage of isoniazid should be increased based on the weight increase of patients.

Risk factors for the treatment outcome of retreated pulmonary tuberculosis patients in China: an optimized prediction model.

Retreatment of tuberculosis (TB) often fails in China, yet the risk factors associated with the failure remain unclear. To identify risk factors for the treatment failure of retreated pulmonary tuberculosis (PTB) patients, we analyzed the data of 395 retreated PTB patients who received retreatment between July 2009 and July 2011 in China. PTB patients were categorized into 'success' and 'failure' groups by their treatment outcome. Univariable and multivariable logistic regression were used to evaluate the association between treatment outcome and socio-demographic as well as clinical factors. We also created an optimized risk score model to evaluate the predictive values of these risk factors on treatment failure. Of 395 patients, 99 (25·1%) were diagnosed as retreatment failure. Our results showed that risk factors associated with treatment failure included drug resistance, low education level, low body mass index (6 months), standard treatment regimen, retreatment type, positive culture result after 2 months of treatment, and the place where the first medicine was taken. An Optimized Framingham risk model was then used to calculate the risk scores of these factors. Place where first medicine was taken (temporary living places) received a score of 6, which was highest among all the factors. The predicted probability of treatment failure increases as risk score increases. Ten out of 359 patients had a risk score >9, which corresponded to an estimated probability of treatment failure >70%. In conclusion, we have identified multiple clinical and socio-demographic factors that are associated with treatment failure of retreated PTB patients. We also created an optimized risk score model that was effective in predicting the retreatment failure. These results provide novel insights for the prognosis and improvement of treatment for retreated PTB patients.

[The association between aflatoxin exposure and primary hepatocellular carcinoma risks: a case-control study in Chongqing].

Objective: To investigate the association between aflatoxin exposure and primary hepatocellular carcinoma (PHC) development. Methods: From December 2013 to May 2016, we selected 214 patients newly diagnosed with PHC as cases, and 214 patients as controls from three hospitals in Chongqing. Cases were confirmed with PHC diagnosis standard. And cases caused by clear reasons such as drug-induced liver injury, alcoholic liver damage, fatty liver and gallstones etiology, were excluded. Controls were included with no cancer and no digestive system disease, and recruited simultaneously with cases. Cases and controls were frequency-matched (1∶1) by same gender and age (±3 years). Peripheral blood and random urine samples were collected and analyzed for serum HBsAg status by biochemistry analyzer, and serum AFB(1)-ALB adduct and urinary AFB(1)-N(7)-GUA adduct by ELISA. Basic information, living habits and history of disease for patients were obtained by questionnaires. We used wilcoxon rank sum test to compare the median of serum AFB(1)-ALB adduct and urinary AFB(1)-N(7)-GUA adduct in cases and controls. Logistic regression analyses were performed to assess risk factors for PHC, and synergism index (S) of aflatoxin with other factors was estimated by the method of Andersson. Results: There was no significant difference in age between PHC cases (50.74±9.67) years and controls (51.15±9.90) years. Logistic regression showed that the odds ratio of HBV infection for PHC development was 46.3 (95% CI: 23.3-88.0). There was a significant difference in median concentrations of serum AFB(1)-ALB adduct (cases vs controls: 146.23 vs 74.42 ng/g albumin, P<0.001), but no difference in median concentrations of urinary AFB(1)-N(7)-GUA adduct was observed (cases vs controls: 0.17 vs 0.14 ng/mg creatinine, P<0.210). The odd ratios for PHC risk after adjustment were 1.9 (95%CI: 1.1-3.4) for AFB(1)-ALB adduct, and 2.1 (95%CI: 1.0-4.2) for AFB(1)-N(7)-GUA adduct. Moreover, we observed a positive interaction of aflatoxin exposure with HBV, alcohol drinking, and diabetes. The S was 4.7 (95%CI: 2.8-7.9), 3.5 (95%CI: 1.0-12.0), and 12.4 (95%CI: 1.8-84.2), respectively for serum AFB(1)-ALB adduct with each of the three factors mentioned, and was 1.9 (95%CI:1.1-3.1), 2.0 (95%CI: 1.1-3.6), and 2.0 (95%CI: 1.1-3.6), respectively for urinary AFB(1)-N(7)-GUA adduct with each of the three factors mentioned. Conclusion: HBV was still the main risk factor, and AFB(1) exposure was also an independent risk factor for PHC in Chongqing. There was a positive interaction of aflatoxin with HBV, alcohol drinking, and diabetes.

Effects of nucleus accumbens oxytocin and its antagonist on social approach behavior.

Severe impairment of social interaction is a core symptom of numerous psychiatric disorders. Oxytocin (OT) has been shown to be involved in various aspects of social behavior related to reproduction, but little is known about its effects on nonreproductive social interaction between adults or the neuroanatomical location where OT exerts its action. Here, we examined the nucleus accumbens, a region of the brain containing high levels of the oxytocin receptor (OTR) and comprising an important node in the neural circuitry possibly related to social interaction. Behavioral effects of a local microinfusion of OT (0.1, 1, and 10 ng/side) and an oxytocin receptor antagonist (OTR-A) (1, 10, and 100 ng/side) were evaluated in naturally high social and low social female and male monogamous mandarin voles (Microtus mandarinus) using the social preference paradigm and open-field tests. The results showed that administration of 1 ng/side OT increased social preference; however, this effect was not apparent at lower or higher doses. OT did not alter anxiety-like behavior or total locomotion. Microinfusions of a selective OTR-A at 10 and 100 ng doses reduced social approach behavior; a dose of 1 ng had no effect. In conclusion, our results suggest that accumbal OT and OTR-A regulate social preferences in voles in a dose-dependent manner.