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Abstract Background and aims This study aimed to examine the cumulative effects of body mass index (BMI), body roundness index (BRI), pulse pressure (PP), triglycerides (TG), high-density lipoprotein cholesterol (HDL) and fasting plasma glucose (FPG) on Type 2 diabetes (T2D) morbidity. Methods A total of 78,456 participants aged older than 45 years were extracted from basic public health services in China. During the 2-year follow-up, 6,942 individuals had developed T2D. The binary logistic regression models and multinomial logistic regression models were conducted to investigate the effects of cumulative metabolic parameters on incident T2D, prediabetes regression and progression. Results We found statistically deleterious impacts of exposure to high cumulative BMI, BRI, PP, TG and low cumulative HDL on T2D morbidity and prediabetes progression. Compared to the group with low cumulative of all five parameters, the adjusted ORs for new-onset T2D for participants presenting with 1–2, 3, and 4–5 elevated metabolic parameters were 1.41(1.31,1.52), 1.93(1.74,2.13) and 2.21(1.94,2.51), respectively. There was additive interaction between FPG level and cumulative metabolic parameters with T2D. Compared with participants with the lowest quartile of FPG and low cumulative of all 5 parameters, those with the highest quartile of FPG and high cumulative of 4–5 parameters had a 14.63 [95% CI (12.27, 17.42)] higher risk of incident T2D. Conclusions Participants with more numbers of high-cumulative metabolic parameters were associated with a higher risk of incident T2D and prediabetes progression. A high level of normal FPG could enhance these risks.

Abstract The purpose of this study was to investigate the relationship between circulating cytokines and liver function and prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with radiotherapy combined with tislelizumab and anlotinib. The liver function indexes and pre-treatment levels of cytokines in 47 patients were measured by chemical method and flow cytometry. The median follow-up was 23.1 months. The objective response and the disease control rates were 46.8% and 68.1%, while overall survival (OS) and progression-free survival (PFS) were 12.6 and 11.4 months, respectively. Adverse events (2.1%) were grade 3–4. In addition to stage, intrahepatic metastasis and Child–Pugh score, pre-treatment interleukin-6 (IL-6) was the main cytokine affecting OS and PFS (p

Abstract Background This study aims to investigate the relationship between gestational metabolic syndrome (GMS) and the Chinese Healthy Eating Index (CHEI) in mid-pregnancy, and to identify potentially beneficial or high-risk dietary habits. We have developed a mid-pregnancy version of CHEI-2022, adapting the Chinese Healthy Eating Index to align with the food quantity recommendations outlined in the 2022 Dietary Guidelines for Chinese Residents for mid-pregnancy. Methods Using the inclusion and exclusion criteria, data from 2411 mid-pregnant individuals were collected through interviews. The Total CHEI score and its component scores were determined through analysis of responses from the food frequency questionnaire. GMS diagnosis involved conducting physical examinations and performing blood biochemical tests. A logistic regression model was employed to analyze the relationship between GMS or related indices and both the total CHEI score and its component scores. Results The study identified an overall GMS prevalence of 21.65% (522 out of 2411 participants). During mid-pregnancy, participants diagnosed with GMS exhibited higher BMI, FBG, 1hPBG, 2hPBG, TC, TG, HDL, SBP, as well as higher educational levels and daily activity, compared to those without GMS (P

AIM: To explore the factors influencing individuals' willingness to participate in ophthalmic clinical trials. METHODS: A questionnaire survey was conducted from January to April 2021 among patients and their family members at Zhongshan Ophthalmic Center, Sun Yat-sen University, in Guangzhou, China. The survey gathered data on respondents' willingness, demographic and socioeconomic profiles, as well as their reasons and concerns regarding engagement in clinical trials. RESULTS: Of the 1078 residents surveyed (mean age 31.2±13.1y; 65.8% females) in Guangzhou, 749 (69.5%) expressed a willingness to participate in future ophthalmic clinical trials. Specific characteristics associated with greater willingness included a younger age, lower annual income, higher education, prior participation experience, previous ophthalmic treatment, and a better understanding of clinical trials. With the exception of age, these characteristics were significantly linked to a higher willingness. The primary barrier to participation, expressed by 64.8% of those willing and 54.4% of those unwilling, was “Uncertain efficacy”. In terms of motivations, the willing group ranked “Better therapeutic benefits” (35.0%), “Professional monitoring” (34.3%), and “Trust in healthcare professionals” (33.1%) as their top three reasons, whereas the unwilling participants indicated “Full comprehension of the protocol” (46.2%) as the key facilitator. CONCLUSION: This study reveals a substantial willingness to participate in ophthalmic clinical trials and demonstrates the predictive role of demographic and socioeconomic factors. Variations in motivators and concerns between willing and unwilling participants highlight the significance of tailored recruitment strategies. Importantly, the need for and trust in healthcare professionals stand out as powerful motivations, underscoring the importance of enhancing physician-patient relationships, adopting patient-centered communication approaches, and addressing individualized needs to improve accrual rates.

Abstract The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infected a substantial proportion of Chinese population, and understanding the factors underlying the severity of the disease and fatality is valuable for future prevention and clinical treatment. We recruited 64 patients with invasive ventilation for COVID-19 and performed metatranscriptomic sequencing to profile host transcriptomic profiles, plus viral, bacterial, and fungal content, as well as virulence factors and examined their relationships to 28-day mortality were examined. In addition, the bronchoalveolar lavage fluid (BALF) samples from invasive ventilated hospital/community-acquired pneumonia patients (HAP/CAP) sampled in 2019 were included for comparison. Genomic analysis revealed that all Omicron strains belong to BA.5 and BF.7 sub-lineages, with no difference in 28-day mortality between them. Compared to HAP/CAP cohort, invasive ventilated COVID-19 patients have distinct host transcriptomic and microbial signatures in the lower respiratory tract; and in the COVID-19 non-survivors, we found significantly lower gene expressions in pathways related viral processes and positive regulation of protein localization to plasma membrane, higher abundance of opportunistic pathogens including bacterial Alloprevotella, Caulobacter, Escherichia-Shigella, Ralstonia and fungal Aspergillus sydowii and Penicillium rubens. Correlational analysis further revealed significant associations between host immune responses and microbial compositions, besides synergy within viral, bacterial, and fungal pathogens. Our study presents the relationships of lower respiratory tract microbiome and transcriptome in invasive ventilated COVID-19 patients, providing the basis for future clinical treatment and reduction of fatality.

Abstract The discovery and utilization of natural products derived from endophytic microorganisms have garnered significant attention in pharmaceutical research. While remarkable progress has been made in this field each year, the absence of dedicated open-access databases for endophytic microorganism natural products research is evident. To address the increasing demand for mining and sharing of data resources related to endophytic microorganism natural products, this study introduces EMNPD, a comprehensive endophytic microorganism natural products database comprising manually curated data. Currently, EMNPD offers 6632 natural products from 1017 endophytic microorganisms, targeting 1286 entities (including 94 proteins, 282 cell lines, and 910 species) with 91 diverse bioactivities. It encompasses the physico-chemical properties of natural products, ADMET information, quantitative activity data with their potency, natural products contents with diverse fermentation conditions, systematic taxonomy, and links to various well-established databases. EMNPD aims to function as an open-access knowledge repository for the study of endophytic microorganisms and their natural products, thereby facilitating drug discovery research and exploration of bioactive substances. The database can be accessed at http://emnpd.idrblab.cn/ without the need for registration, enabling researchers to freely download the data. EMNPD is expected to become a valuable resource in the field of endophytic microorganism natural products and contribute to future drug development endeavors.

Abstract Background To investigate the association of variability in metabolic parameters such as total cholesterol concentrations (TC), uric acid (UA), body mass index (BMI), visceral adiposity index (VAI) and systolic blood pressure (SBP) with incident type 2 diabetes (T2D) and whether variability in these metabolic parameters has additive effects on the risk of T2D. Methods Based on the Beijing Functional Community Cohort, 4392 participants who underwent three health examinations (2015, 2016, and 2017) were followed up for incident T2D until the end of 2021. Variability in metabolic parameters from three health examinations were assessed using the coefficient of variation, standard deviation, variability independent of the mean, and average real variability. High variability was defined as the highest quartile of variability index. Participants were grouped according to the number of high-variability metabolic parameters. Cox proportional hazards models were performed to assess the hazard ratio (HR) and 95% confidence interval (CI) for incident T2D. Results During a median follow-up of 3.91 years, 249 cases of incident T2D were identified. High variability in TC, BMI, VAI and SBP was significantly associated with higher risks of incident T2D. As for UA, significant multiplicative interaction was found between variability in UA and variability in other four metabolic parameters for incident T2D. The risk of T2D significantly increased with the increasing numbers of high-variability metabolic parameters. Compared with the group with low variability for 5 parameters, the HR (95% CI) for participants with 1–2, 3, 4–5 high-variability metabolic parameters were 1.488 (1.051, 2.107), 2.036 (1.286, 3.222) and 3.017 (1.549, 5.877), respectively. Similar results were obtained in various sensitivity analyses. Conclusions High variability of TC, BMI, VAI and SBP were independent predictors of incident T2D, respectively. There was a graded association between the number of high-variability metabolic parameters and incident T2D.

Our previous retrospective observational study demonstrated the safety of laparoscopically assisted subtotal colectomy with ileorectal anastomosis and preservation of the superior rectal artery (SRA), without instances of leakage, in patients with slow-transit constipation (STC). Thus, we extended the enrollment period and enlarged the sample size to detect the differences in the postoperative complications and surgical and functional outcomes between patients who underwent laparoscopically assisted subtotal colectomy with and without SRA preservation. We conducted a retrospective single-center analysis of patients with STC who underwent laparoscopically assisted subtotal colectomy between 2016 and 2020. The diagnosis of STC was based on the colonic transit and anal functional tests and barium enema to exclude secondary causes. Patients were divided into group A, which underwent surgery with SRA preservation, and group B, which underwent ligation of the SRA during surgery. Outcome assessments for both groups included the incidence of anastomotic breakdown, intraoperative complications, length of hospital stay, estimated blood loss, time to first flatus, and complications. Propensity score matching allocated 34 patients to groups A and B each. Postoperative bowel function, including time to first flatus, stool, and oral intake, recovered better in group A than in group B. Anastomotic leakage, a significant postoperative complication, was less frequent in patients with SRA preservation. In conclusion, preservation of the SRA in patients undergoing laparoscopically assisted subtotal colectomy with ileorectal anastomosis for STC is associated with favorable postoperative bowel function recovery and lower anastomotic leakage rates.

Abstract Background Type 2 diabetes (T2D) combined with hypertension has a higher risk of developing cardiovascular diseases. This study aimed to investigate the relationships between the surrogate indicators of insulin resistance (TyG, TG/HDL, and Mets-IR) with the risk of T2D combined with hypertension. Methods This study is based on a functional community cohort from Beijing and the China Health and Retirement Longitudinal Study, comprising 4234 and 4658 participants respectively. Cox proportional hazards models and restricted cubic spline regression were performed to assess the link between TyG, TG/HDL, and Mets-IR with T2D combined with hypertension. The cross-lagged panel analysis and the mediation analysis were used to examine the temporal relationship between insulin resistance and obesity and their temporal relationship with follow-up T2D combined with hypertension. Results In multivariable-adjusted models, higher TyG was associated with a higher risk of developing T2D combined with hypertension, the hazard ratios (95% confidence interval) were 3.46 (2.43–4.93) and 2.02 (1.67–2.44), in two cohorts respectively. A similar positive association was shown for Mets-IR, the hazard ratios (95% confidence interval) were 1.04 (1.03–1.06) and 1.05 (1.03–1.07), in two cohorts respectively. However, the association between TG/HDL with T2D combined with hypertension was different in two cohorts. The restricted cubic spline regression showed a linear association between TyG and T2D combined with hypertension (P-nonlinear > 0.05). The cross-lagged path coefficient from baseline BMI to follow-up TyG index was significantly greater than the path coefficient from baseline TyG to follow-up BMI. TyG partially mediated the effect of BMI on the risk of T2D combined with hypertension and the percentage of mediated association was estimated at 41.58% and 48.41% in two cohorts, respectively. Conclusion These findings indicated positive associations between TyG and Mets-IR with the risk of T2D combined with hypertension in two cohorts. In addition, BMI change may precede TyG index change, and the TyG index plays a mediating role in BMI induced T2D combined with hypertension.

ObjectiveThe study aimed to monitor fetuses with tetralogy of Fallot (TOF) after prenatal counseling and how it influenced the decision of parents to terminate the pregnancy.MethodsFetuses with isolated TOF diagnosed between January 2019 and December 2021 were prospectively enrolled. The follow-up period extended until termination or 6 months after the operation.ResultsOf the 1,026 fetuses diagnosed with cardiac defects, 129 were identified to have isolated TOF and completed the follow-up. A total of 55 (42.6%) fetuses were terminated, with larger maternal age (odds ratio: 0.893, 95% confidence interval: 0.806–0.989, P = 0.031) as the protective factor. The maternal anxiety score, gestational weeks, and pulmonary-to-aortic-diameter ratio lost significance in multivariate analysis. Subjectively, the two most common reasons for terminating the pregnancy were worries about the prognosis (41.8%) and concerns about the possible suffering of the unborn child (18.2%). The prenatal diagnosis was accurate in 73 of the 74 (98.6%) live births. Out of the 64 live births that underwent surgical repair in our center, 57 (89.1%) received primary repair, with a median age of 104 days, and 49 (76.6%) underwent valve-sparing repair. No perioperative death occurred.ConclusionsTermination for fetuses with TOF remains common in China. Live births with TOF can be safely and effectively managed.

Abstract Background This study aimed to evaluate the association between homocysteine-related dietary patterns and gestational diabetes mellitus. Methods A total of 488 pregnant women at 24–28 weeks of gestation between January 2019 and December 2020 were included. Demographic characteristics, dietary intake, and multivitamin supplement intake information were collected using a food frequency questionnaire (FFQ); fasting venous blood samples were collected for serum index detection. Serum homocysteine (Hcy), folic acid, and B12 were selected as response variables, and hyperhomocysteinemia (hHcy)-related dietary patterns were extracted using the reduced rank regression.. The relationship between the score of hHcy-related dietary patterns and GDM was analyzed using a multivariate logistic regression model. Results Three hHcy-related dietary patterns were extracted. Only mode 2 had a positive and significant relationship with the risk of developing GDM. After adjusting for confounding factors, the risk of GDM was significantly increased in the highest quartile array compared with the lowest quartile of the pattern (OR = 2.96, 95% Confidence Interval: 0.939–9.356, P = 0.004). There was no significant correlation between dietary pattern 1 and GDM risk (P > 0.05). Conclusions Homocysteine-related dietary patterns were positively associated with gestational diabetes mellitus. Adjusting dietary patterns may contribute to the intervention and prevention of GDM.

Abstract Background The present study compared the effectiveness and toxicity of two treatment modalities, namely radiotherapy combined with nimotuzumab (N) and chemoradiotherapy (CRT) in patients with locally recurrent nasopharyngeal carcinoma (LR-NPC). Methods Patients with LR-NPC who were treated with radiotherapy were retrospectively enrolled from January 2015 to December 2018. The treatment included radiotherapy combined with N or platinum-based induction chemotherapy and/or concurrent chemotherapy. The comparison of survival and toxicity between the two treatment modalities was evaluated using the log-rank and chi-squared tests. Overall survival (OS) was the primary endpoint. Results A total of 87 patients were included, of whom 32 and 55 were divided into the N group and the CRT group, respectively. No significant differences were noted in the survival rate between the N and the CRT groups (4-year OS rates, 37.1% vs. 40.7%, respectively; P = 0.735). Mild to moderate acute complications were common during the radiation period and mainly included mucositis and xerostomia. The majority of the acute toxic reactions were tolerated well. A total of 48 patients (55.2%) demonstrated late radiation injuries of grade ≥ 3, including 12 patients (37.5%) in the N group and 36 patients (66.5%) in the CRT group. The CRT group exhibited significantly higher incidence of severe late radiation injuries compared with that of the N group (P = 0.011). Conclusion Radiotherapy combined with N did not appear to enhance treatment efficacy compared with CRT in patients with LR-NPC. However, radiotherapy combined with N may be superior to CRT due to its lower incidence of acute and late toxicities. Further studies are required to confirm the current findings.

Abstract Background Given the context of rapid technological change and COIVD-19 pandemics, E-learning may provide a unique opportunity for addressing the challenges in traditional face-to-face continuing medical education (CME). However, the effectiveness of E-learning in CME interventions remains unclear. This study aims to evaluate whether E-learning training program can improve TB health personnel’s knowledge and behaviour in China. Methods This study used a convergent mixed method research design to evaluate the impact of E-learning programs for tuberculosis (TB) health workers in terms of knowledge improvement and behaviour change during the China-Gates TB Project (add the time span). Quantitative data was collected by staff surveys (baseline n = 555; final n = 757) and management information systems to measure the demographic characteristics, training participation, and TB knowledge. Difference-in-difference (DID) and multiple linear regression models were employed to capture the effectiveness of knowledge improvement. Qualitative data was collected by interviews (n = 30) and focus group discussions (n = 44) with managers, teachers, and learners to explore their learning experience. Results Synchronous E-learning improved the knowledge of TB clinicians (average treatment effect, ATE: 7.3 scores/100, P = 0.026). Asynchronous E-learning has a significant impact on knowledge among primary care workers (ATE: 10.9/100, P

Abstract Background E-learning is a growing phenomenon which provides a unique opportunity to address the challenges in continuing medical education (CME). The China-Gates Foundation Tuberculosis (TB) Control Program implemented online training for TB health workers in three provinces of China. We aim to evaluate the implementation of E-learning CME programs, analyse the barriers and facilitators during the implementation process, and to provide policy recommendations. Methods Routine monitoring data were collected through the project office from December 2017 to June 2019. In-depth interviews, focus group discussion with project management personnel, teachers, and trainees (n = 78), and staff survey (baseline n = 555, final n = 757) were conducted in selected pilot areas at the provincial, municipal, and county/district levels in the three project provinces (Zhejiang, Jilin, and Ningxia). Descriptive analysis of quantitative data summarized the participation, registration, and certification rates for training activities. Thematic approach was used for qualitative data analysis. Results By the end of June 2019, the national and provincial remote training platforms had organized 98 synchronous learning activities, with an average of 173.2 people [standard deviation (SD) = 49.8] per online training session, 163.3 people (SD = 41.2) per online case discussion. In the pilot area, 64.5% of TB health workforce registered the asynchronous learning platform, and 50.1% obtained their professional certifications. Participants agreed that E-learning CME was more economical, has better content as well as more flexible work schedules. However, the project still faced challenges in terms of unmet learning needs, disorganized governance, insufficient hardware and software, unsupported environment, and lack of incentive mechanisms. Conclusions Our results suggested that it’s feasible to conduct large scale E-learning CME activities in the three project provinces of China. Training content and format are key facilitators of the program implementation, while the matching of training supply and demand, organizational coordination, internet technology, motivations, and sustainability are key barriers.

Abstract Background World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP). Methods AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort. Results By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1–2) and 33.1% as serious (Grade 3–5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75–169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually. Conclusions Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.

Abstract Background Currently, whether and when intraocular pressure (IOP)-lowering medication should be used in glaucoma suspects with high myopia (GSHM) remains unknown. Glaucoma suspects are visual field (VF) defects that cannot be explained by myopic macular changes or other retinal and neurologic conditions. Glaucoma progression is defined by VF deterioration. Here we describe the rationale, design, and methodology of a randomized controlled trial (RCT) designed to evaluate the effects of medically lowering IOP in GSHM (GSHM study). Methods The GSHM study is an open-label, single-center, RCT for GSHM. Overall, 264 newly diagnosed participants, aged 35 to 65 years, will be recruited at the Zhongshan Ophthalmic Center, Sun Yat-sen University, between 2020 and 2021. Participants will be randomly divided into two arms at a 1:1 ratio. Participants in the intervention arm will receive IOP-lowering medication, while participants in the control arm will be followed up without treatment for 36 months or until they reach the end point. Only one eye per participant will be eligible for the study. If both eyes are eligible, the eye with the worse VF will be recruited. The primary outcome is the incidence of glaucoma suspect progression by VF testing over 36 months. The secondary outcomes include the incidence of changes in the optic nerve head morphology including the retinal nerve fiber layer, and retinal ganglion cell-inner plexiform layer loss, progression of myopic maculopathy, visual function loss, and change in the quality of life. Statistical analyses will include baseline characteristics comparison between the intervention and control groups using a two-sample t-test and Wilcoxon rank sum test; generalized linear models with Poisson regression for the primary outcome; Kaplan-Meier curve and log-rank test for the incidence of the secondary outcome; and longitudinal analyses to assess trends in outcomes across time. Discussion To the best of our knowledge, the GSHM study is the first RCT to investigate the impact of medically lowering IOP in GSHM. The results will have implications for the clinical management of GSHM. Trial registration ClinicalTrials.gov NCT04296916 . Registered on 4 March 2020

Abstract Background With the second largest tuberculosis (TB) burden globally, China is committed to actively engage in international TB clinical trials to contribute to global TB research. However, lack of research capacity among local sites has been identified as a barrier. Main text The China Tuberculosis Clinical Trials Consortium (CTCTC) was initiated by Beijing Chest Hospital with investment from the US National Institutes of Health and technical support from Family Health International 360 in 2013, as a nationwide collaborative clinical trial network to strengthen selected clinical site research capacity and attract TB clinical trials. The program aims to: 1) recruit leading hospitals that care for TB patients; 2) conduct on-site assessment to identify capacity gaps and needs for improvement; 3) design and deliver capacity building activities; 4) attract and deliver high quality results for TB clinical trials. A total of 24 sites have joined CTCTC, covering 20 provinces in China. Twenty-two sites have been accredited by the National Medical Products Administration (NMPA) to be qualified to conduct TB clinical trials. The onsite assessment, extensive trainings among the CTCTC sites and young investigators have resulted in better understanding and improvement of the site capacity in conducting TB clinical trials. The establishment and growth of the CTCTC network has benefited from the good leadership, effective international cooperation and local commitment. Issues in human resources, regulatory environment and sustainability have been challenging the network from continuing growth. Clinical researchers have full-time clinical responsibilities in China and it is thus important to build a cadre of other human resources to assist. The regulatory environment is becoming friendlier in China to introduce international clinical trials to the CTCTC network. Conclusions The CTCTC, with mature management structure and sustainable development model, which are distilled five key lessons for other developing countries or investigators of interest. They are the respectively using assessment-based approach to design tailored training package, understanding the availability of clinical researchers, providing solutions to maintain sustainability, understanding local regulatory environments and working with an international organization with local on-site team, respectively. Although, the experiences and capacity of China’s TB hospitals in conducting clinical research vary. Considerable efforts to continue building the capacity are still needed, although the gap is smaller for a few top-tier hospitals.

Air pollutants are common modifiable risk factors for arthritis. To explore the longitudinal effects of air pollution on arthritis based on a cohort study in middle-aged and elder people of China. Data was obtained from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018. A total of 7449 participants aged 45 years and older were involved in our study. The generalized linear mixed models were conducted to examine the separate and joint effects of household air pollution and outdoor air pollution on arthritis, respectively. We found a strong significant association between air pollution and arthritis incidence. Individuals cooking primarily with solid fuel were more likely in higher risk of arthritis compared with cleaner fuel (OR= 1.15; 95% CI: 1.08–1.23). The group-based trajectory model identified four trajectory groups, compared with group “High-Decreasing rapidly”, adjusted ORs of incident arthritis for group “Middle-Decreasing moderately”, “Low-Decreasing slowly” and “Low-Stably” were 1.36 (95% CI, 1.03–1.79), 1.36 (95% CI, 1.01–1.83) and 1.81 (95% CI, 1.30–2.52), respectively. These associations were generally higher in participants younger than 65 years. In addition, solid fuel use and PM2.5 exposure had additive and multiplicative effects on arthritis. The results suggested that solid fuel use and long-term PM2.5 exposure were associated with a higher incidence of arthritis. Therefore, it is necessary to restrict solid fuel use to reduce household air pollution and make stronger environmental protection policies to reduce PM2.5 concentration.

Sonneratia apetala Buch-Ham., an exotic mangrove species with antidiabetic, antibacterial, and antioxidant capacities, mainly distributes in the southeast coastal areas in China. The present work investigated the protective effects of Sonneratia apetala leaves and branches extraction (SAL) on hyperuricemia (HUA) in mice. Potassium oxonate (PO) and hypoxanthine (HX) were used to establish the HUA model by challenge for consecutive 7 days. Results revealed that SAL inhibited the increases in kidney weight and index compared to the vehicle group. Meanwhile, SAL significantly decreased the levels of uric acid (UA), creatinine (CRE), and blood urea nitrogen (BUN) in serum. Additionally, SAL inhibited the activity of xanthine oxidase (XOD) in the liver. SAL ameliorated PO- and HX-induced histopathological changes. Moreover, it regulated oxidative stress markers including malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) activity, and glutathione (GSH) content. Also, SAL inhibited the increases in renal levels of interleukin-6 (IL-6), interleukin-18 (IL-18), interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), monocyte chemotactic protein 1 (MCP-1), and transforming growth factor-β (TGF-β). SAL remarkably reduced suppressor of cytokine signaling 3 (SOCS3), Janus kinase 2 (JAK2), and subsequent phosphorylation of signal transducer and activator of transcription 3 (STAT3) expression. In addition, SAL inhibited the activation of nuclear factor kappa-B (NF-κB) in the kidney. Furthermore, SAL protected against HUA by regulating renal UA transporters of organic anion transporter (OAT1), urate reabsorption transporter 1 (URAT1), and glucose transporter 9 (GLUT9). These findings suggested that SAL ameliorated HUA by inhibiting the production of uric acid and enhancing renal urate excretion, which are related to oxidative stress and inflammation, and the possible molecular mechanisms include its ability to inhibit the JAK/STAT signaling pathway. Thus, SAL might be developed into a promising agent for HUA treatments.

Recent studies on no-reference image quality assessment (NR-IQA) methods usually learn to evaluate the image quality by regressing from human subjective scores of the training samples. This study presented an NR-IQA method based on the basic image visual parameters without using human scored image databases in learning. We demonstrated that these features comprised the most basic characteristics for constructing an image and influencing the visual quality of an image. In this paper, the definitions, computational method, and relationships among these visual metrics were described. We subsequently proposed a no-reference assessment function, which was referred to as a visual parameter measurement index (VPMI), based on the integration of these visual metrics to assess image quality. It is established that the maximum of VPMI corresponds to the best quality of the color image. We verified this method using the popular assessment database—image quality assessment database (LIVE), and the results indicated that the proposed method matched better with the subjective assessment of human vision. Compared with other image quality assessment models, it is highly competitive. VPMI has low computational complexity, which makes it promising to implement in real-time image assessment systems.

ObjectiveHuangqin decoction (HQD), a classical traditional Chinese medicinal formula, has been commonly used to treat gastrointestinal diseases for thousands of years. We investigated the anti-inflammatory effects and underlying mechanisms of HQD on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC).MethodsExperimental mice were given 3% DSS, and HQD (2.275, 4.55, and 9.1 g/kg), or mesalazine (ME, 200 mg/kg) orally for 7 days. Body weight loss, disease activity index (DAI), colon length, histology, and levels of inflammatory cytokines were measured to evaluate the effects of HQD on colitis. The effects of HQD on the Ras-phosphoinositide-3-kinase (PI3K)-Akt-hypoxia inducible factor 1 alpha (HIF-1α) and nuclear factor-kappa B (NF-κB) pathways were evaluated by Western blot analysis. In addition, the gut microbiota was characterized using high-throughput Illumina MiSeq sequencing.ResultsThe results showed that HQD significantly reduced the body weight loss, ameliorated DAI, restored colon length, and improved the intestinal epithelial cell barrier in mice with DSS-induced colitis. The messenger RNA (mRNA) expression levels of inflammatory mediators were decreased following HQD treatment. Furthermore, the Ras-PI3K-Akt-HIF-1α and NF-κB pathways were significantly inhibited by HQD. Finally, treatment with HQD resulted in recovery of gut microbiota diversity.ConclusionsHQD ameliorates DSS-induced colitis through regulation of the gut microbiota, and suppression of Ras-PI3K-Akt-HIF-1α and NF-κB pathways. Our results suggested that HQD may be a potential candidate for treatment of UC.

Plasma cell neoplasms are characterized by dysregulated proliferation of mature B cells, which can present with either single (solitary plasmacytoma) or systemic (multiple myeloma (MM)) involvement. MM with extramedullary plasmacytoma (EMP) is a rare disease that accounts for approximately 3–5% of all plasmacytomas. EMP with gastrointestinal (GI) system involvement is an even rarer entity, accounting for

Abstract Background Ubiquitination is a basic post-translational modification for cellular homeostasis, and members of the conjugating enzyme (E2) family are the key components of the ubiquitin–proteasome system. However, the role of E2 family in colorectal cancer (CRC) is largely unknown. Our study aimed to investigate the role of Ube2v1, one of the ubiquitin-conjugating E2 enzyme variant proteins (Ube2v) but without the conserved cysteine residue required for the catalytic activity of E2s, in CRC. Methods Immunohistochemistry and real-time RT-PCR were used to study the expressions of Ube2v1 at protein and mRNA levels in CRC, respectively. Western blotting and immunofluorescence, transmission electron microscopy, and in vivo rescue experiments were used to study the functional effects of Ube2v1 on autophagy and EMT program. Quantitative mass spectrometry, immunoprecipitation, ubiquitination assay, western blotting, and real-time RT-PCR were used to analyze the effects of Ube2v1 on histone H4 lysine 16 acetylation, interaction with Sirt1, ubiquitination of Sirt1, and autophagy-related gene expression. Results Ube2v1 was elevated in CRC samples, and its increased expression was correlated with poorer survival of CRC patients. Ube2v1 promoted migration and invasion of CRC cells in vitro and tumor growth and metastasis of CRC cells in vivo. Interestingly, Ube2v1suppressed autophagy program and promoted epithelial mesenchymal transition (EMT) and metastasis of CRC cells in an autophagy-dependent pattern in vitro and in vivo. Moreover, both rapamycin and trehalose attenuated the enhanced Ube2v1-mediated lung metastasis by inducing the autophagy pathway in an orthotropic mouse xenograft model of lung metastasis. Mechanistically, Ube2v1 promoted Ubc13-mediated ubiquitination and degradation of Sirt1 and inhibited histone H4 lysine 16 acetylation, and finally epigenetically suppressed autophagy gene expression in CRC. Conclusions Our study functionally links Ube2v1, an E2 member in the ubiquitin–proteasome system, to autophagy program, thereby shedding light on developing Ube2v1 targeted therapy for CRC patients.

Abstract Background Atrial myxoma accounts for approximately 50% of all cardiac tumors. The majority of myxomas are located in the left atrium and present variable clinical manifestation. Case presentation A young man was transferred to our hospital with sudden onset of resting pain, pallor and numb in right leg. An atrial mobile mass was detected by transthoracic echocardiography. Anticoagulant and antithrombotic therapy were administered, a timely surgery was performed and the mass was confirmed as a myxoma. The patient did not discharge any discomfort post-operation. Conclusion For patients with atrial myxoma, early diagnosis is essential, anticoagulant or antithrombotic therapy and surgery have a great importance to prevent further embolism.