Search

Abstract Background Spontaneous pneumothorax associated with tuberculosis due to clinical manifestations, imaging findings and negative pleural biopsy is rare. Case report A 43-year-old young woman went to the hospital several times because of recurrent dyspnea and was diagnosed with a right spontaneous pneumothorax. She underwent multiple closed thoracic drainage procedures, but the pneumothorax was not completely resolved. Pleural biopsy pathology was chronic inflammation; there was no evidence of tuberculosis. A small amount of pneumothorax persisted, intermittent dyspnea became more severe, and pneumothorax increased. Bronchoscopy showed thickening of the left lung lingular segment mucosa, and the bronchial lavage fluid gene X-PERT/rifampicin resistance test was positive. After one month of anti-tuberculosis treatment, the symptoms of short breath were completely relieved, and chest computerized tomography (CT) showed complete resolution of the right pneumothorax. Conclusions When searching for the cause of spontaneous pneumothorax, people should not overlook tuberculosis-related secondary pneumothorax, which should be diagnosed and treated as soon as possible.

Abstract Background Both Response Evaluation Criteria in Solid Tumors (RECIST) and tumor regression grade (TRG) play key roles in evaluating tumor response. We analyzed the consistency of TRG and RECIST 1.1 for gastric cancer (GC) patients and compared their prognostic values. Methods Patients with GC who received preoperative chemotherapy or chemoimmunotherapy and had records of TRG from December 2013 to October 2021 were enrolled retrospectively. TRG 0–1 and 2–3 are considered as corresponding to complete response (CR)/partial response (PR) and stable disease (SD)/progress disease (PD) in RECIST 1.1, respectively. The primary endpoints were disease-free survival (DFS) and overall survival (OS). The consistency of RECIST and TRG was examined by kappa statistics. Survival analysis was performed using the Kaplan Meier method. Result One hundred fifty seven GC patients were enrolled, including 125 with preoperative chemotherapy and 32 with chemoimmunotherapy. Among them, 56 patients had measurable lesions. Only 19.6% (11/56) of the patients had consistent results between RECIST 1.1 and TRG. TRG was correlated with both OS and DFS (P = 0.02 and 0.03, respectively) while response according to RECIST1.1 was not (P = 0.86 and 0.23, respectively). The median DFS had not reached in the TRG 0–1 group and was 16.13 months in TRG 2–3 group. TRG 2–3 was associated with young age and peritoneal or liver metastasis. Besides, preoperative chemoimmunotherapy had a significantly higher pCR rate than chemotherapy alone (34.4% vs 8.0%, P

Abstract A more common and noninvasive predicting biomarker for programmed cell death 1 (PD-1) antibody remains to be explored. We assessed 46 patients with advanced gastric cancer who received PD-1 antibody immunotherapy and 425-genes next-generation sequencing (NGS) testing. Patients who had a > 25% decline in maximal somatic variant allelic frequency (maxVAF) had a longer progression free survival (PFS) and higher response rate than those who did not (7.3 months vs 3.6 months, p = 0.0011; 53.3% vs 13.3%, p = 0.06). The median PFS of patients with undetectable and detectable post-treatment circulating tumor DNA (ctDNA) was 7.4 months vs. 4.9 months (p = 0.025). Mutation status of TGFBR2, RHOA, and PREX2 in baseline ctDNA influenced the PFS of immunotherapy (p

Abstract Background Preclinical studies suggest synergistic effectiveness of ascorbic acid (AA, vitamin C) and cytotoxic agents in gastrointestinal malignancies. This phase 1 study aimed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AA combined with mFOLFOX6 or FOLFIRI regimens in patients with metastatic colorectal cancer (mCRC) or gastric cancer (mGC). Methods In the dose-escalation phase, patients received AA (0.2–1.5 g/kg, 3-h infusion, once daily, days 1–3) with mFOLFOX6 or FOLFIRI in a 14-day cycle until the MTD was reached. In the speed-expansion phase, AA was administered at the MTD or at 1.5 g/kg if the MTD was not reached at a fixed rate of 0.6, 0.8 or 1 g/min. Pharmacokinetics and preliminary efficacy were also assessed. Results Thirty-six patients were enrolled. The MTD was not reached. The RP2D was established as AA at 1.5 g/kg/day, days 1–3, with mFOLFOX6 or FOLFIRI. No dose-limiting toxicity (DLT) was detected during dose escalation. The most common treatment-emergent adverse events (TRAEs) were sensory neuropathy (50%), nausea (38.9%), vomiting (36.1%) and neutropenia (27.8%). Grade 3–4 TRAEs were neutropenia (13.9%), sensory neuropathy (2.8%), vomiting (2.8%), diarrhea (2.8%) and leukopenia (2.8%). AA exposure was dose-proportional. The objective response rate was 58.3%, and the disease control rate was 95.8%. No difference in efficacy was found between mCRC patients with wild-type RAS/BRAF and mutant RAS or BRAF. Conclusions The favorable safety profile and preliminary efficacy of AA plus mFOLFOX6/FOLFIRI support further evaluation of this combination in mCRC or mGC. Trial registration ClinicalTrial.gov Identifier: NCT02969681.

Abstract Background Pathologic response is evaluated according to the extent of tumor regression and is used to estimate the efficacy of preoperative treatment. Several studies have reported the association between the pathologic response and clinical outcomes of colorectal cancer patients with liver metastases who underwent hepatectomy. However, to date, no data from Chinese patients have been reported. In this study, we aimed to evaluate the association between the pathologic response to pre-hepatectomy chemotherapy and prognosis in a cohort of Chinese patients. Patients and methods In this retrospective study, we analyzed the data of 380 liver metastases in 159 patients. The pathologic response was evaluated according to the tumor regression grade (TRG). The prognostic role of pathologic response in recurrence-free survival (RFS) and overall survival (OS) was assessed using Kaplan–Meier curves with the log-rank test and multivariate Cox models. Factors that had potential influence on pathologic response were also analyzed using multivariate logistic regression and Kruskal–Wallis/Mann–Whitney U tests. Results Patients whose tumors achieved pathologic response after preoperative chemotherapy had significant longer RFS and OS than patients whose tumor had no pathologic response to chemotherapy (median RFS: 9.9 vs. 6.5 months, P = 0.009; median OS: 40.7 vs. 28.1 months, P = 0.040). Multivariate logistic regression and Kruskal–Wallis/Mann–Whitney U tests showed that metastases with small diameter, metastases from the left-side primary tumors, and metastases from patients receiving long-duration chemotherapy had higher pathologic response rates than their control metastases (all P

Abstract Background Fluoropyrimidine and oxaliplatin are widely used for patients with colorectal cancer. This phase II study was conducted to evaluate the efficacy and safety of the combination of S-1, oxaliplatin, and leucovorin (SOL) in the treatment of Chinese patients with metastatic colorectal cancer (mCRC). Methods Eligible patients with untreated mCRC from four hospitals in China received intravenous oxaliplatin (85 mg/m2) on day 1, oral S-1 twice daily (80–120 mg per day) on day 1–7, and leucovorin twice daily (50 mg per day) simultaneously with S-1, every 2 weeks. Results and discussion Forty patients were enrolled in our study. In total, 296 cycles of SOL were administered. The overall response rate was 50.0%. At a median follow-up of 27 months, progression-free survival and overall survival were 7.0 months (95% confidence interval [CI] 6.0–10.6 months) and 22.2 months (95% CI 15.1–29.3 months), respectively. The most common grade 3/4 non-hematological adverse events were diarrhea (n = 8, 20.0%), nausea (n = 3, 7.5%), and vomiting (n = 3, 7.5%). The most common grade 3/4 hematological toxicities were thrombocytopenia (n = 3, 7.5%), neutropenia (n = 1, 2.5%), and abnormal alanine transaminase/aspartate transaminase levels (n = 1, 2.5%). There was one treatment-related death. Conclusions The data indicate that the SOL regimen is effective and moderately tolerated in Chinese patients with mCRC. Trial registration: Clinical trial information: ChiCTR-TNRC-100000838

Abstract The impact of maintenance therapy on progression-free survival and overall survival as well as quality of life of Chinese patients with metastatic colorectal cancer has long been under discussion. Recently, some phase III clinical trials have revealed that maintenance therapy can significantly prolong the progression-free survival while maintain an acceptable safety profile. Based on this evidence and common treatment practice in China, we now generated one Expert Consensus on Maintenance Treatment for Metastatic Colorectal Cancer in China to further specify the necessity of maintenance therapy, suitable candidates for such treatment, and appropriate regimens.

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 Objective The aim of this study was to evaluate the outcome and risk factors for chairside CAD/CAM full cusp coverage restorations on endodontically treated posterior teeth after 3 years of follow-up. Methods A total of 245 endodontically treated posterior teeth of 224 patients were included and restored with CAD/CAM full cusp coverage all-ceramic restorations according to a standardized protocol. Patients were recalled after treatments 1 to 3 years and underwent clinical and radiological examinations. At recall, modified FDI criteria were used to determine treatment outcomes by 2 evaluators. Success was determined when FDI scores were 1–2, and failure was indicated when FDI scores were 5. Logistic regression analysis was performed to evaluate potential risk factors. Results A total of 183 patients presented at recall, and the clinical outcomes of 201 teeth were analyzed with a recall rate of 82.0% for teeth and 81.7% for patients after 1–3 years of follow-up.185 of 201 teeth were found to have FDI scores of 1–2, and the success rate was 92%. No teeth were extracted during the follow-up period. Fourteen failed cases with an FDI score of 5 presented restoration dislocation, fracture of restoration or/and tooth. Logistic regression analysis revealed that oral parafunction (OR 2.281, 95% CI 2.2 ~ 47.5, P value 0.01) was a risk factor for success rate. Conclusion Chairside CAD/CAM all-ceramic full cusp coverage restoration was (could be) a promising alternative for restoring endodontically treated posterior teeth.

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

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 Economic evaluation of nonsurgical root canal treatment (NSRCT) and single-tooth implant (STI) provides useful information for medical decision. This retrospective study aimed to evaluate the cost-effectiveness of NSRCT versus single-tooth implant (STI) after 5-year treatment in a university affiliated hospital in Beijing, China. Methods 211 patients who underwent NSRCT and 142 patients who had STI were included and recalled after 5-year treatment. The propensity scores were used to match the cases of two treatment modalities. At recall, outcomes were determined based on clinical and radiographical examinations. For endodontically treated cases, absence or reduction of radiolucency were defined as success. Marginal bone loss (MBL) ≤ 4 mm were determined as success for implant cases. Direct and indirect costs were calculated in China Yuan (CNY). Patients’ willingness to pay (WTP) for each treatment modality was evaluated by questionnaires. A cost-effectiveness analysis was performed from the societal perspective. Results 170 patients with 120 NSRCT teeth and 96 STI were available at recall. Based on propensity score matching, 76 endodontically treated teeth were matched to 76 implants. Absence of the radiolucency was observed in 58 of 76 endodontically treated teeth (76%) and reduction of the radiolucency in 9 of 76 teeth (12%) and altogether the success rate was 88%. 100% implants were detected with marginal bone loss (MBL) ≤ 4 mm. The cost advantage of NSRCT (4,751 CNY) over STI (20,298 CNY) was more pronounced. Incremental cost effectiveness ratio (ICER) was 129,563 CNY (STI-NSRCT) per success rate gained. It exceeded the patients’ willingness to pay value 7,533 CNY. Conclusions Clinical outcomes of NSRCT and STI could be predictable after 5-year treatment. NSRCT may be more cost-effective than STI for managing endodontically diseased teeth.

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.

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.

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 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 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 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.

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.