Background: Multiple myeloma (MM) is incurable in spite of recent treatment improvements, highlighting the development of new therapies. Chimeric antigen receptor (CAR) T-cell therapy has dramatically changed the therapeutic effectiveness in high-risk B-cell malignancies. For relapsed/refractory multiple myeloma (RRMM), preclinical evaluations of CAR-T therapy have shown promising efficacy, thus various active clinical trials are under way. Herein, we conducted this review to summarize efficacy and safety of CAR-T therapy and provide more evidence to guide clinical treatments. Method: We systematically searched literature based on databases (PubMed, EMBASE, Cochrane Central Register of Controlled Trials), and conference abstracts reported from American Society of Hematology (ASH), European Hematology Association (EHA) and American Society of Clinical Oncology (ASCO), in addition to other sources (www.clinicaltrials.gov, article citations). Data assessed efficacy and safety of CAR-T therapy in patients with RRMM were extracted and evaluated, and then systematically analyzed by Comprehensive Meta-analysis 3.0 (CMA 3.0). Results: A total of 23 studies including 350 participants from different countries, diagnosed as RRMM and treated with CAR-T therapy (containing 7 antigens targeted by CARs) were combined. In summary, we discovered the pooled overall response rate (77%), complete response rate (37%) and minimal residual disease (MRD) negativity rate within responders (78%). Furthermore, the pooled relapse rate of responders was 38% and median progression-free survival was 8 months. The pooled survival rate was 87% at last follow-up (median, 12 months). In addition, the pooled grade 3-4 rates of cytokine release syndrome (CRS) and neurologic toxicities (NT) were 14% and 13%, respectively. Conclusion: Our study suggests that CAR-T therapy has demonstrated efficacy and safety in RRMM patients. BCMA-targeted CAR-T and anti-BCMA contained regimen have shown better efficacy.

Background: The trends of obesity-associated metabolic status in Chinese are lacking, especially those from different regions.Objectives: To examine the trends of obesity and metabolic status among Chinese population in 2012–2020.Methods: In a series cross-sectional study, data on 256,782 participants surveyed between 2014 and 2020 in Beijing, northern China, and 697,170 participants surveyed between 2012 and 2020 in Hunan, southern China were analyzed. Anthropometrics, blood pressure measurements, and blood tests were performed according to standard protocols. Trends in obesity and metabolic status were evaluated using the Joinpoint software.Results: Based on age- and sex-standardized values, the mean BMI values in northern and southern participants were 23.94 (95% CI: 23.93, 23.95) and 23.68 (95% CI: 23.67, 23.69) kg/m2, respectively. Between 2014 and 2020, the overall obesity prevalence among northern participants increased from 12.70% (95% CI: 12.17, 13.23%) to 14.33% (95% CI: 13.97, 14.70%) (P = 0.009), mainly derived by the 20–39 and 40–59 age groups. Moreover, the prevalence of metabolically healthy obese significantly increased from 2.07% (95% CI: 1.84, 2.30%) to 4.33% (95% CI: 4.13, 4.53%) in Northerners. Between 2012 and 2020, no significant trend in obesity was found among overall southern participants, but the prevalence of metabolically unhealthy obese significantly increased from 5.36% (95% CI: 5.18, 5.54%) to 7.35% (95% CI: 7.11, 7.58%), mainly derived by the 20–39 and 40–59 age groups.Conclusions: The trends in obesity and metabolic status were different between southern and northern Chinese. A national weight control plan is needed in China, focusing on young and middle-aged population.

AimTo evaluate the efficacy and safety of recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) in lowering major adverse cardiovascular and cerebrovascular events (MACCEs) in Chinese acute ST-segment elevation myocardial infarction (STEMI) patients.Methods and analysisThe study is designed as a multicentre, randomised, controlled non-inferiority phase IV trial with balanced randomisation (1:1) in patients with STEMI. The planned sample size is 6200 participants (or 3100 per arm). Participants with STEMI will be randomised to receive either rhTNK-tPA or alteplase (rt-PA), with stratification by research centre, age and the time from symptom onset to randomisation. All patients will receive concomitant antiplatelet and anticoagulant therapy before fibrinolytic therapy. The participants assigned to the intervention group will receive an intravenous bolus of 16 mg rhTNK-tPA, while those assigned to the control group will receive an intravenous bolus of 8 mg rt-PA followed by 42 mg infusion over 90 mins. Other medications can also be administered at the discretion of the cardiologists in charge. All participants will be followed up for the primary study endpoint, the occurrence of MACCEs within 30 days after fibrinolytic therapy, which is defined as all-cause mortality, non-fatal re-infarction, non-fatal stroke, percutaneous coronary intervention (PCI) due to thrombolysis failure, and PCI due to reocclusion. Both intention-to-treat and per-protocol analyses will be done for the primary analyses.Ethics and disseminationThe study procedures and informed consent form were approved by all participating hospitals. The results will be disseminated in peer review journals and academic conferences. This multicentre randomised controlled trial will provide high-quality data about the efficacy and safety of rhTNK-tPA and, once approved, its easier use should help improve the application of reperfusion therapy and hence the treatment outcomes of STEMI patients.Trial registration number NCT02835534.

TLR4, miR-155, and inflammatory cytokines may be closely related to ACS. LPS can induce TLR4, miR-155 expression and inflammatory response in SAP and CSF patients. AntagomiR-155 can inhibit this inflammatory response.