TSPAN8+ myofibroblastic cancer-associated fibroblasts promote chemoresistance in patients with breast cancer.

Cancer-associated fibroblasts (CAFs) are abundant stromal cells in the tumor microenvironment that promote cancer progression and relapse. However, the heterogeneity and regulatory roles of CAFs underlying chemoresistance remain largely unclear. Here, we performed a single-cell analysis using high-dimensional flow cytometry analysis and identified a distinct senescence-like tetraspanin-8 (TSPAN8)+ myofibroblastic CAF (myCAF) subset, which is correlated with therapeutic resistance and poor survival in multiple cohorts of patients with breast cancer (BC). TSPAN8+ myCAFs potentiate the stemness of the surrounding BC cells through secretion of senescence-associated secretory phenotype (SASP)-related factors IL-6 and IL-8 to counteract chemotherapy. NAD-dependent protein deacetylase sirtuin 6 (SIRT6) reduction was responsible for the senescence-like phenotype and tumor-promoting role of TSPAN8+ myCAFs. Mechanistically, TSPAN8 promoted the phosphorylation of ubiquitin E3 ligase retinoblastoma binding protein 6 (RBBP6) at Ser772 by recruiting MAPK11, thereby inducing SIRT6 protein destruction. In turn, SIRT6 down-regulation up-regulated GLS1 and PYCR1, which caused TSPAN8+ myCAFs to secrete aspartate and proline, and therefore proved a nutritional niche to support BC outgrowth. By demonstrating that TSPAN8+SIRT6low myCAFs were tightly associated with unfavorable disease outcomes, we proposed that the combined regimen of anti-TSPAN8 antibody and SIRT6 activator MDL-800 is a promising approach to overcome chemoresistance. These findings highlight that senescence contributes to CAF heterogeneity and chemoresistance and suggest that targeting TSPAN8+ myCAFs is a promising approach to circumvent chemoresistance.

Elucidating phylogenetic relationships within the genus Curcuma through the comprehensive analysis of the chloroplast genome of Curcuma viridiflora Roxb. 1810 (Zingiberaceae).

Curcuma viridiflora Roxb., a plant species of significant pharmaceutical interest, has been the subject of limited chloroplast genomic research. In this study, we present the sequencing and assembly of the C. viridiflora chloroplast genome, which is characterized by a circular chromosome spanning 162,212 base pairs and a GC content of 36.20%. The genome encodes 87 protein-coding genes (PCGs), 38 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. A phylogenetic analysis was conducted, incorporating eight related species, and based on the complete chloroplast genome and protein-coding DNA sequences of six related taxa within the genus. Outgroup species Zingiber zerumbet and Zingiber officinale were also included in the analysis. The results indicate a close relationship between C. viridiflora and Curcuma phaeocaulis, Curcuma sichuanensis, and Curcuma yunnanensis. This study provides the first chloroplast genome of C. viridiflora, thereby contributing a valuable genomic resource for future research on medicinal plants within the Curcuma genus.

Comparison of effectiveness and safety of lasmiditan and CGRP-antagonists for the acute treatment of migraine in adults: systematic review and network meta-analysis of randomised trials.

OBJECTIVE: To compare the outcomes associated with the use of lasmiditan, rimegepant, ubrogepant, and zavegepant for the acute management of migraine headaches. METHODS: We searched four electronic databases from database inception to August 31, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the acute treatment of migraine. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of evidence using the CINeMA approach. We conducted frequentist network meta-analyses (NMA) to summarise the evidence. Data were analyzed using R-4.3.1. RESULTS: A total of 18 eligible studies including 10 different types of interventions with 22,429 migraine patients were included. NMA results showed that compared to ubrogepant (25 mg and 50 mg) and zavegepant, lasmiditan (100 mg and 200 mg) exhibits an elevated probability of achieving pain relief within a 2-hour interval. Similarly, relative to zavegepant, rimegepant (75 mg) and ubrogepant (50 mg and 100 mg) demonstrate an enhanced likelihood of sustaining pain relief over a 24-hour period. Furthermore, in contrast to ubrogepant (25 mg) and lasmiditan (50 mg), rimegepant (75 mg) presents a heightened probability of achieving freedom from photophobia within 2 h. Regarding safety, lasmiditan carries the highest risk of adverse events, which are associated with an increased incidence of adverse effects, including dizziness, somnolence, asthenia, paresthesia, and fatigue. CONCLUSIONS: In this NMA, a spectrum of evidence ranging from very low to high levels underscores the favorable efficacy and tolerability of rimegepant 75 mg and ubrogepant 100 mg, positioning them as potential candidates for the acute management of migraine. Concurrently, lasmiditan (100 mg and 200 mg) exhibits notable efficacy, albeit accompanied by an increased susceptibility to adverse events. These findings should still be approached with caution, primarily due to the intrinsic limitations associated with indirect comparisons.

Development of new matrix reference materials for quantitative urine analysis in drug tests.

Accurate quantitative analyses require standardized methods to control and improve the analytical process in the laboratory. The availability of urine reference materials (RMs) may offer a feasible option to improve the accuracy of urine analysis and to control matrix effects. This paper presents the complete process of the development of matrix RMs in urine, including sample preparation, homogeneity, and stability studies, as well as uncertainty assessment. A freeze-drying process was developed, and freeze-dried human and pig urine samples were prepared and verified to have comparable homogeneity to liquid samples and higher stability than liquid human, pig, and artificial urine samples at 4℃ or room temperature and under extreme conditions. A total of 21 authentic urine samples from August 2022 were measured with freeze-dried RMs and spiked urine samples, and the reliability of the quantification of the RMs was compared. The freeze-dried human urine matrix RM appeared to be an excellent tool for daily quality control, as it showed high stability and gave the most consistent results with spiked samples.

Fufang Luohanguo Qingfei granules reduces influenza virus susceptibility via MAVS-dependent type I interferon antiviral signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Luohanguo Qingfei granules (LQG) is a Chinese patent medicine, clinically used to treat flu-like symptoms including cough with yellow phlegm, impeded phlegm, dry throat and tongue. However, the protective activity of LQG against influenza infection is indeterminate. AIM OF THE STUDY: This study is to investigate the therapeutic effect of LQG on influenza infection and elucidate its underlying mechanism. MATERIALS AND METHODS: In vivo: A viral susceptible mouse model induced by restraint stress was established to investigate LQG's beneficial effects on influenza susceptibility. MAVS knockout (Mavs-/-) mice were used to verify the potential mechanism of LQG. In vitro: Corticosteroid (CORT)-treated A549 cells were employed to identify the active ingredients in LQG. Mice morbidity and mortality were monitored daily for 21 days. Histopathologic changes and inflammatory cytokines in lung tissues were examined by H&E staining and ELISA. RNA-seq was used to explore the signaling pathway influenced by LQG and further confirmed by qPCR. Immunoblotting and immunohistochemistry (IHC) were used to determine the protein levels. CO-IP and DARTS were applied to detect protein-protein interaction and compound-protein interaction, respectively. RESULTS: LQG effectively attenuated the susceptibility of restrained mice to H1N1 infection. LQG significantly boosted the production of IFN-ß transduced by mitochondrial antiviral-signaling protein (MAVS), while MAVS deficiency abrogated its protective effects on restrained mice infected with H1N1. Moreover, in vitro studies further revealed that mogroside Ⅱ B, amygdalin, and luteolin are potentially active components of LQG. CONCLUSION: These results suggested that LQG inhibited the mitofusin 2 (Mfn2)-mediated ubiquitination of MAVS by impeding the E3 ligase synoviolin 1 (SYVN1) recruitment, thereby enhancing IFN-ß antiviral response. Overall, our work elaborates a potential regimen for influenza treatment through reduction of stress-induced susceptibility.

The incidence and predisposing factors for irritable bowel syndrome following COVID-19: a systematic review and meta-analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal (GI) disorder. Several studies have analyzed the long-term GI symptoms and IBS following coronavirus disease 2019 (COVID-19). The purpose of this study is to evaluate the incidence and predisposing factors for IBS following COVID-19 by a systematic review and meta-analysis. METHODS: Electronic databases were searched to identify relevant studies. Primary outcomes were the pooled incidence rate of IBS following COVID-19 and the pooled relative risk (RR) for IBS in the COVID-19 group compared to the non-COVID-19 group. Secondary outcomes were the pooled RR and the standardized mean difference (SMD) for predisposing factors in the IBS group compared to the non-IBS group. Heterogeneity was evaluated using Cochran's Q test and I2 statistics. RESULTS: Ten studies were included in this study. The pooled incidence rate of IBS in COVID-19 patients was 12%. The pooled incidence rate of IBS-D, IBS-C and IBS-M was 5%, 2% and 1%. The pooled incidence rate of IBS in 6 and 12 months was 10% and 3%. The pooled RR for IBS in COVID-19 patients was 1.23 [95% confidence interval (CI) = 0.50-3.01] compared to non-COVID-19 patients. The pooled RR or SMD for mild, moderate, and severe disease activity, procalcitonin (PCT), depression or anxiety in IBS patients following COVID-19 was 0.94 (95% CI = 0.74-1.21), 1.19 (95% CI = 0.65-2.21), 1.30 (95% CI = 0.63-2.66), 6.73 (95% CI = 6.08-7.38) and 3.21 (95% CI = 1.79-5.75). CONCLUSION: The incidence of IBS following COVID-19 was 12%. But it was not higher than the general population. We also found some predisposing factors for IBS including depression or anxiety, PCT.

Comparative efficacy of exercise modalities on sleep quality in populations with sleep disorders: A systematic review and network meta-analysis.

The effect of various exercise modalities on people with sleep disorders remains unclear. This network meta-analysis aims to explore the effects of various exercise modalities in improving sleep quality in people with sleep disorders. Four electronic databases were searched from inception to April 8, 2023. We conducted pairwise meta-analyses and frequentist network meta-analyses with random effects models. A total of 17 randomized controlled trials enrolled 1090 participants were included. Compared with passive control, with moderate-to-low certainty of evidence, mind-body exercise combined with treatment as usual [standard mean difference (SMD) = -2.26, 95% confidence interval (CI) (-3.29, -1,24)], moderate aerobic exercise combined with light strength exercise [SMD = -1.26, 95% CI (-2.22, -0.31)], mind-body exercise [SMD = -0.81, 95% CI (-1.37, -0.25)] and moderate aerobic exercise [SMD = -0.75, 95% CI (-1.38, -0.13)] were more effect in improving sleep disorders. Various exercise modalities have favorable effects on sleep quality for people with sleep disorders compared with passive control. However, due to the low quality of evidence, well-designed trials should be conducted to elucidate these promising findings in the future.

Efficacy and safety of pharmacological intervention for smoking cessation in smokers with diseases: A systematic review and network meta-analysis.

OBJECTIVE: To investigate the most effective and best-tolerated drugs for treating diseased smokers. METHODS: Eight databases were searched for randomized controlled trials (RCTs) involving different pharmacological interventions for smoking cessation in disease patients (January 2023). Network meta-analysis was performed using STATA 15.1 software. The Cochrane Risk of Bias Tool assessed the risk of bias, and confidence in evidence was assessed using CINeMA. RESULTS: A total of 60 RCTs involving 13,009 patients of 12 disease categories were included. All trials reported 13 interventions, resulting in 78 comparisons. Network meta-analysis showed that varenicline (OR = 2.30, 95% CI (1.77, 3.00)) and bupropion (OR = 1.65, 95% CI (1.29, 2.11)) showed favorable abstinence effects compared to placebo in the cardiovascular disease population. Nicotine replacement therapy (NRT) had better withdrawal advantages than placebo (OR = 11.18, 95% CI (2.25, 55.54)) in the chronic obstructive pulmonary disease (COPD) population. Some combination treatments showed better results than monotherapy, such as bupropion + NRT was superior to bupropion (OR = 8.45, 95% CI (1.84, 38.89)) and NRT (OR = 4.98, 95% CI (1.25, 19.78)) in mental illness population. The final surface under the cumulative ranking curve indicated that bupropion + NRT achieved the best smoking cessation effect. Overall confidence in the evidence was low. In a comparison of drugs, the results showed that bupropion + NRT had the best safety. CONCLUSIONS: Most interventions show the benefit of quitting smoking compared with placebo, including monotherapy and combination therapy. Moreover, varenicline or bupropion combined with NRT is superior to some monotherapies.

The effectiveness of continuing education programmes for health workers in rural and remote areas: a systematic review and meta-analysis.

INTRODUCTION: Health workers in rural and remote areas shoulder heavy responsibilities for rural residents. This systematic review aims to assess the effectiveness of continuing education programs for health workers in rural and remote areas. METHODS: Eight electronic databases were searched on 28 November 2021. Randomized controlled trials (RCTs) and quasi-experimental studies evaluating the effectiveness of continuing education for health workers in rural and remote areas were included. The quality of the studies was assessed using the risk of bias tool provided by Effective Practice and Organization of Care. A meta-analysis was performed for eligible trials, and the other findings were presented as a narrative review because of inconsistent study types and outcomes. RESULTS: A total of 17 studies were included, four of which were RCTs. The results of the meta-analysis showed that compared to no intervention, continuing education programs significantly improved the knowledge awareness rate of participants (odds ratio=4.09, 95% confidence interval 2.51-6.67, p<0.05). Qualitative analysis showed that 12 studies reported on the level of knowledge of participants, with all showing positive changes. Eight studies measured the performance of health workers in rural and remote areas, with 87.50% (n=7) finding improved performance. Two studies reported on the impact of continuing education programs for health workers in rural and remote areas on patient health, with only one showing a positive change. One study from India measured the health of communities, which showed a positive change. CONCLUSION: The results of this study showed that continuing education programs are an effective way to address the lack of knowledge and skills among health workers in rural and remote areas. Few studies have examined the effectiveness of education programs for health workers in rural and remote areas in improving patient health outcomes. It is not yet known whether the delivery of continuing education programs to health workers in rural areas has a positive impact on patient and community health. Future attention should continue to be paid to the impact on these outcomes.

Effectiveness and Safety of Varenicline for Smoking Cessation: An Overview and Meta-analysis.

OBJECTIVE: An overview, meta-analysis, and trial sequential analysis were conducted to evaluate the efficacy and safety of varenicline for smoking cessation. METHODS: Systematic reviews (SRs) and randomized controlled trials evaluating varenicline versus placebo for smoking cessation were included. A forest plot was used to summarize the effect size of the included SRs. Traditional meta-analysis and trial sequential analysis (TSA) were performed using Stata software and TSA 0.9 software, respectively. Finally, the Grades of Recommendation, Assessment, Development, and Evaluation approach was used to assess the quality of evidence for the abstinence effect. RESULTS: A total of 13 SRs and 46 randomized controlled trials were included. Twelve review studies showed that varenicline was superior to placebo for smoking cessation. The meta-analysis results showed that, compared with the placebo, varenicline significantly increased the odds of smoking cessation (odds ratio = 2.54, 95% confidence interval = 2.20-2.94, P < 0.05, moderate quality). Subgroup analysis showed that there were significant differences in smokers with disease and general smokers ( P < 0.05). Differences were also found in the follow-up time at 12, 24, and 52 weeks ( P < 0.05). The common adverse events were nausea, vomit, abnormal dreams, sleep disturbances, headache, depression, irritability, indigestion, and nasopharyngitis ( P < 0.05). The TSA results confirmed the evidence for the effect of varenicline on smoking cessation. CONCLUSIONS: Existing evidence supports the superiority of varenicline over a placebo for smoking cessation. Varenicline had mild to moderate adverse events but was well tolerated. Future trials should investigate varenicline in combination with other smoking cessation approaches and compare it with other interventions.

Efficacy of internet-based cognitive-behavioral therapy for depression in adolescents: A systematic review and meta-analysis.

Objective: Internet-based cognitive behavior therapy (ICBT) may provide an accessible alternative to face-to-face treatment, but the evidence base in adolescents is limited. This systematic review and meta-analysis aims to comprehensively assess the efficacy of ICBT in addressing depression among adolescents. Methods: Four electronic databases were searched on June 8, 2023. Randomized controlled trials (RCTs) evaluating the efficacy of ICBT for depression in adolescents were included. The quality of the studies was assessed using the risk of bias tool recommended by the Cochrane Handbook. Furthermore, the GRADE approach was employed to gauge the certainty of the obtained evidence. Meta-analysis was conducted using RevMan 5.4, and Egger's test was implemented through Stata for assessment of potential publication bias. Results: A total of 18 RCTs involving 1683 patients were included. In comparison to control groups like attention control, waiting list, and treatment as usual, our meta-analysis findings elucidate a significant reduction in depression scores (SMD = -0.42, 95 % CI: [-0.74, -0.11], p < .05) as well as anxiety scores (SMD = -0.34, 95 % CI: [-0.60, -0.08], p < .05) in adolescents following ICBT interventions. Furthermore, the analysis indicated no notable distinctions in patient's quality of life (QoL) scores. (SMD = 0.12, 95 % CI: [-0.10, 0.34], p > .05). Conclusion: Results provide evidence of the efficacy of ICBT to reduce depressive and anxiety symptoms in adolescents. These research findings are of vital significance for the establishment of evidence-based treatment guidelines in the digital era. Trial registration: PROSPERO registration: CRD42021277562.

The cultural policies of schistosomiasis control in China: a historical analysis.

China has a history of using cultural policies to control infectious diseases, including schistosomiasis, which was once hyperendemic in the country. Since the founding of the People's Republic of China, significant achievements have been made in schistosomiasis control, with a decrease in the number of cases and infection rates. This study provides a historical analysis of cultural policies in schistosomiasis control in China. During the Mao era (1949-1976), socialist ideology shaped cultural policies that included mass mobilization campaigns, propaganda, and cultural education to promote health practices, and community participation and empowerment. During the Reform era (1978-2012), there was a shift towards market-oriented policies and individual responsibility, and cultural policies promoted behavioral change, but there were challenges in implementing them in a rapidly changing society. In the "New Era" of socialism (2012-now), cultural policies are focused on promoting comprehensive schistosomiasis control strategies, technological advancements and innovation, and international cooperation. The Chinese experience in schistosomiasis control provides valuable lessons for other countries facing similar challenges and underscores the importance of cultural policies in promoting health and well-being.

Effectiveness of Multicomponent Interventions in Office-Based Workers to Mitigate Occupational Sedentary Behavior: Systematic Review and Meta-Analysis.

BACKGROUND: Sedentary time in workplaces has been linked to increased risks of chronic occupational diseases, obesity, and overall mortality. Currently, there is a burgeoning research interest in the implementation of multicomponent interventions aimed at decreasing sedentary time among office workers, which encompass a comprehensive amalgamation of individual, organizational, and environmental strategies. OBJECTIVE: This meta-analysis aims at evaluating the effectiveness of multicomponent interventions to mitigate occupational sedentary behavior at work compared with no intervention. METHODS: PubMed, Web of Science, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from database inception until March 2023 to obtain randomized controlled trials (RCTs) assessing the efficacy of multicomponent interventions on occupational sedentary behavior among office-based workers. Two reviewers independently extracted the data and assessed the risk of bias by using the Cochrane Collaboration's risk of bias tool. The average intervention effect on sedentary time was calculated using Stata 15.1. Mean differences (MDs) with 95% CIs were used to calculate the continuous variables. Subgroup analyses were performed to determine whether sit-stand workstation, feedback, and prompt elements played an important role in multicomponent interventions. Further, the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system was used to evaluate the certainty of evidence. RESULTS: A total of 11 RCTs involving 1894 patients were included in the analysis. Five studies were rated as low risk of bias, 2 as unclear risk of bias, and 4 as high risk. The meta-analysis results showed that compared with no intervention, multicomponent interventions significantly reduced occupational sitting time (MD=-52.25 min/8-h workday, 95% CI -73.06 to -31.44; P<.001) and occupational prolonged sitting time (MD=-32.63 min/8-h workday, 95% CI -51.93 to -13.33; P=.001) and increased occupational standing time (MD=44.30 min/8-h workday, 95% CI 23.11-65.48; P<.001), whereas no significant differences were found in occupational stepping time (P=.06). The results of subgroup analysis showed that compared with multicomponent interventions without installment of sit-stand workstations, multicomponent interventions with sit-stand workstation installment showed better effects for reducing occupational sitting time (MD=-71.95 min/8-h workday, 95% CI -92.94 to -51.15), increasing occupational standing time (MD=66.56 min/8-h workday, 95% CI 43.45-89.67), and reducing occupational prolonged sitting time (MD=-47.05 min/8-h workday, 95% CI -73.66 to -20.43). The GRADE evidence summary showed that all 4 outcomes were rated as moderate certainty. CONCLUSIONS: Multicomponent interventions, particularly those incorporating sit-stand workstations for all participants, are effective at reducing workplace sedentary time. However, given their cost, further research is needed to understand the effectiveness of low-cost/no-cost multicomponent interventions.

Efficacy and safety of antidepressants for smoking cessation: A systematic review and network meta-analysis.

To evaluate the effectiveness, safety and tolerability of antidepressants in helping smokers quit tobacco dependence, five databases were searched for randomized controlled trials (RCTS ) on different antidepressant interventions involving smoking cessation in populations (September 2022). The STATA 15.1 software was used to perform network meta-analysis. The Cochrane bias risk tool was used to assess the risk of bias, and CINeMA was used to evaluate the evidence credibility for the effect of different interventions on smoking cessation. In all, 107 RCTs involving 42 744 patients were included. Seven studies were rated as having a low risk of bias. All trials reported 18 interventions and 153 pairwise comparisons were generated. The network meta-analysis showed that compared with placebo, varenicline + bupropion (OR = 3.53, 95% CI [2.34, 5.34]), selegiline + nicotine replacement therapy (NRT) (OR = 3.78, 95% CI [1.20, 11.92]), nortriptyline + NRT (OR = 2.33, 95% CI [1.21, 4.47), nortriptyline (OR = 1.58, 95% CI [1.11,2.26]), naltrexone + bupropion (OR = 3.84, 95% CI [1.39, 10.61]), bupropion + NRT (OR = 2.29, 95% CI [1.87, 2.81]) and bupropion (OR = 1.70, 95% CI [1.53, 1.89]) showed benefits with respect to smoking cessation. In addition, bupropion + NRT showed better effects than bupropion (OR = 1.35, 95% CI [1.12, 1.64]) and NRT (OR = 1.38, 95% CI [1.13, 1.69]) alone. The final cumulative ranking curve showed that varenicline + bupropion was the most likely to be the best intervention. There was moderate- to very-low-certainty evidence that most interventions showed benefits for smoking cessation compared with placebo, including monotherapy and combination therapies. Varenicline + bupropion had a higher probability of being the best intervention for smoking cessation.

The effects of active workstations on reducing work-specific sedentary time in office workers: a network meta-analysis of 23 randomized controlled trials.

BACKGROUND: Active workstations have been proposed as a feasible approach for reducing occupational sedentary time. This study used a network meta-analysis (NMA) to assess and compare the overall efficacy of active workstation interventions according to type and concomitant strategy for reducing work-specific sitting time in office workers. METHODS: PubMed, Web of Science, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from database inception until May 2022 to obtain randomized controlled trials (RCTs) assessing the efficacy of active workstations with or without concomitant strategies for reducing occupational sedentary time in office workers. The risk of bias of the RCTs included in this study was assessed according to the Cochrane Handbook. An NMA with STATA 15.1 was used to construct a network diagram, league figures, and the final surface under the cumulative ranking curve (SUCRA) values. The certainty of evidence was assessed using the grading of recommendations, assessment, development, and evaluation (GRADE) approach. RESULTS: A total of 23 eligible studies including eight different types of interventions with 1428 office workers were included. NMA results showed that compared to a typical desk, multicomponent intervention (standardized mean difference (SMD) = - 1.50; 95% confidence interval (CI) - 2.17, - 0.82; SUCRA = 72.4%), sit-stand workstation + promotion (Reminders of rest breaks, posture variation, or incidental office activity) (SMD = - 1.49; 95%CI - 2.42, - 0.55; SUCRA = 71.0%), treadmill workstation + promotion (SMD = - 1.29; 95%CI - 2.51, - 0.07; SUCRA = 61.6%), and sit-stand workstation (SMD = - 1.10, 95%CI - 1.64, - 0.56; SUCRA = 50.2%) were effective in reducing occupational sedentary time for office workers. CONCLUSIONS: Multicomponent intervention, sit-stand workstation + promotion, treadmill workstation + promotion, and sit-stand workstation appear to be effective in reducing work-specific sedentary time for office workers. Furthermore, multicomponent interventions and active workstations + promotion better reduced work-specific sedentary time than active workstation alone. However, the overall certainty of the evidence was low. TRIAL REGISTRATION: Our study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO); registration number: CRD42022344432.

Complete mitochondrial genome and phylogenetic analysis of Sineleotris saccharae (Perciformes, Odontobutiae).

The freshwater sleeper, Sineleotris saccharae Herre, 1940 is a member of the Odontobutiae family, widely distributed in southern China. In the present study, we determined the complete mitochondrial genome of S. saccharae for the first time and analyzed its evolutionary relationship. The complete mitochondrial genome of S. saccharae was 16,487 bp long, and had 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), 2 ribosomal RNA (rRNAs) and a control region (CR). The mitogenome of S. saccharae shared the same gene organization and orientation as other teleosts. According to phylogenetic research, S. saccharae was sister to S. chalmersi with high support value, providing the monophyly of the genus Sineleotris. These results will be helpful for understanding the systematics of the odontobutids.

SMURF1 attenuates endoplasmic reticulum stress by promoting the degradation of KEAP1 to activate NRF2 antioxidant pathway.

Cancer cells consistently utilize the unfolded protein response (UPR) to encounter the abnormal endoplasmic reticulum (ER) stress induced by the accumulation of misfolded proteins. Extreme activation of the UPR could also provoke maladaptive cell death. Previous reports have shown that NRF2 antioxidant signaling is activated by UPR and serves as noncanonical pathway to defense and reduce excessive ROS levels during ER stress. However, the mechanisms of regulating NRF2 signaling upon ER stress in glioblastoma have not been fully elucidated. Here we identify that SMURF1 protects against ER stress and facilitates glioblastoma cell survival by rewiring KEAP1-NRF2 pathway. We show that ER stress induces SMURF1 degradation. Knockdown of SMURF1 upregulates IRE1 and PERK signaling in the UPR pathway and prevents ER-associated protein degradation (ERAD) activity, leading to cell apoptosis. Importantly, SMURF1 overexpression activates NRF2 signaling to reduce ROS levels and alleviate UPR-mediated cell death. Mechanistically, SMURF1 interacts with and ubiquitinates KEAP1 for its degradation (NRF2 negative regulator), resulting in NRF2 nuclear import. Moreover, SMURF1 loss reduces glioblastoma cell proliferation and growth in subcutaneously implanted nude mice xenografts. Taken together, SMURF1 rewires KEAP1-NRF2 pathway to confer resistance to ER stress inducers and protect glioblastoma cell survival. ER stress and SMURF1 modulation may provide promising therapeutic targets for the treatment of glioblastoma.

Preferences for training needs of village doctors in China: a systematic review.

BACKGROUND: Village doctors, as gatekeepers of the health system for rural residents in China, are often confronted with adversity in providing the basic public healthcare services. OBJECTIVE: We sought to summarize the training contents, training method, training location, and training costs most preferred by village doctors in China and hope to provide evidence and support for the government to deliver better training in the future. METHODS: Eight databases were searched to include studies that reported on the training needs of village doctors in China. We undertook a systematic review and a narrative synthesis of data. RESULTS: A total of 38 cross-sectional studies including 35,545 participants were included. In China, village doctors have extensive training needs. "Clinical knowledge and skill" and "diagnosis and treatment of common disease" were the most preferred training content; "continuing medical education" was the most preferred delivery method; above county- and county-level hospitals were the most desirable training locations, and the training costs were expected to be low or even free. CONCLUSION: Village doctors in various regions of China have similar preferences for training. Thus, future training should focus more on the training needs and preferences of village doctors.

Adverse effects associated with acupuncture therapies: An evidence mapping from 535 systematic reviews.

BACKGROUND AND OBJECTIVE: Considering that physicians and patients widely use acupuncture, it is necessary to explore its adverse effects during treatment. Herein, an evidence map was generated based on published studies to identify acupuncture-induced adverse effects and assess their severity, with the overarching goal of providing references for safe and effective implementation. METHODS: A comprehensive literature search was performed in four public databases (PubMed, Embase, Web of science, and the Cochrane Library) to identify relevant studies published up to 15th June 2022. In addition, relevant studies were explored in the Epistemonikos database and reference lists were retrieved as a supplement. A MeaSurement Tool to Assess systematic Reviews, Version 2 (AMSTAR-2) quality assessment tool was applied to determine the methodological quality of included systematic reviews (SRs) and/or meta-analysis (MAs), whereas Microsoft Excel 2019 tool was used for data extraction and coding. Heatmaps were generated to display disease type, countries of origin for the first authors, and the sample sizes of original studies. Moreover, bubble charts comprehensively presented intervention categories, adverse reaction types, and evidence levels. RESULTS: A total of 535 SRs involving 33 adverse reactions were included. Among them, 22 studies were rated as high quality, 28 as moderate, 106 as low, and the rest were of critically-low quality. Numerous adverse effects were described in the studies, including syncope (86 SRs), organ or tissue injury (233 SRs), systemic reactions (113 SRs), infection (19 SRs), and other adverse events (373 SRs). Importantly, these adverse reactions were mainly associated with 19 acupuncture techniques, including electroacupuncture (n = 67), manual acupuncture (n = 47) and acupoint catgut embedding (n = 41). Furthermore, the 535 SRs described 23 diseases, among which symptoms, signs or clinical findings (83 SRs), mental, behavioral or neurodevelopmental disorders (67 SRs), and diseases of the nervous system (66 SRs) had the highest incidence. CONCLUSION: This evidence mapping explores the adverse effects of acupuncture, showing that there are multiple types of adverse reactions to acupuncture, with milder symptoms. The methodological assessment revealed that most of the included studies were of low- or critically low-quality. Therefore, there is a need for future randomized controlled trials and SRs to comprehensively analyze acupuncture-related adverse events in order to provide reliable and credible evidence.

Nontargeted screening based on EI-MS spectra using statistical methods: An investigative study of synthetic indole/indazole cannabinoids.

RATIONALE: Mass spectrometry has evolved into a highly powerful tool for qualitative and quantitative chemical analyses. However, the identification of trace amounts of previously unknown structures in complex chemical matrix environments remains challenging. The rapid emergence of new synthetic cannabinoid substances is a typical example of this. Existing laboratory techniques are mostly based on methods used for lists of known illegal compounds. This situation poses a challenge to traditional data analysis and the risk of missing the compounds. Therefore, we propose to develop and validate a statistical model to classify newly emerging synthetic cannabinoid substances into a structural class or subclass. METHODS: We obtained 70 electrospray ionization spectra of indole/indazole synthetic cannabinoids from both the actual standard analysis and the SWGDRUG mass spectral library (version 3.10). Each sample consisted of 330 m/z variables and corresponding relative intensities. We first cleared the variables with a variance below 0.1. Principal component analysis (PCA) was performed on the variance-filtered data, and the two principal components were retained to generate new data for hierarchical clustering. After hierarchical clustering, we used the receiver operating characteristic method in this cluster. RESULTS: Seventy synthetic indole/indazole cannabinoids were classified into four clusters. The side chain of cluster 1 is mainly fluorobenzyl, cluster 2 is pentyl, cluster 3 includes compounds from several structures, and cluster 4 is mainly fluoropentyl. The most relevant characteristic ions are m/z 109, m/z 252, and m/z 253 for cluster 1; m/z 144 and m/z 214 for cluster 2; and m/z 232 and m/z 233 for cluster 4. CONCLUSIONS: This study provides a more objective and less time-consuming solution for characterizing synthetic cannabinoids. And this work validates the ability of PCA to extract characteristic fragment ions.