OBJECTIVE To systematically evaluate the efficacy and safety of tislelizumab in the treatment of advanced non- small cell lung cancer （NSCLC）. METHODS Computerized searches were conducted in PubMed， Embase， the Cochrane Library， CNKI， Wanfang and other Chinese and English databases to collect randomized controlled trials （RCTs） on tislelizumab for advanced NSCLC. The search period was from the establishment of the databases to December 2024. After strictly screening the literature， extracting data and conducting quality evaluations in accordance with the inclusion and exclusion criteria， a meta-analysis was performed using RevMan 5.3 and Stata 16.0 software. RESULTS A total of 18 RCTs involving 2 337 patients were included， with 1 283 in the experimental group and 1 054 in the control group. The meta-analysis results showed that the objective response rate [RR＝1.61， 95%CI （1.48， 1.75）， P＜0.000 01]， disease control rate [RR＝1.21， 95%CI （1.13， 1.29）， P＜0.000 01]， progression free survival [HR＝0.55， 95%CI （0.45， 0.66）， P＜0.000 01]， and overall survival [HR＝0.78， 95%CI（0.62， 0.97）， P＝0.03] were significantly better in the experimental group than in the control group. There was no statistically significant difference in the incidence of adverse reactions between the two groups [RR＝1.00， 95%CI （0.73， 1.37）， P＝1.00]； among the common adverse reactions， only the incidence of liver function impairment was significantly higher in the experimental group than in the control group [RR＝1.30， 95%CI （1.10， 1.54）， P＜0.01]. CONCLUSIONS Tislelizumab in combination with chemotherapy or targeted drugs significantly improves the efficacy in patients with advanced NSCLC without increasing the risk of adverse reactions overall. However， liver function should be closely monitored during treatment.

BACKGROUND: The effects of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment on coronavirus disease 2019 (COVID-19) patients have been preliminarily characterized. However, real-world data on the safety and efficacy of intravenous transfusions of MSCs in hospitalized COVID-19 patients at the convalescent stage remain to be reported. METHODS: This was a single-arm, multicenter, real-word study in which a contemporaneous external control was included as the control group. Besides, severe and critical COVID-19 patients were considered together as the severe group, given the small number of critical patients. For a total of 110 patients, 21 moderate patients and 31 severe patients were enrolled in the MSC treatment group, while 26 moderate patients and 32 severe patients were enrolled in the control group. All patients received standard treatment. The MSC treatment patients additionally received intravenous infusions of MSCs at a dose of 4 × 10 7 cells on days 0, 3, and 6, respectively. The clinical outcomes, including adverse events (AEs), lung lesion proportion on chest computed tomography, pulmonary function, 6-min walking distance (6-MWD), clinical symptoms, and laboratory parameters, were measured on days 28, 90, 180, 270, and 360 during the follow-up visits. RESULTS: In patients with moderate COVID-19, MSC treatment improved pulmonary function parameters, including forced expiratory volume in the first second (FEV1) and maximum forced vital capacity (VCmax) on days 28 (FEV1, 2.75 [2.35, 3.23] vs . 2.11 [1.96, 2.35], P  = 0.008; VCmax, 2.92 [2.55, 3.60] vs . 2.47 [2.18, 2.68], P  = 0.041), 90 (FEV1, 2.93 [2.63, 3.27] vs . 2.38 [2.24, 2.63], P  = 0.017; VCmax, 3.52 [3.02, 3.80] vs . 2.59 [2.45, 3.15], P  = 0.017), and 360 (FEV1, 2.91 [2.75, 3.18] vs . 2.30 [2.16, 2.70], P  = 0.019; VCmax,3.61 [3.35, 3.97] vs . 2.69 [2.56, 3.23], P  = 0.036) compared with the controls. In addition, in severe patients, MSC treatment notably reduced the proportion of ground-glass lesions in the whole lung volume on day 90 ( P  = 0.045) compared with the controls. No difference in the incidence of AEs was observed between the two groups. Similarly, no significant differences were found in the 6-MWD, D-dimer levels, or interleukin-6 concentrations between the MSC and control groups. CONCLUSIONS: Our results demonstrate the safety and potential of MSC treatment for improved lung lesions and pulmonary function in convalescent COVID-19 patients. However, comprehensive and long-term studies are required to confirm the efficacy of MSC treatment. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR2000031430.
Humans ; COVID-19/therapy* ; Female ; Male ; Mesenchymal Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adult ; Umbilical Cord/cytology* ; Mesenchymal Stem Cells/cytology* ; SARS-CoV-2 ; Aged ; Treatment Outcome

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

The research on the cardiovascular toxicity of air pollutants is in urgent need of collaborative innovation across multiple models. This paper systematically reviewed the advantages and limitations of four principal research models of cardiotoxicity, including epidemiological model, mammalian model, zebrafish model, and in vitro model. Epidemiological models have been used to demonstrate a significant correlation between exposure to PM_2.5 and both the incidence and mortality of cardiovascular diseases within populations; however, these models face challenges in establishing causal inferences and interpreting individual mechanisms. Mammalian models have been applied to elucidate the pathogenic mechanisms of PM_2.5 at both the systemic and organ-specific levels, yet they encounter difficulties related to interspecies differences and throughput constraints. Zebrafish models, with their transparent embryos and observable development, offer a distinctive opportunity for high-throughput screening and mechanistic investigation of PM_2.5-induced cardiac developmental toxicity. Nonetheless, their cardiac physiological structure diverges from that of mammals, limiting their capacity to accurately model chronic conditions such as coronary heart disease. In vitro models, particularly human heart organoids and chip technologies, have provided profound insights into the direct toxic mechanisms of PM_2.5, including disruptions in calcium homeostasis, cellular senescence, and electrophysiological irregularities at the cellular and molecular levels. Despite these advancements, the complexity and developmental maturity of these models present challenges to their broader application. This paper proposed that the key to overcoming the bottlenecks of single models lies in the construction of an integrated evaluation system that combines “epidemiological studies, mammalian models, zebrafish models, and in vitro models”. By focusing on three aspects, namely model integration, technological convergence, and policy support, it is intended to collaboratively address issues such as standardization of multi-model data, simulation of complex exposure scenarios and susceptible life stages, and transformation pathways. This will provide innovative methodological support for the analysis of the cardiotoxic mechanisms of air pollutants, the assessment of environmental health impacts, and the formulation of precise prevention and control strategies.

OBJECTIVE To explore the effects of Yueju Pill on depression and gastrointestinal function in depressed co-morbid functional dyspepsia mice.METHODS C57BL/6J mice were randomly divided into control group,model group,Yueju Pill low-dose group,Yueju Pill high-dose group and positive drug group.A co-morbidity model was constructed using chronic unpredictable mild stress(CUMS),and the mice were assessed for depression-like behaviour and neuronal damage by behavioural tests and Nissl staining;gastrointestinal function was assessed by HE staining of gastric and intestinal tissues,gastric emptying rate,and small intestinal propul-sive rate;PACAP,VIP,IL-6,TNF-α,and BDNF expression were detected by ELISA;PAC1-R,Vipr1,and Vipr2 protein expres-sion were detected by protein immunoblotting.RESULTS Mice in the model group showed depression-like behaviour,reduced num-ber of hippocampal nidus,slowed gastrointestinal motility,elevated serum inflammatory factors IL-6 and TNF-α(P＜0.05,P＜0.01),and reduced expression of PACAP,VIP,and BDNF(P＜0.05,P＜0.01),The PAC1-R,VPAC1-R,VPAC2-R expression de-creased in the hippocampus and gastric sinus,duodenal tissue(P＜0.05,P＜0.01).Compared with the model group,the low and high dose groups of Yueju Pill improved the above indexes except for Vipr1 and Vipr2(P＜0.05,P＜0.01).CONCLUSION Yueju Pill can reduce inflammatory factors through PACAP/PAC1-R,increase the level of BDNF,and improve the depression-like behaviour and gastrointestinal dysfunction in CUMS mice.

Objective To investigate the predictive value of combined plasma gluconic acid(GA),fumaric acid(FA),and pseudouridine levels at admission for acute kidney injury(AKI)in elderly patients with acute myocardial infarction(AMI).Methods A total of 78 elderly AMI patients transferred from Emergency Department to Coronary Care Unit in Fuwai Hospital during Decem-ber 2021 and July 2022 were enrolled in this prospective study.They were divided into AKI group(40 cases)and non-AKI group(38 cases)according to whether they developed AKI during hospi-talization.Plasma levels of GA,FA and pseudouridine were quantitatively detected with liquid chromatography-tandem mass spectrometry.ROC curve was plotted to assess the predictive value of these three plasma metabolites for AKI in AMI patients.Multivariate logistic regression analy-sis was applied to analyze the clinical risk factors for AKI.Results There were no statistical differences in the plasma levels of GA,FA and pseudouridine between the AKI group and the non-AKI group(P＞0.05).ROC curve analysis revealed that the plasma levels of the three indicators had no predictive value for the development of AKI in elderly AMI patients(AUC=0.576,95％CI:0.449-0.704,P=0.246;AUC=0.595,95％CI:0.467--0.721,P=0.154;AUC=0.563,95％CI:0.435-0.692,P=0.337).Multivariate logistic regression analysis revealed that left ventricu-lar ejection fraction(LVEF)was an independent predictor for AKI development in elderly AMI patients(OR=0.923,95％CI:0.870-0.978,P=0.007).Conclusion Plasma GA,FA and pseud-ouridine cannot predict the development of AKI in elderly AMI patients,while,LVEF is an inde-pendent predictor for the development.

Objective:To evaluate the effects of different types of psychological interventions on the fear of cancer recurrence through a network Meta-analysis.Methods:Randomized controlled trials on the effects of different types of psychological interventions on the fear of cancer recurrence were retrieved from PubMed, PsycINFO, Web of Science, The Cochrane Library, Embase, EBSCO, China Biomedical Literature Database, CNKI, Wanfang Database and Vip Database. The retrieval period was from the establishment of the database to December, 31 2022. Two researchers conducted literature screening, extraction and quality evaluation, and used Stata14.0 software to conduct network Meta-analysis.Results:A total of 29 pieces of research involving 3 068 cancer patients and 11 psychological intervention measures. The results of network Meta-analysis showed that narrative therapy, PERMA(Positive, Engagement, Relationship, Meaning, Accomplishment) happiness theory model, acceptance and commitment therapy and cognitive behavior therapy had statistically significant differences in the intervention effect on the fear of cancer recurrence compared with conventional nursing ( SMD values were -1.93--0.83, all P<0.05); there was no significant difference among narrative therapy, PERMA happiness model, acceptance and commitment therapy and gratitude-expansion behavior theory (all P>0.05). The results of the cumulative probability map showed the best intervention was narrative therapy. Conclusions:The results of this study suggest that narrative therapy, acceptance and commitment therapy, and cognitive behavior therapy may be effective psychological intervention measures to improve the fear of cancer recurrence. However, more studies are still needed for further verification.

ObjectiveTo evaluate the clinical efficacy and safety of Ganjie Bingmei Tablet （甘桔冰梅片， GBT） in treating acute pharyngitis with wind-heat invading the lung syndrome. MethodsUsing multi-center， rando-mized， double-blind， double-dummy， positive and parallel controlled clinical trial design， 144 acute pharyngitis patients with wind-heat invading the lung syndrome from October 8th， 2022 to March 31st， 2023 were collected and randomly assigned to the treatment group and the control group， with 72 cases in each group. The treatment group was treated by GBT （0.4 g each time， 4 times a day） combined with Ganjie Qingyan Granules （甘桔清咽颗粒， GQG） placebo （10 g each time， 3 times a day）， while the control group was treated by GQG （10 g each time， 3 times a day） combined with GBT placebo （0.4 g each time， 4 times a day）， both for 5 days. The clinical efficacy of the two groups was observed， and the disappearance rate of pharyngalgia and the efficacy regarding TCM syndromes were compared between groups after treatment. The visual analog scale （VAS） score before and after treatment was assessed， and the safety was evaluated. ResultsThe disappearance rate of pharyngalgia in the treatment group was 98.61%（71/72）， significantly higher than 80.56%（58/72） in the control group （P＜0.01）. The VAS scores in both groups significantly decreased after treatment （P＜0.05）， and lower score was found in the treatment group than the control group （P＜0.05）. The total effective rate regarding TCM syndromes was 100% in both groups， but the curative rate was significantly higher in the treatment group（73.61%， 53/72） than the control group （62.50%， 45/72， P＜0.05）. There were no obvious adverse reactions in the both groups. ConclusionGBT is effective and safe in treating acute pharyngitis with wind-heat affecting the lung syndrome.

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.

Objective To investigate the possible mechanism of action of Jinqi Qingshu granules(JQQSG)in the treatment of community-acquired pneumonia(CAP)by network pharmacology and molecular docking technology.Methods The TCMSP database and SwissTargetPrediction database were used to obtain and screen the active ingredients and targets of JQQSG,and GeneCards,OMIM,TTD,and DisGeNET databases were used to search for the predicted targets of CAP,and the two targets were mapped and then imported into STRING database to construct a PPI network to screen the key targets,and then the GO and KEGG pathway enrichment were analyzed by the DAVID database,and molecular docking was carried out by the AutoDock Tools software.Results 209 active ingredients and 1 041 targets of JQQSG were obtained after screening;312 targets were co-activated with CAP,and 64 core targets were obtained after PPI network screening.571 biological processes,68 cellular components,and 199 molecular functions were analyzed by GO enrichment,and 165 KEGG pathways were analyzed by KEGG pathway enrichment,mainly involved in protein action,apoptosis and MAPK signaling pathway.Molecular docking suggests that the core target and the core components all have good binding ability.Conclusion The mechanism of action of JQQSG in the treatment of CAP may be related to its regulation of Akt,MAPK signaling pathway,improvement of oxidative stress,and other pathways to exert anti-inflammatory and antioxidant effects,which could lay the foundation for further in-depth study of its specific mechanism of action.