Rheumatoid arthritis （RA） is a common chronic systemic autoimmune disease with synovitis as the main manifestation， which often causes joint swelling and pain or even deformity. It is considered to be an incurable lifelong disease. Although the current Western medicine treatment can alleviate the progression of the disease， it has the clinical limitations of liver injury， cardiovascular complications， and other adverse reactions， along with easy recurrence. Traditional Chinese medicine （TCM） has a long history and has the advantages of individualized treatment and fewer adverse reactions. It can effectively relieve the symptoms of joint swelling and pain in RA patients and slow down the progression of bone destruction， which has attracted wide concern in the medical community. Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway is an important intracellular pathway involved in cell proliferation， differentiation， apoptosis， immune regulation， and other biological behaviors， and plays an important role in the pathophysiological process of RA. In recent years， many studies have confirmed that TCM monomers and compounds can inhibit inflammation and angiogenesis by regulating the JAK/STAT signaling pathway， induce apoptosis and inhibit proliferation of fibroblast-like synoviocytes （FLS）， regulate immune response， and thus exert an effect in the treatment of RA. However， there is still a lack of comprehensive and systematic induction and overview. Therefore， by searching the relevant literature in China National Knowledge Infrastructure （CNKI） and PubMed databases from 2009 to 2024， this study described the mechanism of the JAK/STAT signaling pathway in the occurrence and development of RA and summarized the research progress of TCM monomers and compounds in regulating the JAK/STAT signaling pathway in RA intervention. The study aims to provide new ideas and strategies for the clinical treatment of RA with TCM and the research and development of new drugs.

Pulmonary rehabilitation (PR) has become an indispensable component of the modern care continuum for lung cancer. Substantial evidence confirms its definitive value in improving perioperative outcomes, mitigating treatment-related side effects, and enhancing quality of life in patients with advanced disease. However, a significant "implementation gap" exists between its proven clinical benefits and widespread application, primarily characterized by the lack of standardized protocols, uncertainty in optimal timing, and low patient adherence. Bridging this gap requires a dual-driven approach: harnessing technological innovations such as telerehabilitation, wearable devices, and artificial intelligence to enhance accessibility and personalization, alongside optimizing care models through multidisciplinary team collaboration. This review systematically analyzes the evidence, implementation barriers, and innovative pathways for PR in lung cancer care, aiming to catalyze its transition from an ancillary option to a core standard of care, and envisions a new paradigm of personalized PR that is patient-centered, data-driven, and technologically integrated.

[摘 要] 目的：探讨异位表达血红蛋白亚基（HBA/HBB）对缺氧条件下嵌合抗原受体T细胞（CAR-T细胞）功能障碍的改善作用及其对肿瘤细胞的杀伤效应。方法：全基因合成技术合成靶向HER2的CAR序列，构建共表达HBA或HBB的CAR慢病毒载体，包装慢病毒后感染人原代T淋巴细胞，制备异位表达HBA/HBB的CAR-T细胞，命名为HBA CAR-T和HBB CAR-T。采用缺氧探针检测小鼠实体瘤缺氧状态。通过流式细胞术检测瘤内CAR-T细胞占比、异位表达血红蛋白亚基的CAR-T细胞阳性率及CAR-T细胞的活性氧、凋亡水平。WB法检测HBA CAR-T和HBB CAR-T内相关血红蛋白亚基表达情况，采用细胞计数板计数检测细胞增殖水平，通过萤光素酶报告基因法检测CAR-T细胞对肿瘤细胞的杀伤能力，qPCR检测CAR-T细胞中缺氧诱导因子-1α（HIF-1α）表达水平，利用MitoXpress Intra试剂盒检测CAR-T细胞内氧气含量。结果：不同细胞构建的实体瘤模型均存在明显缺氧情况，且CAR-T细胞浸润水平与缺氧程度呈显著负相关（P < 0.000 1）。HBA CAR-T与HBB CAR-T构建成功（阳性率 > 60%），相应血红蛋白亚基可稳定表达。缺氧环境下HBA CAR-T和HBB CAR-T的ROS水平、凋亡水平显著下降，增殖、对肿瘤细胞的体外杀伤能力显著强于传统CAR-T细胞（均P < 0.05）。HBA CAR-T与HBB CAR-T内HIF-1α表达降低（均P < 0.001），且缺氧程度显著降低（均P < 0.001）。结论：异位表达血红蛋白亚基可改善缺氧条件下CAR-T细胞功能障碍并增强其对肿瘤细胞的体外杀伤作用。

OBJECTIVE To investigate the effects and potential mechanism of curcumin on neurological injury in neonatal rats with bacterial meningitis based on the signal transducer and activator of transcription 1（ STAT1）/ nucleotide-binding domain leucine- rich repeat and pyrin domain-containing receptor 3 （NLRP3） signaling pathway. METHODS Neonatal rats， with an equal number of males and females， were randomly divided into control group， model group， curcumin low-dose （Cur-L）， medium-dose （Cur- M） and high-dose （Cur-H） groups， and Cur-H+STAT1 transcription enhancer [2-（1，8-naphthyridin-2-yl）phenol] group （Cur-H+2- NP group）， with 15 rats in each group. Except for the control group， rats in other groups were injected with a suspension of group B Streptococcus （1×104 cfu/mL， 10 μL） into the cerebellomedullary cistern to establish a bacterial meningitis model. After successful model establishment， rats in Cur-L， Cur-M and Cur-H groups were intraperitoneally injected with 1.25， 2.5 and 5 mg/kg curcumin， respectively， and those in the Cur-H+2-NP group were intraperitoneally injected with 5 mg/kg curcumin and 0.5 mg/kg 2- NP， once a day， for 3 consecutive weeks. After the last administration， modified Loeffler score was conducted， white blood cells （WBC） count in cerebrospinal fluid as well as the contents of inflammatory factors [tumor necrosis factor-α， interleukin-6 （IL-6）， IL-1β and IL-18]， brain water content and blood-brain barrier permeability were detected； the histopathological changes of hippocampus and cortex tissues were observed. The percentage of apoptosis in hippocampal/cortical tissue cells， the positive expression of ionized calcium-binding adapter molecule-1 （Iba-1）， the co-localization of Iba-1 and NLRP3， as well as the expressions of proteins related to the STAT1/NLRP3 signaling pathway （phosphorylated STAT1， NLRP3， apoptosis-associated speck-like protein containing a CARD， gasdermin D， caspase-1， IL-1β and IL-18） were examined. RESULTS Compared with the control group， the neurons in the hippocampal/cortical tissues of rats in the model group exhibited significant morphological abnormalities， accompanied by neuronal edema and necrosis， as well as infiltration of inflammatory cells. The modified Loeffler score and the number of Nissl bodies were significantly decreased/reduced in the model group， while the WBC count， levels of inflammatory factors， brain water content， blood-brain barrier permeability， HE staining score， number of degenerated neurons， percentage of apoptotic cells， positive expression of Iba-1， percentage of Iba-1 and NLRP3 co-localization- positive cells， and expressions of pathway-related proteins were all significantly rose/increased/upregulated （P＜0.05）. Compared with the model group， the histopathological changes in the hippocampal/cortical tissues of rats in all curcumin dosage groups were alleviated to varying degrees， with significant improvements in all quantitative indicators （P＜0.05）； conversely， 2-NP significantly reversed the ameliorative effects of curcumin on these quantitative indicators （P＜0.05）. CONCLUSIONS Curcumin can alleviate cerebral edema and blood-brain barrier damage， reduce neuroinflammation， inhibit cell apoptosis and pyroptosis， and thereby alleviate neuronal injury in neonatal rats with bacterial meningitis. The underlying mechanism may be related to the inhibition of the STAT1/NLRP3 signaling pathway.

ObjectiveTo investigate the mechanism of action of remifentanil （RMZL） in alleviating lung ischemia-reperfusion injury （LIRI） in rats by inhibiting pyroptosis through modulating hypoxia inducible factor-1α （HIF-1α）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. MethodsRats were stochastically assigned into Control group， LIRI group， RMZL low-dose group， RMZL medium-dose group， RMZL high-dose group， and RMZL high-dose+HIF-1α activator dimethyloxallyl glycine （DMOG） group， with 18 rats in each group. Rats in Control group only had their left pulmonary hilum free and did not undergo ischemia-reperfusion treatment. Except for the Control group， LIRI models were constructed in all other groups. Rats in LIRI group were intraperitoneally injected with an equal amount of physiological saline 15 minutes before constructing LIRI model； rats in Control group were intraperitoneally injected with an equal amount of physiological saline 15 minutes before freeing left pulmonary hilum； rats in other groups were intraperitoneally injected with corresponding dose of drug 15 minutes before constructing LIRI model. The wet/dry weight ratio of lungs was calculated. HE staining was used to study lung tissue pathology. Immunofluorescence staining was used to detect the relative fluorescence intensity of gasdermin D （GSDMD） and NLRP3 double positive cells in lung tissue. ELISA was used to detect interleukin-1β and IL-18 in lung tissue. Western blot was used to detect HIF-1α， NLRP3， cysteine-aspartic protease-1 （Cleaved caspase-1）， and gasdermin D-N （GSDMD-N） proteins in lung tissue. ResultsCompared to the Control group， the LIRI group showed disordered alveolar structure， thickened alveolar septa， and abundant inflammatory cell infiltration in rats. The lung wet/dry weight ratio， relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue， IL-1β， IL-18 levels， and HIF-1α， NLRP3， Cleaved caspase-1， and GSDMD-N proteins increased （P0.05）. For the LIRI group， rats in the RMZL low， medium， and high-dose groups displayed attenuated alveolar septal thickening and reduced inflammatory cell infiltration. The lung wet/dry weight ratio， relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue， IL-1β， IL-18 levels， and HIF-1α， NLRP3， Cleaved caspase-1， and GSDMD-N proteins declined， and the RMZL high-dose group showed the most prominent trend （P0.05）. Compared with the RMZL high-dose group， rats in the RMZL high-dose+DMOG group exhibited thickened alveolar septa and more inflammatory cell infiltration， along with increased lung wet/dry weight ratio， relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue， levels of IL-1β and IL-18， and protein expression of HIF-1α， NLRP3， Cleaved caspase-1， and GSDMD-N （P0.05）. ConclusionRMZL may inhibit pyroptosis in LIRI rats by suppressing HIF-1α/NLRP3 pathway.

Objective Based on data from the Global Burden of Disease Study 2023 (GBD 2023), this study analyzes the trends in disease burden and years lived with disability (YLD) of bladder cancer in China from 1990 to 2023. Methods Epidemiological data on bladder cancer in China were obtained from the GBD 2023 database.The age-standardized prevalence rate (ASPR), YLD and population attributable fraction (PAF) of risk factors were calculated.Temporal trends were evaluated using the estimated annual percentage change (EAPC), and Joinpoint regression was applied to compute the annual percent change (APC) and average annual percent change (AAPC) for trend analysis. Results Between 1990 and 2023, the number of bladder cancer patients requiring rehabilitation services increased from 213 568 cases to 587 191 cases, representing a 175.0% increase.The YLD rose from 22 158 to 56 620, marking a 155.6% growth.The ASPR increased from 22.6/100 000 to 25.7/100 000 (EAPC=0.06), indicating a stable trend.The age-standardized YLD rate (ASYR) remained at 2.5/100 000 (EAPC=-0.32), indicating a downward trend.Notably, gender disparities in disease burden were evident, with male patients and YLD being 4.63 times and 4.25 times higher than their female counterparts, respectively.Risk factor analysis showed that smoking and high fasting plasma glucose were the main risk factors for bladder cancer.The ASYR attributable to high fasting plasma glucose showed an increasing trend in males (EAPC=0.13) but a decreasing trend in females (EAPC=-1.41). Conclusion The demand for rehabilitation and disease burden of bladder cancer in China have significantly increased, with particularly heavy burdens among males and the elderly population.It is urgent to formulate targeted interventions, strengthen tobacco control, occupational protection, and weight management, and establish an integrated rehabilitation service system to address the increasingly severe disease burden caused by bladder cancer.

ObjectiveTo systematically evaluate the rehabilitation effect of blood flow restriction training (BFRT) as an adjunctive rehabilitation intervention on lower-limb motor function, balance ability, walking endurance and activities of daily living in stroke patients. MethodsRandomized controlled trials (RCT) on BFRT combined with rehabilitation training for stroke patients published from database inception to January 31, 2026 were retrieved from CNKI, Wanfang data, PubMed, Embase, Cochrane Library and Web of Science. Two researchers independently conducted literature screening, data extraction and bias risk assessment based on the PICO principle. Meta-analysis, subgroup analysis and sensitivity analysis were performed using RevMan 5.4.1 and Stata 17.0. ResultsA total of 15 RCT were included, involving 712 stroke patients including 354 in the control group and 358 in the experimental group. Compared with rehabilitation training, combination of BFRT significantly improved Fugl-Meyer Assessment-Lower Extremities scores (MD = 1.77, 95%CI 0.02 to 3.52, P = 0.047), Berg Balance Scale scores (MD = 5.39, 95%CI 2.20 to 8.59, P < 0.001) and 6-Minute Walk Test distance (MD = 10.24, 95%CI 7.76 to 12.72, P < 0.001). There was no significant difference in modified Barthel Index scores and Timed Up and Go Test results between two groups (P > 0.05). Subgroup analysis indicated that the intervention protocol with a duration of more than four weeks and BFRT combined with resistance training achieved better rehabilitation effect. ConclusionAs an adjunctive rehabilitation method, BFRT can significantly improve lower-limb motor function, balance and walking endurance of stroke patients, while its effect on activities of daily living and functional mobility remains unclear. The protocol of BFRT combined with resistance training for more than four weeks is preferentially recommended, which is more suitable for chronic stroke patients with stable condition, basic walking ability and no cognitive impairment.

AIM:To investigate the protective effects of soy isoflavones on retinal ganglion cells(RGCs)damage in diabetic rats and related mechanisms.METHODS: Totally 80 male SD rats(80 eyes), aged 4-6 weeks, were randomly divided into four groups(n=20 per group): a control group, a diabetic model group, a low-dose soy isoflavone treatment group, and a high-dose soy isoflavone treatment group. Among them, the control group was fed normal chow, while the diabetic group, soy isoflavone low-dose-treated group, and soy isoflavone high-dose-treated group were fed high-fat chow. After a feeding period of 4 wk, rats in the diabetic group, as well as those in the soy isoflavone low-dose and high-dose treatment groups, were injected intraperitoneally with streptozotocin(STZ)at a dose of 50 mg/kg to establish a diabetic model. Rats in the control group received an equivalent volume of sodium citrate buffer acid. The soy isoflavone low-dose-treated group was administered 360 mg/kg of soy isoflavones daily via gavage, while the soy isoflavone high-dose-treated group received 540 mg/kg of soy isoflavones daily via gavage. Both the control group and the diabetic group were given an equal amount of purified water daily via gavage. Body weight and blood glucose levels were measured at 4 and 8 wk post-gavage treatment. The eyes were extracted and the retinas were dissected at 8 wk following the gavage treatment. The number of RGCs in each group was determined using immunochemical tissue staining and protein blotting techniques, while the superoxide dismutase(SOD)activity and malondialdehyde(MDA)content of the rat retinal tissue were measured through histochemical methods.RESULTS: Compared with diabetic rats, treatment with high-dose soy isoflavones for 8 wk resulted in a reduction of blood glucose to 8.9±1.23 mmol/L, an increase in intraretinal SOD activity to 849.93±63.71 U/mgprot, a decrease in MDA content to 45.77±0.59 nmol/mgprot, and an increase in the number of RGCs to 76±1 cells/mm2, which is comparable to the control group's data(all P<0.05).CONCLUSION: Soy isoflavones can reduce retinal oxidative stress in diabetic rats and protect RGCs.

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

Eightly-four novel thioheterocyclic nucleoside derivatives were designed, synthesized, and evaluated for antitumor activity in vitro and in vivo. Most of the compounds inhibited the growth of HCT116 and HeLa cancer cells in vitro, among them 33a and 36b exhibited potent activity against HCT116 cells (IC₅₀ = 0.27 and 0.49 μmol/L, respectively). Both compounds 33a and 36b inhibited cell metastasis, arrested the cell cycle in the G₂/M phase, and induced apoptosis in vitro. Mechanistic studies revealed that 33a and 36b increased ROS levels, led to DNA damage, ER stress, and mitochondrial dysfunction, and inhibited autophagy in HCT116 cells. Biological information analysis, RNA-sequencing, Gene Set Enrichment Analysis (GSEA), drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and SPR experiments identified that compounds 33a and 36b showed antitumor activity by suppressing the c-MYC pathway. c-MYC silencing assays indicated that c-MYC proteins participated in 33a-mediated anticancer activities in HCT116 cells. More importantly, compound 33a presented favorable pharmacokinetic properties in mice (T _1/2 = 6.8 h) and showed significant antitumor efficacy in vivo without obvious toxicity, showing promising potential for further clinical development.