ObjectiveTo systematically compare the effects of diverse electromagnetic stimulation protocols on hand function and activities of daily living (ADL) in stroke patients using network meta-analysis (NMA), and screen the optimal stimulation strategy for post-stroke hand dysfunction rehabilitation. MethodsNMA was performed in accordance with the PRISMA-NMA statement. Databases of CNKI, Wanfang data, VIP, CBM, PubMed, Web of Science and Embase were searched from database inception to April, 2026 for eligible randomized controlled trials (RCTs) comparing different electromagnetic stimulation protocols for post-stroke hand impairment. The Cochrane Risk of Bias tool and PEDro scale were used to assess methodological quality of included studies, while the GRADE system was adopted to grade evidence quality of primary outcomes of Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and modified Barthel Index (MBI). After literature screening, data extraction and bias evaluation, RevMan 5.4 and Stata 17.0 were used for meta-analysis and NMA. ResultsA total of 22 RCT involving 17 electromagnetic stimulation protocols were finally included. The PEDro scores ranged from six to ten. The top five protocols for improving FMA-UE score were repetitive peripheral magnetic stimulation (rPMS) + repetitive transcranial magnetic stimulation (rTMS), intermittent theta-burst stimulation (iTBS) + rPMS, iTBS + transcranial direct current stimulation (tDCS), transcutaneous electrical acupoint stimulation (TEAS) and contralaterally controlled functional electrical stimulation (CCFES). tDCS was the most effective on MBI, followed by TEAS and iTBS+rPMS. Evidence quality for FMA-UE and MBI was moderate. Funnel plots suggested low risk of publication bias, and consistency tests verified good coherence between direct and indirect comparisons in network models. ConclusionElectromagnetic stimulation significantly facilitates upper limb and hand functional recovery, and improves ADL in stroke patients. The combined central-peripheral magnetic stimulation protocol may be the most effective on motor rehabilitation, whereas tDCS on ADL.

ObjectiveTo study the regulatory effects of Yinchenhao Tang combined with Yinchen Zhufu Tang on the expression of regulatory T （Treg）/helper T 17 （Th17） cells cultured in vitro from the patients with hepatitis B virus-related acute-on-chronic liver failure （HBV-ACLF）. MethodsFresh peripheral blood was collected from the patients with HBV-ACLF for the separation of peripheral blood mononuclear cells （PBMCs）. Immunomagnetic beads were used to isolate primary Treg and naive CD4⁺ T cells. After in vitro expansion， naive CD4⁺ T cells were induced to differentiate into Th17 cells. Rats were treated with the clearing method （Yinchenhao Tang）， warming method （Yinchen Zhufu Tang）， and combination of clearing method with warming method （Yinchenhao Tang combined with Yinchen Zhufu Tang， also known as Wenyang Jiedu Huayu Prescription）， respectively， and then the medicated plasma samples were collected. Meanwhile， blank plasma was collected from the rats treated with normal saline. Cells were classified into blank， clearing method （5.04 g·kg^-1）， warming method （6.21 g·kg^-1）， and combination of clearing method with warming method （17.1 g·kg^-1） groups and treated with corresponding plasma. The frequency of Treg/Th17 cells was detected by flow cytometry. The level of transforming growth factor-β （TGF-β） was measured by the enzyme-linked immunosorbent assay. The cytometric bead array （CBA） was employed to measure the levels of interleukin-10 （IL-10）， interleukin-17A （IL-17A）， tumor necrosis factor-α （TNF-α）， and interleukin-23 （IL-23）. The mRNA and protein levels of Forkhead box P3 （FoxP3） and retinoic acid-related orphan receptor-gamma t （ROR-γt） were determined by Real-time PCR and Western blot， respectively. ResultsCompared with the blank group， the combination of clearing method with warming method group showed decreased frequency of Treg and Th17 cells， lowered levels of Treg cytokines （TGF-β and IL-10） and Th17 cytokines （TNF-α， IL-17A， and IL-23）， and down-regulated mRNA and protein levels of FoxP3 and ROR-γt （P<0.01）. Compared with the clearing method group， the combination of clearing method with warming method group showed decreased Treg cell frequency and down-regulated mRNA and protein levels of FoxP3. Meanwhile， the combination group showed decreased Th17 cell frequency， lowered levels of TGF-β， IL-10， TNF-α， IL-17A， and IL-23， and down-regulated mRNA and protein levels of ROR-γt （P<0.05， P<0.01）. Compared with the warming method group， the combination of clearing method with warming method group showed decreased frequency of Treg cells and down-regulated mRNA and protein levels of FoxP3. Meanwhile， the combination group showed decreased Th17 cell frequency， declined levels of TGF-β， IL-10， TNF-α， IL-17A， and IL-23， and down-regulated mRNA and protein levels of ROR-γt （P<0.05）. ConclusionThe combination of clearing method with warming method can down-regulate the expression of specific cytokines of Treg and Th17 cells， inhibit the over activation of Treg and Th17 cells， and reduce the secretion of cytokines such as TGF-β， IL-10， TNF-α， IL-17A， and IL-23， thereby alleviating inflammation and improving the prognosis of the patients with liver failure.

ObjectiveTo investigate the differential expression of intestinal flora in patients with different traditional Chinese medicine （TCM） syndrome types （Yang Huang syndrome， Yin-Yang Huang syndrome， and Yin Huang syndrome） of hepatitis B virus-related acute-on-chronic liver failure （HBV-ACLF） and clarify the biological basis of jaundice and Yin Huang syndrome in liver failure. MethodsA total of 20 cases of HBV-ACLF patients were included in the Yang Huang group， 20 cases in the Yin-Yang Huang group， 16 cases in the Yin Huang group， and 20 healthy adult volunteers. 16S rRNA gene sequencing was used to detect the diversity， species distribution， and differences of the subjects' intestinal flora， and bioinformatics analysis was conducted. ResultsCompared with those in the healthy control group， the species richness and diversity of intestinal flora in the HBV-ACLF Yang Huang group， Yin-Yang Huang group， and Yin Huang group were significantly reduced， and there were significant differences in the composition of intestinal flora compared with healthy volunteers. However， there were no significant differences in the species richness， diversity， and composition of intestinal flora among the three groups. LEfSe analysis showed that compared with the healthy control group， the HBV-ACLF Yang Huang group showed significant enrichment of Staphylococcus aureus（P<0.01）. Yin-Yang Huang group showed significant enrichment of s_Ileibacterium valens（P<0.05，P<0.01）， and the Yin Huang group showed significant enrichment of Enterococcus faecium and Streptococcus sali varius（P<0.05）. These strains may be biomarkers between the three groups of patients and the healthy control group. Compared with that in the Yin-Yang Huang group， Tyzzerella_nexilis was significantly enriched in the Yang-Huang group， and Streptococcus lactiae was significantly enriched in the Yin-Yang Huang group. Compared with that in the Yang-Huang group and the Yin-Yang Huang group， Enterococcus faecalis was significantly enriched in the Yin Huang group. The above strains may be biomarkers among the three groups of patients， and Enterococcus faecium may be a biomarker for the transition from the Yang Huang group to the Yin Huang group. ConclusionsThere are significant differences in the intestinal flora between patients with HBV-ACLF Yang Huang syndrome， Yin-Yang Huang syndrome， and Yin Huang syndrome. Enterococcus faecium is significantly enriched in the Yin Huang syndrome group， suggesting that dysbiosis of the intestinal flora may be the biological basis for jaundice and Yin Huang syndrome in liver failure.

ObjectiveTo study the expression differences of regulatory T cells （Treg） and T helper 17 cells （Th17） in the peripheral blood of patients with hepatitis B virus-related acute-on-chronic liver failure （HBV-ACLF） in five types of traditional Chinese medicine （TCM） syndrome. MethodsA total of 144 patients with HBV-ACLF were included and divided into five types of TCM syndrome， including 34 cases of heat-toxin amassment syndrome， 44 cases of dampness-heat amassment syndrome， 27 cases of Qi-deficiency and stasis jaundice syndrome， 21 cases of spleen-kidney Yang deficiency syndrome， and 18 cases of liver-kidney Yin deficiency syndrome. Meanwhile， 30 healthy volunteers were included as controls. The frequency of Treg and Th17 cells in the peripheral blood of subjects in each group was detected by flow cytometry， and the Treg/Th17 ratio was calculated. Cytometric bead array （CBA） was used to detect the levels of cytokines interleukin （IL）-10， transforming growth factor-β （TGF-β）， tumor necrosis factor-α （TNF-α）， IL-17A， and IL-23. Real-time fluorescence quantitative PCR （Real-time PCR） detected the mRNA expression of forkhead box P3 （FoxP3） and retinoic acid-related orphan receptor gamma t （ROR-γt）. Results（1） Compared with that in the healthy control group， the frequency of Treg and Th17 cells in patients with various TCM syndrome types of HBV-ACLF increased （P<0.05）. Compared with that in the heat-toxin amassment syndrome group， the frequency of Treg and Th17 cells decreased in the dampness-heat amassment syndrome group （P<0.05）， while the frequency of Treg and Th17 cells increased in the Qi-deficiency and stasis jaundice syndrome group， spleen-kidney Yang deficiency syndrome group， and liver-kidney Yin deficiency syndrome group （P<0.05）. Compared with that in the dampness-heat amassment syndrome group， the frequency of Treg and Th17 cells increased in the dampness-heat amassment syndrome group， spleen-kidney Yang deficiency syndrome group， and liver-kidney Yin deficiency syndrome group （P<0.05）. Compared with that in the Qi-deficiency and stasis jaundice syndrome group， the frequency of Treg and Th17 cells increased in the spleen-kidney Yang deficiency syndrome group （P<0.05）， while the frequency of Treg and Th17 cells decreased in the liver-kidney Yin deficiency syndrome group （P<0.05）. Compared with the spleen-kidney Yang deficiency syndrome group， the frequency of Treg and Th17 cells decreased in the liver-kidney Yin deficiency syndrome group （P<0.05）. （2） Compared with that in the healthy control group， the Treg/Th17 cell ratio in patients with various TCM syndromes of HBV-ACLF decreased （P<0.05）. Compared with that in the heat-toxin amassment syndrome group， the Treg/Th17 cell ratio increased in the dampness-heat amassment syndrome group （P<0.05）， while it decreased in the Qi-deficiency and stasis jaundice syndrome group， spleen-kidney Yang deficiency syndrome group， and liver-kidney Yin deficiency syndrome group （P<0.05）. Compared with that in the dampness-heat amassment syndrome group， the Treg/Th17 cell ratio decreased in the Qi-deficiency and stasis jaundice syndrome group， spleen-kidney Yang deficiency syndrome group， and liver-kidney Yin deficiency syndrome group （P<0.05）. Compared with that in the Qi-deficiency and stasis jaundice syndrome group， the Treg/Th17 cell ratio increased in the spleen-kidney Yang deficiency syndrome group and liver-kidney Yin deficiency syndrome group （P<0.05）. Compared with the spleen-kidney Yang deficiency syndrome group， the Treg/Th17 cell ratio in the liver-kidney Yin deficiency syndrome group increased （P<0.05）. （3） Compared with those in the healthy control group， the levels of Treg-related cytokines IL-10 and TGF-β， as well as Th17-related cytokines TNF-α， IL-17A， and IL-23， were elevated in patients with various TCM syndrome types of HBV-ACLF （P<0.05）. There was no significant difference in TNF-α levels among different TCM syndrome types. Compared with those in the heat-toxin amassment syndrome group， the levels of IL-10， TNF-β， IL-17A， and IL-23 in the dampness-heat amassment syndrome group， Qi-deficiency and stasis jaundice syndrome group， spleen-kidney Yang deficiency syndrome group， and liver-kidney Yin deficiency syndrome groups increased （P<0.05）. Compared with those in the dampness-heat amassment syndrome group， the levels of IL-10， TGF-β， IL-17A， and IL-23 increased in the Qi-deficiency and stasis jaundice syndrome group， spleen-kidney Yang deficiency syndrome group， and liver-kidney Yin deficiency syndrome group （P<0.05）. Compared with those in the Qi-deficiency and stasis jaundice syndrome group， the levels of IL-10， TGF-β， IL-17A， and IL-23 in the spleen-kidney Yang deficiency syndrome group increased （P<0.05）， while those in the liver-kidney Yin deficiency syndrome group decreased （P<0.05）. Compared with those in the spleen-kidney Yang deficiency syndrome， the levels of IL-10， TGF-β， IL-17A， and IL-23 in the liver-kidney Yin deficiency syndrome group decreased （P<0.05）. （4） Compared with that in the healthy control group， the mRNA of Treg/Th17 cell specific transcription factors FoxP3 and ROR-γt were elevated in patients with various TCM syndrome types of HBV-ACLF （P<0.05）. Compared with that in the heat-toxin amassment syndrome group， the mRNA of FoxP3 and ROR-γt increased in the Qi-deficiency and stasis jaundice syndrome group， spleen-kidney Yang deficiency syndrome group， and liver-kidney Yin deficiency syndrome group （P<0.05）. Compared with that in the dampness-heat amassment syndrome group， the mRNA of FoxP3 and ROR-γt increased in the Qi-deficiency and stasis jaundice syndrome group， spleen-kidney Yang deficiency syndrome group， and liver-kidney Yin deficiency syndrome （P<0.05）. Compared with that in the Qi-deficiency and stasis jaundice syndrome group， the mRNA of FoxP3 and ROR-γt in the spleen-kidney Yang deficiency syndrome group increased （P<0.05）， and it decreased in the liver-kidney Yin deficiency syndrome group （P<0.05）. Compared with that in the spleen-kidney Yang deficiency syndrome group， the mRNA of FoxP3 and ROR-γt decreased in the liver-kidney Yin deficiency syndrome group （P<0.05）. ConclusionThe frequency and ratio of Treg/Th17 cells， as well as the expression of related cytokines and specific receptors in peripheral blood of patients with HBV-ACLF in five types of TCM syndromes are different， which has certain reference value for TCM syndrome differentiation and treatment of patients with HBV-ACLF.

Allergic rhinitis （AR） is one of the most common chronic non-infectious inflammatory diseases in children. Traditional Chinese medicine （TCM） employs a comprehensive therapeutic system integrating treatment by stages and syndrome differentiation and treatment， demonstrating significant advantages in the management of pediatric AR. This article systematically reviews the clinical treatment methods and underlying mechanisms of TCM for pediatric AR in recent years. It is found that internal therapies （such as herbal formulas or Chinese patent medicines like Xiaoqinglong decoction， Yiqi tuomin decoction）， external therapies （including intradermal needles， acupoint application， tuina， and herbal nasal therapy）， as well as combined internal and external approaches （oral herbs combined with acupoint application）， have demonstrated significant effects in alleviating clinical symptoms， improving immune indicators， and reducing recurrence rates in children with AR. The underlying mechanisms are primarily associated with the regulation of signaling pathways such as Toll-like receptor/nuclear factor-kappa B and mitogen-activated protein kinase， thereby modulating immune balance， suppressing inflammatory responses， inhibiting pyroptosis， reducing mucus secretion， and promoting nasal mucosal repair.

Age-related macular degeneration (AMD) is a disease that affects the vision of elderly individuals worldwide. Although current therapeutics have shown effectiveness against AMD, some patients may remain unresponsive and continue to experience disease progression. Therefore, in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment. Recently, studies have suggested that dysfunction of mitochondria can lead to the aggregation of reactive oxygen species (ROS) and activation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) innate immunity pathways, ultimately resulting in sterile inflammation and cell death in various cells, such as cardiomyocytes and macrophages. Therefore, combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management. Notably, emerging evidence indicates that natural products targeting mitochondrial quality control (MQC) and the cGAS/STING innate immunity pathways exhibit promise in treating AMD. Here, we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways, as well as their interconnected mediators, which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses, thereby hoping to offer new insights into therapeutic interventions for AMD treatment.

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

Objective:To explore the longitudinal effect of learning stress on learning burnout in vocational college students, and the mediating role of academic procrastination.Methods:A total of 1 212 vocational college students were selected, and two follow-up surveys were conducted at 12-week intervals in September (T1) and November (T2) of 2024 using the basic situation questionnaire, the burnout inventory-student survey, the learning pressure questionnaire and the brief academic procrastination scale. SPSS 26.0 software was used to compare the demographic characteristics of students' depersonalization using t test and single factor analysis of variance. Bootstrap was used to analyze the relationship among learning stress, academic procrastination and learning burnout. Results:The scores of learning stress at T1 and T2 for vocational college students were 14.47±3.52 and 14.52 ±3.50, the scores of academic procrastination at T1 and T2 were 27.14±9.07 and 27.21±9.04, and the scores of learning burnout T1 and T2 were 39.38±8.76 and 39.69±8.79.The t-test showed that the score of learning burnout at T1 of students aged 18 and below (36.70±8.72) was lower than students aged 18 above (40.15±8.63, t=-5.81, P<0.01). The score of learning burnout for liberal arts students at T1(40.82±8.54) was higher than that of science students (37.68±8.72, t=6.31, P<0.01). Single factor analysis of variance showed that the score of learning burnout for grade 1 students at T1(35.19±8.45) was lower than that of grade 2 students (41.33±7.98) and grade 3 students (38.92±9.88), and learning burnout score of grade 2 students at T1 was higher than that of grades 3 students ( F=61.59, P<0.01). The score of learning burnout for high-achieving students at T1(36.23±8.34) was lower than that of middle-achieving students (39.82±8.52) and low-achieving students (45.42±9.14), and the score of learning burnout for middle-achieving students at T1 were lower than that of low-achieving students ( F=36.53, P<0.01). Bootstrap test showed that academic procrastination T2 played a partial mediating role in the relationship between learning stress T1 and learning burnout T2 (effect size=0.04, 95% CI=0.03-0.07). Academic procrastination T1 played a partial mediating role in the relationship between learning stress T1 and learning burnout T2 (effect size=0.05, 95% CI=0.04-0.07). Conclusion:Learning stress can directly affect learning burnout in vocational college students, and also can indirectly affect learning burnout through the mediating effect of academic procrastination.

Objective:This study constructed a mouse model carrying the human SNCA gene with E46K and A53T double mutations through transgenic technology,providing a suitable experimental animal model for drug screening,safety evaluation,pathogenesis research of Parkinson's disease,and studies on neurodegenerative diseases associated with abnormal α-synuclein aggregation.Methods:Using transgenic techniques,we introduced the human SNCA gene with the E46K and A53T mutations into the C57BL/6J mouse genome.These mutations are associated with familial PD and are known to promote α-Synuclein aggregation and neurotoxicity.The resulting B6-hSNCA E46K/A53T transgenic mice were systematically evaluated through behavioral tests to assess motor dysfunction,immunohistochemistry to characterize α-Synuclein pathology,and Western blotting to quantify molecular changes.Additionally,the therapeutic potential of glial cell line-derived neurotrophic factor(GDNF)delivered via adeno-associated virus(AAV)was assessed.Results:The B6-hSNCA E46KA53T double-mutant mice exhibitα-Synuclein aggregation in brain regions such as the cortex,brainstem,and cerebellum starting from 1-months-old.Phosphorylated α-Synuclein protein at serine 129 is detected in regions including the cortex and hippocampus.By 2-months-old,these mice begin to show significant declines in limb strength and motor coordination,as evidenced by grip strength and rotarod tests,displaying motor impairments reminiscent of Parkinson's disease.From 3-months-old,high-performance liquid chromatography(HPLC)reveals a reduction in dopamine and its metabolites in the striatum.Following treatment with AAV-GDNF injection,the mice demonstrate partial improvement in motor behaviors,as observed in rotarod and grip strength behavioral tests.Conclusion:The B6-hSNCA E46KA53T double-mutant mouse model effectively simulates the onset and progression of Parkinson's disease,demonstrating high clinical relevance.This model not only serves as a valuable tool for investigating the pathogenesis of Parkinson's disease but also provides a critical experimental platform for screening and safety evaluation of drugs targeting abnormal α-Synuclein aggregation.It holds significant potential for advancing the development of early diagnostic methods and targeted therapeutic strategies for Parkinson's disease.

Background and Aims:Microsatellite-stable(MSS)colorectal cancer(CRC)generally exhibits poor responsiveness to immune checkpoint inhibitors(ICIs),and effective immunotherapy strategies remain lacking.Anti-angiogenic agents such as bevacizumab(BEV)can improve the tumor immune microenvironment and act synergistically with ICIs.This multicenter real-world study compared the efficacy of different immunotherapy-based combination regimens in patients with MSS/MSI-L/pMMR advanced CRC,aiming to identify the optimal treatment strategy.Methods:A total of 100 patients with MSS/MSI-L/pMMR advanced CRC who received systemic treatment between November 2019 and February 2025 at four tertiary hospitals in Hunan,China,were retrospectively enrolled.Patients were classified into six treatment groups:chemotherapy alone,chemotherapy+targeted therapy,immunotherapy alone,immunotherapy+chemotherapy,immunotherapy+targeted therapy,and immunotherapy+chemotherapy+targeted therapy.The primary endpoints were overall survival(OS)and progression-free survival(PFS),while secondary endpoints were objective response rate(ORR)and disease control rate(DCR).Additionally,among patients receiving immunotherapy,subgroup analysis was performed according to BEV administration.Results:Among all 100 patients,the immunotherapy+chemotherapy+targeted therapy group achieved the highest ORR(32.0%)and DCR(76.0%)and was the only regimen yielding a complete response(CR).Compared with chemotherapy or immunotherapy alone,the triplet regimen significantly improved OS(P<0.05);although PFS improvement did not reach statistical significance,a clear late-stage separation of survival curves was observed.In the immunotherapy subgroup,BEV-containing regimens achieved markedly better outcomes than non-BEV regimens,with DCR of 75.0%vs.48.8%,median OS of 18.9 vs.11.5 months,and median PFS of 13.8 vs.7.2 months(all P<0.001).Cox regression analysis showed that compared with chemotherapy alone,the triplet regimen significantly reduced the risk of death(HR=0.11)and disease progression(HR=0.25)(both P=0.002).Vascular invasion was identified as an adverse prognostic factor for PFS(HR=3.0,P=0.007).Conclusion:This multicenter real-world study demonstrated that combining immunotherapy with chemotherapy and targeted therapy significantly improves DCR and survival outcomes in patients with MSS/MSI-L/pMMR advanced CRC,with BEV-containing triplet regimens providing the most pronounced benefit.BEV may enhance immune responsiveness by modulating the tumor microenvironment and promoting effector T-cell infiltration,offering a promising therapeutic direction for"immune-cold"CRC.Prospective randomized studies are warranted to further validate its clinical value and define appropriate patient populations.