ObjectiveTo observe the clinical effectiveness and safety of Qingfei Shenshi Decoction （清肺渗湿汤） combined with western medicine for patients with bronchial asthma of heat wheezing syndrome， and to explore its potential mechanism of action. MethodsEighty-six participants with bronchial asthma of heat wheezing syndrome were randomly divided into treatment group and control group， each group with 43 participants. The control group received conventional western medicine， and the treatment group was additionally administered Qingfei Shenshi Decoction orally on the basis of the control group， 1 dose per day. Both groups were treated for 14 days. The primary outcome measure was clinical effectiveness； secondary outcome measures included traditional Chinese medicine （TCM） syndrome score， asthma control test （ACT） score， pulmonary function indices such as forced expiratory volume in 1 second （FEV₁）， forced vital capacity （FVC）， peak expiratory flow （PEF）， serum inflammatory factor levels including interleukin-4 （IL-4）， tumour necrosis factor-α （TNF-α）， and high-sensitivity C-reactive protein （hs-CRP）， and immune function indices including CD3⁺， CD4⁺， CD8⁺， CD4⁺/CD8⁺. All outcome measures were evaluated before and after treatment. Vital signs were monitored， and electrocardiography， blood routine， urine routine， liver function， and renal function tests were performed before and after treatment. Adverse events and reactions during the study were recorded. ResultsA total of 80 patients completed the trial with 40 in each group. The total clinical effective rate of the treatment group was 97.5% （39/40）， which was significantly higher than that of the control group （85.0%， 34/40， P＜0.05）. After treatment， both groups showed decreased TCM syndrome scores， IL-4， TNF-α， hs-CRP， and CD8⁺ levels， as well as increased ACT scores， CD3⁺， CD4⁺， CD4⁺/CD8⁺， FEV₁， FVC， and PEF levels （P＜0.05 or P＜0.01）. Moreover， the improvements in these indices were more significant in the treatment group than in the control group （P＜0.05 or P＜0.01）. No significant abnormalities in safety indicators were observed in either group， and no adverse events or reactions occurred. ConclusionQingfei Shenshi Decoction combined with conventional western medicine for patients with bronchial asthma of heat wheezing syndrome can effectively improve the clinical symptoms， pulmonary function， and clinical effectiveness， with good safety. Its mechanism may be related to reducing inflammatory factor levels and regulating T lymphocyte subsets to improve immune function.

Retinopathy of prematurity(ROP)is a leading cause of childhood blindness, with extremely preterm and very-low-birth-weight infants now constituting the main high-risk group. ROP progresses in two stages: early retinal microvascular degeneration and progressive vascular arrest, followed by abnormal neovascularization in the avascular area. Early oxidative and nitrosative stress—amplified by oxygen fluctuations and immature antioxidant defenses—drives the two-phase pathogenesis via hypoxia-inducible factor/vascular endothelial growth factor(HIF/VEGF), NOX/STAT3, and nuclear factor erythroid 2 related factor 2(Nrf2)-antioxidant response element(ARE)pathways, mediating apoptosis of endothelial cells, damage to barrier and pathological angiogenesis. This review systematically analyzes different oxygen-induced retinopathy(OIR)models, elucidates key signaling pathways including Notch, Wnt in physiological and pathological vascularization, with particular emphasis on the biphasic effects of Nrf2 and the differential roles of NOX signaling between phases. We also discuss the limitations of anti-VEGF therapy and oxygen management principles. Reactive oxygen species(ROS)play context-dependent roles across vaso-obliteration and neovascularization phases. Based on mechanistic insights, we propose future directions including combined/sequential interventions, ferroptosis and lipid peroxidation targeting, nano-delivery systems for enhanced bioavailability, and perinatal safety assessment strategies, aiming to provide translatable mechanistic basis for reducing pathological neovascularization while promoting physiological vascular development.

ObjectiveTo systematically quantify the multidimensional effect of virtual reality-based exergaming (VREG) on health outcomes among individuals with cognitive impairment under the framework of the International Classification of Functioning, Disability and Health (ICF). MethodsMeta-analysis was conducted in accordance with the PRISMA statement. PubMed, Cochrane Library, Embase, Scopus, Web of Science, CNKI, Wanfang Data and VIP were researched for randomized controlled trials (RCTs) investigating VREG for cognitive impairment, with the search deadline set on February 1, 2026. The Cochrane Risk of Bias 2.0 tool was adopted to evaluate the methodological quality of included studies. A three-level meta-analytic model was implemented with R 4.4.2. The GRADE framework was further used to rate the certainty of pooled evidence. ResultsA total of 22 RCTs were included. VREG might improve global cognitive function (SMD = 0.69, 95%CI 0.11 to 1.28, P = 0.022), memory (SMD = 0.47, 95%CI 0.07 to 0.87, P = 0.023), attention (SMD = 0.62, 95%CI 0.23 to 1.01, P = 0.004), executive function (SMD = 0.42, 95%CI 0.09 to 0.75, P = 0.013), balance (SMD = 0.54, 95%CI 0.07 to 1.00, P = 0.027), muscle strength (SMD = 0.63, 95%CI 0.37 to 0.88, P = 0.001), mobility (SMD = 0.29, 95%CI 0.04 to 0.54, P = 0.024) and quality of life (SMD = 0.29, 95%CI 0.03 to 0.56, P = 0.029). No significant effect was observed for depressive symptoms, comprehensive physical fitness and fall risk (all P > 0.05). Subgroup and meta-regression analyses indicated that session duration < 45 minutes produced the largest improvement in attention (SMD = 0.95, 95%CI 0.55 to 1.34, P < 0.001); intervention cycles of twelve to 24 weeks were optimal for mobility (SMD = 0.85, 95%CI 0.44 to 1.25, P < 0.001); age negatively correlated to balance improvement (β = -0.11, 95%CI -0.20 to -0.02, P = 0.020), suggesting less intervention benefits among older participants. ConclusionVREG is an effective non-pharmacological intervention to improve multidimensional physical and mental health in people with cognitive impairment. Protocols featuring short single sessions with long-term duration should be prioritized.

OBJECTIVE:Elevated blood pressure increases the risk of cardiovascular diseases.Isometric exercise training has been shown to significantly reduce resting blood pressure,but the factors influencing its effectiveness remain unclear,and specific application guidelines are yet to be established.This study aims to evaluate the impact of isometric exercise training on resting blood pressure through meta-analysis,explore its moderating factors,and provide evidence-based recommendations based on its dose-response relationship.METHODS:Following the PRISMA guidelines,a systematic search was conducted in PubMed,Embase,Cochrane Library,Scopus,and Web of Science databases using keywords"Isometric exercise training,""Systolic blood pressure,"and"Diastolic blood pressure,"covering literature up to September 2024.Randomized controlled trials involving isometric exercise training and resting blood pressure were included.Three independent researchers performed literature screening and data extraction,assessing bias risk and quality grades using the Risk of Bias 2.0 tool and GRADE framework.Main effect pooling,publication bias assessment,subgroup,and regression analysis were conducted using R software(version 4.3.4).RESULTS:A total of 28 articles(comprising 32 randomized controlled trials)involving 977 participants were included.(1)Meta-analysis results indicated that isometric exercise training significantly reduced resting systolic blood pressure(MD=-8.01,95％CI=-9.22 to-6.80,P＜0.01,I2=18.20％,low evidence grade)and diastolic blood pressure(MD=-3.46,95％CI=-4.64 to-2.28,P＜0.01,I2=0％,moderate evidence grade)compared to no exercise.(2)Subgroup analysis results revealed significant influences of gender,health status,exercise modality,frequency,intensity,duration,sets per session,rest duration,and baseline blood pressure on the main effects for both systolic(P＜0.01)and diastolic blood pressure(P＜0.05).(3)Regression analysis results did not show any significant influencing factors,but body mass index(β=-4.11,P=0.091)showed a significant negative trend on the main effect for systolic blood pressure.(4)No significant publication bias was observed in the meta-analysis results(P＞0.05).CONCLUSION:(1)Isometric exercise training significantly lowers systolic(low evidence grade)and diastolic(moderate evidence grade)blood pressure with clinically meaningful thresholds.(2)Participant characteristics(gender,health status,baseline blood pressure,and body mass index)and isometric exercise training protocols(modality,frequency,intensity,duration,cycle,sets per session,and rest duration)influence its antihypertensive effects.(3)The article recommends the optimal blood pressure management prescription:three sessions per week,with four sets per session,each set lasting 2 minutes with a 2-minute rest,at an intensity of 95％HRpeak using isometric wall squat exercises;the intervention period can be adjusted around a 6-week node.Future high-quality research is urgently needed to further validate and support these conclusions.

OBJECTIVE:Elevated blood pressure increases the risk of cardiovascular diseases.Isometric exercise training has been shown to significantly reduce resting blood pressure,but the factors influencing its effectiveness remain unclear,and specific application guidelines are yet to be established.This study aims to evaluate the impact of isometric exercise training on resting blood pressure through meta-analysis,explore its moderating factors,and provide evidence-based recommendations based on its dose-response relationship.METHODS:Following the PRISMA guidelines,a systematic search was conducted in PubMed,Embase,Cochrane Library,Scopus,and Web of Science databases using keywords"Isometric exercise training,""Systolic blood pressure,"and"Diastolic blood pressure,"covering literature up to September 2024.Randomized controlled trials involving isometric exercise training and resting blood pressure were included.Three independent researchers performed literature screening and data extraction,assessing bias risk and quality grades using the Risk of Bias 2.0 tool and GRADE framework.Main effect pooling,publication bias assessment,subgroup,and regression analysis were conducted using R software(version 4.3.4).RESULTS:A total of 28 articles(comprising 32 randomized controlled trials)involving 977 participants were included.(1)Meta-analysis results indicated that isometric exercise training significantly reduced resting systolic blood pressure(MD=-8.01,95％CI=-9.22 to-6.80,P＜0.01,I2=18.20％,low evidence grade)and diastolic blood pressure(MD=-3.46,95％CI=-4.64 to-2.28,P＜0.01,I2=0％,moderate evidence grade)compared to no exercise.(2)Subgroup analysis results revealed significant influences of gender,health status,exercise modality,frequency,intensity,duration,sets per session,rest duration,and baseline blood pressure on the main effects for both systolic(P＜0.01)and diastolic blood pressure(P＜0.05).(3)Regression analysis results did not show any significant influencing factors,but body mass index(β=-4.11,P=0.091)showed a significant negative trend on the main effect for systolic blood pressure.(4)No significant publication bias was observed in the meta-analysis results(P＞0.05).CONCLUSION:(1)Isometric exercise training significantly lowers systolic(low evidence grade)and diastolic(moderate evidence grade)blood pressure with clinically meaningful thresholds.(2)Participant characteristics(gender,health status,baseline blood pressure,and body mass index)and isometric exercise training protocols(modality,frequency,intensity,duration,cycle,sets per session,and rest duration)influence its antihypertensive effects.(3)The article recommends the optimal blood pressure management prescription:three sessions per week,with four sets per session,each set lasting 2 minutes with a 2-minute rest,at an intensity of 95％HRpeak using isometric wall squat exercises;the intervention period can be adjusted around a 6-week node.Future high-quality research is urgently needed to further validate and support these conclusions.

OBJECTIVE: To investigate the regulatory effects of two traditional mineral medicines (TMMs), Gypsum Fibrosum (Shigao, GF) and Terra Flava Usta (Zaoxintu, TFU), on gut-beneficial bacteria in mice, and preliminarily explore their mechanisms of action. METHODS: Mice were randomly divided into 3 groups (n=10 per group): the control group (standard diet), the GF group (diet supplemented with 2% GF), and the TFU group (diet supplemented with 2% TFU). After 4-week intervention, 16S rRNA gene sequencing was used to analyze the changes in the gut microbiota (GM). Scanning electron microscopy, in combination with coumarin A tetramethyl rhodamine conjugate and Hoechst stainings, was used to observe the bacteria and biofilm formation. RESULTS: Principal coordinate analysis revealed that GF and TFU significantly altered the GM composition in mice. Further analysis revealed that GF and TFU affected different types of gut bacteria, suggesting that different TMMs may selectively modulate specific bacterial populations. For certain bacteria, such as Faecalibaculum and Ileibacterium, both GF and TFU exhibited growth-promoting effects, implying that they may be sensitive to TMMs and that different TMMs can increase their abundance through their respective mechanisms. Notably, Lactobacillus reuteri, a widely recognized and used probiotic, was significantly enriched in the GF group. Random forest analysis identified Ileibacterium valens as a potential indicator bacterium for TMMs' impact on GM. Further mechanistic studies showed that gut bacteria formed biofilm structures on the TFU surface. CONCLUSIONS This study provides new insights into the interaction between TMMs and GM. As safe and effective natural clays, GF and TFU hold promise as potential candidates for prebiotic development.
Animals ; Gastrointestinal Microbiome/drug effects* ; Bacteria/growth & development* ; Mice ; Biofilms/drug effects* ; Male ; RNA, Ribosomal, 16S/genetics*

ObjectiveTo investigate the potential mechanisms of Zingiberis Rhizoma in treating inflammatory bowel disease （IBD） by integrating network pharmacology with in vitro and in vivo experiments. MethodsTraditional Chinese Medicine Systems Pharmacology Database And Analysis Platform （TCMSP）， Traditional Chinese Medicine Integrated Database （TCMID） Database were used to obtain the active component targets of Zingiberis Rhizoma. GeneCards was used to obtain the IBD targets. DAVID was used to perform Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses on core targets. Cytoscape 3.10.2 was used to establish the "active component-disease target-signaling pathway" interaction network. Mice were randomly assigned to control， model， and Zingiberis Rhizoma （400 mg·kg^-1） groups. An IBD model was induced via dextran sulfate sodium （DSS）. The colonic tissue was collected post-treatment to assess histology， expression of Ly6C⁺ monocytes/macrophages， and mRNA levels of Toll-like receptor 4 （TLR4）， and inflammatory cytokines. The effect of Zingiberis Rhizoma aqueous extract on RAW264.7 cell viability was evaluated. Furthermore， the effects of the extract at 100， 10， and 1 mg·L^-1 on LPS-induced differentiation of RAW264.7 cells into Ly6C^hi monocytes/macrophages， mRNA levels of TLR4 and inflammatory cytokines， and protein levels of factors in the TLR4/mitogen-activated protein kinase （MAPK） signaling pathway. ResultsA total of 241 targets were identified for Zingiberis Rhizoma and 6 787 for IBD， with 122 shared targets among Zingiberis Rhizoma， ulcerative colitis （UC）， and Crohn's disease （CD）. The enrichment analyses yielded 297 GO terms and 88 KEGG pathways. Associations were noted between Zingiberis Rhizoma's active component targets and IBD targets. In vivo experiments： Compared with the control group， the model group showed decreased body weight and disease activity index （DAI）（P<0.01）， shortened colon length， damaged mucosal epithelium with inflammatory cell infiltration， raised pathological scores （P<0.05）， increased Ly6C^hi and Ly6C^lo monocytes/macrophages （P<0.05）， and up-regulated mRNA levels of TLR4， TNF-α， IL-1β， and IL-6 （P<0.05） and protein levels of TLR4， phosphorylated extracellular signal-regulated protein kinase 1/2 （p-ERK1/2）， and phosphorylated p38 MAPK （p-p38 MAPK） （P<0.05）. Zingiberis Rhizoma intervention reversed these changes and reduced Ly6C^hi monocytes/macrophages （P<0.01）. In vitro experiments： compared with the control， LPS increased the proportion and number of Ly6C^hi monocytes/macrophages and mRNA levels of TLR4， TNF-α， IL-1β， and IL-6 （P<0.01） and enhanced the expression of TLR4， p-ERK1/2， and p-p38 MAPK （P<0.05）. Zingiberis Rhizoma reduced Ly6C^hi monocytes/macrophages （P<0.05）， down-regulated the mRNA levels of inflammatory cytokines （P<0.05）， and suppressed the TLR4/MAPK pathway （P<0.05）. ConclusionZingiberis Rhizoma alleviates IBD by suppressing the TLR4/ERK/p38 MAPK signaling pathway and reducing inflammatory cytokine levels in Ly6C^hi monocytes/macrophages.

ObjectiveTo clarify the repair effect of Mume Fructus on the intestinal mucosal epithelial barrier in the mouse model of inflammatory bowel disease （IBD） and explore the repair mechanism. MethodsThirty-six male C57BL/6 mice were randomly assigned into six groups： normal， model， low-， medium-， and high-dose （200， 400， and 800 mg·kg^-1） Mume Fructus， and sulfasalazine （300 mg·kg^-1）. Except the normal group， the rest groups had free access to 2% dextran sulfate sodium （DSS） solution for seven days to establish the IBD model， followed by a seven-day drug intervention. The body weight change and disease activity index （DAI） were recorded. After the last administration， spleen and colon tissue samples were collected to analyze the differences in colon length and spleen index. Hematoxylin-eosin staining was used to observe the morphology of the colon tissue. The level of diamine oxidase （DAO） in the serum was measured by the DAO assay kit. Immunohistochemistry was employed to determine the expression of tight junction proteins such as Claudin-1， Occludin， and zonula occludens-1 （ZO-1） in the colon tissue. Real-time PCR was performed to measure the mRNA levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in the colon tissue. Finally， Western blot was employed to determine the protein levels of mitogen-activated protein kinase kinase （MEK）， extracellular signal-regulated kinase （ERK）， phosphorylated （p）-MEK， and phosphorylated ERK in the colon tissue. ResultsCompared with the normal group， the model group exhibited decreases in body weight and colon length （P<0.01）， increases in DAI， spleen index， and serum DAO level （P<0.01）， damaged colonic epithelium and goblet cells， and obvious infiltration of inflammatory cells. In addition， the model group exhibited higher positive expression of Claudin-1， Occludin， and ZO-1 （P<0.01）， higher mRNA levels of TNF-α and IL-1β （P<0.01）， and higher protein levels of p-MEK and p-ERK （P<0.05， P<0.01） than the normal group. However， sulfasalazine and three doses of Mume Fructus markedly decreased the body weight and DAI （P<0.05）， recovered the colon length and spleen index， alleviated colon tissue damage， lowered the level of DAO in the serum （P<0.01）， and down-regulated the mRNA levels of TNF-α and IL-1β （P<0.01） and the protein levels of p-MEK and p-ERK （P<0.05）. Sulfasalazine and low- and medium-dose Mume Fructus increased the positive expression of Occludin， Claudin-1， and ZO-1 （P<0.05， P<0.01）. Furthermore， high-dose Mume Fructus elevated the protein expression of Occludin （P<0.05）. ConclusionMume Fructus can restore the expression of intestinal epithelial tight junction proteins by inhibiting the phosphorylation of proteins in the MEK/ERK signaling pathway and down-regulating the levels of TNF-α and IL-1β， thus repairing the intestinal mucosal barrier in the mouse model of IBD.

ObjectiveTo investigate the modulating effect of modified Wumeiwan （MWMW） on the ulcerative colitis （UC）-associated intestinal helper T cell 17 （Th17）/regulatory T cell （Treg） balance and intestinal flora by using a human flora-associated model of UC patients with dampness-heat obstruction syndrome， thus providing a new idea for the UC-related research and therapeutic strategies. MethodsThe 24 male C57BL/6J mice were randomized into normal control， model， and MWMW groups （n=8）. Model and MWMW groups were first treated with an antibiotic cocktail （vancomycin， 0.1 g·kg^-1； neomycin sulfate， 0.2 g·kg^-1； ampicillin， 0.2 g·kg^-1； metronidazole， 0.2 g·kg^-1） for 21 days. At the end of antibiotic treatment， the gavage of fecal microbiota suspension from UC patients with dampness-heat obstruction syndrome was started at a dose of 0.2 mL·d^-1 for 19 consecutive days， by which a human flora-associated model of UC was obtained. The MWMW group was administrated daily with MWMW liquid （12.5 g·kg^-1）， while the normal control and model groups were administrated by gavage with an equal amount of sterile water for 7 consecutive days. The symptoms of dampness-heat obstruction were observed. The colon length and spleen index were measured and calculated， and the proportions of Th17 and Treg cells were detected by flow assay. The intestinal flora was analyzed by 16S rRNA high-throughput sequencing. ResultsCompared with the normal control group， the model group showed shortened colon （P<0.05） and increased spleen index （P<0.01）. Compared with the model group， the MWMW group showed prolonged colon （P<0.01） and decreased spleen index （P<0.05）. After the intervention of MWMW， the Th17 proportion and Th17/Treg ratio in the colon decreased （P<0.01）， and the proportion of Treg cells increased （P<0.05）. The number of species and alpha and beta diversity of intestinal flora in mice were regulated by MWMW （P<0.05）. In terms of intestinal flora composition， MWMW increased the relative abundance of several phyla （Firmicutes， Proteobacteria， Fusobacteriota， Actinobacteriota， and Gemmatimonadota）， the genus Bacteroides， and two species （Bacteroides thetaiotaomicron and B. fragilis） in model mice. Moreover， Spearman's correlation analysis showed that the relative abundance of B. thetaiotaomicron and B. fragilis were negatively correlated with the Th17 level （P<0.05）. In addition， the above changes in intestinal flora caused the changes in microbial genes involved in 14 pathways， such as glycolysis， amino acid degradation， inorganic nutrient metabolism， biosynthesis of pyrimidine deoxyribonucleotides， antibiotic resistance， and degradation of polysaccharides. ConclusionsThe human flora-associated model successfully simulated the changes （marked by a decrease in the abundance of Bacteroides） of intestinal flora in UC patients with dampness-heat obstruction syndrome. MWMW can enrich the abundance of beneficial bacteria such as B. thetaiotaomicron and B. fragilis and promote the synergistic intestinal immune modulation with the metabolic functions centered on glycolysis， amino acid metabolism， and nucleotide synthesis through bacterial polysaccharide utilization sites to reduce the Th17/Treg ratio， thereby exerting a protective effect on UC.

Objective To investigate the effects of scutellarin(SCU)on apoptosis of nucleus pulposus cells and the Janus kinas 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway in intervertebral disc degeneration(IVDD)model rats.Methods IVDD rats were randomly divided into IVDD group,SCU low and high dose groups(SCU-L,SCU-H groups),SCU high dose+JAK2 activator bispecific protein phosphatase 19(DUSP19)group(SCU-H+DUSP19 group)and control group.Enzyme-linked immunosorbent assay(ELISA)method was applied to detect inflammatory factors and oxidative stress level in intervertebral disc tissues.Eosin stai-ning(HE)staining microscopy was used to observe pathological damage of intervertebral disc tissue.Transferase mediated dUTP notch end labeling(TUNEL)staining microscopy was applied to detect apoptosis of nucleus pulpo-sus cells in intervertebral disc tissue.Western blot was applied to detect the expression of JAK2/STAT3 signaling pathway related proteins.Results Animals in the IVDD group were suffered from partial rupture of the fibrous ring in the intervertebral disc tissue,abnormal shrinkage of the nucleus pulposus structure with reduction of nucleus pul-posus cells and blurred boundary with the fibrous ring.The level of TNF-α,IL-1β,ROS and apoptosis rate of nu-cleus pulposus cells,the expression of Bax,cleaved caspase-3,p-JAK2/JAK2,p-STAT3/STAT3 were all elevated and the expression of SOD,type Ⅱ collagen,and polysaccharides decreased(P＜0.05).The morphology,cell structure,density of fibrous ring and nucleus pulposus in the intervertebral disc tissue of the SCU-L and SCU-H groups were improved as compared to IVDD group.The degeneration was alleviated to varying degrees.The level of TNF-α,IL-1β,ROS,apoptosis rate of nucleus pulposus cells and the expression of Bax,cleaved caspase-3,p-JAK2/JAK2,p-STAT3/STAT3 were all reduced and the expression of SOD,type Ⅱ collagen,and polysaccha-rides significantly increased(P＜0.05).DUSP19 partially reverses the effect of SCU on apoptosis of IVDD rats.Conclusions SCU may alleviate apoptosis of nucleus pulposus cells in IVDD rats.