Ischemic stroke （IS） represents a major global health challenge with complex pathological mechanisms. Although modern therapies such as intravenous thrombolysis and endovascular thrombectomy have advanced， their application remains constrained by narrow therapeutic time windows， hemorrhagic risks， and uneven distribution of medical resources. Traditional Chinese medicine （TCM） demonstrates unique value in the prevention and treatment of IS， owing to its multi-component， multi-target， and holistic regulatory characteristics. This review summarized the molecular mechanisms by which active ingredients and compound formulations of TCM exert therapeutic effects against IS through the regulation of inflammatory responses， oxidative stress， excitatory toxicity， apoptosis， and autophagy. Studies have indicated that components such as curcumin， baicalin， and astragaloside Ⅳ inhibit microglial activation and the nucleotide-binding oligomerization domain （NOD）-like receptor protein 3 （NLRP3） inflammasome to attenuate neuroinflammation， activate the nuclear factor erythroid 2-related factor 2（Nrf2）/heme oxygenase-1 （HO-1） pathway to alleviate oxidative stress， modulate glutamate receptor function to counteract excitatory toxicity， and regulate the B-cell lymphoma 2（Bcl-2）/Bcl-2-associated X protein （Bax）， cysteine aspartate-specific protease （Caspase）， and phosphatidylinositol 3 kinases （PI3K）/protein kinase B （Akt） signaling pathways to suppress neuronal apoptosis. Recent research has further revealed that TCM can modulate ferroptosis by targeting key proteins glutathione peroxidase 4 （GPX4） and acyl-coenzyme A synthetase long-chain family member 4 （ACSL4） to maintain iron homeostasis， intervene in the "microbiota-gut-brain axis" to ameliorate dysbiosis and reduce neuroinflammation， utilize exosomes for brain-targeted drug delivery， and influence neural repair processes through epigenetic regulation. Furthermore， the review discussed the integrated mechanisms of compound formulations， such as Buyang Huanwu Decoction， in improving cerebral microcirculation and promoting neurovascular remodeling via multi-component synergy. It also analyzed the strategy and advantages of integrating TCM with Western medicine for IS treatment， providing a novel theoretical foundation and research directions for future investigations and clinical translation of TCM in IS management.

Objective To analyze the disease burden and trends of bladder cancer in China and globally from 1992 to 2021.  Methods Using the GBD 2021 database, the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates of bladder cancer in China and globally from 1992–2021 were analyzed. Average annual percentage change (AAPC) was calculated using Joinpoint regression. Subgroup analyses by sex and age were conducted, and a Bayesian age-period-cohort (BAPC) model was used to predict trends in age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) for the next 15 years.  Results In 2021, China reported 106 000 new cases (ASIR: 5.14/100 000), 571 000 prevalent cases (age-standardized prevalence rate, ASPR: 26.61/100 000), 43 000 deaths (ASMR: 2.34/100 000), and a DALY rate of 45.31/100 000. From 1992–2021, China showed upward trends in ASIR and ASPR but declines in ASMR and DALYs, while global ASIR, ASMR, and DALYs decreased overall with slow ASPR growth. The peak cases in China and globally were both concentrated in the 65-79 age group, with a significantly higher burden on males than females. In China, smoking-related ASMR and ASDR exceeded global averages and rose, whereas high glucose-related indexes were lower and declined. Projections for 2021–2036 indicated that the global incidence and mortality rates would be rising, but ASIR/ASPR would be declining, while in China, the incidence rate would continue to rise, and the mortality rate will stabilize, with a significant increase in ASIR and a gradual decrease in ASPR.  Conclusion From 1992 to 2021, the incidence of bladder cancer in China has shown a continuous upward trend and is projected to persist in the future, with significant gender and age differences. Particular attention should be given to elderly males aged 85-89. The disease burden of bladder cancer attributable to smoking continues to rise, highlighting the urgent need to strengthen tobacco control policies.

Cholangiocarcinoma (CCA) is a malignant tumor originating from cholangiocytes. However, it remains unclear about the pathogenesis of this carcinoma, which may be related to multiple factors. Currently, CCA is mainly treated by surgery, chemotherapy, and radiotherapy. Among them, surgery is the only potentially curative option for CCA. Nevertheless, the high malignancy and asymptomatic nature of CCA may lead to poor treatment outcomes. It has been demonstrated that Chinese medicine (CM) plays a significant role in various antitumor applications. Meanwhile, CM exhibits fewer side effects and high availability. Moreover, the in vitro application of CM monomers has been explored in many domestic and foreign studies. This article mainly reviews the signaling pathways and molecular mechanisms of CM monomers in the treatment of CCA in recent years. These findings are expected to provide new insights into the treatment of CCA.
Cholangiocarcinoma/drug therapy* ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Bile Duct Neoplasms/drug therapy* ; Medicine, Chinese Traditional ; Animals ; Signal Transduction/drug effects*

OBJECTIVE: To analyze the clinical characteristics of elderly patients with sepsis, identify the key factors affecting their clinical outcomes, construct a death risk assessment scale for elderly patients with sepsis, and evaluate its predictive value. METHODS: A retrospective case-control study was conducted. The clinical data of sepsis patients admitted to intensive care unit (ICU) of the First Affiliated Hospital of Wenzhou Medical University from September 2021 to September 2023 were collected, including basic information, clinical characteristics, and clinical outcomes. The patients were divided into non-elderly group (age ≥ 65 years old) and elderly group (age < 65 years old) based on age. Additionally, the elderly patients were divided into survival group and death group based on their 30-day survival status. The clinical characteristics of elderly patients with sepsis were analyzed. Univariate and multivariate Logistic regression analyses were used to screen the independent risk factors for 30-day death in elderly patients with sepsis, and the regression equation was constructed. The regression equation was simplified, and the death risk assessment scale was established. The predictive value of different scores for the prognosis of elderly patients with sepsis was compared. RESULTS: (1) A total of 833 patients with sepsis were finally enrolled, including 485 in the elderly group and 348 in the non-elderly group. Compared with the non-elderly group, the elderly group showed significantly lower counts of lymphocyte, T cell, CD8⁺ T cell, and the ratio of T cells and CD8⁺ T cells [lymphocyte count (×10⁹/L): 0.71 (0.43, 1.06) vs. 0.83 (0.53, 1.26), T cell count (cells/μL): 394.0 (216.0, 648.0) vs. 490.5 (270.5, 793.0), CD8⁺ T cell count (cells/μL): 126.0 (62.0, 223.5) vs. 180.0 (101.0, 312.0), T cell ratio: 0.60 (0.48, 0.70) vs. 0.64 (0.51, 0.75), CD8⁺ T cell ratio: 0.19 (0.13, 0.28) vs. 0.24 (0.16, 0.34), all P < 0.01], higher natural killer cell (NK cell) count, acute physiology and chronic health evaluation II (APACHE II) score, ratio of invasive mechanical ventilation (IMV) during hospitalization, and 30-day mortality [NK cell count (cells/μL): 112.0 (61.0, 187.5) vs. 95.0 (53.0, 151.0), APACHE II score: 16.00 (12.00, 21.00) vs. 13.00 (8.00, 17.00), IMV ratio: 40.6% (197/485) vs. 31.9% (111/348), 30-day mortality: 28.9% (140/485) vs. 19.5% (68/348), all P < 0.05], and longer length of ICU stay [days: 5.5 (3.0, 10.0) vs. 5.0 (3.0, 8.0), P < 0.05]. There were no statistically significant differences in the levels of inflammatory markers such as C-reactive protein (CRP), procalcitonin (PCT), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and interleukins (IL-2, IL-4, IL-6, IL-10) between the two groups. (2) In 485 elderly patients with sepsis, 345 survived in 30 days, and 140 died with the 30-day mortality of 28.9%. Compared with the survival group, the patients in the death group were older, and had lower body mass index (BMI), white blood cell count (WBC), PCT, platelet count (PLT) and higher IL-6, IL-10, N-terminal pro-brain natriuretic peptide (NT-proBNP), total bilirubin (TBil), blood lactic acid (Lac), and ratio of in-hospital IMV and continuous renal replacement therapy (CRRT). Multivariate Logistic regression analysis indicated that BMI [odds ratio (OR) = 0.783, 95% confidence interval (95%CI) was 0.678-0.905, P = 0.001], IL-6 (OR = 1.073, 95%CI was 1.004-1.146, P = 0.036), TBil (OR = 1.009, 95%CI was 1.000-1.018, P = 0.045), Lac (OR = 1.211, 95%CI was 1.072-1.367, P = 0.002), and IMV during hospitalization (OR = 6.181, 95%CI was 2.214-17.256, P = 0.001) were independent risk factors for 30-day death in elderly patients with sepsis, and the regression equation was constructed (Logit P = 1.012-0.244×BMI+0.070×IL-6+0.009×TBil+0.190×Lac+1.822×IMV). The regression equation was simplified to construct a death risk assessment scale, namely BITLI score. Receiver operator characteristic curve (ROC curve) analysis showed that the area under the ROC curve (AUC) of BITLI score for predicting death risk was 0.852 (95%CI was 0.769-0.935), and it was higher than APACHE II score (AUC = 0.714, 95%CI was 0.623-0.805) and sequential organ failure assessment (SOFA) score (AUC = 0.685, 95%CI was 0.578-0.793). The determined cut-off value of BITLI score was 1.50, while achieving a sensitivity of 83.3% and specificity of 74.0%. CONCLUSIONS Elderly patients with sepsis often have reduced lymphocyte counts, severe conditions, and poor prognosis. BMI, IL-6, TBil, Lac, and IMV during hospitalization were independent risk factors for 30-day death in elderly patients with sepsis. The BITLI score constructed based above risk factors is more precise and reliable than traditional APACHE II and SOFA scores in predicting the outcomes of elderly patients with sepsis.
Humans ; Sepsis/mortality* ; Aged ; Retrospective Studies ; Risk Assessment ; Case-Control Studies ; Prognosis ; Male ; Female ; Intensive Care Units ; Risk Factors ; Aged, 80 and over ; Logistic Models ; Middle Aged

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major health concern in northwest China; however, the impact of particulate matter (PM) exposure during sand-dust storms (SDS) remains poorly understood. Therefore, this study aimed to investigate the association between PM exposure on SDS days and COPD hospitalization risk in arid regions. METHODS: Data on daily COPD hospitalizations were collected from 323 hospitals from 2018 to 2022, along with the corresponding air pollutant and meteorological data for each city in Gansu Province. Employing a space-time-stratified case-crossover design and conditional Poisson regression, we analyzed 265,379 COPD hospitalizations. RESULTS: PM exposure during SDS days significantly increased COPD hospitalization risk [relative risk ( RR) for PM _2.5, lag 3:1.028, 95% confidence interval ( CI): 1.021-1.034], particularly among men and the elderly, and during the cold season. The burden of PM exposure on COPD hospitalization was substantially high in Northwest China, especially in the arid and semi-arid regions. CONCLUSION Our findings revealed a positive correlation between PM exposure during SDS episodes and elevated hospitalization rates for COPD in arid and semi-arid zones in China. This highlights the urgency of developing region-specific public health strategies to address adverse respiratory outcomes associated with SDS-related air quality deterioration.
Humans ; China/epidemiology* ; Pulmonary Disease, Chronic Obstructive/chemically induced* ; Particulate Matter/analysis* ; Hospitalization/statistics & numerical data* ; Male ; Female ; Middle Aged ; Aged ; Air Pollutants/analysis* ; Environmental Exposure/adverse effects* ; Spatio-Temporal Analysis ; Adult ; Sand ; Air Pollution

Postoperative nausea and vomiting (PONV) are common complications that mainly occur within 24 h after orthognathic surgery. The incidence of nausea and vomiting after orthognathic surgery remains high and is a difficult problem for patients and surgeons. These complications not only affect wound healing and increase the risk of postoperative bleeding. Vomit and blood may also cause nausea and vomiting, which results in a vicious cycle. Frequent nausea and vomiting are a painful experience and more serious than postoperative pain. They are one of the main reasons for postoperative infection, delayed discharge, and increased hospitalization costs and affect patient satisfaction. In this review, the author combined literature review and clinical experience and summarized and analyzed the causes of orthognathic nausea and vomiting and prevention and treatment strategies to improving the related clinical process.
Humans ; Postoperative Nausea and Vomiting/etiology* ; Orthognathic Surgical Procedures/adverse effects*

AIM:To investigate the immunosuppressive effects of M2-like tumor-associated macrophages(M2-TAMs)on CD8+T cells within the tumor microenvironment of esophageal cancer.METHODS:Multiplex fluores-cence immunohistochemistry was used to analyze the distribution of immune cells in esophageal cancer tissues.An in vitro co-culture system was established,and flow cytometry along with Calcein-AM/PI staining was employed to assess the im-pact of M2-TAMs on CD8+T cell function.The GEPIA database was utilized to evaluate the prognostic significance of PDCD1 expression in esophageal cancer patients and to analyze the correlations between gene expressions.Immunohisto-chemistry(IHC)was performed to detect the expression of TGF-β1 in esophageal cancer tissues.Flow cytometry and en-zyme-linked immunosorbent assay(ELISA)were used to measure PD-1,IFN-γ and TNF-α expression in CD8+T cells fol-lowing treatment with a TGF-β1 inhibitor.RESULTS:Compared with early-stage(stage I)esophageal cancer patients,the patients with advanced disease(stages Ⅱ to Ⅳ)exhibited dynamic changes in the infiltration of CD4+T cells,CD8+T cells,Tregs,and M2-TAMs within tumor tissues,with significant correlations observed among these cell populations(P<0.05).The distribution of M2-TAMs and Tregs was positively correlated with poor prognosis(P<0.05),while that of CD8+T cells was negatively correlated(P<0.05).In contrast,CD4+T cell infiltration showed no significant association with clinical outcomes(P>0.05).Co-culture of CD8+T cells with M2-TAMs resulted in significant downregulation of CD107a,granzyme B,IFN-γ and TNF-α expression(P<0.01).Additionally,M2-TAM-treated CD8+T cells co-cultured with esophageal cancer cells led to reduced apoptosis of cancer cells.High expression of PDCD1 was significantly associated with poor prognosis(P<0.05),and significant correlations were observed between CD8A and PDCD1 expression,as well as between TGF-β1 and CD274 gene expression(P<0.01).TGF-β1 was also significantly associated with CD163+macro-phage infiltration and the progression of esophageal cancer(P<0.05).Treatment with a TGF-β1 inhibitor in the M2-TAM and CD8+T cell co-culture system significantly down-regulated PD-1 expression and increased the secretion of IFN-γ and TNF-α(P<0.01).CONCLUSION:The TGF-β1 derived from M2-TAMs inhibits the antitumor activity of CD8+T cells in the esophageal cancer microenvironment,suggesting potential therapeutic targets for overcoming immunosuppression in esophageal cancer.

This study aims to prepare nanobodies for the epitopes of spike protein(S)of porcine ep-idemic diarrhea virus(PEDV),and verify its reactivity.The expression vector pCZN1-SN was con-structed by the prokaryotic expression system,and SN fragment was expressed in prokaryotic ex-pression and purified by Ni-NTA chromatography column.The SN nanobodies were displayed u-sing phage display technology and screened from the natural nanobody library.The results showed that SN fragments with a size of 26 kDa were obtained by prokaryotic induction,and the specific nanobodies were obtained through three rounds screening by phage display technology.One strain with the best reactivity was selected for prokaryotic expression and purified.The nanobodies were obtained with a size of 14 kDa by Western blot and demonstrated to have a good binding ability to PEDV SN protein.In summary,nanobodies with epitope fragments of PEDV S protein were suc-cessfully screened and prepared based on the phage display technology,which provided a new way for the in-depth application of nanobodies.

BACKGROUND:Osteoporosis is a significant contributor to the global burden of disease and disability.Plasma proteins are involved in complex biological processes and play a crucial role in uncovering disease mechanisms and identifying potential therapeutic targets.Although existing studies have suggested an association between plasma proteins and osteoporosis,the causal nature of these associations is not fully clarified.Therefore,it is imperative to identify the causal proteins associated with osteoporosis and potential therapeutic targets for the amelioration and management of this condition using large-scale plasma protein data.OBJECTIVE:To evaluate the causal relationship between plasma proteins and osteoporosis based on the UK Biobank database as source information using the two-sample Mendelian randomization.METHODS:A total of 1 001 plasma protein-related genome-wide significant quantitative trait loci(P<5×10-8)were obtained from the UK Biobank database and used as instrumental variables,with linkage disequilibrium excluded.Summary data on osteoporosis were collected from the FinnGen database,which included 438 872 individuals of European descent.The study was analyzed using inverse variance weighting,MR-Egger regression,weighted median,and several sensitivity analyses to ensure the robustness of the results.Further,a protein-protein interaction network was constructed,and Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted to explore the functional relevance and potential mechanisms of plasma proteins.RESULTS AND CONCLUSION:(1)The Mendelian randomization analysis using the inverse variance weighted method identified 50 plasma proteins that have causal associations with osteoporosis(P<0.05).Among them,20 plasma proteins,including chromosome 19 open reading frame 12(odds ratio[OR]=0.610;95%confidence interval[CI]:0.483-0.769,P=2.967×10-5)and epidermal growth factor(EGF;OR=0.877;95%CI:0.770-0.999,P=0.049),might be associated with a reduced risk of osteoporosis.In contrast,30 plasma proteins,such as C-C motif chemokine ligand(CCL)18(OR=1.091;95%CI:1.037-1.147,P=0.001)and CD209(OR=1.036;95%CI:1.003-1.070,P=0.034),might be associated with an increased risk of osteoporosis.After Bonferroni correction,only chromosome 19 open reading frame 12 showed a significant causal association with osteoporosis.(2)Multiple sensitivity analyses revealed no evidence of pleiotropy or heterogeneity,indicating the robustness of the results.(3)The construction of the PPI network identified core proteins such as EGF,CCL5,C-X-C motif chemokine ligand(CXCL)13,CXCL5,vascular endothelial growth factor C,CCL17,CCL18,TEK receptor tyrosine kinase,tyrosine kinase with immunoglobulin like and EGF like domains 1,and CCL23.(4)Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that these plasma proteins play essential roles in the immune system,influencing osteoporosis through processes such as signal transduction,cell migration,and chemotaxis.(5)This study reveals the potential causal associations between 1 001 plasma proteins and osteoporosis,highlighting the utility of a large-scale,data-driven approach to identify new biomarkers and drug targets in diverse populations.Additionally,our findings suggest that processes such as immune signaling,cell migration,and chemotaxis play significant roles in the pathogenesis of osteoporosis,offering new directions for research under specific genetic backgrounds and environmental factors.Finally,the core proteins identified in this study(e.g.,EGF,CCL5,and CXCL13)may serve as novel biomarkers or therapeutic targets,providing a new basis for the precise prevention and treatment of osteoporosis.

Objective To compare of the efficacy of two distinct debridement techniques in membrane induction therapy for chronic tibial osteomyelitis.Methods A retrospective study was conducted on 52 patients with Cierny-Mader type IV A/B chronic tibial osteomyelitis who were treated at the Third Affiliated Hospital of Zunyi Medical University between July 2016 and December 2023.Five patients were diagnosed and treated before 2020,while 47 were managed from 2020 onward.Patients were divided into two groups:a local debridement group(n=28)and an en bloc osteotomy group(n=24).Perioperative outcomes—including operative time,incision length,intraoperative blood loss,and length of hospital stay—were assessed,along with clinical efficacy at 6 months,12 months,and final follow-up.Clinical outcomes were evaluated using the Hospital for Special Surgery(HSS)knee score,the American Orthopaedic Foot&Ankle Society(AOFAS)ankle-hindfoot score,joint range of motion(knee flexion-extension and ankle plantarflexion-dorsiflexion),recurrence rate,and the Paley classification for infectious bone defects.Results The local debridement group exhibited significantly less intraoperative blood loss(P<0.05),shorter operative time(P<0.05),and reduced hospital stay(P<0.05),as well as higher AOFAS and HSS scores at both 6 and 12 months postoperatively(P<0.05).In contrast,the osteotomy group demonstrated superior Paley classification outcomes at 6 months,12 months,and final follow-up(P<0.05),along with lower rates of infection recurrence.Longitudinal analysis indicated significant improvements in AOFAS scores,HSS scores,and joint mobility over time in both groups(P<0.05).However,no statistically significant differences were observed between groups in terms of functional scores or joint mobility parameters at final follow-up(P>0.05).Conclusion En bloc osteotomy combined with the induced membrane technique(Masquelet technique)enables more comprehensive debridement,minimizes the necessity for repeated surgical interventions,reduces postoperative complications,lowers the risk of recurrence,and promotes enhanced bone healing.