ObjectiveTo investigate the effects of Huanglian Jiedutang （HLJDT） on cognitive function in mice with ischemic stroke （IS） and to elucidate whether its neuroprotective effects are mediated by inhibition of the nuclear factor-κB （NF-κB） signaling pathway and subsequent suppression of NF-κB-regulated neuronal apoptosis. MethodsAn IS model was established using middle cerebral artery occlusion （MCAO）. Sixty C57BL/6J mice were randomly assigned to five groups （n =12 per group）， i.e.， sham operation， model， HLJDT low-dose （3.9 g·kg^-1·d^-1）， HLJDT high-dose （7.8 g·kg^-1·d^-1）， and Ginkgo biloba extract （GBE， 31.2 mg·kg^-1·d^-1）. Post-operatively， neurological deficit scores （Longa score）， cerebral infarct volume assessed by 2，3，5-triphenyltetrazolium chloride （TTC） staining， and brain water content were evaluated. Learning and memory were assessed using new object recognition （NOR） and fear conditioning （FC） tests. Hippocampal pathology was examined via hematoxylin and eosin （HE） staining. Immunofluorescence detected expression of glial fibrillary acidic protein （GFAP， astrocyte marker）， cellular oncogene Fos （c-Fos， neuronal activation marker）， and glutamate decarboxylase 65 （GAD65）. Western blot measured nuclear factor-κB inhibitor protein α （IκBα）， phosphorylated IκBα （p-IκBα）， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， ionic calcium binding adapter molecule 1 （Iba-1）， tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and apoptosis-related proteins， such as cleaved cysteinyl aspartate-specific protease 3 （Caspase-3）， B-cell lymphoma 2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Real-time quantitative PCR （Real-time PCR） was used to assess mRNA levels of Iba-1， TNF-α， IL-1β， NF-κB p65， cleaved Caspase-3， Bax， and Bcl-2. ResultsCompared with the sham group， the model group exhibited significantly increased neurological deficit scores， brain water content， and cerebral infarct volume （P<0.01）. Hippocampal CA1 neurons were disorganized， showing nuclear pyknosis and karyolysis. NOR exploration time and FC freezing time were significantly reduced （P<0.01）. GFAP and c-Fos expression were increased， while GAD65 expression was decreased （P<0.01）. Cleaved Caspase-3 and Bax were upregulated， Bcl-2 was downregulated， and the Bax/Bcl-2 ratio was elevated （P<0.01）. Expression levels of p-IκBα， p-NF-κB p65， IL-1β， TNF-α， and Iba-1 were significantly increased （P<0.01）. Compared with the model group， HLJDT high-dose， low-dose， and GBE groups showed significant improvements in all parameters （P<0.01）. Among them， the HLJDT high-dose group showed the most pronounced neuronal structural recovery and superior performance in NOR and FC tests （P<0.01）. In this group， GFAP and c-Fos decreased， GAD65 increased （P<0.01）， apoptosis-related protein expression was reversed， and NF-κB signaling and related inflammatory factor expression were suppressed （P<0.01）. ConclusionHLJDT ameliorates cognitive dysfunction in mice after IS， potentially by inhibiting the NF-κB signaling pathway， thereby reducing neuroinflammation and hippocampal neuronal apoptosis.

BACKGROUND:Traditional treatments for corneal alkali burns are limited,especially in controlling inflammation,preventing neovascularization,and inhibiting corneal scarring.Natural,synthetic,or composite materials provide a wide range of treatment options.However,the mechanism by which biomaterials promote corneal alkali burn repair has not yet been systematically understood. OBJECTIVE:To summarize the current research on biomaterials in promoting corneal alkali burn repair in and outside China,and review the mechanism and application of biomaterials in repairing corneal alkali burn. METHODS:The first author searched"cornea,alkali burn,amniotic membrane,hyaluronic acid,collagen,chitosan,polymer materials"as Chinese keywords and"amniotic membrane,hyaluronic acid,collagen,chitosan,polymer,cornea,alkali burn"as English keywords in PubMed,Web of Science,CNKI,and WanFang databases.According to inclusion and exclusion criteria,76 eligible articles were finally included for review. RESULTS AND CONCLUSION:(1)In the field of corneal alkali burn repair,biomaterials such as amniotic membrane,hyaluronic acid,collagen,chitosan,and degradable polymer materials have been widely studied and applied.Each of these biomaterials has its own characteristics,advantages,and disadvantages,and stands out in different aspects.(2)First and foremost,amniotic membranes are considered one of the most promising biomaterials due to their abundance of bioactive factors.They are biocompatible and can regulate the corneal inflammatory response.However,there are issues with donor shortages and susceptibility to infectious diseases.(3)Hyaluronic acid has good moisturizing properties and biocompatibility,and is able to improve the survival rate of corneal cells and increase corneal transparency.(4)The good biocompatibility and scaffold structure of collagen enable the promotion of corneal cell adhesion and proliferation,as well as the reconstruction of corneal tissue structure.(5)Chitosan is recognized for its good biocompatibility and degradability,making it suitable as a carrier for drug delivery and cell transplantation.(6)Degradable polymer materials have good controllability over degradation and can provide a good support and delivery platform for the repair of corneal alkali burns,but further research is needed on their stability and biocompatibility.(7)Overall,there is currently no single biomaterial that can completely address the repair problem of corneal alkali burns,and each biomaterial has its own specific application scenarios and limitations.(8)Future research directions should focus on further improving the properties and structure of biomaterials,exploring more effective combination applications,and deeply understanding the interaction mechanism between biomaterials and corneal tissue,in order to enhance the therapeutic effect of corneal alkali burns and the quality of life of patients.

BACKGROUND: The American Heart Association (AHA) introduced the concept of cardiovascular-kidney-metabolic (CKM) health and stage, reflecting the interaction among metabolism, chronic kidney disease (CKD), and the cardiovascular system. However, the association between CKM stage and the long-term risk of cardiovascular disease (CVD) has not been validated. This study aimed to evaluate the long-term CVD risk associated with CKM health metrics and CKM stage using data from a population-based cohort study. METHODS: In total, 5293 CVD-free participants were followed up to around 13 years in the Chinese Multi-provincial Cohort Study (CMCS). Considering the pathophysiologic progression of CKM health metrics abnormalities (comprising obesity, central adiposity, prediabetes, diabetes, hypertriglyceridemia, CKD, and metabolic syndrome), participants were divided into CKM stages 0, 1, and 2. The time-dependent Cox regression models were used to estimate the cardiovascular risk associated with CKM health metrics and stage. Additionally, broader CVD outcomes were examined, with a specific assessment of the impact of stage 3 in 2581 participants from the CMCS-Beijing subcohort. RESULTS: Among participants, 91.2% (4825/5293) had at least one abnormal CKM health metric, 8.8% (468/5293), 13.3% (704/5293), and 77.9% (4121/5293) were in CKM stages 0, 1, and 2, respectively; and 710 incident CVD cases occurred during a median follow-up time of 13.3 years (interquartile range: 12.1 to 13.6 years). Participants with each poor CKM health metric exhibited significantly higher CVD risk. Compared with stage 0, the hazard ratio (HR) (95% confidence interval [CI]) for CVD incidence was 1.31 (0.84-2.04) in stage 1 and 2.27 (1.57-3.28) in stage 2. Significant interactive impacts existed between CKM stage and age or sex, with higher CVD risk related to increased CKM stages in participants aged <60 years or females. CONCLUSION These findings highlight the contribution of CKM health metrics and CKM stage to the long-term risk of CVD, suggesting the importance of multi-component recognition and management of poor CKM health in CVD prevention.
Humans ; Female ; Male ; Cardiovascular Diseases/etiology* ; Middle Aged ; Adult ; Cohort Studies ; Renal Insufficiency, Chronic/metabolism* ; Aged ; Risk Factors ; Metabolic Syndrome/metabolism* ; China ; East Asian People

OBJECTIVE To construct ensemble learning models for predicting high-use days of budesonide based on meteorological factors， thereby providing reference for hospital pharmacy management. METHODS Meteorological data for 2024 and outpatient budesonide usage data from the jurisdiction of Sanming Hospital of Integrated Traditional Chinese and Western Medicine were collected. High-use days were defined as the 75th percentile of outpatient budesonide usage， and a corresponding dataset was established. The prediction task was formulated as a classification problem， and three ensemble learning models were developed： Random Forest， Extreme Gradient Boosting （XGBoost）， and Histogram-based Gradient Boosting Classifier. Model performance was evaluated using accuracy， precision， recall， F1-score， and log-loss. Model interpretability was analyzed using Shapley Additive Explanations （SHAP）. RESULTS The Histogram-based Gradient Boosting Classifier achieved the best performance （accuracy＝0.75， F1-score＝0.48）， followed by XGBoost （accuracy＝0.74， F1-score＝0.43） and Random Forest （accuracy＝0.72， F1-score＝0.22）. SHAP results suggested that the prediction results of the last two models have the highest correction. CONCLUSIONS Ensemble learning models can effectively predict high-use days of budesonide， with the Histogram- based Gradient Boosting Classifier demonstrating the best predictive performance. Low temperature， high humidity， and low atmospheric pressure show significant positive impacts on the prediction of daily budesonide usage.

ObjectiveTo clarify the graded quantitative diagnostic characteristics of lung qi deficiency syndrome in chronic obstructive pulmonary disease （COPD） based on latent class analysis combined with a hidden structure model. MethodsClinical data， including the four diagnostic methods of traditional Chinese medicine （TCM）， were collected from 745 COPD patients with lung qi deficiency syndrome. Latent class modeling was performed using R 4.1.2 software， and each patient was classified into one of three severity categories （mild， moderate， or severe） based on probabilistic parameterization， parameter estimation， and model fitting. A database was established for different severity levels of lung qi deficiency syndrome. Based on this， Lantern 5.0 software was used to construct hidden structure models for mild， moderate， and severe lung qi deficiency syndrome， and syndrome differentiation rules were developed through comprehensive clustering. ResultsA latent class model was constructed using 28 symptoms and signs with a frequency greater than 10%. Considering TCM theory and model simplicity， the optimal model was determined when the number of latent classes was three， categorizing lung qi deficiency syndrome into mild （298 cases）， moderate （164 cases）， and severe （283 cases）. Hidden structure models were separately developed for each severity level， and syndrome differentiation rules were established. A comparison of common symptoms in the syndrome differentiation rules for mild and moderate lung qi deficiency syndrome showed no statistically significant differences in diagnostic values and weights （P＞0.05）， leading to their combined analysis and the development of a unified syndrome differentiation rule. Value and weight of quantitative diagnosis of mild-to-moderate lung qi deficiency syndrome were as followed： shortness of breath （diagnostic value 9.3， diagnostic weight 86.92%）， dyspnea on exertion （8.2， 76.64%）， low voice and reluctance to speak （6.7， 62.62%）， poor appetite （4.0， 37.38%）， loose stools （4.0， 37.38%）， weak cough sound （2.9， 27.10%）， wheezing （2.3， 21.50%）， fatigue （1.8， 16.82%）， spontaneous sweating （1.7， 15.89%）， susceptibility to colds （1.6， 14.95%）， swollen tongue （1.4， 13.08%）， teeth marks on the tongue edge （1.2， 11.21%）， deep pulse （1.6， 14.95%）， with a diagnostic threshold of 10.3. Value and weight of quantitative diagnosis of severe lung qi deficiency syndrome were as followed： weak cough sound （15.1， 61.13%）， soreness and weakness of the waist and knees （12.6， 51.01%）， shortness of breath （11.1， 44.94%）， low voice and reluctance to speak （8.3， 33.60%）， frequent nocturia （6.1， 24.70%）， spontaneous sweating （3.7， 14.98%）， susceptibility to colds （3.5， 14.17%）， teeth marks on the tongue edge （7.8， 31.58%）， pale tongue body （1.9， 7.69%）， white tongue coating （5.5， 22.27%）， thin pulse （1.5， 6.07%）， with a diagnostic threshold of 23.7. ConclusionThe combination of latent class analysis and a hideen structure model effectively clarified the graded quantitative diagnostic characteristics of lung qi deficiency syndrome， providing a reference for the quantitative diagnosis of other fundamental syndromes in TCM.

Objective:To investigate the relationship between the serum levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), S100 calcium binding protein B (S100B) with glycolipid metabolism, pregnancy outcome in pregnant women with gestational diabetes.Methods:The clinical data of 153 pregnant women with gestational diabetes (research group) and 153 healthy pregnant women (control group) in the Second Affiliated Hospital of Xi ′an Medical University from January 2020 to October 2023 were retrospectively analyzed. The serum levels of VEGF, MMP-9 and S100B were measured by enzyme linked immunosorbent assay, and the fasting blood glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting insulin and glycated hemoglobin were measured, and the homeostasis model assessment insulin resistance index (HOMA-IR) was calculated. The adverse outcomes of pregnant women with gestational diabetes were recorded. Pearson method was used to analyze the correlation between glycolipid metabolism indexes and VEGF, MMP-9, S100B in pregnant women with gestational diabetes. Multivariate Logistic regression was used to analyze the independent risk factors of adverse pregnancy outcome in pregnant women with gestational diabetes. Receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of VEGF, MMP-9 and S100B on adverse pregnancy outcome in pregnant women with gestational diabetes. Results:The fasting blood glucose, fasting insulin, glycated hemoglobin, HOMA-IR, triglyceride, total cholesterol, LDL-C, VEGF, MMP-9 and S100B in research group were significantly higher than those in control group: (9.42 ± 0.65) mmol/L vs. (4.13 ± 0.46) mmol/L, (16.58 ± 2.37) mU/L vs. (13.41 ± 2.05) mU/L, (7.28 ± 0.46)% vs. (4.35 ± 0.39)%, 4.83 ± 0.42 vs. 2.71 ± 0.37, (3.41 ± 0.67) mmol/L vs. (2.85 ± 0.63) mmol/L, (5.54 ± 1.56) mmol/L vs. (5.12 ± 1.50) mmol/L, (3.14 ± 0.97) mmol/L vs. (2.86 ± 0.93) mmol/L, (184.02 ± 30.25) ng/L vs. (156.33 ± 26.41) ng/L, (45.78 ± 7.56) μg/L vs. (29.36 ± 5.03) μg/L and (117.51 ± 25.12) ng/L vs. (89.74 ± 22.46) ng/L, the HDL-C was significantly lower than that in control group: (1.34 ± 0.27) mmol/L vs. (1.42 ± 0.30) mmol/L, and there were statistical differences ( P<0.01 or <0.05). Pearson correlation analysis result showed that VEGF, MMP-9, S100B in pregnant women with gestational diabetes were positively correlated with fasting blood glucose, fasting insulin, glycated hemoglobin, HOMA-IR, triglyceride, total cholesterol and LDL-C ( P<0.01), negatively correlated with HDL-C ( P<0.01). Among 153 pregnant women with gestational diabetes, 49 had adverse pregnancy outcome, and 104 had good pregnancy outcome. The VEGF, MMP-9 and S100B in pregnant women with adverse pregnancy outcome were significantly higher than those in pregnant women with good pregnancy outcome: (212.75 ± 28.63) ng/L vs. (170.49 ± 26.58) ng/L, (52.37 ± 7.14) μg/L vs. (42.68 ± 6.35) μg/L and (136.83 ± 23.62) ng/L vs. (108.41 ± 21.35) ng/L, and there were statistical differences ( P<0.01). Multivariate Logistic regression analysis result showed that VEGF, MMP-9 and S100B were independent risk factors for adverse pregnancy outcome in pregnant women with gestational diabetes ( OR = 7.013, 5.382 and 6.129; 95% CI 5.206 to 9.447, 3.449 to 8.398 and 3.520 to 10.673; P<0.01). ROC curve analysis result showed that the area under the curve of VEGF, MMP-9 combined S100B in predicting adverse pregnancy outcome in pregnant women with gestational diabetes was significantly larger than that of VEGF, MMP-9 and S100B alone (0.945 vs. 0.863, 0.847 and 0.801; P<0.05 or <0.01), with sensitivity of 89.80% and specificity of 91.30%. Conclusions:The high serum levels of VEGF, MMP-9 and S100B are associated with abnormal glycolipid metabolism and adverse pregnancy outcome in pregnant women with gestational diabetes, and the combination of the three indexes has a high predictive value for adverse pregnancy outcome.

Objective To investigate the relationship between the levels of serum suppressor of cytokine signaling 3(SOCS3),growth differentiation factor-15(GDF-15)and liver fibrosis in patients with type 2 dia-betes mellitus(T2DM)combined with non-alcoholic fatty liver disease(NAFLD).Methods A total of 320 patients with T2DM combined with NAFLD who were hospitalized in this hospital from May 2023 to May 2024 were selected as the study group,and another 320 patients with simple T2DM admitted during the same period were selected as the control group.The levels of serum SOCS3 and GDF-15 were determined by en-zyme-linked immunosorbent assay(ELISA).Pearson correlation analysis was used to analyze the correlation between SOCS3,GDF-15 levels and liver fibrosis indicators.Logistic regression analysis was used to analyze the factors affecting the degree of liver fibrosis.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of serum SOCS3 and GDF-15 for the degree of liver fibrosis in patients.Results Compared with the control group,the levels of serum SOCS3,GDF-15,5,type Ⅲ procollagen peptide,laminin and type Ⅳ col-lagen in the study group were significantly increased(P＜0.05).There were statistically significant differ-ences in the levels of type Ⅲ procollagen peptide,laminin and type Ⅳ collagen between the mild to moderate group and the severe group(P＜0.05).Compared with the mild to moderate group,the levels of serum SOCS3 and GDF-15 in the severe group were significantly increased(P＜0.05).The results of Pearson corre-lation analysis showed that serum SOCS3 and GDF-15 in patients with T2DM combined with NAFLD were positively correlated with type Ⅲ procollagen peptide,laminin,and type Ⅳ collagen(P＜0.05).Serum SOCS3,GDF-1 5,type Ⅲ procollagen peptide,laminin and type Ⅳ collagen are risk factors affecting the degree of liver fibrosis in patients with T2DM combined with NAFLD(P＜0.05).The results of the ROC curve showed that the combined diagnosis of serum SOCS3 and GDF-15 for the degree of liver fibrosis in patients with T2DM complicated with NAFLD had the highest area under the curve(AUC),which was superior to the individual diagnosis of each(both P＜0.05),with a corresponding sensitivity of 69.08％and a specificity of 85.71％.The combined diagnosis of the degree of liver fibrosis in patients with T2DM complicated with NAFLD by serum SOCS3,GDF-15,type Ⅲ procollagen peptide,laminin,and type Ⅳ collagen had the highest AUC,which was superior to the individual diagnosis of each index(all P＜0.001),with a corresponding sensi-tivity of 89.47％and a specificity of 97.02％.Conclusion The levels of serum SOCS3 and GDF-15 are elevated in patients with T2DM combined with NAFLD,.The combined diagnosis of serum SOCS3,GDF-15,type Ⅲ procolla-gen peptide,laminin,and type Ⅳ collagen has a high value in the degree of liver fibrosis in patients.

Objective:To evaluate preoperative high-resolution thin-layer cervical enhanced CT used to predict the venous route of the submental flap reflux vein and its relationship with adjacent structures in order to guide the anatomical understanding and protection of submental flap in pharyngeal cancer surgery.Methods:Sixty consecutive patients with pharyngeal cancer who underwent submental flap repair surgery in our department from March 2022 to December 2024, as well as 60 patients who were accepted neck dissection suffering other cancers, were selected. Before surgery, high-resolution cervical enhanced CT scans were performed, and the position of the transverse section of the facial vein in the venous phase horizontal image gradually variation tendency was focused layer by layer. The direction and adjacent relationship of the submental flap reflux veins were determined and recorded. Combined with 60 patients with other head and neck tumors who underwent neck dissection in our department during the same period (a total of 120 cases, 240 sides), the classification and management of the draining veins of Fang′s mental flap were conducted. Type Ⅰ mainly drains into the internal jugular vein; Type Ⅱ mainly drains into the external jugular vein and Type Ⅲ mainly drains into the anterior jugular vein (often accompanied by an external jugular draining branch). The status and proportion of venous drainage were analyzed.Results:Vascular predictive coincidence rate was 98.3% (59/60) among the 60 patients with pharyngeal cancer. Only one patient was predicted to have a simple return to the external jugular vein. However, during the operation, in addition to the main return to the external jugular vein, a small portion also returned to the internal jugular vein. Submental flap reflux vessels were classified into three types based on intraoperative submental flap venous return in 60 cases of laryngopharyngeal cancer, in conjunction with the analysis of venous return patterns from 240 cervical CT scans. Type Ⅰ mainly refluxed to the internal jugular vein, accounting for 42.1%. Type Ⅱ mainly refluxed to the external jugular vein (47.9%). Type Ⅲ mainly refluxed to the anterior jugular vein (10.0%). The total detection rate of CT reading of 240 venous reflux was 98.7% (237/240). Vascular predictive coincidence rate was 97.9%(235/240).Conclusion:The detailed analysis of submental venous return vessels can accurately predict the direction of reflux veins and its surrounding areas by preoperative high-resolution enhanced CT scan. This provides reliable guidance for the anatomy and protection of the submental flap reflux veins during surgery.

Objective:To compare the survival outcomes of different subsequent treatment regimens in patients with locally advanced hypopharyngeal squamous cell carcinoma (HPSCC) who achieved partial response (PR) after neoadjuvant chemotherapy based on the gross tumor volume regression rate (GTVRR).Methods:This retrospective study included patients with locally advanced HPSCC treated at the Department of Head and Neck Surgery, Beijing Tongren Hospital, from January 2011 to December 2023. The cohort included 135 males and 3 females, aged from 35 to 77 years. All patients received 2-3 cycles of TPF regimen (paclitaxel+cisplatin+5-fluorouracil) neoadjuvant chemotherapy. Subsequent treatments included concurrent chemoradiotherapy or surgery combined with postoperative adjuvant radiotherapy. The impacts of different subsequent treatment modalities on the survivals and prognoses of patients were compared based on GTVRR thresholds of 50% and 70%. The χ 2 test was used to analyze influencing factors; survival analysis and intergroup comparisons were performed using the Kaplan-Meier method and Log-rank test; prognostic factors were assessed using univariate and multivariate Cox regression analyses. Results:The 5-year OS and PFS rates were 56.5% and 47.9%, respectively, while, the 10-year OS and PFS rates were 25.8% and 21.2%, respectively. The median OS was 75 months, and the median PFS was 48 months. The laryngeal function preservation rate for the entire cohort was 83.3%. The patients who underwent surgery combined with postoperative radiotherapy had significantly better OS and PFS outcomes than those treated with concurrent chemoradiotherapy ( P<0.05). Stratification based on GTVRR revealed that the surgery plus postoperative radiotherapy regimen was particularly effective for PR patients with a GTVRR of 30%-70%, showing significantly better OS and PFS compared to the concurrent chemoradiotherapy group ( P<0.05). Conclusion:The optimal subsequent treatment for PR-HPSCC may be surgery-based comprehensive treatment, particularly for patients with a GTVRR of 30%-70%. This study offers valuable insights for the stratified treatment of HPSCC, which could contribute to improving overall patient prognosis.