ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

Objective To analyze the occurrence status of low blood pressure (BP) in patients with refractory heart failure (RHF) and its relationship with comorbidities. Methods A retrospective analysis was conducted on the clinical data of 360 patients with RHF who were hospitalized in department of cardiology of Affiliated Nantong Hospital of Shanghai University from May 2021 to May 2025. These patients were divided into the RHF with BP group and the RHF group based on their blood pressure at admission. The general data and comorbidities were compared between both groups. Multivariate logistic regression analysis was used to identify the risk factors for coexisting BP. Results The heart rate (HR), N-terminal pro-B-type natriuretic peptide (NT-proBNP), blood urea nitrogen, high-sensitivity cardiac troponin T, right atrial diameter, proportion of cardiac function grade IV, use rate of diuretics and prevalence rate of dilated cardiomyopathy (DCM) in the RHF with BP group were higher while the high-density lipoprotein cholesterol (HDL-C), albumin, left ventricular ejection fraction, use rate of lipid-lowering drugs and prevalence rate of coronary heart disease were lower compared to the RHF group, and the differences were statistically significant (P<0.05). Multivariate logistic regression analysis suggested that increased HR (OR=1.685, 95%CI: 1.106-2.569), increased NT-proBNP (OR=1.772, 95%CI: 1.138-2.759), decreased HDL-C (OR=0.605, 95%CI: 0.400-0.917) and DCM (OR=1.956, 95%CI: 1.176-3.255) were independent risk factors affecting BP in RHF patients (P<0.05). Conclusion The incidence rate of low blood pressure in elderly RHF patients is about 19.17%. Increased heart rate, increased NT-proBNP, decreased HDL-C and dilated cardiomyopathy are closely linked to the occurrence of low blood pressure, and they can be used as clinically related factors to identify patients at high risk of low blood pressure.

ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

Extensive evidence has demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) can ameliorate obesity. Our previous studies revealed that (Ex-4)₂-Fc, a long-acting GLP-1RA we developed, depends on the leptin pathway to treat obesity. However, the mechanisms linking (Ex-4)₂-Fc and leptin resistance remain largely unclear. To address this question, we explored the mechanism of GLP-1RAs from the perspective of the gut microbiota, as increasing evidence indicates an important link between the gut microbiota and obesity. This study aimed to explore the potential role of the gut microbiota in the treatment of GLP-1RAs. We found that (Ex-4)₂-Fc treatment reshaped obesity-induced gut microbiota disturbances and substantially increased the abundance of Akkermansia muciniphila (Am). In addition, (Ex-4)₂-Fc did not respond well in antibiotic-treated (ATB) Obese mice. Subsequent studies have shown that this defect can be overcome by gavage with Am. In addition, we found that Am enhanced (Ex-4)₂-Fc therapy by producing the metabolite inosine. Inosine regulates the macrophage adenosine A2A receptor (A2A) pathway to indirectly reduce leptin levels in adipocytes Thus, elucidating the role of metabolites in regulating the leptin pathway will provide new insights into GLP-1RAs therapy and may lead to more effective strategies for guiding the clinical use of antidiabetic agents.

Objective To investigate the modulatory effect of Yulian Pills(composed of Coptidis Rhizoma and Euodiae Fructus)on splenic memory follicular T helper cell(mTfh)in mice with dextran sodium sulfate(DSS)-induced ulcerative colitis.Methods Forty BALB/c mice were randomly divided into normal group,model group,Yulian Pills group(0.5 g·kg-1)and Mesalazine group(0.3 g·kg-1),10 mice in each group.The mouse model of ulcerative colitis was induced by ad libitum drinking 3%DSS solution for 7 days.During the experiment,the mental state,faecal characteristics,blood in stool and body mass of the mice were recorded daily,and the length and mass of the colon were measured and the colon mass index was calculated;HE staining was used to observe the pathological and morphological changes of the colon tissue;ELISA was used to determine the expression levels of interleukin(IL)-6 and IL-15 in the colon tissues;flow cytometry was used to determine the mTfh cell subpopulation in the spleen tissue expression;Western Blot was used to determine the protein expression levels of Roquin-1,AMPK-α,p-AMPK-α in colon tissues.Results Compared with the normal group,the mice in the model group showed a significant decrease in body mass(P＜0.01),a significant shortening of colon length(P＜0.01),significant increase in colon mass(P＜0.05)and colon mass index(P＜0.01),and severe pathological damage to colon tissues;the expression levels of the pro-inflammatory cytokines IL-6 and IL-15 in the colon tissues were significantly increased(P＜0.01);cell expression levels of CD4+CCR7-CXCR5+CD62L+,CD4+CCR7+CXCR5+ GL7+,CD4+CCR7-CXCR5+GL7+ were significantly increased in spleen tissues(P＜0.01),whereas the expression level of CD4+CCR7+CXCR5+CD62L+ cell was significantly decreased(P＜0.01);and protein expression levels of Roquin-1,AMPK-α,p-AMPK-α were significantly reduced in the colonic tissues(P＜0.05).Compared with the model group,mice in the Yulian Pills group and Mesalazine group showed a significant increase in body mass(P＜0.05),a significant extension of colon length(P＜0.01),a significant reduction in colon mass(P＜0.05),a significant decrease in the colon mass index(P＜0.01),and a more obvious improvement in pathological damage of the colon tissues;a significant decrease in the expression levels of IL-6 and IL-15 in the colon tissues(P＜0.01);cell expression levels of CD4+CCR7-CXCR5+CD62L+,CD4+CCR7+CXCR5+GL7+,CD4+CCR7-CXCR5+GL7+ in splenic tissues was significantly reduced(P＜0.01),whereas the expression level of CD4+CCR7+CXCR5+CD62L+ cell was significantly increased(P＜0.01);the protein expression levels of Roquin-1,AMPK-α,and p-AMPK-α were significantly increased in colon tissues(P＜0.05,P＜0.01).Conclusion The therapeutic effect of Yulian Pills on DSS-induced ulcerative colitis mice can ameliorate the histopathological damage of colon,which may be related to the activation of the Roquin-1/MPK-α signalling pathway,the down-regulation of the expressions of inflammatory cytokines IL-6 and IL-15,and the modulation of the homeostasis of the mTfh cell subpopulation.

Objective:To explore the risk factors of acute kidney injury (AKI) in patients with moderate and severe renal insufficiency after receiving voriconazole for injection and to establish a model for predicting the occurrence risk.Methods:The study was designed as a retrospective study. The subjects were selected from patients with moderate to severe renal insufficiency who were hospitalized in Jiaozuo People′s Hospital of Henan Province from January 1, 2020 to December 31, 2022 and received treatment with voriconazole for injection. Through the hospital information system, clinical data of patients were collected, including basic information, clinical diagnosis, laboratory test indexes, comorbid diseases, and co-medication. Patients were divided into AKI and non-AKI groups according to whether voriconazole-related AKI occurred. AKI risk factors were analyzed using multiple logistic regression, and prediction models were established accordingly. Calibration curves were plotted using R4.2.3 software, and the model was internally validated using the k-fold cross-validation method.Results:A total of 146 patients were enrolled in the study with an age of 72.4±13.8 years, including 84 males and 62 females; 61 patients (41.8%) of which developed voriconazole-related AKI. Compared with the non-AKI group, the white blood cell count, neutrophils percentage, proportion of patients with basic renal diseases, and proportion of patients with cardiovascular diseases were higher in the AKI group; the days of voriconazole injection treatment, proportion of patients with hematological diseases, and proportion of patients receiving glycopeptide drugs were lower in the AKI group. The results of multiple logistic regression showed that albumin [X 1, odds ratio( OR)=0.946, 95% confidence interval( CI): 0.915-0.977, P=0.001], neutrophil percentage (X 2, OR=1.013, 95 %CI: 1.000- 1.026, P=0.001), and complicated with underlying renal diseases (X 3, OR=2.230, 95 %CI: 1.110-4.483, P= 0.046) were independent influencing factors of AKI caused by voriconazole for injection in patients with moderate and severe renal insufficiency. The prediction model was established and the joint prediction factor Y=14.32X 1+0.23X 2-X 3. When the maximum value of Youden index was 0.382, the best tangent point of receiver operating characteristic curve was -11.33. The internal cross-validation results showed that the accuracy of the model was 0.70 and the Kappa coefficient (consistency) was 0.37. Conclusions:The incidence of AKI in patients with moderate and severe renal insufficiency after receiving voriconazole for injection was 41.8%. Albumin, neutrophil percentage and underlying renal diseases were the independent influencing factors. The calculation of joint predictors based on the above indicators was helpful to predict the risk of AKI and had a certain reference value for clinic.

Objective:To explore the risk factors of acute kidney injury (AKI) in patients with moderate and severe renal insufficiency after receiving voriconazole for injection and to establish a model for predicting the occurrence risk.Methods:The study was designed as a retrospective study. The subjects were selected from patients with moderate to severe renal insufficiency who were hospitalized in Jiaozuo People′s Hospital of Henan Province from January 1, 2020 to December 31, 2022 and received treatment with voriconazole for injection. Through the hospital information system, clinical data of patients were collected, including basic information, clinical diagnosis, laboratory test indexes, comorbid diseases, and co-medication. Patients were divided into AKI and non-AKI groups according to whether voriconazole-related AKI occurred. AKI risk factors were analyzed using multiple logistic regression, and prediction models were established accordingly. Calibration curves were plotted using R4.2.3 software, and the model was internally validated using the k-fold cross-validation method.Results:A total of 146 patients were enrolled in the study with an age of 72.4±13.8 years, including 84 males and 62 females; 61 patients (41.8%) of which developed voriconazole-related AKI. Compared with the non-AKI group, the white blood cell count, neutrophils percentage, proportion of patients with basic renal diseases, and proportion of patients with cardiovascular diseases were higher in the AKI group; the days of voriconazole injection treatment, proportion of patients with hematological diseases, and proportion of patients receiving glycopeptide drugs were lower in the AKI group. The results of multiple logistic regression showed that albumin [X 1, odds ratio( OR)=0.946, 95% confidence interval( CI): 0.915-0.977, P=0.001], neutrophil percentage (X 2, OR=1.013, 95 %CI: 1.000- 1.026, P=0.001), and complicated with underlying renal diseases (X 3, OR=2.230, 95 %CI: 1.110-4.483, P= 0.046) were independent influencing factors of AKI caused by voriconazole for injection in patients with moderate and severe renal insufficiency. The prediction model was established and the joint prediction factor Y=14.32X 1+0.23X 2-X 3. When the maximum value of Youden index was 0.382, the best tangent point of receiver operating characteristic curve was -11.33. The internal cross-validation results showed that the accuracy of the model was 0.70 and the Kappa coefficient (consistency) was 0.37. Conclusions:The incidence of AKI in patients with moderate and severe renal insufficiency after receiving voriconazole for injection was 41.8%. Albumin, neutrophil percentage and underlying renal diseases were the independent influencing factors. The calculation of joint predictors based on the above indicators was helpful to predict the risk of AKI and had a certain reference value for clinic.

Objective To evaluate the effect of preoperative pulmonary artery pressure on perioperative prognosis of the recipients with end-stage heart failure undergoing heart transplantation. Methods Clinical data of 105 recipients receiving heart transplantation were retrospectively analyzed. The mean pulmonary artery pressure (mPAP) was used as the diagnostic criterion. The optimal cut-off value of mPAP for predicting perioperative prognosis of heart transplant recipients was determined. According to the optimal cut-off value of mPAP, all recipients were divided into the low mPAP group (n=66) and high mPAP group (n=39). Intraoperative indexes (cardiopulmonary bypass time, aortic occlusion time, assisted circulation time and cold ischemia time of donor heart) and postoperative indexes [intra-aortic balloon pump (IABP) support rate, IABP support time, extracorporeal membrane oxygenation (ECMO) support rate, ECMO support time, mechanical ventilation time, length of ICU stay, incidence of moderate and severe tricuspid regurgitation and perioperative mortality rate] were compared between the low and high mPAP groups. The prognosis of the two groups was compared. Results The optimal cut-off value of mPAP in predicting clinical prognosis of heart transplant recipients was 30.5 mmHg. In the high mPAP group, the ECMO support rate and perioperative mortality rate were higher than those in the low mPAP group (both P < 0.05). No significant differences were observed in the cardiopulmonary bypass time, aortic occlusion time, assisted circulation time, cold ischemia time of donor heart, IABP support rate, IABP support time, ECMO support time, mechanical ventilation time, length of ICU stay and incidence of moderate and severe tricuspid regurgitation between two groups (all P > 0.05). No significant differences were noted in the 1-, 2-, 3- and 4- survival rates between two groups (all P > 0.05). Conclusions Preoperative mPAP in patients with end-stage heart failure is intimately correlated with perioperative prognosis of heart transplant recipients. The optimal cut-off value of mPAP in predicting perioperative prognosis of heart transplant recipients is 30.5 mmHg. In the high mPAP group, perioperative ECMO support rate and perioperative mortality rate are high, which do not affect the medium and long-term prognosis of the recipients undergoing heart transplantation.

Objective:To explore the distribution of airborne pollen in summer and autumn in Taiyuan, analyze the correlation between pollen characteristics, meteorological factors and allergic sensitization, and provide for the prevention and treatment of allergic diseases in this. Methods:The gravity sedimentation method was used to investigate the types, quantities and dispersion patterns of airborne pollen in Taiyuan City from July 21, 2022 to October 20, 2022. he meteorological and patient information was collected during the same period SPSS 26.0 software. Results:①A total of 17 118 pollen grains were collected, and identified as 14 families, 10 genera, and 4 species. The peak period for pollen dispersal in summer and autumn in Taiyuan City from late August to early September. airborne pollen Artemisia（66.62%）, Cannabis/Humulus（17.79%）, Sophora japonica（8.18%）, Chenopodiaceae/Amaranthaceae（2.83%）, Gramineae（2.11%）. ②The concentration of airborne pollen in Taiyuan City positively correlated with the average temperature（5-20℃） and maximum temperature（11-30℃） within a certain range（r=0.547, 0.315, P<0.05）. ③The content of airborne pollen in Taiyuan City positively correlated with the number of visits and allergen positive rate of patients with allergic rhinitis（AR） in our hospital（r=0.702, 0.747, P<0.05）. Conclusion:The peak period for airborne pollen dispersal during the summer and autumn seasons in Taiyuan City from late August to early September. The dominant pollen is Artemisia, Cannabis/Humulus, Sophora japonica, Chenopodiaceae/Amaranthaceae, Gramineae, and the absolute advantage pollen is Artemisia. Meteorological factors pollen content. Within a certain range, temperature the diffusion and transportation of pollen. The number of pollen grains the number of visits, which can serve as an environmental warning indicator for AR patients to take preventive, thereby reducing the risk of allergies.
Male ; Humans ; Seasons ; Pollen ; Rhinitis, Allergic ; Allergens ; Cities