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.

Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.

Objective:To discuss whether safranal affects the proliferation,migration,and phenotypic transformation of the vascular smooth muscle cells(VSMCs)in a high-glucose environment and to clarify the function of safranal in the prevention and treatment of diabetic(DM)vascular complications.Methods:The SD rats were selected as experimental subjects;primary VSMCs were cultured from rat thoracic aortas and divided into control group,25 mmol·L-1 high glucose(HG)group,HG+20 μmol·L-1 safranal group,HG+40 μmol·L-1 safranal group,and HG+80 μmol·L-1 safranal group.The cells in control group received no treatment;the cells in 25 mmol·L-1 HG group were pretreated with 25 mmol·L-1 HG;the cells in HG+20,40,and 80 μmol·L-1 safranal groups were further treated with 20,40,and 80 μmol·L-1 safranal respectively for 48 h on the basis of 25 mmol·L-1 HG group.Cell counting kit-8(CCK-8)method was used to determine the appropriate concentration of safranal and detect the viabilities of the VSMCs in various groups;cell scratch healing assay was used to detect the scratch healing rates of the VSMCs in various groups;Transwell chamber assay was used to detect the numbers of the migration VSMCs in various groups;immunofluorescence method was used to detect the fluorescence intensities of alpha-smooth muscle actin(α-SMA)and rabbit anti-osteopontin(OPN)in the VSMCs in various groups;Western blotting method was used to detect the expression levels of OPN,α-SMA,and proliferating cell nuclear antigen(PCNA)in the VSMCs in various groups.Results:Under microscope,on the 4th day of in vitro culture,the spindle-shaped or triangular cells crawled out from the edge of the thoracic aorta tissue blocks,with long spindle being the most common morphology.On the 14th,the cells gradually covered the bottom of the dish;when cell density reached 80%-90%,the characteristic"hills and valleys"growth pattern appeared.Third-generation cells were taken for immunofluorescence identification;immunofluorescence staining with VSMC-specific marker α-SMA showed positive expression of α-SMA protein in the primarily cultured VSMCs.The CCK-8 assay results showed that compared with control group,the cell viability of the cells in 160 μmol·L-1 safranal group was significantly decreased(P<0.01),indicating toxic damage to the cells.Under the conditions of safranal concentrations at 20,40,and 80 μmol·L-1 respectively,after 48 h intervention on VSMCs,no significant adverse effect on cell viability was observed;considering both the effect and toxicity of safranal,these three concentrations were used in subsequent cell experiments.After 48 h intervention,compared with control group,the activity of the VSMCs in 25 mmol·L-1 HG group was increased(P<0.001);compared with 25 mmol·L-1 HG group,the activities of the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually decreased(P<0.05).The cell scratch healing assay and Transwell assay results showed that after 48 h intervention,the scratch healing rate of the VSMCs in 25 mmol·L-1 HG group was significantly higher than that in control group(P<0.01),and the number of transmembrane cells through the Transwell chamber was significantly increased(P<0.05);compared with 25 mmol·L-1 HG group,the scratch healing rates of the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually decreased(P<0.05),and the number of transmembrane cells was decreased(P<0.05).The immunofluorescence staining results showed that compared with control group,the fluorescence intensity of α-SMA protein in the VSMCs in 25 mmol·L-1 HG group was significantly weakened(P<0.001),while the fluorescence intensity of OPN protein was significantly enhanced(P<0.001);compared with 25 mmol·L-1 HG group,the fluorescence intensities of α-SMA protein in the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were gradually increased(P<0.05),and the fluorescence intensities of OPN were gradually weakened(P<0.05).The Western blotting method results showed that compared with control group,the expression level of α-SMA protein in the VSMCs in 25 mmol·L-1 HG group was decreased(P<0.05),and the expression levels of PCNA and OPN proteins were increased(P<0.01);compared with 25 mmol·L-1 HG group,the expression level of α-SMA protein in the VSMCs in HG+20,40,and 80 μmol·L-1 safranal groups were increased(P<0.05),and the expression levels of PCNA and OPN proteins were decreased(P<0.05).Conclusion:Safranal can inhibit the proliferation,migration,and phenotypic transformation of the VSMCs induced by high glucose.

Objective To study the intervention effect of nursing staff's participation in antimicrobial stewardship(AMS)on the rational use of antimicrobial agents,and explore its role in constructing a scientific healthcare-associa-ted infection(HAI)control management.Methods The data on perioperative prophylactic use of antimicrobial agents,surgical-related HAI control,and pathogen detection before therapeutic use of antimicrobial agents among hospitalized patients in a hospital from January 2016 to December 2024 were collected.Relevant evaluation indica-tors before and after nursing staff participating in AMS were compared.2016-2018,2019-2021,and 2022-2024 were stages before intervention,during intervention,and after intervention,respectively.Results After nursing staff participated in AMS,the use rate of prophylactic antimicrobial agents 0.5-1 hour before surgery and discon-tinuation rate of antimicrobial agents within 24 hours after class Ⅰ incision surgery increased from 64.54％and 81.41％before intervention to 75.31％and 84.56％after intervention,respectively.Incidences of surgical-related HAI and surgical site infection in patients decreased from 3.11％and 0.96％before intervention to 1.37％and 0.17％after intervention,respectively.Pathogen detection rates before restricted-and special-grade antimicrobial agents treatment increased from 50.80％and 68.70％before intervention to 55.19％and 80.53％after interven-tion,respectively.Proportion of blood specimen from which coagulase-negative Staphylococcus was detected de-creased from 29.30％before intervention to 21.26％after intervention.Proportion of respiratory specimen from which Haemophilus influenzae was detected increased from 2.00％to 3.98％.Differences were all statistically sig-nificant(all P＜0.05).Conclusion As important members of the AMS team,nursing staff can effectively reduce irrational antimicrobial use,optimize medication timing and duration,and have a positive effect on ensuring patient safety through participating in the use and management of antimicrobial agents in hospitalized patients.

Objective:To study the level of regulatory T cell(Treg)in peripheral blood of diffuse large B-cell lymphoma(DLBCL)patients at initial diagnosis,and its value in the evaluation of efficacy and prognosis.Methods:A total of 72 newly diagnosed DLBCL patients admitted to the Second Affiliated Hospital of Anhui Medical University from January 2018 to February 2022 were selected as research objects,and 17 healthy volunteers were taken as the control group.The level of CD4+CD25+CD127lowTreg in peripheral blood of patients was detected by flow cytometry,and a comparative analysis was conducted in conjunction with the clinical characteristics of patients.Results:The percentage of Treg in peripheral blood before treatment was correlated with Ann Arbor stage,IPI score,ECOG score and hemoglobin(HB).The levels of Treg in peripheral blood at initial diagnosis were significantly lower than that of healthy con-trols(3.85±0.22 vs 5.15±0.31,P=0.007).DLBCL patients were divided into high Treg group and low Treg group according to the me-dian percentage of CD4+CD25+CD127lowTreg in peripheral blood to CD4+T cells at initial diagnosis,the total effective rate of high Treg group was significantly higher than that of low Treg group(P=0.035).ECOG score(P=0.040)and low level of Treg before treatment(P=0.014)were independent risk factors for progression-free survival(PFS)in DLBCL patients.Having B symptom(P=0.028),ECOG score≥2(P=0.041)and low level of Treg before treatment(P=0.036)were independent risk factors for OS.PFS(P=0.020)and OS(P=0.036)in low Treg group were significantly lower than those in high Treg group.Conclusion:The low percentage of CD4+CD25+CD127lowTreg in peripheral blood of newly diagnosed DLBCL patients indicates a poor prognosis.

OBJECTIVE To analyze the clinical distribution characteristics and drug resistance of Enterobacter cloa-cae in Gansu Province from 2019 to 2023,providing reference for the prevention and control of E.cloacae infec-tions in this region.METHODS Data on the distribution and drug resistance of E.cloacae from hospitals in mem-ber units of the Gansu Antimicrobial Surveillance Network between 2019 and 2023 were collected.In vitro drug susceptibility testing was performed by the Kirby-Bauer disk diffusion(K-B)method,minimum inhibitory con-centration method,and fully automated instrumentation,followed by analysis of the susceptibility results.RESULTS From 2019 to 2023,a total of 402 490 bacterial strains were isolated and cultured in Gansu Province,including 17 417 strains of E.cloacae,with a detection rate of 4.33％.The bacteria were primarily iso-lated from sputum specimens(62.81％),followed by urine(7.37％)and wound pus specimens(6.07％).The de-partmental distribution was dominated by internal medicine(44.96％)and surgery(28.50％).The highest detec-tion rate was observed in the adult group(15-65 years,45.79％).E.cloacae exhibited varying degrees of resist-ance to over 20 antibacterial drugs,but the overall drug resistance rate showed a declining trend(P＜0.05).The highest drug resistance rate was observed for cefazolin(96.40％-98.38％),while the lowest was for tigecycline(0.44％—2.92％).Carbapenem-resistant E.cloacae demonstrated an increasing trend in drug resistance rates,with imipenem resistance ranging from 2.79％to 3.71％(P=0.044)and meropenem resistance ranging from 1.29％to 3.41％(P＜0.05).CONCLUSIONS The isolation rate of E.cloacae in Gansu Province remains stable,with a declining trend in drug resistance to multiple antibacterial drugs.However,the increasing drug resistance to carbapenems warrants attention.

The liver performs multiple life-sustaining functions. Hepatic diseases, including hepatitis, cirrhosis, and hepatoma, pose significant health and economic burdens globally. Along with the advances in nanotechnology, mesoporous silica nanoparticles (MSNs) exhibiting diversiform size and shape, distinct morphological properties, and favorable physico-chemical features have become an ideal choice for drug delivery systems and inspire alternative thinking for the management of hepatic diseases. Initially, we introduce the physiological structure of the liver and highlight its intrinsic cell types and correlative functions. Next, we detail the synthesis methods and physicochemical properties of MSNs and their capacity for controlled drug loading and release. Particularly, we discuss the interactions between liver and MSNs with respect to the passive targeting mechanisms of MSNs within the liver by adjusting their particle size, pore diameter, surface charge, hydrophobicity/hydrophilicity, and surface functionalization. Subsequently, we emphasize the role of MSNs in regulating liver pathophysiology, exploring their value in addressing liver pathological states, such as tumors and inflammation, combined with multi-functional designs and intelligent modes to enhance drug targeting and minimize side effects. Lastly, we put forward the problems, challenges, opportunities, as well as clinical translational issues faced by MSNs in the management of liver diseases.

Objective:To analyze the efficacy of different doses of esketamine in maintaining general anesthesia in elderly patients undergoing radical resection of esophageal cancer.Methods:A total of 98 elderly patients who underwent radical resection of esophageal cancer and admitted from Jun. 2023 to May. 2025 in Shangqiu First People’s Hospital were selected and divided into Group A ( n=50, 0.25 mg·kg -1·h -1) and Group B ( n=48,0.5 mg·kg -1·h -1) according to the dose of esketamine. The following situations between the two groups were compared: (1) hemodynamics [mean arterial pressure (MAP), heart rate (HR) ] before anesthesia induction (T0), 30 minutes after the start of the operation (T1), and at extubation (T2) ; (2) Stress inflammatory indicators [norepinephrine (NE), C-reactive protein (CRP) ] before the operation and 1 day after the operation; (3) Analgesia status [Dosage of propofol and remifentanil, remedial analgesia rate, and the degree of analgesia was evaluated by visual analogue scale (VAS) 2 hours after the operation]; (4) Postoperative recovery [postoperative eye-opening time, extubation time, anesthesia recovery time, and postoperative recovery quality was evaluated using the Chinese version of the 15-item Quality of Recovery (QoR-15) Scale 1 day after the operation]; (5) Safety. Results:(1) At time T1, MAP of both groups was lower than that at time T0,and at time T2, MAP of group B was higher than that at time T1 ( P<0.05). At times T1 and T2, HR of both groups was lower than that at time T0, and HR of both groups at time T2 was higher than that at time T1 ( P<0.05). At time T1, MAP and HR in group B were lower than those in group A ( P<0.05). (2) The dosages of propofol and remifentanil in group B were lower ( P<0.05) ,while the comparison of remedial analgesia rate and VAS score between the two groups showed P>0.05. (3) One day after the operation,the levels of serum NE and CRP in both groups were higher than those before the operation,while those in group B were even lower ( P<0.05). (4) The incidence of adverse reactions in group B (20.83%) was slightly higher than that in group A (10.00%). (5) The eye-opening time,extubation time and anesthesia recovery time after surgery in group B were all longer than those in group A ( P<0.05), while the comparison of QoR-15 scores between the two groups showed P>0.05. Conclusions:In the maintenance of general anesthesia for elderly patients undergoing radical resection of esophageal cancer, the intraoperative hemodynamic fluctuations of low-dose esketamine are smaller. Although the dosages of propofol and remifentanil are higher and the postoperative recovery time is longer, there are no significant differences in analgesic effect, adverse reactions or recovery quality, while the stress and inflammatory responses of high-dose esketamine are smaller.

Objective:To study the level of regulatory T cell(Treg)in peripheral blood of diffuse large B-cell lymphoma(DLBCL)patients at initial diagnosis,and its value in the evaluation of efficacy and prognosis.Methods:A total of 72 newly diagnosed DLBCL patients admitted to the Second Affiliated Hospital of Anhui Medical University from January 2018 to February 2022 were selected as research objects,and 17 healthy volunteers were taken as the control group.The level of CD4+CD25+CD127lowTreg in peripheral blood of patients was detected by flow cytometry,and a comparative analysis was conducted in conjunction with the clinical characteristics of patients.Results:The percentage of Treg in peripheral blood before treatment was correlated with Ann Arbor stage,IPI score,ECOG score and hemoglobin(HB).The levels of Treg in peripheral blood at initial diagnosis were significantly lower than that of healthy con-trols(3.85±0.22 vs 5.15±0.31,P=0.007).DLBCL patients were divided into high Treg group and low Treg group according to the me-dian percentage of CD4+CD25+CD127lowTreg in peripheral blood to CD4+T cells at initial diagnosis,the total effective rate of high Treg group was significantly higher than that of low Treg group(P=0.035).ECOG score(P=0.040)and low level of Treg before treatment(P=0.014)were independent risk factors for progression-free survival(PFS)in DLBCL patients.Having B symptom(P=0.028),ECOG score≥2(P=0.041)and low level of Treg before treatment(P=0.036)were independent risk factors for OS.PFS(P=0.020)and OS(P=0.036)in low Treg group were significantly lower than those in high Treg group.Conclusion:The low percentage of CD4+CD25+CD127lowTreg in peripheral blood of newly diagnosed DLBCL patients indicates a poor prognosis.