AIM:To explore the mechanism of doxorubicin/copper(DOX/Cu)complex induced copper death in hepatocellular carcinoma cells.METHODS:Human hepatocellular carcinoma cell line Huh7 was treated with DOX/Cu 0,2.5,4,7.5,10 and 12.5 μmol/L.The cell viability was detected by CCK-8 method.The cell proliferation level was observed by laser microscopy and proliferation kit.The cell invasion ability was determined by cell scratch assay.The flow cytometry was used to de-tect intracellular reactive oxygen species(ROS)and copper ion levels.And the western blot was used to detect intracellular iron-sulfur cluster proteins expression levels.RESULTS:With the increase of DOX/Cu concentration,cell viability,cell prolifera-tion and invasion ability decreased gradually.The copper ion chelating agent(TTM)can significantly restore the effects of DOX/Cu on cell viability.After DOX/Cu treatment,intracellular copper ion and ROS levels related to coproptosis were significantly increased,accompanied by the loss of iron-sulfur cluster proteins.CONCLUSION:DOX/Cu can inhibit hepatocellular carcinoma cells through cuproptosis.

Objective:To construct and validate a depression risk prediction model for middle-aged and elderly patients with diabetes.Methods:Data were extracted from the fifth wave (2020) of the China Health and Retirement Longitudinal Study (CHARLS). A total of 900 diabetic patients were identified, and after excluding those with missing data or invalid questionnaires, 769 patients were included in the analysis. Patients were randomly divided into a training set and a validation set in a 7∶3 ratio. Univariate analysis and logistic regression analysis were performed to screen the optimal predictors of depression in diabetic patients, and a nomogram model was developed. The predictive performance of the model was assessed by the area under the receiver operating characteristic curve ( AUC). Model calibration and accuracy were evaluated using bootstrap resampling, calibration plots, and the Hosmer-Lemeshow test. The clinical utility was further assessed by decision curve analysis (DCA) and clinical impact curves (CIC) . Results:Among the 769 patients, 366 (47.59%) had depression. Logistic regression analysis showed that place of residence, pain, difficulty in toileting, difficulty in bathing, sleep duration, physical exercise, life satisfaction, and children's satisfaction were independent predictors of depression in diabetic patients. A nomogram was constructed based on these variables, yielding an AUC of 0.775. At the optimal cutoff value of 0.557, the model demonstrated a sensitivity of 59.1% and a specificity of 84.8%, indicating good discriminative ability. The Hosmer-Lemeshow test showed (χ 2=15.821, P=0.105), suggesting good agreement between predicted and observed outcomes. In the validation set, the AUC was 0.778, with Hosmer-Lemeshow (χ 2=8.557, P=0.575). DCA and CIC indicated favorable clinical applicability of the model. Conclusions:The depression risk prediction model constructed in this study demonstrated good predictive performance. It can assist clinicians in early identification of high-risk individuals with diabetes and provide a theoretical basis for targeted interventions.

AIM:To explore the mechanism of doxorubicin/copper(DOX/Cu)complex induced copper death in hepatocellular carcinoma cells.METHODS:Human hepatocellular carcinoma cell line Huh7 was treated with DOX/Cu 0,2.5,4,7.5,10 and 12.5 μmol/L.The cell viability was detected by CCK-8 method.The cell proliferation level was observed by laser microscopy and proliferation kit.The cell invasion ability was determined by cell scratch assay.The flow cytometry was used to de-tect intracellular reactive oxygen species(ROS)and copper ion levels.And the western blot was used to detect intracellular iron-sulfur cluster proteins expression levels.RESULTS:With the increase of DOX/Cu concentration,cell viability,cell prolifera-tion and invasion ability decreased gradually.The copper ion chelating agent(TTM)can significantly restore the effects of DOX/Cu on cell viability.After DOX/Cu treatment,intracellular copper ion and ROS levels related to coproptosis were significantly increased,accompanied by the loss of iron-sulfur cluster proteins.CONCLUSION:DOX/Cu can inhibit hepatocellular carcinoma cells through cuproptosis.

Objective:To construct and validate a depression risk prediction model for middle-aged and elderly patients with diabetes.Methods:Data were extracted from the fifth wave (2020) of the China Health and Retirement Longitudinal Study (CHARLS). A total of 900 diabetic patients were identified, and after excluding those with missing data or invalid questionnaires, 769 patients were included in the analysis. Patients were randomly divided into a training set and a validation set in a 7∶3 ratio. Univariate analysis and logistic regression analysis were performed to screen the optimal predictors of depression in diabetic patients, and a nomogram model was developed. The predictive performance of the model was assessed by the area under the receiver operating characteristic curve ( AUC). Model calibration and accuracy were evaluated using bootstrap resampling, calibration plots, and the Hosmer-Lemeshow test. The clinical utility was further assessed by decision curve analysis (DCA) and clinical impact curves (CIC) . Results:Among the 769 patients, 366 (47.59%) had depression. Logistic regression analysis showed that place of residence, pain, difficulty in toileting, difficulty in bathing, sleep duration, physical exercise, life satisfaction, and children's satisfaction were independent predictors of depression in diabetic patients. A nomogram was constructed based on these variables, yielding an AUC of 0.775. At the optimal cutoff value of 0.557, the model demonstrated a sensitivity of 59.1% and a specificity of 84.8%, indicating good discriminative ability. The Hosmer-Lemeshow test showed (χ 2=15.821, P=0.105), suggesting good agreement between predicted and observed outcomes. In the validation set, the AUC was 0.778, with Hosmer-Lemeshow (χ 2=8.557, P=0.575). DCA and CIC indicated favorable clinical applicability of the model. Conclusions:The depression risk prediction model constructed in this study demonstrated good predictive performance. It can assist clinicians in early identification of high-risk individuals with diabetes and provide a theoretical basis for targeted interventions.

OBJECTIVE To explore the effects and potential mechanism of evodiamine on inflammatory response and apoptosis of epithelial cells in asthma model rats. METHODS SD rats were separated into control group， model group， evodiamine low-dose group （10 mg/kg）， evodiamine high-dose group （20 mg/kg）， dexamethasone group （positive control， 0.5 mg/kg）， epidermal growth factor （EGF） group [mitogen-activated protein kinase （MAPK） activator， 10 μg]， evodiamine high-dose+EGF group （20 mg/kg evodiamine+10 μg EGF）， with 10 rats in each group. Except for the control group， the other groups were sensitized by 3-point injection of 10% ovalbumin（OVA）-aluminium hydroxide mixture and stimulated by inhalation of 2%OVA nebulized liquid to establish an asthma model. The count of inflammatory cells （macrophages and lymphocytes） in bronchoalveolar lavage fluid （BALF） was detected in each group； pathological changes of lung tissue in rats were observed； the apoptosis of airway epithelial cells， the levels of serum inflammatory factors [tumor necrosis factor-α， interleukin-6 （IL-6） and IL-4]， the expressions of pathway-related proteins p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， signal transduction and transcription activating factor 1 （STAT1）] and apoptosis-related proteins [B cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax）] were all detected in lung tissue. RESULTS Compared with the control group， bronchial mucosal edema， thickening of alveolar septa and extensive infiltration of inflammatory cells were observed in the lung tissue of rats in the model group； the number of inflammatory cells， apoptosis rate of airway epithelial cells， the levels of inflammatory factors， p-38 MAPK/p-38 MAPK， and the protein expressions of Bax and STAT1 were increased significantly； the expressions of Bcl-2 protein and Bcl-2/Bax were reduced significantly （P＜0.05）. Compared with the model group， the pathological changes in lung tissues were alleviated to varying degrees in evodiamine low-dose and high-dose groups， and dexamethasone groups， and the above indicators were significantly reversed. However， the change trends of corresponding indicators in the EGF group were opposite to the above （P＜0.05）. EGF could significantly attenuate the effect of high-dose evodiamine on inflammatory response in asthmatic rats （P＜0.05）. CONCLUSIONS Evodiamine can relieve inflammatory reactions and inhibit the apoptosis of airway epithelial cells in asthmatic rats， the mechanism of which may be associated with inhibiting p38 MAPK/STAT1 signaling pathway.

OBJECTIVE To explore the effects and potential mechanism of evodiamine on inflammatory response and apoptosis of epithelial cells in asthma model rats. METHODS SD rats were separated into control group， model group， evodiamine low-dose group （10 mg/kg）， evodiamine high-dose group （20 mg/kg）， dexamethasone group （positive control， 0.5 mg/kg）， epidermal growth factor （EGF） group [mitogen-activated protein kinase （MAPK） activator， 10 μg]， evodiamine high-dose+EGF group （20 mg/kg evodiamine+10 μg EGF）， with 10 rats in each group. Except for the control group， the other groups were sensitized by 3-point injection of 10% ovalbumin（OVA）-aluminium hydroxide mixture and stimulated by inhalation of 2%OVA nebulized liquid to establish an asthma model. The count of inflammatory cells （macrophages and lymphocytes） in bronchoalveolar lavage fluid （BALF） was detected in each group； pathological changes of lung tissue in rats were observed； the apoptosis of airway epithelial cells， the levels of serum inflammatory factors [tumor necrosis factor-α， interleukin-6 （IL-6） and IL-4]， the expressions of pathway-related proteins p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， signal transduction and transcription activating factor 1 （STAT1）] and apoptosis-related proteins [B cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax）] were all detected in lung tissue. RESULTS Compared with the control group， bronchial mucosal edema， thickening of alveolar septa and extensive infiltration of inflammatory cells were observed in the lung tissue of rats in the model group； the number of inflammatory cells， apoptosis rate of airway epithelial cells， the levels of inflammatory factors， p-38 MAPK/p-38 MAPK， and the protein expressions of Bax and STAT1 were increased significantly； the expressions of Bcl-2 protein and Bcl-2/Bax were reduced significantly （P＜0.05）. Compared with the model group， the pathological changes in lung tissues were alleviated to varying degrees in evodiamine low-dose and high-dose groups， and dexamethasone groups， and the above indicators were significantly reversed. However， the change trends of corresponding indicators in the EGF group were opposite to the above （P＜0.05）. EGF could significantly attenuate the effect of high-dose evodiamine on inflammatory response in asthmatic rats （P＜0.05）. CONCLUSIONS Evodiamine can relieve inflammatory reactions and inhibit the apoptosis of airway epithelial cells in asthmatic rats， the mechanism of which may be associated with inhibiting p38 MAPK/STAT1 signaling pathway.

Objective:To investigate the impacts of Schisandrin B(Sch B)on airway inflammation and airway remodeling in asthmatic rats by regulating Noxa/Heat shock protein 27(Hsp27)/nuclear factor-κB(NF-κB)signaling pathway.Methods:SD male rats were randomly separated into control group(normal feeding),asthma group,Sch B-L group(40 mg/kg),Sch B-H group(80 mg/kg),positive control group(0.5 mg/kg dexamethasone),Vector group(tail vein injection of empty plasmid+80 mg/kg Sch B),Noxa group(tail vein injection of Noxa overexpression plasmid+80 mg/kg Sch B),with 6 rats in each group.Except the control group,6 groups of rats were sensitized and stimulated with ovalbumin to establish asthma rat model,and were given drug intervention,once a day for four weeks.RT-qPCR was applied to measure the expression of Noxa in lung tissue;differential white blood cell counts in bronchoalveolar lavage fluid(BALF)were performed;ELISA was applied to measure the levels of IL-4,INF-α,IL-13 and IL-5 in rat serum;HE staining was applied to observe the histopathology of lung tissue of rats in each group;expression of Noxa protein and phosphorylation levels of Hsp27 and NF-κB in lung tissue were detected by Western blot.Results:Compared with the Vector group,the expression lev-el of Noxa in the left lung tissue of the Noxa group was obviously increased;compared with the control group,the right lung tissue structure of the rats in the asthma group was obviously damaged,the tracheal tube was obviously narrowed,the interstitium was mas-sively inflammatory infiltration,the thickness of the bronchial smooth muscle,the thickness of the basement membrane and the cir-cumference of the basement membrane were obviously increased,and the cells in the BALF were obviously increased,the total num-ber,eosinophils,neutrophils,and lymphocytes were obviously increased,and macrophages were obviously decreased,the levels of serum TNF-α,IL-4,IL-5 and IL-13 were obviously increased,the expression levels of Noxa,p-Hsp27/Hsp27,p-NF-κB p65/NF-κB p65 in the left lung tissue were obviously increased(P<0.05);compared with the asthma group,the duct stenosis in the right lung tis-sue of the Sch B-L group,the Sch B-H group and the positive control group were obviously improved,the inflammatory infiltration was reduced,the thickness of the bronchial smooth muscle,the thickness of the basement membrane and the circumference of the base-ment membrane were obviously reduced,and the cells in the BALF were obviously reduced,the total number,eosinophils,neutro-phils,and lymphocytes were obviously decreased,and macrophages were obviously increased,the levels of serum TNF-α,IL-4,IL-5 and IL-13 were obviously decreased,the expression levels of Noxa,p-Hsp27/Hsp27,p-NF-κB p65/NF-κB p65 in the left lung tissue were obviously decreased and was dependent on dose(P<0.05);overexpression of Noxa attenuated the ameliorating effects of Sch B on airway inflammation and airway remodeling in asthmatic rats.Conclusion:Sch B can effectively ameliorate airway inflammation and airway remodeling in asthmatic rats by regulating Noxa/Hsp27/NF-κB signaling pathway.

Objective To retrospectively analyze the efficacy and safety of abatacept(ABA)in anti citrullinated peptide antibody(ACPA)positive rheumatoid arthritis(RA).Methods Clinical data from ACPA positive RA patients who visited the Department of Rheumatology and Immunology at the Second Hospital of Hebei Medical University from May 2020 to January 2023 and were treated with ABA were retrospectively collected and analyzed,to evaluate the efficacy and safety of ABA at 12 weeks and 24 weeks of treatment.Efficacy evaluation measures included RA disease activity score-28(DAS-28),clinical disease activity index(CDAI),and remission criteria of RA of American College of Rheumatology(ACR).Results A total of 35 ACPA-positive RA patients were included in the final analysis.The DAS-28,CDAI,ACR20,ACR50,and ACR70 remission rates at 12 weeks after treatment were 34.29%,31.43%,60.00%,28.57%,and 14.29%,respectively;the DAS-28,CDAI,ACR20,ACR50,and ACR70 remission rates at 24 weeks after treatment were 74.29%,82.86%,85.71%,54.29%,and 31.43%,respectively;in addition,the remission rate at 24 weeks was significantly higher than that at 12 weeks(P﹤0.05).Among the 35 patients included in the analysis,4 patients experienced respiratory tract infections,3 patients experienced transient creatinine elevation,and 4 patients experienced elevated blood uric acid.Conclusion In the real world,ABA's clinical remission rate is consistent with expectations,and clinical combination drug regimens are flexible and diverse,with high drug safety.

With the progress of society and the continuous improvement of people′s living standards in China, the public′s demand for medical services is becoming increasingly diversified. How to move hospital services forward and improve medical services centered on patients has become a key consideration for hospitals to enhance patients′ sense of medical satisfaction. A certain hospital has established a one-stop patient service hotline, integrating functions such as number inquiry, medical consultation, appointment registration, appointment examination, praise and suggestions, complaint follow-up, etc., injecting a complaint handling management mode, and responding to and solving patient feedback problems in a timely manner. Since the launch of the patient service hotline, it has effectively solved the problems that patients encountered during their visits, effectively reduced the hospital′s complaint rate, and initially formed a service closed-loop management. From March to October 2023, the demand ratio of the 12345 hotline in the hospital has continuously decreased, and was significantly lower than the average level of 22 municipal hospitals in Beijing. In the future, we should further improve the communication skills between doctors and patients, focus on managing appeals and services, and continue to strengthen proactive governance.

Objective:To construct an evidence-based prediction model for early recurrence after surgery of hepatocellular carcinoma (HCC) based on Meta-analysis and to do external validation study.Methods:The literatures in Chinese National Knowledge Infrastructure, Wanfang, VIP, Chinese Science Citation Database (CSCD), Chinese Social Science Citation System (CCSCI), PubMed, Web of Science and IEEE databases between January 2019 and December 2023 were searched based on the subject words. According to the inclusion and exclusion criteria, 9 literatures were included to screen the risk factors affecting the early recurrence of HCC. When the same risk factor was found in ≥5 included literatures, Meta-analysis was performed by using Review Manager 5.4.1 software. External validation data were collected from 401 patients with primary HCC who underwent surgery in Liaoning Cancer Hospital between March 2014 and March 2017. The patients were divided into early recurrence group (176 cases) and early non-recurrence group (225 cases) according to whether they relapsed 2 years after surgery. The OR values of all risk factors obtained in the Meta-analysis were converted into modeling, and postoperative early recurrence rate of HCC in the Meta-analysis was used to calculate β 0, and finally the logistic model was obtained. The OR value was incorporated into the logit (P) model, and the morbidity (P) of the external validation data was calculated. Taking the recurrence 2 years after surgery or not as the dependent variable and P as the independent variable, the receiver operating characteristic (ROC) curve was drawn to calculate the area under the curve (AUC). Results:A total of 8 risk factors for early HCC recurrence were screened out from 9 literatures (x 1: alpha-fetoprotein ≥ 400 ng/ml; x 2: tumor number ≥ 2; x 3: the longest tumor diameter ≥ 5 cm; x 4: Barcelona staging B-C; x 5: microvascular invasion; x 6: moderate to low differentiation; x 7: incomplete capsule; x 8: nonanatomic hepatectomy). The Meta-analysis included 1 757 HCC cases, with 960 postoperative early recurrences and an early recurrence rate of 45.36%, finally the β 0 value was -0.201. The predictive model for 2-year recurrence of HCC was constructed and calculated as logit (P) = -0.201+0.835x 1+0.905x 2+0.783x 3+1.008x 4+0.765x 5+0.831x 6+1.533x 7+0.940x 8. Analysis of variance by external validation data showed that the differences in ascites, alpha-fetoprotein, tumor number, tumor diameter, Barcelona staging, microvascular invasion, tumor differentiation degree, capsule invasion, resection type, and systemic inflammation index were statistically significant between early recurrence group and early non-recurrence group (all P < 0.05). ROC curve analysis showed that AUC of postoperative early recurrence of HCC predicted by the model was 0.718, (95% CI: 0.689-0.753), the optimal cut-off value was 3.11, the Yoden index was 0.288, the sensitivity was 69.32%, and the specificity was 69.56%. Conclusions:The evidence-based prediction model constructed based on Meta-analysis for postoperative early recurrence of HCC has a high predictive value. However, further verification and optimization with big data is still needed.