Objective To investigate the current situation of off-label use of immune checkpoint inhibitors(ICIs)in China and the cognition of medical staff.Methods From August 31 to September 9,2022,a nationwide survey questionnaire was sent to medical staff in the form of electronic questionnaire.The questionnaire included 13 questions,covering four dimensions:Drug allocation,current situation of medication beyond the instructions,cognition of medication beyond the instructions and current situation of medication beyond the instructions.Results A total of 745 questionnaires were collected.75.70％of respondents reported off-label use of ICIs in their hospitals,with the most common type being off-label indications.The primary reasons for such practices included support from authoritative domestic and international guidelines,clinical research data validation,and approved indications in foreign regulatory documents.85.37％of respondents believed off-label use could offer new hope for patients,while 68.86％considered it unlikely to increase adverse reactions.44.97％of respondents' hospitals had not established off-label use registration systems for ICIs.88.86％of respondents emphasized the need for stricter regulations governing off-label use of immunotherapeutic agents.Conclusion Off-label use of ICIs is common,and there is a lack of unified guidance in clinical practice.It is urgent to form norms and consensus on the management of off-label use of ICIs.

Objective To investigate the current situation of off-label use of immune checkpoint inhibitors(ICIs)in China and the cognition of medical staff.Methods From August 31 to September 9,2022,a nationwide survey questionnaire was sent to medical staff in the form of electronic questionnaire.The questionnaire included 13 questions,covering four dimensions:Drug allocation,current situation of medication beyond the instructions,cognition of medication beyond the instructions and current situation of medication beyond the instructions.Results A total of 745 questionnaires were collected.75.70％of respondents reported off-label use of ICIs in their hospitals,with the most common type being off-label indications.The primary reasons for such practices included support from authoritative domestic and international guidelines,clinical research data validation,and approved indications in foreign regulatory documents.85.37％of respondents believed off-label use could offer new hope for patients,while 68.86％considered it unlikely to increase adverse reactions.44.97％of respondents' hospitals had not established off-label use registration systems for ICIs.88.86％of respondents emphasized the need for stricter regulations governing off-label use of immunotherapeutic agents.Conclusion Off-label use of ICIs is common,and there is a lack of unified guidance in clinical practice.It is urgent to form norms and consensus on the management of off-label use of ICIs.

Objective:To explore the incidence and risk factors of parastomal hernia after colostomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 145 patients undergoing colostomy in Xinxiang Central Hospital from January 2015 to January 2019 were collected. There were 86 males and 59 females, aged(59±11) years. Patients received pelvic and abdominal computed tomography once every 6 months after colostomy to detect the occurrence of parastomal hernia. Measurement data with normal distribution were represented as Mean± SD, and the independent sample t test was used for comparison between groups. Measurement data with skewed distribution were represented as M(range). Count data were represented as absolute numbers, and chi-square test or Fisher exact probability was used for comparison between groups. Kaplan-Meier method was used to analyze the cumulative annual incidence of parastomal hernia. Logarithmic rank test was used to analyze the cumulative incidence based on clinical variables. COX proportional hazard regression model was used for univariate and multivariate analyses. Results:(1) Incidence of parastomal hernia after colostomy. All the 145 patients were followed up for 86(range, 60?108)months after colostomy, of which 46 cases had parastomal hernia and 99 cases had no parastomal hernia. There were significant differences in gender, age, body mass index (BMI) and chronic liver disease between patients with and without parastomal hernia after colostomy ( χ2=23.28, t=13.27, χ2=6.17, 5.82, P<0.05). (2) Annual cumulative incidence of parastomal hernia after colostomy. The 1-, 3-, and 5-year cumulative incidence of parastromal hernia after colostomy was 8.5%, 26.4% and 42.7%, respectively. When the follow-up time is more than 5 years, the incidence of parastromal hernia tended to be stable. The 5-year incidence of parastomal hernia after colostomy in female patients was higher than that in male patients (70.7% vs 20.3%, χ2=12.37, P<0.05). The 5-year incidence of parastomal hernia after colostomy in patients≥60 years old was higher than that in patients under 60 years old (49.8% vs 20.0%, χ2=10.52, P<0.05). The 5-year incidence of parastomal hernia after colostomy in patients with BMI >28 kg/m 2 was higher than that in patients with BMI ≤28 kg/m 2 (55.3% vs 33.2%, χ2=11.76, P<0.05). The 5-year incidence of parastomal hernia after colostomy in patients with chronic liver disease was higher than that in patients with non-chronic liver disease (45.2% vs 32.4%, χ2=15.32, P<0.05). (3) Analysis of risk factors for parastomal hernia after colostomy. Results of multivariate analysis showed that female, age >60 years old, BMI ≥28 kg/m 2 and chronic liver disease were independent risk factors for parastomal hernia after colostomy ( hazard ratio=2.70, 2.51, 1.85, 5.88, 95% confidence intervals as 1.39?6.74, 1.01?4.59, 1.02?4.87, 1.05?8.24, P<0.05). Conclusions:The incidence of parastomal hernia after colostomy is increasing year by year, and tends to be stable after 5 years. Female, age >60 years old, BMI≥28 kg/m 2, and chronic liver disease are independent risk factors for parastomal hernia after colostomy.

OBJECTIVE To explore the construction of the physical identification model of twenty-five people of yin and yang by combining the hand diagnosis image analysis of machine learning,in order to enrich the input of physical identification features.METHODS Based on the theory of twenty-five people of yin and yang,the hand images of 542 patients with cardiovascular disease were collected by self-developed hand diagnosis acquisition equipment.The key points of the hand were extracted by the Mediapipe palm key point algorithm,and the palm area was segmented by geometry to obtain the length and color gamut characteristics of different parts.The physician with clinical license was used to determined the patient's yin and yang twenty-five constitution according to the e-lectronic medical record,and the patient's constitution was identified by comparing Random Forest,Logistic Regression,Xgboost algo-rithm and Light GBM.RESULTS This study successfully constructed a TCM constitution identification model based on hand charac-teristics,which can identify ten basic constitution types including gold wood,gold fire,gold water,gold soil,wood fire,wood water,wood soil,water fire,water soil and fire soil.After sample equalization,the Random Forest model performed best in physical identifi-cation,with an accuracy rate of 0.69,which was significantly better than other models.CONCLUSION The constitution identifica-tion model of TCM hand diagnosis based on hand characteristics can realize the constitution identification of the five elements of TCM.However,due to the use of only hand diagnosis data of TCM,the accuracy needs to be improved.Compared with the traditional body mass scale,it is more objective,convenient,highly stable and consistent.In the future,multimodal integration with face diagno-sis and whole body inspection can be carried out to promote the accuracy,intelligence and multi-dimensional evaluation ability of TCM constitution identification technology.

Objective The CRISPR/Cas9 system was utilized to generate an Apoe knockout mice model to support further investigations of the role of Apoe in lipid metabolism and atherosclerosis.Methods Two single guide RNAs designed for Apoe in C57BL/6J mice were co-injected with Cas9 mRNA into fertilized eggs,followed by transplantation into ICR recipient mice to obtain F0 generation mice.KO mice were identified by polymerase chain reaction(PCR)screening of tail DNA.Apoe mRNA expression in various tissues was assessed by quantitative real-time PCR and lipid indexes were measured in serum samples.Lipid accumulation in the inner lining of aortic vessels was detected by oil red O staining.Results PCR and sequencing confirmed the successful construction of Apoe KO mice(C57BL/6-Apoeem1/Nifdc).Apoe mRNA levels were significantly reduced in the liver,brain,spleen,kidney,and lung tissues of Apoe KO homozygous mice(Apoe-/-),as shown by reverse transcription quantitative real-time PCR.Serum total cholesterol and low-density lipoprotein cholesterol levels were increased in Apoe-/-mice,and high-density lipoprotein cholesterol levels were decreased in male Apoe-/-mice.Extensive lipid plaques were observed in the inner lining of the arteries in Apoe-/-mice compared with WT mice,under normal chow consumption conditions.Conclusions This study successfully established an Apoe KO mice model exhibiting a typical abnormal lipid metabolism phenotype with arterial lipid accumulation,even without a high-fat diet intervention.This work provides background data for the Apoe KO mice resource and a new model for the study of abnormal lipid metabolism.

OBJECTIVE To explore the construction of the physical identification model of twenty-five people of yin and yang by combining the hand diagnosis image analysis of machine learning,in order to enrich the input of physical identification features.METHODS Based on the theory of twenty-five people of yin and yang,the hand images of 542 patients with cardiovascular disease were collected by self-developed hand diagnosis acquisition equipment.The key points of the hand were extracted by the Mediapipe palm key point algorithm,and the palm area was segmented by geometry to obtain the length and color gamut characteristics of different parts.The physician with clinical license was used to determined the patient's yin and yang twenty-five constitution according to the e-lectronic medical record,and the patient's constitution was identified by comparing Random Forest,Logistic Regression,Xgboost algo-rithm and Light GBM.RESULTS This study successfully constructed a TCM constitution identification model based on hand charac-teristics,which can identify ten basic constitution types including gold wood,gold fire,gold water,gold soil,wood fire,wood water,wood soil,water fire,water soil and fire soil.After sample equalization,the Random Forest model performed best in physical identifi-cation,with an accuracy rate of 0.69,which was significantly better than other models.CONCLUSION The constitution identifica-tion model of TCM hand diagnosis based on hand characteristics can realize the constitution identification of the five elements of TCM.However,due to the use of only hand diagnosis data of TCM,the accuracy needs to be improved.Compared with the traditional body mass scale,it is more objective,convenient,highly stable and consistent.In the future,multimodal integration with face diagno-sis and whole body inspection can be carried out to promote the accuracy,intelligence and multi-dimensional evaluation ability of TCM constitution identification technology.

Objective The CRISPR/Cas9 system was utilized to generate an Apoe knockout mice model to support further investigations of the role of Apoe in lipid metabolism and atherosclerosis.Methods Two single guide RNAs designed for Apoe in C57BL/6J mice were co-injected with Cas9 mRNA into fertilized eggs,followed by transplantation into ICR recipient mice to obtain F0 generation mice.KO mice were identified by polymerase chain reaction(PCR)screening of tail DNA.Apoe mRNA expression in various tissues was assessed by quantitative real-time PCR and lipid indexes were measured in serum samples.Lipid accumulation in the inner lining of aortic vessels was detected by oil red O staining.Results PCR and sequencing confirmed the successful construction of Apoe KO mice(C57BL/6-Apoeem1/Nifdc).Apoe mRNA levels were significantly reduced in the liver,brain,spleen,kidney,and lung tissues of Apoe KO homozygous mice(Apoe-/-),as shown by reverse transcription quantitative real-time PCR.Serum total cholesterol and low-density lipoprotein cholesterol levels were increased in Apoe-/-mice,and high-density lipoprotein cholesterol levels were decreased in male Apoe-/-mice.Extensive lipid plaques were observed in the inner lining of the arteries in Apoe-/-mice compared with WT mice,under normal chow consumption conditions.Conclusions This study successfully established an Apoe KO mice model exhibiting a typical abnormal lipid metabolism phenotype with arterial lipid accumulation,even without a high-fat diet intervention.This work provides background data for the Apoe KO mice resource and a new model for the study of abnormal lipid metabolism.

Objective:To determine the effect of community management based on the Roy′s adaptation model (RAM) in patients with chronic obstructive pulmonary disease (COPD).Methods:This study was a cluster randomized controlled study, with the community as the cluster unit, and selected 805 COPD patients from 8 communities in Xuzhou City who had completed community registration before June 2019. A total of 735 patients actually completed follow-up and participated in intervention evaluation. They were randomly divided into control group (362 cases) and intervention group (373 cases) by random number table method. The control group received routine follow-up, while the intervention group received RAM intervention for 6 months. The forced expiratory volume in 1 second (FEV1)/forced volume vital capacity (FVC) ratio (FEV 1/FVC) and the modified British medical research council (mMRC) were used to assess the pulmonary function. The hospital anxiety and depression scales (HADS) were used to evaluate the mental health. The Chinese version of the Short Form Coping and Adaption Processing Scale (CAP-15) was used to assess the adaptive capacity. And the St. George′s Respiratory Questionnaire (SGRQ) was used to evaluate the quality of life in COPD patients. The t test or χ 2 test was used for pre-intervention comparisons between groups, and the repetitive measure analysis of variance (ANOVA) was used for post-intervention comparisons between groups. Results:After 6 months intervention, there were no significant differences in FEV 1/FVC radio between the two groups [(0.61±0.11) vs (0.62±0.12)] ( P=0.172). The scores of mMRC [(2.04±0.33) vs (2.77±0.31) points], HAD-A [(5.28±4.28) vs (6.99±4.41) points], HAD-D [(5.82±5.12) vs (7.27±4.93) points] and SGRQ [(40.17±9.30) vs (53.69±9.77) points] were all lower in the intervention group than those in the control group (all P<0.001). The CAPS-15 score was higher in the intervention group than that in the control group [(35.87±3.62) vs (26.1±3.47)] ( P<0.001). Conclusion:RAM could be used in community management of COPD patients, which could improve their dyspnea symptoms and psychological and physiological functions, also improve their adaptability and quality of life.

Objective:To study the effect of blood volume feedback control system on improving intradialytic-hypotension (IDH) in maintenance hemodialysis (MHD) patients.Methods:It was a prospective cohort study. Thirty MHD patients with recurrent IDH in the Dialysis Center of the First Affiliated Hospital of Zhejiang University School of Medicine from March 2021 to March 2022 were selected. A self-control study was conducted in MHD patients. The patients were treated with routine hemodialysis in both baseline phase (A1) and reversal phase (A2), while with hemodialysis under the blood volume feedback control system in intervention phase (B). Each phase lasted for 4 weeks (12 hemodialysis sessions). The average occurrences of IDH and IDH-related adverse events (IDH-RAE, stopping dehydration for more than 10 minutes or getting off the hemodialysis machine 10 minutes earlier due to IDH) of each patient between phase A1, B, and A2 were calculated and compared. In a total of 1 080 dialysis records, a logistic regression analysis model was established with age, sex and intervention as independent variables and with the occurrence of IDH-RAE as the outcome.Results:A total of 30 eligible patients were included in the study, including 14 males (46.7%) and 16 females (53.3%), aged 63.0 (56.5, 72.5) years old, with a median dialysis age of 84.0 (37.2, 120.0) months. The average times of IDH in 30 MHD patients decreased from 1.17 (0.83, 1.67) in stage A1 (before intervention) to 0.33 (0.25, 0.58) in stage B (after intervention) ( P<0.05). The frequency of IDH-RAE decreased significantly from 0.29 (0.19, 0.47) in stage A1 to 0.17 (0,0.25) in stage B ( P<0.05). Logistic regression analysis results indicated that the use of blood volume feedback control system reduced the risk of IDH-RAE by 53% ( OR=0.47, 95% CI 0.34-0.64, P<0.001). Conclusions:The application of blood volume feedback control system can effectively reduce the occurrences of IDH and the risk of IDH-RAE in MHD patients.

Objective:To explore the effect of group cognitive behavior therapy (GCBT) on anxiety, depression and quality of life in patients with chronic obstructive pulmonary disease (COPD) in community.Methods:From August to November 2019, patients with moderate COPD in 18 communities in Xuzhou City were randomly divided into the intervention group ( n=240) and the control group ( n=223). The control group received routine management and the intervention group received group cognitive behavioral therapy intervention for 8 weeks on the basis of routine management.Before and after the intervention, FEV 1% predicted value and FEV 1/FVC were measured by pulmonary function tester.Hospital Anxiety and Depression Scale (HADS) was used to evaluate the anxiety and depression of patients.St.George's respiratory questionnaire (SGRQ), COPD assessment test (CAT) and modified medical research council dyspnea (mMRC) were used to evaluate the quality of life of patients.SPSS 20.0 software was used for analysis.The χ 2 test, independent sample t-test, paired sample t-test were used for statistical analysis. Results:After 8 weeks of intervention, the anxiety and depression scores of the intervention group were lower than those of the control group (anxiety: (8.23±4.02) vs (10.71±3.60); depression: (7.87±3.73) vs (10.20±3.72)( t=6.415, 6.185, both P<0.01). After the intervention, there was no significant difference in FEV 1%((51.7±12.3)% vs (52.0±12.6)%) predicted value and FEV 1/FVC((57.3±10.8)% vs (56.9±10.7)%) between the two groups( t=-0.259, 0.400, both P>0.05). The scores of CAT, mMRC and SGRQ in the intervention group were lower than those in the control group((17.35±5.78) vs (20.90±8.00), (1.55±0.82) vs (2.30±1.21), (41.78±21.56) vs (57.08±24.46))( t=-5.061, -7.227, -6.580, all P<0.01). Conclusion:Group cognitive behavioral therapy can relieve the anxiety and depression and improve the quality of life of patients with COPD.