Objective To screen key autophagy-related genes in alcoholic hepatitis (AH) and investigate potential biomarkers and therapeutic targets for AH. Methods Two AH gene chips in Gene Expression Omnibus (GEO) and autophagy-related data sets obtained from MSigDB and GeneCards databases were used, and the key genes were verified and obtained by weighted gene co-expression network analysis (WGCNA). The screened key genes were subject to gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) and immune infiltration analyses. Messenger RNA (mRNA)- microRNA (miRNA) network was constructed to analyze the expression differences of key autophagy-related genes during different stages of AH, which were further validated by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) in the liver tissues of AH patients and mice. Results Eleven autophagy-related genes were screened in AH (EEF1A2, CFTR, SOX4, TREM2, CTHRC1, HSPB8, TUBB3, PRKAA2, RNASE1, MTCL1 and HGF), all of which were up-regulated. In the liver tissues of AH patients and mice, the relative expression levels of SOX4, TREM2, HSPB8 and PRKAA2 in the AH group were higher than those in the control group. Conclusions SOX4, TREM2, HSPB8 and PRKAA2 may be potential biomarkers and therapeutic targets for AH.

Objective To explore the current situation and influencing factors of caregiver readiness of elderly patients with chronic heart failure.Methods From March 2021 to April 2022,the convenient sampling method was used to select 335 caregivers of elderly patients with chronic heart failure who were hospitalized in 6 hospitals in Hangzhou as the survey subjects.The general information questionnaire,Caregiver Readiness Scale and Caregiver Burden Scale were used to investigate the caregivers of elderly patients with chronic heart failure.Results A total of 326 valid questionnaires were collected.The score of Caregiver Readiness Scale for elderly patients with chronic heart failure was(18.88±6.36),and 61.04%of the caregivers had mild to moderate burden.The results of multiple linear regression analysis showed that the caregiver's age,education level and cumulative care time were the positive influencing factors of the caregiver readiness,and the caregiver burden was the negative influencing factor of the caregiver readiness(P＜0.001).Conclusion The caregiver readiness of elderly patients with chronic heart failure is at a medium level.Caregivers who are older,more educated,have a longer cumulative caregiving time,and have a lighter caregiving burden are more prepared.Medical staff should pay attention to the motivation of caregivers,provide professional support from multiple aspects,and reduce the burden of care,increase readiness level.

OBJECTIVE To explore and establish a long-term mechanism for rational control of intravenous fluids in hospitals. METHODS On the basis of the establishment of rules and regulations， through the exploration and implementation of the core technical strategy of “six-step method”， a new mode of intravenous infusion control was established. The contents of the “six-step method” were as follows： the first step was to sort out the diseases that did not require intravenous infusion； the second step was to sort out the alternative drugs/dosage forms； the third step was to sort out the alternative routes of infusion； the fourth step was to develop drug specifications； the fifth step was to explore the personalized medication needs of clinical departments； the sixth step was to develop a department-specific integrated infusion regimen. The utilization rate of intravenous fluids in inpatients and the average daily amount of intravenous fluids per bed in inpatients were used as the main indicators to evaluate the control effect. RESULTS The comparison of the average values of three months before and after the implementation of the “six-step” management mode in the department of thoracic surgery of our hospital showed that after management and control， the average utilization rate of intravenous fluids in inpatients decreased by 1.74%， the average daily use of intravenous fluids in inpatients per bed decreased by 0.30 bags/bottle， and the per capita use of infusion drugs under key control gradually decreased. CONCLUSIONS The “six-step” management mode can reduce the utilization rate of intravenous fluids in inpatients， and this management mode is practical and feasible.

OBJECTIVE To provide reference for rational use of cyclin-dependent kinase 4/6 （CDK4/6） inhibitors. METHODS Retrieved from Web of Science， PubMed， SpringerLink， CNKI， Wanfang Data and VIP database， and so on， the literature about lung toxicity related to CDK4/6 inhibitors were collected and analyzed statistically with Excel 2013 software. RESULTS A total of 12 literature which met the inclusion and exclusion criteria were included； 13 patients were involved， among which 3 cases were from the United States， 3 from Japan， 2 from India， and 1 from Israel， Spain， France， Australia and Saudi Arabia respectively； all patients were female， aged between 43-89 years， of whom 8 were treated with palbocicilib， 3 with abemacilib， and 2 with ribociclib. The lung toxicity of patients after medication occurred from 1 week to 15 months； the majority of patients were hospitalized with the symptom such as difficulty breathing， chest tightness， shortness of breath， dry cough， etc. The lung toxicity mainly manifested as interstitial lung disease， eosinophilic pneumonia， mediastinal and pulmonary granulomatous reaction， drug-induced pneumonia， diffuse alveolar damage， organizing pneumonia and so on. The shortest treatment duration was 3 weeks， and the longest was 6 months. The treatment measures included drug withdrawal， intravenous use of antibiotics， intravenous use of systemic steroids， oxygen inhalation， and so on； after treatment， 8 patients improved or recovered， and 5 patients died due to deterioration. One patient developed lung toxicity again after reuse of such drugs and must stop drugs permanently. CONCLUSIONS Lung toxicity related to CDK4/6 inhibitors possibly cause mortality. It is necessary to make early judgment， stop the drug in time， and give patients systemic steroids， oxygen inhalation and other treatment measures as soon as possible.

Objective:To explore the effects of anhedonia, childhood abuse, and depression on suicidal ideation, and the mediating role of anhedonia in adolescents.Methods:A total of 7 431 middle school students were invited to participate in the study. Suicidal ideation, depression, childhood abuse, and anhedonia were assessed by the Positive and Negative Suicide Ideation Scale (PANSI), Self-Rating Depression Scale (SDS), Childhood Trauma Questionnaire (CTQ) and Temporal Experience of Pleasure Scale (TEPS); according to the score of suicidal ideation, a total score of 36 was used as the cut-off score, all students were divided into the group with suicidal ideation ( n=1 265) and the group without suicidal ideation ( n=6 166). Difference test was performed using independent sample t-test and χ 2 test; Correlation analysis was performed by Pearson correlation; The process macro program compiled by Hayes was used to conduct the regulated mediation model analysis; The mediation effect values and 95%bootstrap confidence intervals of depressive symptoms between childhood maltreatment and suicidal ideation were analyzed by the bootstrap method; Simple slope analysis was utilized to examine the interaction effects for depression and anhedonia. Results:The detection rate of adolescent suicidal ideation was 17.02% (1 265/7 431);Childhood abuse significantly positively predicted depression ( β=0.56, P<0.001); depression significantly positively predicted suicidal ideation ( β=0.59, P<0.001); depression and anhedonia interaction significantly predicted suicidal ideation ( β=-0.05, P<0.001); simple slope analysis indicates that low anhedonia depression predicted suicidal ideation ( β=0.51, P<0.001) than the high anhedonia group ( β=0.47, P<0.001). Conclusion:Depression partially mediates the effects of childhood abuse on suicidal ideation, and anhedonia modulates the effects of childhood abuse on suicidal ideation. As the level of anhedonia gradually increases, the predictive effect of depression on suicidal ideation gradually decreases.

Objective:To know the clinical characteristics of liver injury related to thalidomide and its analogs.Methods:The relevant databases at home and abroad (up to August 31, 2022) were searched and the case reports on thalidomide and its analogs-associated liver injury were collected. The patients′ gender, age, primary disease, drug use, occurrence of liver injury (onset time, clinical manifestations, liver function status, liver injury classification, etc.), treatment and outcome were recorded and descriptively analyzed.Results:A total of 18 patients were enrolled, including 11 males and 7 females, aged from 36 to 93 years with an average age of 60 years. The primary disease was multiple myeloma in 16 patients, plasma cell leukemia and myelodysplastic syndrome in 1 patient each. Thalidomide was used in 9 patients, lenalidomide in 6 patients and pomalidomide in 3 patients. The time from the beginning of medication to the occurrence of liver injury ranged from 4 to 232 days and it was ≤ 60 days in 15 patients. The classification of liver injury was hepatocellular type in 9 patients, cholestasis type in 7 patients, and unable to be determined due to lack of data in 2 patients. Different degrees of abnormal liver function appeared in 18 patients, mainly including elevated alanine aminotransferase and aspartate aminotransferase (in 16 patients), elevated total bilirubin (in 14 patients), and elevated alkaline phosphatase (in 12 patients). Clinical symptoms were recorded in 15 patients, including jaundice (in 13 cases), fatigue (in 7 cases) and nausea (in 4 cases). After diagnosis of liver injury, thalidomide or its analogues were discontinued in all 18 patients, and 4 cases received symptomatic and supportive therapy. Liver function in 13 patients was improved or returned to normal within 7 to 28 days after drug withdrawal, and 5 patients died (2 cases died of liver failure, 3 cases died of primary diseases or other complications).Conclusions:Thalidomide and its analogs associated liver injury mostly occurs within 2 months after drug administration and the clinical symptoms were similar to those caused by other drugs. After drug withdrawal, the liver function in most patients could be improved or return to normal, but a few may progress to liver failure and death.

Objective:To know the clinical characteristics of liver injury related to thalidomide and its analogs.Methods:The relevant databases at home and abroad (up to August 31, 2022) were searched and the case reports on thalidomide and its analogs-associated liver injury were collected. The patients′ gender, age, primary disease, drug use, occurrence of liver injury (onset time, clinical manifestations, liver function status, liver injury classification, etc.), treatment and outcome were recorded and descriptively analyzed.Results:A total of 18 patients were enrolled, including 11 males and 7 females, aged from 36 to 93 years with an average age of 60 years. The primary disease was multiple myeloma in 16 patients, plasma cell leukemia and myelodysplastic syndrome in 1 patient each. Thalidomide was used in 9 patients, lenalidomide in 6 patients and pomalidomide in 3 patients. The time from the beginning of medication to the occurrence of liver injury ranged from 4 to 232 days and it was ≤ 60 days in 15 patients. The classification of liver injury was hepatocellular type in 9 patients, cholestasis type in 7 patients, and unable to be determined due to lack of data in 2 patients. Different degrees of abnormal liver function appeared in 18 patients, mainly including elevated alanine aminotransferase and aspartate aminotransferase (in 16 patients), elevated total bilirubin (in 14 patients), and elevated alkaline phosphatase (in 12 patients). Clinical symptoms were recorded in 15 patients, including jaundice (in 13 cases), fatigue (in 7 cases) and nausea (in 4 cases). After diagnosis of liver injury, thalidomide or its analogues were discontinued in all 18 patients, and 4 cases received symptomatic and supportive therapy. Liver function in 13 patients was improved or returned to normal within 7 to 28 days after drug withdrawal, and 5 patients died (2 cases died of liver failure, 3 cases died of primary diseases or other complications).Conclusions:Thalidomide and its analogs associated liver injury mostly occurs within 2 months after drug administration and the clinical symptoms were similar to those caused by other drugs. After drug withdrawal, the liver function in most patients could be improved or return to normal, but a few may progress to liver failure and death.

Objective:To explore the effects of anhedonia, childhood abuse, and depression on suicidal ideation, and the mediating role of anhedonia in adolescents.Methods:A total of 7 431 middle school students were invited to participate in the study. Suicidal ideation, depression, childhood abuse, and anhedonia were assessed by the Positive and Negative Suicide Ideation Scale (PANSI), Self-Rating Depression Scale (SDS), Childhood Trauma Questionnaire (CTQ) and Temporal Experience of Pleasure Scale (TEPS); according to the score of suicidal ideation, a total score of 36 was used as the cut-off score, all students were divided into the group with suicidal ideation ( n=1 265) and the group without suicidal ideation ( n=6 166). Difference test was performed using independent sample t-test and χ 2 test; Correlation analysis was performed by Pearson correlation; The process macro program compiled by Hayes was used to conduct the regulated mediation model analysis; The mediation effect values and 95%bootstrap confidence intervals of depressive symptoms between childhood maltreatment and suicidal ideation were analyzed by the bootstrap method; Simple slope analysis was utilized to examine the interaction effects for depression and anhedonia. Results:The detection rate of adolescent suicidal ideation was 17.02% (1 265/7 431);Childhood abuse significantly positively predicted depression ( β=0.56, P<0.001); depression significantly positively predicted suicidal ideation ( β=0.59, P<0.001); depression and anhedonia interaction significantly predicted suicidal ideation ( β=-0.05, P<0.001); simple slope analysis indicates that low anhedonia depression predicted suicidal ideation ( β=0.51, P<0.001) than the high anhedonia group ( β=0.47, P<0.001). Conclusion:Depression partially mediates the effects of childhood abuse on suicidal ideation, and anhedonia modulates the effects of childhood abuse on suicidal ideation. As the level of anhedonia gradually increases, the predictive effect of depression on suicidal ideation gradually decreases.

OBJECTIVE To e xplore the research hots pots and development frontiers of ursolic acid in recent 20 years，and to provide reference for researchers in this field. METHODS Research literatures related to ursolic acid in Web of Science from Jan. ， 1，2002 to Dec. 31，2021 were collected ，and visualization analysis was performed on countries or regions ，research institutions ， authors，journals and keywords involved in the literatures using CiteSpace software ，to obtain the spatial and temporal distribution of ursolic acid and research frontiers. The research status and development frontier of ursolic acid were further analyzed by analyzing keywords co-occurrence ，keyword emergence ，keyword clustering ，etc. RESULTS & CONCLUSIONS Totally 3 528 valid papers were included in this study ，and the top three countries were China ，India and the United States. Analysis of publishing institutions showed that Chinese Academy of Sciences ，Univisity of Karachi and China Medical University were the top 3 research institutions in the list of publication amount. Analysis of published journals showed that Molecules （127 articles），Journal of Ethnopharmacology（90 articles），Journal of Agricultural and Food Chemistry （75 articles）had high number of literatures on ursolic acid. The analysis of keyword analysis showed that pharmacological effects ，such as antitumor activity of ursolic acid ， antioxidant activity ，antibacterial activity and anti-inflammatory activity ，are always the focus of the research ；the mechanism ursolic acid induced apoptosis ，oxidative stress and autophagy ，the research on ursolic acid signaling pathway ，drug delivery of ursolic acid nanoparticles were the research direction in the future.

Objective:To understand the clinical features of granulomatous hepatitis (GH) induced by intravesical instillation with Bacille Calmette-Guérin vaccine (BCG).Methods:Case reports of GH which was confirmed by liver biopsy and induced by intravesical BCG therapy were collected by searching PubMed and Elsevier databases as of December 2021. The following information of patients including general information, intravesical BCG situations (dose, times of instillation, traumatic catheterization occurrence), GH occurrence (onset time, clinical manifestations, laboratory tests and liver biopsy results), other adverse reactions, treatments, and outcomes were extracted and analyzed descriptively.Results:A total of 23 patients, who were all male, were entered in the analysis, aged from 34 to 80 years with a median age of 66 years. The primary diseases were bladder cancer in 22 patients and ureteral carcinoma in 1 patient. The times of instillation until GH occurred were recorded in 19 patients. Of them, 2 patients had instillation once and the time was 16 at most. Ten patients had traumatic catheterization during the last instillation, including hematuria in 7 patients, pain in 2 patients, and difficulty in urethral intubation in 1 patient. Time from the last instillation to the onset of GH was from 3 h to 440 days (≤7 days in 18 patients, 10, 14, 21, 180, and 440 days in 1 patient respectively) with a median time of 3 days. Among the 23 patients, 21 had fever, 12 had jaundice, 9 had hepatomegaly, 7 had fatigue, 5 had anorexia, 2 had weight loss, and 1 had night sweats; 12 manifested as GH alone and 11 had concomitant adverse reactions. Abnormal liver function appeared in 22 patients, mainly including elevated alkaline phosphatase and elevated aspartate aminotransferase (each in 17 patients). Mycobacterium bovis identification/culture results were recorded in 20 patients and 7 were positive. Liver biopsies showed noncaseating granuloma of epithelioid in 10 patients, noncaseating granuloma in 7 patients, epithelioid granuloma in 4 patients, and hepatic granuloma without details in 2 patients. After discontinuation of BCG instillations and treatments with anti-tuberculosis agents and/or corticosteroids, 22 patients were improved and 1 patient died of BCG sepsis and multiple organ failure.Conclusions:GH usually occurs within 1 week after intravesical instillation with BCG and mainly manifests as fever, jaundice, hepatomegaly, and abnormal liver function, which may be accompanied by other adverse reactions related to BCG instillation. Liver biopsy can help the diagnosis. The prognosis is good after combination therapy with anti-tuberculosis agents and corticosteroids, but death may occur in severe cases.