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 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 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 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 explore the mechanism of human umbilical cord mesenchymal stem cell (HUC-MSC) alleviating ischemia-reperfusion injury (IRI) of liver cells through mitochondrial transfer. Methods Normal human liver cell line L02 was divided into the blank control group, oxygen-glucose deprivation (OGD) group, experimental control group, and L02 and HUC-MSC co-culture group (L02+HUC-MSC group). L02+HUC-MSC group was further divided into 10:1 co-culture subgroup (group A), 4:1 co-culture subgroup (group B), 2:1 co-culture subgroup (group C), 1:1co-culture subgroup (group D) and 1:2 co-culture subgroup (group E) according to different co-culture ratio of L02 and HUC-MSC. The apoptosis rate and relative reactive oxygen species (ROS) level of L02 cells were detected by flow cytometry. The MitoTracker positive rate of L02 cells was detected by flow cytometry. The mitochondrial transfer from HUC-MSC to L02 cells was observed by laser confocal microscope. Results The apoptosis rate and relative ROS level of L02 cells in the OGD group were significantly higher than those in the blank control group (both P < 0.05). Compared with the OGD group, the apoptosis rates of L02 cells in group B, C, D and E were significantly decreased (all P < 0.05), and the relative ROS level of L02 cells in group E was significantly declined (P < 0.05). The MitoTracker positive rate of L02 cells did not significantly differ between group A and experimental control group (P>0.05), whereas the MitoTracker positive rates of L02 cells in group B, C, D and E were significantly higher than that in the experimental control group in a concentration-dependent manner (all P < 0.05). Under the laser confocal microscope, mitochondrial transfer fromHUC-MSC to L02 cells could be observed through tunneling nanotube (TNT). Conclusions HUC-MSC may alleviate cell apoptosis and reduce ROS level of liver cells after IRI via direct mitochondrial transfer between cells.

Objective:To discuss the onset and development pattern and characteristics of refeeding syndrome (RFS) induced by nutrition support and to provide reference for rational drug use in parenteral nutrition management.Methods:Case reports of RFS from CNKI, Wanfang, VIP database and Pubmed from 2000 to 2020 were retrieved. The clinical data were collected and statistically analyzed.Results:A total of 17 reports, including 17 cases, were included in the analysis. Patients were 6 males(35.29%) and 11 females (64.71%). The distribution of age was from 29 weeks in a premature neonate to 87 years old. 12 cases (70.59%) of RFS occurred within 3 days after starting the nutrition support. The most common clinical manifestation were cardiovascular system symptoms (88.23%), with dyspnea as the most reported symptom (41.17%). 15 patients (88.23%) recovered after appropriate intervention and 2 patients died(11.76%).Conclusions:Refeeding syndrome is a potentially fatal condition. The risk of RFS should be assessed before initiating nutrition support. Patients at risk of RFS must be monitored closely at the early stage of nutritional support.

Objective:To deliver understanding of the latest research progress on clinical trials and approval of dermatological drugs in China in 2020.Methods:A registration and information disclosure platform for drug clinical studies and a query system for domestic and imported drugs in the National Medical Products Administration of China were searched for registered clinical trials and approved dermatological drugs, respectively. The number and stages of clinical trials, indications and classification of involved products, and listed dermatological drugs in 2020 were summarized and depicted.Results:There were 157 dermatological drug trials registered in China in 2020, accounting for 6.16% of all the 2 548 clinical drug trials, including 127 (80.9%) initiated by Chinese pharmaceutical enterprises and 25 (15.9%) international multicenter trials. Among the 127 drug trials initiated by Chinese pharmaceutical enterprises, bioequivalence trials were mostly common, accounting for 55.9% (71/127) . Compared with global pharmaceutical enterprises, domestic pharmaceutical companies initiated significantly decreased proportions of international multicenter trials (1.9% [3/157] vs. 14.0% [22/157], P < 0.001) , but significantly increased proportions of phaseⅠclinical trials and bioequivalence trials (24.4% [31/127] vs. 10.0% [3/30], 55.9% [71/127] vs. 0, respectively, both P < 0.001) . Totally, 90 kinds of dermatological drug were involved in all the trials, psoriasis, atopic dermatitis and melanoma were the most common indications, and innovative drugs accounted for 53.3% (48/90) ; the proportion of innovative drugs was significantly lower in domestic pharmaceutical companies than in global pharmaceutical companies (43.2% [32/74] vs. 16/16, P < 0.001) . In addition, 28 dermatological drugs developed by 22 pharmaceutical companies were approved in China in 2020, of which 21 drugs were developed by domestic pharmaceutical companies. Conclusion:Clinical drug trials carried out by domestic pharmaceutical companies mostly focus on generic drugs, and it is still necessary for domestic pharmaceutical companies to further improve the innovation ability.

Objective:To study the clinical effect of early loading restoration a superhydrophilic implant after 1 year, so as to provide reference evidence for clinical practice.Methods:A total of 41 patients with dental defects, including 20 males and 21 females [age (52.3±13.1) years old], were enrolled in the Department of VIP, Hangzhou Dental Hospital (Pinghai Hospital) from July 2017 to January 2019. A total of 74 superhydrophilic implants were implanted, including 27 maxillary implants and 47 mandiolar implants. All patients without bone augmentation or soft tissue transplantation, the maxilla was taken impression 4 weeks after implant implantation, with 6 weeks of loading, the mandible was taken impression 2 weeks after implant implantation, with 4 weeks of loading. The stability of the implant was measured by resonance frequency analyzer before implant implantation, impression and loading. Periapical radiograph were taken immediately after mold removal, immediately after loading and reexamination 1 year after loading, to measure and record the changes in the bone level of the mesial and distal margins of the implant.Results:No biological complications occurred in all implants before loading restoration, and the implant survival rate was 100%(74/74). In 2 cases, the implant stability quotient (ISQ) value of the implant at the mandibular site was lower than 65 at 2 weeks after surgery, and the restoration was delayed. The ISQ values of the other 72 implants at the time of implantation (75.22±4.32) were not significantly different from those at the time of modeling (75.13±4.23) ( P>0.05), but the ISQ values at the moment of weight loading (76.46±3.73) were significantly higher than those at modeling ( P<0.05). All the early loading implants were reviewed 1 year after early loading, and none of them were loose or fell off, and the implant survival rate was 100%(72/72). X-ray measurement and evaluation showed that after 1 year of early loading restoration, the mean marginal bone absorption of 72 implants was (0.18±0.06) mm, among which the mandibular was (0.17±0.06) mm and the maxillary was (0.19±0.06) mm, showing no statistical difference ( P>0.05). After 1 year of early loading restoration, the mean marginal bone absorption of 72 implants was (0.17±0.05) mm, including (0.17±0.06) mm for mandibular and (0.16±0.05) mm for maxillary, showing no statistical difference ( P>0.05). Conclusions:In the limited scope of this clinical study, it has been proved that early loading of superhydrophilic implant is a safe and feasible treatment scheme, and the bone resorption at the implant edge after long-term early loading restoration needs further follow-up study.

The diagnostic reference level (DRL) for adults radiation dose in CT examination based on a large-scale national survey data is released in the form of national health industry standards (WS/T 637-2018) after more than ten years of exploration by radiologists, imaging technologists, radiation protection specialists and radiographers. Its principles and method are in line with international practices and the actual situation in China, which basically cover frequently-used CT examination items for adults. Compared with DRL in several other countries or organizations, radiation exposure to the patients as a whole is at a reasonably low level. The 50^th percentile (achievable dosimetry levels) and 25^th percentile (indicative level of unusually low dosimetry) are given as additional tools for radiation dose optimization guidance. In daily activities of radiological diagnosis, the radiation dose should be matched with image quality and clinical diagnostic tasks, and the frequency of unjustifiable high or low radiation dose should be reduced.