ObjectiveThis study aimed to investigate the current status of biosafety management in laboratory animal institutions in Hunan Province, identify management shortcomings, and provide targeted recommendations for improvement. MethodsA questionnaire survey was conducted in July 2023 among 40 laboratory animal institutions in Hunan Province, covering topics such as the establishment of laboratory management system and its overall operation status, emergency management for incidents, medical waste disposal, animal transportation, personnel practitioner management, environmental disinfection, and equipment maintenance. The awareness of biosafety, animal bite incidents, and vaccination history was surveyed from at least one animal feeder or experimental operation practitioner from each institution, totaling 50 practitioners. Through literature review and comparative analysis, this paper analyzed the current status of biosafety management in production, transportation, and use of laboratory animals in Hunan Province from aspects such as biosafety management systems, personnel training, disinfection of environmental facilities and waste disposal, and provided recommendations. ResultsAmong the 40 laboratory animal institutions in Hunan Province,39 institutions (97.5%) had established laboratory management systems, 37 (92.5%) had emergency response plans for incidents of to transport laboratory animals, 15 (37.5%) had complete records of emergency drills for laboratory animal biosafety, and 39 (97.5%) had established protocols for carcass and waste management. Moreover, 26 institutions (65.0%) had laboratory biosafety risk assessment reports. 4 out of 8 (50.0%) production units had emergency plans for animal transportation, with 7 (87.5%) using special vehicles to transport laboratory animals. 2 (4.0%) of the 50 practitioners were unaware of emergency response plans, 6 participants (12.0%) did not consistently wear personal protective equipment, and 38 participants (76.0%) had been bitten or scratched by laboratory animals. The results of the survey showed that emergency management, transportation management and personnel management of laboratory animal incidents still need improvement in Hunan Province. Relevant functional departments should strengthen supervision and management efforts, establish local regulations for the transportation management of laboratory animals, ensure strict compliance with relevant documents, conduct emergency drills in all units, and strengthen training for practitioners. ConclusionWhile daily management practices in the 40 laboratory animal institutions in Hunan Province are generally satisfactory, there remains a need for further improvement in emergency management, transportation management, personnel management, etc. Gradually enhancing the level of laboratory animal safety management is essential to collectively safeguard public health safety.

The emergency management of biosafety for laboratory animals in Hunan Province is an essential component of the province's implementation of the national biosafety strategy.To strengthen the prevention and control of biosafety risks in laboratory animals and to ensure a quick and effective response to laboratory animal biosafety emergencies,Hunan Province has formulated the"Emergency Response Plan for Laboratory Animal Biosafety Emergencies in Hunan Province".This plan aims to minimize damages caused to practitioners,public health,and laboratory animal industry,protect lives and property,and safeguard public safety and social stability.This paper analyzes the necessity,guiding ideology,principles,and basis for formulating the plan.It details the main contents of the plan,which includes scope of application,incident classification,organizational structure and responsibilities,monitoring and early warning mechanisms,emergency reporting and response,post-incident assessment,and safeguard measures.Moreover,this paper provides a summary and outlook on the emergency management of biosafety laboratory animals in Hunan Province in recent years.

Objective:To study the predictive value of vasoactive-inotropic score (VIS), fluid overload (FO) and lactate level for the outcome of preterm infants with refractory septic shock.Methods:Preterm infants diagnosed with refractory septic shock and required hydrocortisone treatment in our Department from January 2016 to December 2021 were analyzed retrospectively. Preterm infants were assigned into three gestational age groups (<28 weeks, 28-31 weeks, 32-36 weeks). According to the outcome of the disease, the children were further divided into good prognosis group and poor prognosis group. The relationship between the maximum VIS, FO and the mean lactic acid before hydrocortisone and the outcome of refractory septic shock was analyzed by receiver operating characteristic (ROC) curve, the cut-off point of ROC curve was calculated to obtain the predictive efficacy of the three indicators for the outcome of refractory septic shock in preterm infants.Results:A total of 50 preterm infants with refractory septic shock and received hydrocortisone treatment were enrolled, including 20 in the good prognosis group and 30 in the poor prognosis group. There were no significant differences in the maximum VIS, FO and mean lactic acid before hydrocortisone treatment between the two groups of gestational age of <32 weeks ( P> 0.05). The maximum VIS, FO and mean lactic acid of gestational age of 32-36 weeks in the poor prognosis group were higher than those in the good prognosis group, VIS: 56.1±15.7 vs. 37.1±12.9, FO (%): 108.2 (78.6,137.7) vs. 55.5 (10.3, 100.7), and mean lactic acid (mmol/L): 8.3 (4.6, 12.0) vs. 4.8 (-0.8, 10.5), all P<0.05. The area under the ROC curve of the mean lactic acid was the largest, the cut-off value was 4.1 mmol/L, and the Youden index was 1.732. Conclusions:VIS, FO and lactate level are difficult to be used for determining the outcome of refractory septic shock in preterm infants of <32 weeks. While the mean lactic acid has the best predictive performance in preterm infants of 32-36 weeks.

Objective:To investigate the expectations of community nurses and patients with chronic diseases in Shanghai on the "Internet + nursing service" model and programs, in order to provide a theoretical reference for improving "Internet + nursing service" in Shanghai.Methods:Using the convenient sampling method, a total of 255 nurses and 150 patients with chronic diseases from 15 community health service centers in Jing'an District of Shanghai were selected as the research objects from January to February 2021. They were investigated by "Internet + nursing service" questionnaire for nurses and "Internet + nursing service" questionnaire for patients. In this study, a total of 255 "Internet + nursing service" questionnaires for nurses were issued and 250 valid questionnaires were returned. The effective response rate was 98.0% (250/255) . A total of 150 "Internet + nursing service" questionnaires for patients were issued and 148 valid questionnaires were returned. The effective response rate was 98.7% (148/150) .Results:Among the 250 community nurses, 31.6% (79/250) nurses understood "Internet + nursing service" and 29.6% (74/250) of nurses were willing to participate in "Internet + nursing service". Among the 148 patients with chronic diseases, 50.0% (74/148) of the patients did not understand the "Internet + nursing service" and 48.0% (71/148) of the patients expressed their willingness to participate in the "Internet + nursing service". The service items that patients with chronic diseases requires more were blood glucose monitoring (27.0%, 40/148) , subcutaneous injection (25.0%, 37/148) and intramuscular injection (23.6%, 35/148) . The service items that community nurses were more willing to perform were blood glucose monitoring (42.0%, 105/250) , venous blood collection (41.2%, 103/250) and intramuscular injection (40.0%, 100/250) . There were statistical differences between community nurses and patients with chronic diseases in the expected professional title of nurse practitioners and expected working years of nurse practitioners ( P<0.05) . Conclusions:Community nurses and patients with chronic diseases need to improve their cognition of "Internet + nursing service". Relevant departments should increase the awareness of "Internet + nursing service" through the media and the Internet. When improving rules and regulations for "Internet + nursing service", they should conduct full research on both the supply and demand sides of nurses and patients and take data orientation as the goal of the policy to effectively meet the needs of patients and ensure their health.

Objective:To study the real-world outcome of China FDA-approved Sofosbuvir (SOF)/Velpatasvir (VEL) in Northwest China.Methods:In this multicenter, prospective, real-world cohort study, we recruited patients from 10 sites from Northwest China, who were chronically infected with HCV GTs 1-6 from 06/2018 to 09/2019. Patients received SOF (400mg)/VEL (100mg) for 12 weeks, and with ribavirin 900-1200 mg for GT3 cirrhosis and for any genotype decompensated cirrhosis. The primary endpoint was sustained virological response at 12-weeks post-treatment (SVR12) and safety. The secondary endpoint was the change of liver function after the achievement of SVR12.Results:Totally, 143 patients were enrolled in the study, four patients were lost to follow-up and one died during the follow-up, 138 patients were included in per-protocol analysis. Of the 138 patients, the mean age 53 years, 53.6% male, 94.2% Han nationality, 53.6% liver cirrhosis, 10.1% HBsAg +, 6.5% renal dysfunction, 5.1% treatment-experienced, and 16.7% patients received ribavirin treatment. The genotype distribution was as follows: 35.5% GT1, 42.8% GT2, 15.9% GT3, and 5.8% un-typed. The SVR12 rate was 96.5% (138/143, 95% CI: 93.5%-99.6%) for intention-to-treat analysis, and in per-protocol analysis, all 138 patients obtained SVR12 (100%). Compared with baseline, the serum total bilirubin, ALT and AFP levels decreased (all P < 0.05), as well as increased ALB and platelet count (all P < 0.001) at post-treatment 12-weeks. Overall adverse events (AEs) rate is 29.0%, and the most common AEs were anemia (14.5%) and fatigue (8.0%). Severe side effects (edema and fatigue) occurred in 2 patients, one of whom needed a short-term interruption of treatment due to fatigue. Conclusion:In this real-world cohort study, 12-week SOF/VEL regimen with or without ribavirin achieved high SVR12 rates (96.5%-100% overall) with excellent safety profile among patients with HCV GT1/2/3 infection including patients with GT3 and cirrhosis, and led to improvement of liver function.

BRAF is a serine/threonine kinase that harbors activating mutations in ∼7% of human malignancies and ∼60% of melanomas. Despite initial clinical responses to BRAF inhibitors, patients frequently develop drug resistance. To identify candidate therapeutic targets for BRAF inhibitor resistant melanoma, we conduct CRISPR screens in melanoma cells harboring an activating BRAF mutation that had also acquired resistance to BRAF inhibitors. To investigate the mechanisms and pathways enabling resistance to BRAF inhibitors in melanomas, we integrate expression, ATAC-seq, and CRISPR screen data. We identify the JUN family transcription factors and the ETS family transcription factor ETV5 as key regulators of CDK6, which together enable resistance to BRAF inhibitors in melanoma cells. Our findings reveal genes contributing to resistance to a selective BRAF inhibitor PLX4720, providing new insights into gene regulation in BRAF inhibitor resistant melanoma cells.

Objective:To establish microbial limit test methods for three Hospital Preparations: the Jianer Granule, Anti-inflammatory and anti-itching Liquor and Baicao Lotion. Methods:According to the four general principles of the Chinese Pharmacopoeia (edition 2015), to test the applicability for three kinds of hospital preparations with microbial count method using outine method, medium dilution method, membrane filtration method and neutralizer combined membrane filtration method. The applicability test of control bacteria test for three kinds hospital preparations was carried out by routine method, membrane filtration method and neutralizer combined with membrane filtration method. Results:The microbial limit test of Jianer Granule was tested by routine method. The microbial limit test of Anti-inflammatory and anti-itching Liquor was tested by membrane filtration method. The microbial limit test of Baicao Lotion was tested by neutralizer combined with membrane filtration method. Conclusions:Established the methods of microbial limit test for three kinds hospital preparations which are accurate and reliable.

Objective:To investigate the gap between the health education and the best evidence among nurses and patients with postdialysis fatigue (PDF) , find out the problems and analyze the reasons, and provide a reference and basis for future clinical nursing decisions among the dialysis room nurses.Methods:By searching the evidence-based guideline websites and integrating the best evidence comprehensively, a health knowledge questionnaire for dialysis room nurses and patients with PDF was made. In December 2018, a total of 7 nurses and 56 patients in the dialysis room of Dongzhimen Hospital, Beijing University of Chinese Medicine were selected by purpose sampling method, and they were investigated by the health knowledge questionnaire for dialysis room nurses and patients.Results:The score of the PDF knowledge questionnaire for the 7 nurses was (56.43±4.37) , with a highest score of 64 and a lowest score of 51, and the standard-reaching rate was 28.57% (2/7) . The score of the PDF knowledge questionnaire for the 56 patients was (52.41±9.54) , with a highest score of 70 and a lowest score of 20, and the standard-reaching rate was 28.57% (16/56) . Patients and nurses received verbal health education and small lectures in the department, and there was no unified education content.Conclusions:There is no unified and scientific education content nor standardized education model. Evidence-based health education should be carried out for nurses to improve the awareness of nurses and patients in this regard, thereby reducing patients' fatigue.

Objective To establish the quality standard of Wuji-Jianwei granules. Methods The contents of Bupleuri Radix, Codonopsis Radix, Paeoniae Radix Alba, Corydalis Rhizoma in Wuji-Jianwei granules were identified by using the thin layer chromatography (TLC) method. The contents of peoniflorin was determined by the high performance liquid chromatography (HPLC) method. Results The TLC had strong specificity and high separation, negative control without interference. The linear range was 0.124 8-0.748 8 μg for peoniflorin (r=0.999 6). The average recovery was 94.42% (RSD=1.46%) and the content of peoniflorin was 0.725 3 mg/g. Conclusions The method is accurate and reasonable, and can be used for the quality control of Wuji-Jianwei granules.