Objective:To investigate the predictive value of serum β 2-microglobulin (β 2M) and pro-inflammatory cytokines for post-stroke depression (PSD) in patients with acute ischemic stroke (AIS). Methods:Patients with AIS admitted to the Department of Neurology, the Affiliated Municipal Hospital of Xuzhou Medical University from January 2020 to May 2023 were included retrospectively. At the 6-month outpatient follow-up, the Self-rating Depression Scale (SDS) was used to assess depression. Multivariate logistic regression analysis was used to determine the independent influencing factors of PSD. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of individual and combined independent influencing factors on PSD. Results:A total of 161 patients were enrolled, including 82 males (50.93%), aged 61.78±11.95 years; 47 patients (29.20%) developed PSD. Univariate analysis showed that the proportion of males, serum β 2M, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, high-sensitivity C-reactive protein level, and baseline National Institutes of Health Stroke Scale (NIHSS) score in the PSD group were significantly different from those in the non-PSD group (all P<0.05). Multivariate logistic regression analysis showed that serum β 2M (odds ratio [ OR] 4.257, 95% confidence interval [ CI]1.441-12.574; P=0.009), IL-1β ( OR 1.415, 95% CI 1.116-1.793; P=0.004), IL-6 ( OR 1.262, 95% CI 1.020-1.561; P=0.032), and TNF-α ( OR 1.246, 95% CI 1.021-1.521; P=0.030) were the independent influencing factors of PSD. ROC curve analysis showed that the area under the curve of serum β 2M for predicting PSD was 0.753 (95% CI 0.668-0.838), with an optimal cutoff value of 2.255 mg/L. The sensitivity and specificity were 59.6% and 80.7%, respectively. When serum β 2M was combined with IL-1β, IL-6 and TNF-α for prediction, the area under the curve increased to 0.893 (95% CI 0.837-0.948). Conclusion:The serum β 2M in combination with pro-inflammatory cytokines has good predictive value for PSD.

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 investigate associations of serum β 2-microglobulin (β 2M) with baseline stroke severity and outcome at 3 months after onset in patients with acute ischemic stroke (AIS). Methods:Patients with first-ever AIS admitted to the Department of Neurology, the Affiliated Municipal Hospital of Xuzhou Medical University from January 2018 to May 2022 were included retrospectively. The severity of stroke was evaluated according to the National Institute of Health Stroke Scale score at admission. ≤8 was defined as mild stroke, and >8 was defined as moderate to severe stroke. At 3 months after onset, the modified Rankin Scale was used to evaluate the clinical outcome, ≤2 points was defined as good outcome and >2 points was defined as poor outcome. Multivariate logistic regression analysis was used to determine associations of β 2M with the severity and outcome of stroke. Results:A total of 463 patients with AIS were enrolled, including 263 males (56.68%), aged 62.89±11.77 years. There were 319 patients (68.89%) in the mild stroke group and 144 (31.10%) in the moderate to severe stroke group; 304 patients (65.66%) in the good outcome group and 159 (34.34%) in the poor outcome group. Univariate analysis showed that the β 2M in the moderate to severe stroke group and the poor outcome group were significantly higher than those in the mild stroke group and the good outcome group, respectively (all P<0.05). Multivariate logistic regression analysis showed that β 2M was an independent influencing factor for stroke severity (odds ratio 2.476, 95% confidence interval 1.621-3.783; P<0.001) and poor outcome (odds ratio 5.179, 95% confidence interval 2.941-11.121; P<0.001) in patients with AIS. Conclusion:There is a significant independent correlation between high serum β 2M and the severity and poor outcome of stroke in patients with AIS.

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.

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.

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.