Objective To specifically extract and analyze nascent proteins synthesized by bone marrow mesenchymal stem cells(BMSCs)after transplantation into ischemic hearts using a technique employing mutant methionyl-tRNA synthetase(MetRSL247G)for nascent protein labeling,in order to explore the potential mechanisms of action in BMSCs post-transplantation.Methods Point mutation at position 274 of the MetRS gene in BMSCs was induced via lentiviral infection to enable azidonorleucine(ANL)-mediated labeling of nascent proteins in BMSCs.The labeling efficiency was verified by means of fluorescent non-canonical amino-acid tagging(FUNCAT).Thirty healthy female C57BL/6J mice(8-10 weeks old)were divided into control and experimental groups,with 15 mice in each group.The acute myocardial infarction model was constructed by ligating the left anterior descending coronary artery in experimental group,while control mice underwent only thoracotomy without coronary ligation.After modeling,both groups received intramyocardial injections of MetRSL247G-modified BMSCs(MetRSL247G-BMSCs)at 3 different sites in the peri-infarct ischemic region.Mice were intraperitoneally injected with ANL every 6 hours for 4 times on postoperative days 0,2,and 6(n=5 for each time point)respectively,euthanized 24 h after the last injection,and cardiac tissues were isolated.The newly synthesized and labeled proteins produced by BMSCs after transplantation into the myocardium of experimental and control groups were collected,using an enrichment technique for ANL-tagged proteins and liquid chromatography-tandem mass spectrometry(LC-MS)analysis.Gene ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,protein-protein interaction(PPI)analysis,and heatmap visualization analysis were performed to identify differentially expressed proteins at the 3 time points and screen key pathways and genes.Results Under fluorescence microscopy,the MetRSL247G lentivirus-infected BMSCs were observed to be labelled with mCherry signals,confirming the successful construction of the MetRSL247G-BMSCs cell line.Green fluorescent signals were detected only in nascent proteins in culture medium containing both MetRSL247G-BMSCs and ANL,validating the sensitivity and specificity of the labeling method.GO analysis revealed that differentially expressed proteins were primarily involved in basic cellular biological processes such as extracellular exosome formation,extracellular matrix organization,and focal adhesion.KEGG and PPI analyses indicated that the differential proteins were mainly involved in complement and coagulation cascade pathway,actin cytoskeleton regulation pathway,and apoptosis pathway.Heatmap analysis showed significantly upregulated expression of anti-apoptosis and cell adhesion-related factors in experimental group on day 1(P＜0.05),upregulated anti-apoptotic factors,pro-apoptotic factors,and cell adhesion-related factors on day 3(P＜0.05),and upregulated anti-apoptotic factors,cell differentiation-related factors,and cell adhesion-related factors on day 7(P＜0.05)compared with control group.Expression of apoptosis-inducing factor 1 was significantly downregulated on days 1 and 7(P＜0.05).On day 3,most differentially expressed proteins,including anti-apoptosis factors(Protein S100-A11,Clusterin,Gelsolin),pro-apoptosis factor(Cathepsin B),cell differentiation-related factor(Transgelin-2),and cell adhesion-related factors(Cofilin-1,Periostin,Fibronectin)were significantly upregulated(P＜0.05).Conclusions The MetRSL247G mutation enables BMSCs to incorporate ANL and synthesize labeled proteins,confirming the feasibility of this nascent protein labeling technique.Nascent proteins of BMSCs in ischemic myocardium primarily contribute to extracellular exosome secretion and extracellular matrix organization.BMSCs may adapt to and respond to ischemic and hypoxic environments by influencing complement and coagulation cascades,activating inflammatory factors,regulating actin cytoskeleton structure,and modulating apoptosis,thereby maintaining the survival of BMSCs.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To investigate the correlation between physical examination results and age of submariners,so as to provide scientific guidance for the health management of submariners.Methods A total of 331 submariners who underwent physical examination at a naval hospital in 2022 were selected for this research.There were 174 submariners aged≤26 years and 157 submariners aged>26 years.Physical examination results were statistically analyzed.Results Body mass index,basophil count,alanine aminotransferase,fasting blood glucose,total cholesterol,triglycerides,systolic blood pressure and diastolic blood pressure were positively correlated with age,while erythrocyte count and direct bilirubin were negatively correlated with age.The proportions of submariners aged>26 years with overweight,gallbladder polyps,elevated total cholesterol and elevated triglycerides were significantly higher than those aged≤26 years(P<0.05).The proportion of submariners aged>26 years with erythrocytosis was significantly lower than that of submariners aged≤26 years(P<0.05).Conclusion Some physical indicators of submariners are age-dependent,with older crews having higher incidences of overweight,gallbladder polyps and hyperlipidaemia.Individual health management measures should be developed for submariners with different ages.

OBJECTIVE: This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance (HIVDR) in patients with ART failure from 2014 to 2020 in Hainan, China. METHODS: A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan. We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences. Drug resistance mutations (DRMs) were analyzed using the Stanford University HIV Drug Resistance Database. RESULTS: A total of 307 HIV-infected patients with ART failure were included, and 241 available pol sequences were obtained. Among 241 patients, CRF01_AE accounted for 68.88%, followed by CRF07_BC (17.00%) and eight other subtypes (14.12%). The overall prevalence of HIVDR was 61.41%, and the HIVDR against non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 59.75%, 45.64%, and 2.49%, respectively. Unemployed patients, hypoimmunity or opportunistic infections in individuals, and samples from 2017 to 2020 increased the odd ratios of HIVDR. Also, HIVDR was less likely to affect female patients. The common DRMs to NNRTIs were K103N (21.99%) and Y181C (20.33%), and M184V (28.21%) and K65R (19.09%) were the main DRMs against NRTIs. CONCLUSION The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.
Humans ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV-1/genetics* ; Cross-Sectional Studies ; Phylogeny ; Anti-HIV Agents/therapeutic use* ; Drug Resistance, Viral/genetics* ; HIV Infections/epidemiology* ; Mutation ; China/epidemiology* ; Prevalence ; Genotype

Objective:To explore stigma and related factors among family members of patients with mental disorders in psychiatric hospitals.Methods:Totally 1 365 family members of inpatients with mental disorders were-surveyed,and were assessed with the Perceived Devaluation-Discrimination Scale and a self-made demographic characteristics questionnaire.Results:The screening rate of stigma among the patient's family members was 61.5％.Males(OR=2.26,95％CI:1.06-5.01),age group of 18-29 years(OR=1.91,95％CI:1.15-3.20),monthly income ≥500 yuan(P＜0.05),disease duration of 0.5-＜lyear(OR=3.14,95％CI:1.66-6.03),care for patients within＜lyear(P＜0.05),teachers(OR=2.32,95％CI:1.24-3.44),self-employed person(OR=1.63,95％CI:1.02-2.24),civil servants(OR=1.77,95％CI:1.09-2.45),schizophrenia(OR=1.87,95％CI:1.32-2.42),affective disorders(OR=1.52,95％CI:1.03-2.016)were the main riskfactors of stigma.Conclusions:Family members of patients with mental disorders generally have a severe stigma,especially of patients with schizophrenia and affective disorders.

Objective:To understand the current situation of knowledge, attitude and practice about target temperature management (TTM) in patients with severe traumatic brain injury (STBI) among intensive care unit ICU nurses and analyze the influencing factors, so as to provide a reference for conducting ICU nurses′ TTM training for patients with STBI.Methods:Applying the method of cross-sectional study, from November to December 2022, a stratified whole-group sampling method was used, stratified by first-, second-, and third-level hospitals, and a self-designed questionnaire on the current status of ICU nurses′TTM for patients with STBI was used to investigate the current status of knowledge, attitude, and practice of neurosurgical ICU, emergency ICU, and comprehensive ICU nurses in 22 second- and third-level hospitals in 11 cities in Gansu Province, and multiple linear regression analysis was used to analyze the factors influencing ICU nurses′ knowledge, attitude, and practice scores.Results:A total of 543 valid questionnaires were returned, and the scores of ICU nurses on the TTM total score, knowledge, attitude and practice dimensions of STBI patients were (76.75 ± 10.42), (7.38 ± 2.74), (39.57 ± 4.87), (29.80 ± 7.18) points respectively. The results of multiple linear regression analysis showed that the factor influencing ICU nurses′ scores on the TTM knowledge dimension for STBI patients was having attended TTM-related training ( t = 2.16, P<0.05); the factors influencing ICU nurses′ scores on the TTM attitude dimension for STBI patients were college, bachelor′s degree and the position of nurse practitioner ( t = 2.65, 2.91, 2.14, all P<0.05); and the factors influencing ICU nurses′ scores on the TTM practice dimension for STBI patients were the age group of 36 to 45 years old, the department having TTM-related criteria and having knowledge of TTM-related guidelines ( t = -2.46, 2.64, 3.85, all P<0.05). Conclusions:ICU nurses have a more positive attitude toward TTM in patients with STBI, but the level of knowledge and practice needs to be improved. Managers should conduct relevant training according to the current situation and influencing factors to improve ICU nurses′ knowledge and practice of TTM in patients with STBI, ensuring the effectiveness and safety of TTM.

Objective: To establish three types of xenotransplantation models using human myeloma cell lines ARP1, MM.1S, and NCI-H929 and to compare the proliferation, tumor load, and biological characteristics of the three types of cells after transplantation. Methods: Suspensions of human myeloma cell lines ARP1, MM.1S, and NCI-H929 were implanted into NOD/SCID mice by subcutaneous injection or tail vein injection. The survival of the mice was observed weekly, and the tumor load was measured. Flow cytometry was used to detect the proportion of CD138(+) cells in tumor tissue or the mouse bone marrow. CD138(+) cells and light chains were detected by immunofluorescence. Light chains in bone marow and peipheral blood were measured by ELISA, and bone disease was assessed by micro-CT. Results: Mice injected with ARP1, MM.1S, and NCI-H929 cells all formed tumors subcutaneously in about 2 weeks. Immunofluorescence detection supported plasma cell tumors. Kappa light chains were detected in the peripheral blood of ARP1 mice on day 20 after tail vein transplantation (8.2±1.0 ng/ml) . After 6 weeks of tail vein transplantation, mice in the ARP1 group showed signs of weight loss, mental depression, and dragging legs, and human CD138(+)CD38(+) cells were detected in the bone marrow (BM) . Furthermore, bortezomib (BTZ) treatment given once the tumor was established significantly reduced the tumor burden[ (5.7±0.2) % vs (21.3±2.1) %, P<0.01]. Human CD138(+)CD38(+) cells were not detected in the BM of the MM.1S or NCI-H929 groups. Conclusion: The results of this study suggest that the mouse models constructed by the three cell lines (ARP1, MM.1S, and NCI-H929) can be used as models for the pathogenesis and clinical research of MM.
Animals ; Bortezomib/therapeutic use* ; Cell Line, Tumor ; Disease Models, Animal ; Humans ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Multiple Myeloma/drug therapy*

OBJECTIVES: To study the association between hepatocyte growth factor (HGF) and treatment response in mice with hypoxic pulmonary arterial hypertension (HPAH) and the possibility of HGF as a new targeted drug for HPAH. METHODS: After successful modeling, the HPAH model mice were randomly divided into two groups: HPAH group and HGF treatment group (tail vein injection of recombinant mouse HGF 1 mg/kg), with 10 mice in each group. Ten normal mice were used as the control group. After 5 weeks, echocardiography was used to measure tricuspid peak velocity, right ventricular systolic pressure, right ventricular hypertrophy index, and right ventricular/body weight ratio; the Griess method was used to measure the content of nitric oxide in serum; ELISA was used to measure the serum level of endothelin-1; transmission electron microscopy was used to observe changes in the ultrastructure of pulmonary artery. RESULTS: Compared with the HGF treatment and normal control groups, the HPAH group had significantly higher tricuspid peak velocity, right ventricular systolic pressure, right ventricular hypertrophy index, and right ventricular/body weight ratio (P<0.05). The transmission electron microscopy showed that the HPAH group had massive destruction of vascular endothelial cells and disordered arrangement of the elastic membrane of arteriolar intima with rupture and loss. The structure of vascular endothelial cells was almost complete and the structure of arterial intima elastic membrane was almost normal in the HGF treatment group. Compared with the normal control and HGF treatment groups, the HPAH group had significantly higher serum levels of nitric oxide and endothelin-1 (P<0.05). CONCLUSIONS Increasing serum HGF level can alleviate the impact of HPAH on the cardiovascular system of mice, possibly by repairing endothelial cell injury, improving vascular remodeling, and restoring the normal vasomotor function of pulmonary vessels.
Animals ; Body Weight ; Endothelial Cells ; Endothelin-1 ; Hepatocyte Growth Factor/therapeutic use* ; Hypertrophy, Right Ventricular ; Hypoxia ; Mice ; Nitric Oxide ; Pulmonary Arterial Hypertension/drug therapy*

Background::It is controversial whether the apolipoprotein E epsilon 4 allele ( APOE ε4) is a risk gene for human immunodeficiency virus (HIV)-related neurocognitive impairment. This meta-analysis aimed to summarize evidence of the associations between APOE ε4 and cognitive impairment in people living with HIV (PLWH). Methods::Our study conducted a systematic literature search of PubMed, Web of Science, Embase, Google Scholar, and ProQuest for studies published before April 11, 2022 that evaluated associations between APOE ε4 and cognitive impairment in adult PLWH (aged ≥18 years). We calculated pooled odds ratios (ORs) of global cognitive impairment and 95% confidence intervals (CIs) and standardized mean differences (SMDs) for specific cognitive domains between APOE ε4 carriers and non-carriers. Subgroup meta-analyses were used to evaluate the result profiles across different categorical variables. Results::Twenty studies met the inclusion criteria, including 19 that evaluated global cognitive impairment. APOE ε4 was significantly associated with global cognitive impairment in PLWH (OR = 1.36, 95% CI = [1.05, 1.78], number of estimates [ k] = 19, P = 0.02, random effects). Subgroup meta-analysis based percentage of females showed evident intergroup differences in global cognitive performance between ε4 carriers and non-carriers ( P = 0.015). APOE ε4 carriers had lower cognitive test scores than non-carriers in all seven cognitive domains, including fluency (SMD = -0.51, 95% CI = [-0.76, -0.25], P < 0.001, k = 4, I2= 0%), learning (SMD = -0.52, 95% CI = [-0.75, -0.28], P < 0.001, k = 5, I2 = 0%), executive function (SMD = -0.41, 95% CI= [-0.59, -0.23], P < 0.001, k= 8, I2= 0%), memory (SMD=-0.41, 95% CI= [-0.61, -0.20], P < 0.001, k= 10, I2= 36%), attention/working memory (SMD=-0.34, 95% CI= [-0.54, -0.14], P= 0.001, k= 6, I2= 0%), speed of information processing (SMD = -0.34, 95% CI = [-0.53, -0.16], P < 0.001, k = 8, I2 = 0%), and motor function (SMD = -0.19, 95% CI = [-0.38, -0.01], P = 0.04, k = 7, I2 = 0%). Conclusions::Our meta-analysis provides significant evidence that APOE ε4 is a risk genotype for HIV-associated cognitive impairment, especially in cognitive domains of fluency, learning, executive function, and memory. Moreover, the impairment is sex specific. Meta analysis registration::PROSPERO, CRD 42021257775.

Objective:To evaluate the clinical and ultrasonographic features for early diagnosis and prediction of lateral cervical lymph node metastasis of medullary thyroid microcarcinoma.Methods:From Jan 2010 to Jan 2020 233 patients undergoing primary surgery were categorized as "medullary thyroid microcarcinoma" and "medullary thyroid macrocarcinoma". The preoperative clinical and ultrasonographic characteristics, the diagnostic positive rate of preoperative serum calcitonin and fine needle aspiration (FNA) were investigated between two groups. All patients with medullary thyroid microcarcinoma were divided on the basis of wether there was lateral cervical lymph node metastasis.Results:There were statistically significant differences in initial diagnostic method(χ 2=32.290, P=0.000), TNM staging(χ 2=50.300, P=0.000) between medullary thyroid microcarcinoma and medullary thyroid macrocarcinoma. Medullary thyroid microcarcinoma showed more malignant ultrasonic features. The diagnostic accuracy of preoperative serum calcitonin was higher than FNA for medullary thyroid micro carcinoma(χ 2=47.933, P=0.000). Multivariate regression analysis demonstrated that the abutment/perimeter ≥1/4( OR=25.475, 95%CI: 2.320-279.771), preoperative serum calcitonin >65 ng/L( OR=32.663, 95%CI:2.433-438.409) were the independent factor for lateral cervical lymph node metastases of medullary thyroid microcarcinoma. Conclusions:The combination of ultrasonography and serum calcitonin helps establish early diagnosis of medullary thyroid microcarcinoma. Medullary thyroid microcarcinoma with the abutment/perimeter ≥1/4, serum calcitonin >65 ng/L predicts lateral cervical lymph node metastases.