Aim To investigate the anti-Zika virus(ZIKV)mechanism of diterpenoid compound 9 from Euphorbia helioscopia in vitro.Methods The cytotox-icity of compound 9 was evaluated using the CCK-8 as-say.A ZIKV-infected Vero cell model was established,and the antiviral activity was assessed through RT-qPCR,plaque assay,Western blot,and immunofluores-cence.Furthermore,the mechanism of action was elu-cidated using multi-cell line validation,nanoparticle tracking analysis,cellular thermal shift assay,and mo-lecular docking.Results In Vero cells,compound 9 exhibited an EC50 of(3.95±0.15)μmol·L-1 and a CC50 of(272.12±8.56)μmol·L-1,demonstrating significantly higher antiviral efficacy than the positive control drug ribavirin(RBV).Its virus inactivation effect was time-dependent and could significantly re-duce viral load and plaque formation.Studies revealed that compound 9 altered the physicochemical properties of ZIKV particles,including reducing surface charge and increasing particle size distribution.Additionally,it significantly enhanced the thermal stability of the prM protein.Molecular docking analysis indicated that compound 9 formed a high-affinity interaction with the prM protein(binding energy:-38.52 kJ·mol-1)and stabilized its structure through hydrophobic interac-tions.Conclusion Compound 9 exerts in vitro anti-ZIKV activity by directly inactivating the virus,disrup-ting viral particle integrity,and targeting the prM pro-tein.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Aim To investigate the anti-Zika virus(ZIKV)mechanism of diterpenoid compound 9 from Euphorbia helioscopia in vitro.Methods The cytotox-icity of compound 9 was evaluated using the CCK-8 as-say.A ZIKV-infected Vero cell model was established,and the antiviral activity was assessed through RT-qPCR,plaque assay,Western blot,and immunofluores-cence.Furthermore,the mechanism of action was elu-cidated using multi-cell line validation,nanoparticle tracking analysis,cellular thermal shift assay,and mo-lecular docking.Results In Vero cells,compound 9 exhibited an EC50 of(3.95±0.15)μmol·L-1 and a CC50 of(272.12±8.56)μmol·L-1,demonstrating significantly higher antiviral efficacy than the positive control drug ribavirin(RBV).Its virus inactivation effect was time-dependent and could significantly re-duce viral load and plaque formation.Studies revealed that compound 9 altered the physicochemical properties of ZIKV particles,including reducing surface charge and increasing particle size distribution.Additionally,it significantly enhanced the thermal stability of the prM protein.Molecular docking analysis indicated that compound 9 formed a high-affinity interaction with the prM protein(binding energy:-38.52 kJ·mol-1)and stabilized its structure through hydrophobic interac-tions.Conclusion Compound 9 exerts in vitro anti-ZIKV activity by directly inactivating the virus,disrup-ting viral particle integrity,and targeting the prM pro-tein.

Background and purpose:DDX is an adenosine triphosphate(ATP)-dependent RNA helicase closely related to mRNA regulation,tumor proliferation and invasion.This article aimed to explore the effect of DDX6,a member of the DDX family,on the stability of CKMT1A mRNA,as well as the effect of the DDX6 CKMT1A axis on the proliferation and migration ability of human nasopharyngeal carcinoma cell CNE2 and its molecular mechanism.Methods:We retrieved the data of expressions of DDX6 and CKMT1A in human head and neck squamous cell carcinoma from The Cancer Genome Atlas(TCGA)database and performed a correlation analysis.Western blot was performed to detect the expressions of CKMT1A and DDX6 in human nasopharyngeal carcinoma tissues and normal nasopharyngeal tissues preserved by Affiliated Hospital of Nantong University.This study was approved by the Ethics Committee of Affiliated Hospital of Nantong University(Number:2022-L114).We used transwell assay to detect cell migration ability,EdU assay to detect cell proliferation ability,and colony formation assay to detect clone formation ability.We transfect with lentivirus and plasmids to construct sh-DDX6,sh-CKMT1A,sh-CKMT1A+sh-DDX6 and oe-CKMT1A cell models derived from the human nasopharyngeal carcinoma cell line CNE2,preserved by Affiliated Hospital of Nantong University,to clarify the impact of DDX6 and CKMT1A expression levels on the malignant biological phenotypes of nasopharyngeal carcinoma cells.BALB/c nude mice subcutaneous xenograft tumor model was constructed to detect the effects of DDX6 and CKMT1A on nasopharyngeal carcinoma cells in mice.RNA stability assay was used to detect the effect of DDX6 knockout on CKMT1A mRNA and further clarify the molecular mechanism of DDX6.Results:DDX6 was highly expressed,CKMT1A level was low in human nasopharyngeal carcinoma tissue,and DDX6 was negatively correlated with CKMT1A expression.DDX6 inhibited protein translation of CKMT1A by disrupting its mRNA stability.Low expression of CKMT1A in CNE2 cells enhanced cell migration and proliferation ability,while high expression inhibited migration and proliferation ability.Knocking out DDX6 reversed the progression of malignant behavior caused by downregulation of CKMT1A.Low expression of CKMT1A promoted tumor cell growth in BALB/c nude mice subcutaneous xenograft tumor model,while low expression of DDX6 inhibited tumor cell growth.Knocking out DDX6 and CKMT1A simultaneously restored the inhibitory effect caused by knocking down DDX6 alone.Conclusion:DDX6 in nasopharyngeal carcinoma cells disrupts the stability of CKMT1A mRNA,negatively regulates CKMT1A protein translation,upregulates the proliferation and migration ability of nasopharyngeal carcinoma cells,and promotes malignant progression of nasopharyngeal carcinoma.

Objective:To determine the pharmacodynamics of ciprofol for adjunctive sedation in elderly patients undergoing neuraxial anesthesia.Methods:This was a prospective study. American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients of either sex, aged ≥65 yr, with a body mass index of 18-30 kg/m 2, scheduled for elective knee replacement under neuraxial anesthesia from June to September 2023 in the Second Hospital of Shanxi Medical University, were selected. After completion of neuraxial anesthesia, ciprofol was pumped intravenously at a loading dose of 0.05 mg/kg (administered for approximately 4 min). The maintenance dose was determined by the sequential method. The initial maintenance dose was 0.2 mg·kg -1·h -1, and the dose gradient was 0.02 mg·kg -1·h -1. If the patient was satisfactorily sedated, the dose of ciprofol was decreased by 0.02 mg·kg -1·h -1 in the next patient; if the sedation was unsatisfactory, the dose of ciprofol was increased by 0.02 mg·kg -1·h -1 in the next patient, and the trial was terminated after 8 transitions. The occurrence of adverse reactions was recorded during administration and emergence. The median effective dose (ED 50), 95% effective dose (ED 95) and the corresponding 95% confidence interval ( CI) of ciprofol were calculated using the probit regression analysis. Results:Thirty-five patients were finally included in this study.The ED 50 of ciprofol for adjunctive sedation was 0.246 mg·kg -1·h -1 (95% CI 0.217-0.300 mg·kg -1·h -1), and the ED 95 was 0.325 mg·kg -1·h -1 (95% CI 0.284-0.771 mg·kg -1·h -1) in elderly patients undergoing knee arthroplasty under neuraxial anesthesia. During the administration of ciprofol, bradycardia occurred in 4 cases (11%), hypotension in 2 cases (6%), and hypoxemia in 2 cases (6%), which improved after treatment. No injection pain, abnormal limb movements, agitation during emergence, dizziness, headache, nausea and vomiting and postoperative delirium developed in patients. Conclusions:The ED 50 of ciprofol for adjunctive sedation is 0.246 mg·kg -1·h -1 and the ED 95 is 0.325 mg·kg -1·h -1 in elderly patients undergoing neuraxial anesthesia.

In November 2023, the seventh National Nucleic Acid Vaccine Conference was held to deeply discuss the immune mechanism, safety risks, advantages, and disadvantages of nucleic acid vaccines, and review the safety and effectiveness of COVID-19 vaccines developed by nucleic acid vaccine technology. Some prospectives were formed in the meeting that in the post-pandemic era, nucleic acid vaccine technology will play a role in the following areas: dealing with pathogens that are difficult to be prevented by traditional vaccines, promoting the upgrading of traditional live attenuated vaccines, contributing to the development of multivalent and combined vaccines, and rapid response to emerging and re-emerging infectious diseases. These views point out the direction for the future development of nucleic acid vaccine technology.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

Endovascular treatment of Stanford type B aortic dissection (type B dissection) has been widely used. There will be complications such as aortic dilatation, which will lead to poor prognosis of some patients. With more in-depth researches, it was found that there was a possible correlation between the prognosis of type B dissection and tears, such as the increasing of aortic diameter would be faster with longer tears, and the location of the tear will affect the thrombosis of the false lumen. Studies on hemodynamics have also found that different characteristics of tears of aortic dissection can cause changes in the pressure, blood flow rate and blood capacity in the true and false lumens recently. The hemodynamic changes can be used to predict the prognosis of type B dissection. The main characteristics of tears included the size, position, number of tears, residual tears and stent graft induced new entry. Describing the effect of tear characteristics on the development of type B dissection, can provide the basis for the clinical treatment and further research of type B dissection.
Humans ; Aortic Dissection/surgery* ; Hemodynamics ; Prognosis ; Blood Vessel Prosthesis Implantation/adverse effects* ; Thrombosis/etiology* ; Endovascular Procedures/adverse effects* ; Aortic Aneurysm, Thoracic/surgery* ; Stents/adverse effects* ; Treatment Outcome