Nipah virus (NiV) and related viruses form a distinct henipavirus genus within the Paramyxoviridae family. NiV continues to spillover into the humans causing deadly outbreaks with increasing human-bat interaction. NiV encodes the large protein (L) and phosphoprotein (P) to form the viral RNA polymerase machinery. Their sequences show limited homologies to those of non-henipavirus paramyxoviruses. We report two cryo-electron microscopy (cryo-EM) structures of the Nipah virus (NiV) polymerase L-P complex, expressed and purified in either its full-length or truncated form. The structures resolve the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, as well as a tetrameric P protein bundle bound to the L-RdRp domain. L-protein C-terminal regions are unresolved, indicating flexibility. Two PRNTase domain zinc-binding sites, conserved in most Mononegavirales, are confirmed essential for NiV polymerase activity. The structures further reveal anchoring of the P protein bundle and P protein X domain (XD) linkers on L, via an interaction pattern distinct among Paramyxoviridae. These interactions facilitate binding of a P protein XD linker in the nucleotide entry channel and distinct positioning of other XD linkers. We show that the disruption of the L-P interactions reduces NiV polymerase activity. The reported structures should facilitate rational antiviral-drug discovery and provide a guide for the functional study of NiV polymerase.
Nipah Virus/chemistry* ; Cryoelectron Microscopy ; Viral Proteins/genetics* ; RNA-Dependent RNA Polymerase/genetics* ; Phosphoproteins/genetics* ; Humans ; Models, Molecular ; Protein Binding

ObjectiveTo analyze the factors influencing meropenem-related liver injury （MRLI） and to explore their clinical predictive value. MethodsA retrospective case-control study was conducted， and the Chinese Hospital Pharmacovigilance System （CHPS） was used to establish a retrieval scheme. A total of 1 625 hospitalized cases using meropenem from January 2018 to December 2022 were collected. Patients were divided into case group （n=62） and control group （n=1 563） based on the presence or absence of liver injury. Clinical data and laboratory indicators from both groups were collected and analyzed. The t-test was used for comparison of normally distributed continuous data between the two groups， while the Mann-Whitney U test was used for comparison of continuous data not conforming to a normal distribution. The chi-square test was used for comparison of categorical data between the two groups. A multivariate Logistic regression analysis was performed to identify the influencing factors for MRLI. A Logistic regression equation was established， and the predictive value of these factors was assessed using the receiver operating characteristic （ROC） curve. ResultsThe results of univariate analysis indicated that the rates of male patients， hypoproteinemia， shock， intensive care unit （ICU） admissions， sepsis， and liver， gallbladder， and cardiovascular diseases， the levels of alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， gamma-glutamyl transpeptidase （GGT）， aspartate aminotransferase （AST）， creatinine （CREA）， and procalcitonin （PCT）， and the number of hospitalization days were significantly higher in the case group than in the control group （P<0.05）， and that the platelet levels in the case group were significantly lower than those in the control group （P<0.05）. The multivariate Logistic regression analysis showed that male sex （odds ratio ［OR］=2.080， 95% confidence interval ［CI］： 1.050 — 4.123， P=0.036）， admission to the ICU （OR=8.207， 95%CI： 4.094‍ ‍—‍ ‍16.453， P<0.001）， comorbidity with gallbladder disease （OR=8.240， 95%CI： 3.605‍ ‍—‍ ‍18.832， P<0.001）， ALP （OR=1.012， 95%CI： 1.004‍ ‍—‍ ‍1.019， P=0.004）， GGT （OR=1.010， 95%CI： 1.005‍ ‍—‍ ‍1.015， P<0.001）， and PLT （OR=0.997， 95%CI： 0.994‍ ‍—‍ ‍0.999， P=0.020） were the influential factors for MRLI. The areas under the ROC curve of ALP， GGT， and PLT were 0.589， 0.637， and 0.595， respectively， and the AUC of them combined was 0.837. ConclusionMale sex， ICU admission， comorbidity with gallbladder disease， increased ALP， increased GGT， and decreased PLT were influencing factors for MRLI， and a combination of factors has a better predictive value for the occurrence of MRLI.

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

OBJECTIVES: To investigate the inhibitory effect of Fuzheng Huaji Decoction against non-small cell lung cancer (NSCLC) cells in vitro and explore the underlying mechanism. METHODS: The active ingredients and targets of Fuzheng Huaji Decoction were identified using TCMSP and SwissTargetPrediction databases. NSCLC-related targets from GeneCards and PharmGKB were intersected with the targets of the Decoction, and a protein-protein interaction (PPI) network was constructed to identify the core targets, which were analyzed with GO and KEGG pathway enrichment analysis. Cultured A549 cells were treated with different concentrations of Fuzheng Huaji Decoction-medicated serum, and the changes in cell proliferation, apoptosis, and protein expressions were examined using CCK-8 assay, annexin V-FITC/PI staining and Western blotting. RESULTS: Fuzheng Huaji Decoction contained 140 active ingredients, and 707 drug-disease intersecting targets were identified. Among these targets, TP53, AKT1, HIF1A, GAPDH, ALB, EGFR, CTNNB1, and TNF were identified as the core targets which were involved in the biological processes related to kinases and receptors and the PI3K-AKT, Ras, calcium, and MAPK pathways. Molecular docking studies indicated strong binding affinity of the active ingredients with TP53, AKT1, and HIF1A. In cultured A549 cells, treatment with 2.5%, 5%, and 10% Fuzheng Huaji Decoction-medicated serum significantly inhibited cell proliferation, promoted cell apoptosis, and downregulated the expression levels of HIF1A, p-AKT (Thr308), and TP53 proteins. CONCLUSIONS Fuzheng Huaji Decoction inhibits proliferation of NSCLC cells possibly by downregulating the expressions of HIF1A, p-AKT (Thr308), and TP53.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Lung Neoplasms/metabolism* ; A549 Cells ; Proto-Oncogene Proteins c-akt/metabolism* ; Protein Interaction Maps ; Signal Transduction/drug effects* ; Cell Line, Tumor

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective To improve the survival rate and life quality of peritoneal dialysis(PD)patients,we es-tablished a retraining model based on ADDIE model,including optimizing the content,form and frequency.Methods From January 1,2022 to May 3,2023,based on the 5 stages of ADDIE model,we investigated the needs of pa-tients,invited 55 experts in the peritoneal dialysis field to design the final draft of the retraining model through 2 rounds of Delphi expert consultations,and 23 peritoneal dialysis patients were preexperimented to evaluate and re-vise the retraining model.Results The questionnaire recovery rates of the 2 rounds of expert consultation were 100％and 96.36％,respectively.The coordination coefficients of the first-level catalog were 0.379 and 0.384,and the coordination coefficients of the second-level catalog were 0.446 and 0.427,respectively.The Chi-square test showed that P＜0.05,indicating statistical significance.The content of the retraining model included 4 sections,33 subdirectories and 9 training forms,which were combined online and offline.The training frequency was different due to the different contents,and the single content of a single training form was mainly 15 min.Conclusion The PD patient retraining model constructed in this study is scientific,reliable and innovative.Its content is easy to un-derstand and diverse in forms.The training duration and frequency are in line with the memory rule,and the eval-uation takes into account both process and result.

Bipolar affective disorder refers to a category of mood disorders characterized clinically by the presence of both manic or hypomanic episodes and depressive episodes.Lithium stands out as the primary pharmacological intervention for managing bipolar affective disorder.However,its therapeutic dosage closely approaches toxic levels.Toxic symptoms appear when the blood lithium concentration surpasses 1.4 mmol/L,typically giving rise to gastrointestinal and central nervous system reactions.Cardiac toxicity is rare but serious in cases of lithium poisoning.The study reports a case of a patient with bipolar affective disorder who reached a blood lithium concentration of 6.08 mmol/L after the patient took lithium carbonate sustained-release tablets beyond the prescribed dosage daily and concurrently using other mood stabilizers.This resulted in symptoms such as arrhythmia,shock,impaired consciousness,and coarse tremors.Following symptomatic supportive treatment,including blood dialysis,the patient's physical symptoms gradually improved.It is necessary for clinicians to strengthen the prevention and recognition of lithium poisoning.

BACKGROUND:Jaws are most vulnerable to osteoporosis.Adipose-derived mesenchymal stem cells and bone morphogenetic protein 2 have the effect of promoting bone regeneration in osteoporosis.However,the repair effect of bone morphogenetic protein 2 modified adipose-derived mesenchymal stem cells on alveolar bone defects in osteoporosis is rarely reported. OBJECTIVE:To explore the repair effect of adipose-derived mesenchymal stem cells overexpressing bone morphogenetic protein 2 on alveolar bone defects in osteoporosis rats. METHODS:(1)The rat adipose-derived mesenchymal stem cells were infected with lentivirus overexpressing bone morphogenetic protein 2 gene,and identified by detecting the expression of green fluorescent protein and bone morphogenetic protein 2.(2)Osteoporosis rat model was established by ovariectomy.A 3 mm×3 mm×3 mm cylindrical defect was prepared at the first molar position on both sides of the upper jaw.(3)Gelatin sponge was implanted in rats of the sham operation group and osteoporosis group.In the adipose-derived stem cell group,the adipose-derived mesenchymal stem cells infected with empty vector lentivirus and gelatin sponge complex were implanted.In the adipose-derived mesenchymal mesenchymal stem cell group overexpressing bone morphogenetic protein 2,a complex of adipose-derived mesenchymal stem cells overexpressing bone morphogenetic protein 2 and gelatin sponge was implanted.Relevant indexes were tested one month later. RESULTS AND CONCLUSION:(1)The transfection efficiency of the adipose-derived mesenchymal stem cell group and adipose-derived mesenchymal stem cell group overexpressing bone morphogenetic protein 2 reached more than 70%.Compared with the adipose-derived mesenchymal stem cell group,the level of bone morphogenetic protein-2 protein in the adipose-derived mesenchymal stem cell group overexpressing bone morphogenetic protein-2 was significantly higher(P<0.05).(2)A large amount of new bone could be seen in the bone defect area of the sham operation group.Compared with the sham operation group,the osteoporotic group had a small amount of new bone formation;the new bone area was significantly reduced,and alkaline phosphatase,osteocalcin,and bone morphogenetic protein 2 mRNA and protein levels were significantly reduced.Compared with the osteoporosis group,the adipose-derived mesenchymal stem cell group and the adipose-derived mesenchymal stem cell group overexpressing bone morphogenetic protein 2 had a large number of new bone formation;the area of new bone was significantly increased,and the levels of alkaline phosphatase,osteocalcin,and bone morphogenetic protein 2 mRNA and protein were significantly increased.Moreover,the adipose-derived mesenchymal stem cell group overexpressing bone morphogenetic protein 2 was superior to the adipose-derived mesenchymal stem cell group(all P<0.05).(3)The results showed that bone morphogenetic protein 2 was less expressed in the alveolar bone of osteoporosis rats,and adipose-derived mesenchymal stem cells overexpressing bone morphogenetic protein 2 could promote osteogenesis and regeneration of alveolar bone defects in osteoporosis rats.

Objective:To explore the prognosis efficacy of psycho-cardiological therapy and management on patients with coronary atherosclerosis disease (CAD).Methods:This was a clinical randomized controlled study. This study included inpatients with CAD at the cardiology department in Beijing Anzhen Hospital, Capital Medical University from August 2021 to January 2024. The patients enrolled in this study were asked for basic information, and received measurements for depression, anxiety, sleep quality and living quality by the scales of Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder scale-7 (GAD-7), Athens Insomnia Scale (AIS), EuroQol 5-dimension 5-level (EQ-5D-5L) respectively. The patients were randomly grouped into a regular treatment group and a psycho-cardiological treatment group which included WeChat management or antidepressant/antianxiety medical therapy according to the situation. After the patients discharging from hospital for 2, 4, 12, 24, 48, 72, and 96 weeks, professional cardiovascular doctors would follow up by telephone, WeChat, and outpatient department, including scales (2-48 weeks), and cardiac events (2-96 weeks). Kaplan-Meier survival curve and multivariate Cox proportional hazards model were used for analyzing the association between psycho-cardiological treatment and cardiac events.Results:This study recruited a total of 552 patients with CAD, aged 61.0(54.0, 67.0) years, and 379 (68.7%) were male. There were 279(50.5%) in the regular treatment group and 273(49.5%) in the psycho-cardiological treatment group. After treatment for 4, 12 and 48 weeks, the PHQ-9 score in psycho-cardiological was significantly lower than the regular treatment group; After treatment for 12 weeks, the EQ-5D-5L effective value in psycho-cardiological group was higher than the regular treatment group; After treatment for 2, 4, 12, 24 and 48 weeks, the EQ-5D-5L VAS score in psycho-cardiological group was higher than the regular therapy group (all P<0.05). The Kaplan-Meier survival curve showed that, during the different follow-up periods, the rate of cardiac events in psycho-cardiological treatment group was lower than regular treatment group (log-rank P<0.001). The multivariate Cox proportional hazards model adjusted the factor of age, the psycho-cardiological treatment contributed to reducing the cardiac events rate by 80.3% ( HR=0.197, 95% CI: 0.067-0.582, P=0.003). Conclusion:Psycho-cardiological treatment is beneficial for improving psychological stress, living quality, and reducing cardiac events, and helps to improve prognosis and psycho-cardiological rehabilitation in CAD patients.

Objective: To understand sleep quarity among primary and middle school students in Shenzhen City, so as to provide data support for sleeping quality improvement. Methods: A survey was conducted among 8 742 children selected from two 12 year schools in Longhua District of Shenzhen City, by purposive sampling method from December 22, 2020 to January 15, 2021. The general information was investigated with the self designed questionnaire, and sleep disturbance was investigated and evaluated with the Sleep Disturbance Scale for Children (SDSC). And Chi square test was applied for data analysis. Results: About 47.61 % of primary and middle school students in Shenzhen City reported sleep disturbance, 10.84% of students had moderate to severe sleep disturbance. The overall rate of sleep disturbance and moderate and to severe sleep disturbance among primary school students (48.03%, 10.04%), junior middle schools (45.89%, 11.30%), senior middle schools (52.61%, 16.83%) were found of statistically significant differences ( χ 2=8.89, 27.05, P <0.05). The time to fall asleep for primary school students, junior school students and senior school students at night during the study period were 22:00-23:00 (90.35%), 22:00-23:00 (62.37%), and 23:00-01:00 (61.44%), respectively, and the time to fall asleep of the different stages students were found of statistically significant differences ( χ 2=1 470.17, P <0.01). About 41.04% of students could fall asleep within 15 minutes and 50.57% could fall asleep within 15 to 30 minutes, and the differences in the latency for different stages students to fall asleep at night were of statistical significance ( χ 2=82.92, P <0.01); 8.03% of primary and middle school students had a night sleep time of over 9 hours, and 45.97 % had a night sleep time of 8-9 hours, and the differences in the night sleep time among different stages students were of statistical significance ( χ 2=1 292.86, P <0.01). Conclusions The main sleep problems among primary and secondary school students in Shenzhen City are insufficient sleep and poor sleep quality. The relevant departments should emphasize the sleep health education among children and their parents, so as to improve their sleep quality.