Objective To quantitatively assess the exposure-response association between exposure to heatwave and sudden death, estimate the attributable excess deaths, and identify potential vulnerable subgroups. Methods A time-stratified case-crossover study was conducted among residents who died from sudden death in Jiangsu Province, China between 2015 and 2021. Heatwave events in Jiangsu Province, defined using varying relative temperature thresholds and durations, were identified using temperature data from the China Meteorological Administration Land Data Assimilation System (CLDAS V2.0). Individual heatwave exposure was assessed based on each subject's residential address. The exposure-response association between heatwave and sudden death was evaluated using conditional logistic regression model combined with a Distributed Lag Nonlinear Model(DLNM). Heatwave-attributable excess deaths were estimated. Stratified analyses by sex and age were performed to assess potential effect modifications. Results Under all definitions, exposure to heatwave was significantly associated with an increased risk of sudden death, and the risk increased with the intensity of heatwave. Using the P95_3d definition (temperature exceeding the 95th percentile for ≥3 consecutive days), heatwave was significantlyassociated with a 56% increased risk of sudden death (95% CI: 31%, 86%). The population-attributable fraction of sudden death due to heatwave exposure was 1.45% (95% CI: 0.97%, 1.90%). Stratified analyses indicated no statistically significant differences in the association between heatwave exposure and sudden death across age or sex subgroups. Conclusion Heatwave exposure was associated with an increased risk of sudden death. Reducing heatwave exposure during summer may help lower the occurrence of sudden death.

Osteoporotic fractures(OPF) refer to the fractures caused by minor violence in the state of osteoporosis, seriously threatening the life and health of elderly patients. Drug and surgical therapies have limitations such as single targets, diverse adverse reactions, and poor prognosis. Kidney-tonifying traditional Chinese medicine(TCM) has good potential in the treatment of OPF. TCM can promote the healing of OPF by promoting angiogenesis in the early stage of bone healing, promoting osteogenic differentiation of bone marrow mesenchymal stem cells in the stage of bone repair, maintaining the balance of osteogenic and osteoclastic system in the stage of bone remodeling, and regulating the oxidative stress responses throughout the process of OPF healing. TCM can alleviate the pathological state of osteoporosis and promote fracture healing in OPF patients via multiple pathways and targets, demonstrating the advantages and potential of biphasic regulation.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Osteoporotic Fractures/metabolism* ; Animals ; Fracture Healing/drug effects* ; Medicine, Chinese Traditional ; Kidney/metabolism* ; Osteogenesis/drug effects*

OBJECTIVE: Previous studies have shown that insomnia is closely related to erectile dysfunction（ED）. However, the causal relationship between them is still unclear. Mendelian randomization (MR) provides a new method for studying the relationship between the two, and the theory of heart-kidney interaction in TCM provides a new idea for exploring the causal relationship between them. METHODS: Based on the statistical data collected by genome-wide association studies (GWAS), the causal relationship between insomnia and ED was discussed by MR. Inverse variance weighted (IVW) is the main analysis method, and weighted median (WME), simple mode (SM), weighted mode (WM) and MR Egger method were the supplementary analysis to evaluate the causal effect. MR-Egger intercept test, Cochran Q test and leave-one-out method were used in sensitivity analysis to verify the reliability of MR results. RESULTS: Thirty-nine SNPs significantly related to insomnia were finally included for MR analysis. The results of IVW method in MR analysis showed that insomnia had a significant causal relationship with the increased risk of ED (OR = 3.111，95% CI= 1.566－6.181，P=1.193×10－3). The results obtained by MR-Egger method, WME method, WM method and SM method were consistent with IVW method in the direction of effect. The sensitivity results suggested that the results of this study were robust. CONCLUSION Our study reveals the causal relationship between insomnia and ED, which provides a new basis for future clinical practice and prevention and treatment of ED.
Causality ; Sleep Initiation and Maintenance Disorders/genetics* ; Erectile Dysfunction/genetics* ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Humans ; Male ; Heart/physiology* ; Kidney/physiology* ; Polymorphism, Single Nucleotide ; Data Interpretation, Statistical

Objective To prepare humanized monoclonal antibodies(Mabs)targeting Acinetobacter baumannii(Ab)based on single memory B cell sequencing technology,construct the immune repertoire of the core protein of Ab,hemolysin-coregulated protein(Hcp),and express its Mabs with binding activity.Methods E.coli BL21 harboring the recombinant plasmid pGEX-6p-1-Hcp was constructed.Hcp protein was obtained using protein expression and affinity chromatography.Female SPF BALB/c mice(6～8 weeks old,weighing 18～20 g)were immunized intramuscularly with antigen Hcp to generate specific memory B cells.Single antigen-specific memory B cells were sorted using flow cytometry.The immune repertoire of Hcp was constructed using single-cell sequencing technology,and bioinformatics analysis was performed on the sequencing results.Mabs were obtained using antibody humanization techniques.The in vitro binding activity of the antibodies was detected by ELISA.Results The target protein Hcp with a purity>95%was obtained after expression and purification.The immune repertoire of Hcp was successfully constructed,and the results of BCR clonotype identification and analysis,CDR3 region characteristic analysis,and V-J gene pairing characteristic analysis were achieved.Antibody humanization got 7 Mabs,that is,IgG1-1,IgG1-2,IgG2-1,IgG2-2,IgG3-1,IgG4-1 and IgG4-2.ELISA results showed IgG1-1,IgG3-1,IgG4-1,and IgG4-2 had an antibody binding titer of 1∶1 280,IgG2-2 of 1∶10 240,IgG2-1 of 1∶5 120,and IgG1-2 of 1∶160.Conclusion Single-cell sequencing technology enables rapid,accurate,and efficient construction of an Hcp protein immune repertoire containing extensive antibody information.Utilizing this immune repertoire allows for the expression of Mabs with binding activity.

Objective To analyze the current status and latent profiles on the decision fatigue of nurses. Methods A total of 812 nurses from four public tertiary hospitals in Guangdong Province were selected as the research subjects using the convenience sampling method. The Decisional Fatigue Scale, the Nursing Work Environment Scale, the Nurses Job Stress Scale, and the Chinese version of 10-item Connor-Davidson Resilience Scale were used to assess the level of decision fatigue, work environment, job stress level, and resilience among nurses. The characteristics of latent profiles on the decision fatigue of nurses were analyzed, and multinomial logistic regression was used to analyze the influencing factors of latent profiles on the decision fatigue of nurses. Results The median and 25th and 75th percentiles of the scores of the decision fatigue of nurses were 10.0 (9.0, 15.0). The average scores for work environment, job stress, and resilience were (107.9±24.0), (86.1±23.8), and (23.6 ± 8.3), respectively. The result of latent profile analysis showed that the decision fatigue of nurses could be classified into three types: low fatigue-energetic, medium fatigue-avoidant and high fatigue-burnout, accounting for 15.0%, 59.6%, and 25.4%, respectively. The results of multinomial logistic regression showed that the risk of being classified as medium fatigue-avoidant was higher among practice nurse than nurse (P<0.05). Nurse with a monthly income of 5 000 to 10 000 yuan had higher risk of being classified as medium fatigue-avoidant than those with >10 000 yuan (P<0.05). And nurse with poorer work environment scores had higher risk of being classified as medium fatigue-avoidant than those with higher scores (P<0.01). Nurse with higher score on job stress and lower score on resilience had higher risk of being classified as medium fatigue-avoidant and high fatigue-burnout, than those with lower score of job stress and higher score on resilience (all P<0.01). Conclusion There is a heterogeneity in the decision fatigue of nurses, which can be categorized into three categories: low fatigue-energetic, medium fatigue-avoidant and high fatigue-burnout. The influencing factors of latent profile on the decision fatigue of nurses are job title, individual monthly income, work environment, job stress, and resilience.

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Objective:To investigate alterations in the glymphatic system of spinocerebellar ataxia type 3 (SCA3) patients based on quantitative MRI, and its association with genetic information and motor dysfunction.Methods:The study was a cross-sectional study. This prospective study recruited 39 confirmed SCA3 patients (SCA3 group) and 40 matched healthy controls (HC group) who were seen at the Southwest Hospital of Army Medical University from May 2017 to June 2023. All subjects underwent cranial MRI scanning. Clinical assessments were conducted on all participants using the scale for the assessment and rating of ataxia (SARA) and the international cooperative ataxia rating scale (ICARS). The automatic segmentation and volume measurement of the choroid plexus based on Freesurfer 6.0; the perivascular interstitial space (PVS) was automatically segmented based on the deep-learning model VB-Net, and the volume of the PVS in each brain region was quantified after manual correction. Independent samples t-test and Mann-Whitney U-test were used to analyze the changes in the class lymphatic system in the SCA3 group and the HC group. Pearson partial correlation analysis was used to explore the relationship between CAG repeats, the glymphatic system, and motor dysfunction. Results:The standardized choroid plexus volume in the SCA3 group was (1.24±0.36)×10 3 mm 3, and that in the HC group was (0.96±0.34)×10 3 mm 3, with a statistically significant difference ( t=4.01, P<0.001). PVS volumes in the frontal lobe, temporal lobe, parietal lobe, basal ganglia, cerebellum, thalamus, and brainstem regions in the SCA3 group were significantly higher than those of HC group ( P<0.05). Partial correlation analysis revealed that CAG repeats in SCA3 group were positively correlated with SARA, ICARS, and basal ganglia PVS volumes ( r=0.65, 0.58, 0.29; P=0.001, 0.001, 0.042). Cerebellar and temporal lobe PVS volumes were positively correlated with SARA ( r=0.59, 0.47; P=0.001, 0.003), and positively correlated with ICARS scores ( r=0.61, 0.40; P=0.001, 0.011). Choroid plexus volume was positively correlated with cerebellar and basal ganglia PVS volumes ( r=0.41, 0.31; P=0.009, 0.043). Conclusions:The glymphatic system of SCA3 patients have significant alteration and have association with CAG repeats and motor dysfunction.

Objective:To investigate vitamin D levels and the effect of exogenous vitamin D supplementation in the first trimester among pregnant women in our center.Methods:This was a prospective cohort study. A total of 98 women in the first trimester who were followed-up regularly in Peking Union Medical College Hospital from December 1 st 2020 to December 1 st 2021 were enrolled. Subjects who had medical conditions that affect vitamin D absorption or metabolism were excluded. Questionnaires were administered, and 25-hydroxyvitamin D [25(OH)D] levels were detected using liquid chromatography tandem mass spectrometry (LC/MS/MS) method. According to the basic 25(OH)D level, different dosages of exogenous vitamin D were supplemented. After 4 weeks, 25(OH)D levels were detected again to evaluate the effect of supplementation. T test, analysis of variance, χ2 test, and multiple linear regression analysis were used for analysis. Results:The mean age of enrolled subjects was (33.5±4.0) years. The baseline 25(OH)D level was (41.2±20.0) nmol/L. Briefly, 70.4% (69/98) subjects were deficient in vitamin D, and 42.9% (42/98) patients were using vitamin D supplementation at the time of 25(OH)D testing. Single-factor analysis showed that vitamin D supplementation ( t=-4.21, P<0.001), season ( t=2.59, P=0.011), and nut-eating frequency ( t=2.67, P=0.009) were related to 25(OH)D levels. Multiple linear regression analysis showed that only vitamin D supplementation had a relationship with 25(OH)D level ( B=13.84, P=0.006). According to the baseline 25(OH)D level, 400-5 000 U/d vitamin D3 was supplemented regularly for (4.1±2.5) weeks, and 25(OH)D levels significantly increased after supplementation [(64.1±18.1) vs (37.3±16.6) nmol/L, t=-9.36, P<0.001]. The ascending range was negatively associated with basic 25(OH)D level ( B=-0.66, P<0.001) and positively associated with supplementary dosage ( B=0.51, P<0.001). 25(OH)D levels increased by 0.51 nmol/L on average per 1 μg (40 U) of vitamin D supplementation daily. Conclusions:The proportion of vitamin D deficiency was high in the first trimester among pregnant women in our center. Exogenous vitamin D supplementation could significantly increase 25(OH)D levels, and the effect was negatively associated with basic 25(OH)D level but positively associated with supplementary dosage.

Aim To explore the material basis of anti-tumor effect of Compound Muji Granules. Methods The anti-tumor pharmacodynamics of Compound Muji Granules in vitro was studied by microfluidic chip technology. The fingerprint of Compound Muji Granules was established by HPLC. The "Spectrum-Material-Effect" of Compound Muji Granules was analyzed by grey correlation analysis,partial least squares regression analysis and network pharmacology approach. Results Seven batches of Compound Muji Granules with different extraction methods were successfully established. The results of grey correlation analysis showed that there was a positive correlation between Compound Muji Granules and 7 of the 14 components with pharmacodynamic correlation coefficient >0.80. The contribution of anti liver tumor was peak number 48(luteolin)>6(gallic acid)>19(chlorogenic acid)>59(quercetin)>67(kaempferol)>65(naringin)>38(ellagic acid),in that order. Conclusions Through the establishment of "Spectrum-Material-Effect" research method,it is clear that the above seven active monomers may be the anti-tumor material basis of Compound Muji Granules.

Humans ; Mycobacterium tuberculosis/genetics* ; Microspheres ; Antitubercular Agents/pharmacology* ; Mutation ; Microbial Sensitivity Tests ; Fluoroquinolones ; Drug Resistance, Bacterial/genetics* ; Tuberculosis, Multidrug-Resistant/microbiology*