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.

ObjectiveThis study aimed to investigate the anti-Mycoplasma pneumoniae (MP) activity of luteolin and elucidate its underlying mechanisms. MethodsLuteolin was identified as the primary active compound from the polyphenol extract ofF. diotrys using network pharmacology. Its efficacy was evaluated against two MP strains: the standard strain M129 and the multidrug-resistant strain M19. A modified culture medium with visual characteristics was employed to determine the minimum inhibitory concentration (MIC) of luteolin. The expression of key proteins involved in MP growth and pathogenicity was assessed by qRT-PCR following luteolin treatment. Additionally, the viability of A549 cells infected with MP was compared between luteolin-treated and untreated groups. In vivo anti-MP activity was evaluated using a mouse model, and the expression of inflammatory cytokines in lung tissues was analyzed. ResultsLuteolin effectively inhibited both MP strains, with MIC₉₀ values of 100 mg/L for M19 and M129. Treatment with luteolin significantly downregulated the expression of adhesion proteins P1 and P30 in both strains. However, the expression of P65, HMW3, TrmB, and CARDS TX was reduced only in the M19 strain following luteolin intervention. Luteolin also enhanced the growth and viability of A549 cells infected with MP. In the mouse model, luteolin treatment resulted in steady weight gain and was well tolerated. The bacteriostatic rate of luteolin in lung tissues was 50.7%, significantly higher than the 25.2% observed in the roxithromycin group. Furthermore, luteolin reduced the expression of inflammatory factors, including IL-6, TNF-α, and HMGB1, in MP-infected mice. ConclusionLuteolin effectively and safely inhibits the proliferation and pathogenicity of MP, particularly the drug-resistant M19 strain, by downregulating the expression of toxicity-associated proteins (P1, P30, P65, HMW3, TrmB, CARDS TX) and modulating host inflammatory responses. These findings suggest that luteolin may offer a novel therapeutic strategy for treating MP infections, especially those caused by drug-resistant strains.

ObjectiveThis study aimed to investigate the anti-Mycoplasma pneumoniae (MP) activity of luteolin and elucidate its underlying mechanisms. MethodsLuteolin was identified as the primary active compound from the polyphenol extract ofF. diotrys using network pharmacology. Its efficacy was evaluated against two MP strains: the standard strain M129 and the multidrug-resistant strain M19. A modified culture medium with visual characteristics was employed to determine the minimum inhibitory concentration (MIC) of luteolin. The expression of key proteins involved in MP growth and pathogenicity was assessed by qRT-PCR following luteolin treatment. Additionally, the viability of A549 cells infected with MP was compared between luteolin-treated and untreated groups. In vivo anti-MP activity was evaluated using a mouse model, and the expression of inflammatory cytokines in lung tissues was analyzed. ResultsLuteolin effectively inhibited both MP strains, with MIC₉₀ values of 100 mg/L for M19 and M129. Treatment with luteolin significantly downregulated the expression of adhesion proteins P1 and P30 in both strains. However, the expression of P65, HMW3, TrmB, and CARDS TX was reduced only in the M19 strain following luteolin intervention. Luteolin also enhanced the growth and viability of A549 cells infected with MP. In the mouse model, luteolin treatment resulted in steady weight gain and was well tolerated. The bacteriostatic rate of luteolin in lung tissues was 50.7%, significantly higher than the 25.2% observed in the roxithromycin group. Furthermore, luteolin reduced the expression of inflammatory factors, including IL-6, TNF-α, and HMGB1, in MP-infected mice. ConclusionLuteolin effectively and safely inhibits the proliferation and pathogenicity of MP, particularly the drug-resistant M19 strain, by downregulating the expression of toxicity-associated proteins (P1, P30, P65, HMW3, TrmB, CARDS TX) and modulating host inflammatory responses. These findings suggest that luteolin may offer a novel therapeutic strategy for treating MP infections, especially those caused by drug-resistant strains.

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

AIM To explore the clinical effects of Supplemented Buyang Huanwu Decoction on postoperative patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern.METHODS One hundred and twenty patients were randomly assigned into control group(60 cases)for 6-week intervention of conventional treatment,and observation group(60 cases)for 6-week intervention of both Supplemented Buyang Huanwu Decoction and conventional treatment.The changes in clinical effects,TCM syndrome scores,spinal cord conduction signals(SEP amplitude,MEP amplitude),serum neurotrophic factors(NGF,IGF-1,BDNF),coagulation and inflammatory indices(PT,APTT,TNF-α,IL-1 β)and incidence of adverse reactions were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,TNF-α,IL-1β(P＜0.05),increased spinal cord conduction signals,coagulation and inflammatory indices(P＜0.05),and shortened PT,APTT(P＜0.05),especially for the observation group(P＜0.05).No significant difference in incidence of adverse reactions was found between the two groups(P＞0.05).CONCLUSION For the patients with lumbar vertebral fracture complicated with spinal cord injury due to Qi Deficiency and Blood Stasis Pattern,Supplemented Buyang Huanwu Decoction can safely and effectively promote neurological function recovery.

Background Enhancing the sense of honor and belonging among medical staff is a key component of establishing a modern hospital management system. Compared to medical staff at general hospitals, medical staff at oncology hospitals are more prone to job burnout, yet few studies in China have focused on job burnout among employees in oncology hospitals. Objective To propose a hypothetical model in which job well-being moderates the relationship between stressors and occupational burnout, to explore how stressors influence burnout and potential moderating role of job well-being, and to provide better understanding of job burnout and motivate employees based on the double-edge sword effect of stressors. Methods A cross-sectional survey was conducted in May 2022 at a tertiary oncology specialty hospital in Chongqing, China. A total of 1 898 medical staff were recruited. Data were collectedthrough four scales including a general information questionnaire, Maslach Burnout Inventory-Human Service Survey, Work Stressor Scale, and Occupational Well-being Scale for Medical Staff. Independent sample t-tests and one-way ANOVA were used for univariate comparisons of job burnout. Pearson correlation analysis was employed to examine the relationships between job burnout, stressors, and job well-being. Hierarchical linear regression was conducted to identify factors influencing job burnout and to examine potential moderating role of job well-being in the relationship between stressors and job burnout. Results A total of 2 123 questionnaires were distributed, with 1 898 valid responses, yielding an effective response rate of 89.4%. The prevalence of job burnout was 60.1%. The correlation coefficient was 0.717 (P<0.001) between stressors and burnout, −0.784 (P<0.05) between job well-being and burnout, and −0.744 (P<0.001) between stressors and job well-being. The quadratic stressors showed a statistically significant effect on burnout (β=0.404, P<0.01). Job well-being positively moderated the relationship between the linear stressors and burnout (β=1.289, P<0.001) and negatively moderated the relationship between the quadratic stressors and job burnout (β=−0.571, P<0.01), explaining 7.1% of the variance. Conclusion Job burnout prevalence is relatively high among employees in oncology hospitals. There is a curvilinear relationship between stressors and job burnout, with job well-being moderating this relationship. From a practical perspective, it is recommended to establish a tiered stress alert system to monitor employees’ stress levels and prevent prolonged exposure to high-pressure conditions. Additionally, improving employees’ job well-being through institutional incentives and developmental support can enhance its moderating role in mitigating the adverse effects of stressors on job burnout. Meanwhile, fostering coordinated responses between organizations and individuals is crucial for strengthening mental health management systems, thereby supporting a healthy, stable, and sustainable development of the healthcare workforce.

BACKGROUND: China is seeing a growing demand for rehabilitation treatments for post-stroke upper limb spastic paresis (PSSP-UL). Although acupuncture is known to be effective for PSSP-UL, there is room to enhance its efficacy. OBJECTIVE: This study explored a semi-personalized acupuncture approach for PSSP-UL that used three-dimensional kinematic analysis (3DKA) results to select additional acupoints, and investigated the feasibility, efficacy and safety of this approach. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This single-blind, single-center, randomized, controlled trial involved 74 participants who experienced a first-ever ischemic or hemorrhagic stroke with spastic upper limb paresis. The participants were then randomly assigned to the intervention group or the control group in a 1:1 ratio. Both groups received conventional treatments and acupuncture treatment 5 days a week for 4 weeks. The main acupoints in both groups were the same, while participants in the intervention group received additional acupoints selected on the basis of 3DKA results. Follow-up assessments were conducted for 8 weeks after the treatment. MAIN OUTCOME MEASURES: The primary outcome was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) response rate (≥ 6-point change) at week 4. Secondary outcomes included changes in motor function (FMA-UE), Brunnstrom recovery stage (BRS), manual muscle test (MMT), spasticity (Modified Ashworth Scale, MAS), and activities of daily life (Modified Barthel Index, MBI) at week 4 and week 12. RESULTS: Sixty-four participants completed the trial and underwent analyses. Compared with control group, the intervention group exhibited a significantly higher FMA-UE response rate at week 4 (χ² = 5.479, P = 0.019) and greater improvements in FMA-UE at both week 4 and week 12 (both P < 0.001). The intervention group also showed bigger improvements from baseline in the MMT grades for shoulder adduction and elbow flexion at weeks 4 and 12 as well as thumb adduction at week 4 (P = 0.007, P = 0.049, P = 0.019, P = 0.008, P = 0.029, respectively). The intervention group showed a better change in the MBI at both week 4 and week 12 (P = 0.004 and P = 0.010, respectively). Although the intervention group had a higher BRS for the hand at week 12 (P = 0.041), no intergroup differences were observed at week 4 (all P > 0.05). The two groups showed no differences in MAS grades as well as in BRS for the arm at weeks 4 and 12 (all P > 0.05). CONCLUSION: Semi-personalized acupuncture prescription based on 3DKA results significantly improved motor function, muscle strength, and activities of daily living in patients with PSSP-UL. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR2200056216. Please cite this article as: Huang XY, Liao OP, Jiang SY, Tao JM, Li Y, Lu XY, Li YY, Wang C, Li J, Ma XP. Three-dimensional kinematic analysis can improve the efficacy of acupoint selection for post-stroke patients with upper limb spastic paresis: A randomized controlled trial. J Integr Med. 2025; 23(1): 15-24.
Humans ; Male ; Female ; Middle Aged ; Acupuncture Points ; Upper Extremity/physiopathology* ; Biomechanical Phenomena ; Single-Blind Method ; Aged ; Stroke/therapy* ; Acupuncture Therapy/methods* ; Stroke Rehabilitation/methods* ; Adult ; Muscle Spasticity/therapy* ; Paresis/physiopathology* ; Treatment Outcome

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective : To explore the causal relationship between 46 phenotypes ( including 15 seropositive case- control phenotypes and 31 quantitative antibody-measurement phenotypes) and ulcerative colitis( UC) using two- sample bidirectional Mendelian randomization( TSMR) . Methods: Single nucleotide polymorphisms ( SNPs) sig- nificantly associated with the relative abundance of the 46 antibody sera were extracted as instrumental variables ac- cording to preset thresholds . Summary statistics for UC were obtained from the OPEN GWAS database ( n = 47 745) . MR-Egger regression , weighted median method ( WME) , inverse variance weighting ( IVW) , the simple mode method (SM) , and weighted multitude method (WM) were used to estimate the causal relationship between antibody levels and UC , primarily using the IVW method . The results were assessed according to the effect indica- tor dominance ratios (OR) and 95% confidence intervals (CI) . Sensitivity analysis , heterogeneity test , gene plei- otropy test , and outlier test (MR-PRESSO) were combined to verify the stability and reliability of the results , and the causal association study was performed again using reverse Mendelian randomization(MR) . Results : IVW re- sults showed that Epstein-Barr( EB) virus EA-D antibody levels ( OR = 0. 806 , 95% CI = 0. 693 - 0. 939 , P < 0. 01) , Epstein-Barr virus EBNA-1 antibody levels ( OR = 1 . 870% , 95% CI = 1 . 480 - 2. 360 , P < 0. 000 1) , Anti-polyomavirus 2 IgG seropositivity (OR = 0. 570 , 95% CI = 0. 435 - 0. 746 , P < 0. 000 1) were associated with UC . The inverse MR analysis revealed a causal effect on anti-polyomavirus 2 IgG seropositivity , and none of the a- bove revealed genetic pleiotropy or significant heterogeneity of IVs . Conclusion EB virus EBNA-1 antibody levels are positively associated with the risk of UC , while EB virus EA-D antibody levels and anti-polyomavirus 2 IgG se- ropositivity are negatively associated with the risk of UC , indicating that they are protective factors for UC .

Objective: To analyze the changes in homologous immunity after RhCE-matched transfusion in positive patients with RhCE blood group antibodies, and to provide precise transfusion strategies for chronic anemia patients. Methods: Patients with chronic anemia in our hospital from January 2020 to March 2024 (continuously receiving blood transfusions for more than 6 months) were enrolled, and 63 cases of unexpected antibody screening positive and identified as RhCE blood group antibodies were selected as the research subjects. The changes in unexpected antibody yield rate after ABO and RhCcDEe isotype blood transfusion were observed. Patients with MNS, Kidd, or Lewis blood group antibodies were screened for corresponding negative donors using monoclonal antibodies for extended typing transfusion based on RhCcEe typing, and the changes in unexpected antibody yield rate after transfusion were observed. Blood group genotyping was performed when serological techniques failed to resolve discrepancies or detect abnormal antigen expression. Results: After RhCcDEe-matched transfusions, RhCE antibodies disappeared in 62 patients, while 1 patient developed anti-Ce. The latter did not develop blood type isotype immunity after receiving RhccEE donor blood. Among the 62 patients, 9 developed unexpected antibodies against other systems: anti-M (4 cases), anti-Mur (2), anti-S (1), anti-Jka (1), and anti-Lea (1). No additional alloimmunization occurred after extended antigen-matched transfusions. A patient with serologically weak e phenotype was genotyped as DCe/DcE, with gene sequencing revealing an 827C>A mutation in exon 6 of the RHCE gene, forming the RHCE 01.31 allele. Conclusion: Precise transfusion strategies incorporating RhCE, MNS, Kidd, and Lewis blood group antigen typing can reduce the probability of blood group homologous immunity. RhCE complex antibodies and RhCE variants pose difficulties for clinical RhCE typing transfusion, which can be addressed through cross-matching and genetic analysis.