Objective: To investigate the efficacy of implantable neuromuscular electrical stimulation system on stress urinary incontinence (SUI) model in female rats. Methods: A total of 21 female infertile SD rats were randomly divided into the control，sham stimulation，and stimulation groups，with 7 rats in each group.All rats received vaginal dilation (VD) to simulate postpartum SUI.One week after VD，the control group was given normal feeding，stimulators were implanted in the pelvic floor muscles of the sham stimulation and stimulation groups.The sham stimulation group received normal feeding for 2 weeks，and the stimulation group received pelvic floor electrical stimulation (PFES) for 2 consecutive weeks.The leak point pressure (LPP) of each rat was measured with cystometry before VD (baseline value)，1 week after VD，and 2 weeks after PFES. Results: In the control group and sham stimulation group，LPP increased after 2 weeks of treatment compared with that after 1 week of VD，but it still did not return to the baseline level (P<0.001).In the stimulation group，after 2 consecutive weeks of PFES，LPP increased significantly compared with that 1 week after VD，and returned to the baseline value (P>0.05).There was no significant difference in the LPP baseline values and levels after 1 week of VD among the 3 groups (P>0.05).The LPP in the stimulation group after 2 weeks of PFES was significantly higher than that in the sham stimulation group and stimulation group (P<0.001). Conclusion: The implantable neuromuscular electrical stimulation system is effective in short-term intervention of SUI in female rats，the further studies are needed to confirm the long-term efficacy and safety of the system，the optimal stimulation sites，optimal stimulation parameters，and potential mechanisms of action.

Objective: To evaluates the association between maternal overweight/obesity during pregnancy and offspring risk of metabolic dysfunction associated steatotic liver disease (MASLD), providing theoretical evidence for early life MASLD prevention. Methods: An online search was conducted across ten databases (CNKI, Wanfang, SinoMed, PubMed, Embase, Web of Science, Cochrane Library, PROSPERO, PQDT Global, ScienceDirect) for research literature on the association between maternal overweight/obesity during pregnancy and the development of MASLD in offspring, with the search period spanning from January 2014 to December 2024. Two researchers independently screened literature, extracted data, and assessed study quality. Statistical analysis was performed using R 4.3.3. Results: Ten studies involving 10 229 participants were included, comprising 4 cohort studies and 6 case control studies. Cohort studies showed that maternal overweight and obesity significantly increased offspring MASLD risk ( RR=1.59, 95%CI=1.06-2.39, P <0.05), with moderate heterogeneity ( I 2=56.9%, P =0.07). Case control studies indicated a positive association between maternal overweight/obesity during pregnancy and offspring risk of MASLD( OR=2.00, 95%CI=1.68-2.39, P < 0.05), with low heterogeneity ( I 2=48.8%, P =0.08). Conclusions Maternal overweight/obesity during pregnancy positively correlates with offspring MASLD risk. Gestational weight management may reduce the risk.

OBJECTIVE To analyze the influencing factors of voriconazole trough concentration and adverse drug reactions （ADR） in renal transplant recipients. METHODS Data from inpatients who received voriconazole and therapeutic drug monitoring in our hospital between January 2022 and August 2023 were retrospectively analyzed. Patients were divided into renal transplant group and non-renal transplant group based on transplantation status. A 1∶1 propensity score matching （PSM） method was used to balance differences in baselines between the two groups. Voriconazole trough concentrations， target attainment rate， clinical efficacy， and ADR were compared between the two groups. Multiple linear regression （backward） was used to analyze the factors influencing voriconazole trough concentrations in the renal transplant group. Univariate analysis and binary Logistic regression were used to identify independent risk factors for ADR in the renal transplant group. RESULTS After PSM， 48 patients were included in each group. There were no statistically significant differences in the mean voriconazole trough concentration， target attainment rate or efficacy rate between the two groups （P＞0.05）. The total incidence of ADR was significantly higher in the renal transplant group than in the non-renal transplant group （P＜0.05）. Multiple linear regression analysis showed that age， average daily dose， pulmonary infection， total bilirubin during medication， day-1 loading dose， use of the original drug， concomitant immunosuppressant use， and the occurrence of ADR were factors influencing voriconazole trough concentration in renal transplant patients （P＜0.05）. Binary Logistic regression analysis showed that abnormal direct bilirubin during medication [OR＝7.747， 95%CI （1.334， 45.005）， P＝0.023] was an independent risk factor for ADR in renal transplant patients receiving voriconazole. CONCLUSIONS Age， average daily dose， pulmonary infection， use of the original drug， day-1 loading dose， total bilirubin during medication， concomitant immunosuppressant use， and the occurrence of ADR are the factors influencing voriconazole trough concentration in renal transplant patients. Furthermore， patients with abnormal direct bilirubin during medication are more susceptible to ADR.

Objective To construct a universal influenza mRNA vaccine and evaluate its immunogenicity.Methods The antigen sequence of hemagglutinin(HA),nucleoprotein(NP)and matrix protein 2 ectodomain(M2e)in influenza A/California/04/2009 was optimized.HA,NP and 3 tandem M2e(3M2e)were cloned into pcDNA3.1 vector,respectively.Then the mRNAs were synthesized by linearization,in vitro transcription,enzymatic capping and enzymatic tailing,and named as mRNA-HA,mRNA-NP and mRNA-3M2e,respectively.The protein expression of the 3 kinds of mRNAs in 293T cells was detected by immunofluorescence assay.Comb-mRNA vaccine was prepared by enveloped mRNA-HA,mRNA-NP and mRNA-3M2e with lipid nanoparticles,respectively,and the particle size and potential were identified.Twenty-eight 6-week-old female BALB/c mice(18～22 g)were randomly divided into LNP group(n=14)and Comb-mRNA group(n=14).Hemagglutination inhibition(HI)method and microneutralization(MN)test were used to evaluate the serum antibody titer induced by Comb-mRNA vaccines.The mice were infected by 5LD50 wild-type H1 N1 influenza virus to evaluate the protective efficacy.Results The mRNA-HA,mRNA-NP and mRNA-3M2e were successfully constructed,and the 3 mRNAs could be expressed in 293T cells.The average size of mRNA encapsulated by lipid nanoparticles was 119.53±6.5 nm,and the average potential was-8.23±1.3 mV.The geometric mean titer(GMT)of HI and MN in the Comb-mRNA group were 179.6 and 201.6,compared with the LNP group.The ratio of IFN-γ+CD4+/CD8+Tcells was increased.The Comb-mRNA group could provide protection against 5LD50 wild type influenza H1 N1 virus after 2 weeks of booster immunization.Conclusion Comb-mRNA,an influenza vaccine candidate,can induce immune responses and protect mice from influenza virus challenge.

ObjectiveTo investigate the role of proinflammatory cytokines tumor necrosis factor alpha （TNFα） and interleukin-1β （IL-1β） in rostral ventromedial medulla （RVM） in chronic postsurgical pain （CPSP） induced by skin/muscle incision and retraction （SMIR）. MethodsSD rats were randomly divided into 5 groups： ① Sham group； ② SMIR group； ③ SMIR+TNFα/IL-1β neutralizing antibody group； ④ SMIR+TNFα/IL-1β group and ⑤ SMIR+vehicle group. 50% paw mechanical withdrawal threshold （MWT） was measured by the up-down method， immunofluroscence was used to detect the TNFα and IL-1β expression and ELISA for the 5-Hydroxytryptamine （5-HT） level. ResultsSMIR elicited persistent nociceptive sensitization， upregulated TNFα and IL-1β expression in RVM neurons and astrocytes. Microinjection of TNFα or IL-1β neutralizing antibody into RVM inhibited the development of nociceptive sensitization and decreased the level of 5-HT in both RVM and spinal dorsal horn. While microinjection of recombinant TNFα or IL-1β into RVM enhanced the development of nociceptive sensitization and increased the level of 5-HT in both RVM and spinal dorsal horn. ConclusionUp-regulation of proinflammatory cytokines in RVM may contribute to SMIR induced CPSP by promoting 5-HT release.

ObjectiveTo investigate the inhibitory effect of Mahuang Xixin Fuzitang on the migration of dendritic cells （DCs） in mice and its underlying mechanism. MethodMouse bone marrow-derived DCs were isolated and cultured. The morphological changes of the cells at different stages were observed under a microscope， and the CD11c⁺ proportion was detected by flow cytometry to identify DC purity. Cells were treated with Mahuang Xixin Fuzitang （1， 2， 5， 10， 20， 40， 50， 100 g·L^-1） for 24 hours， and the effect of Mahuang Xixin Fuzitang on cell proliferation was assessed using the cell counting kit-8 （CCK-8） assay to determine the appropriate concentrations for treatment. After modeling by lipopolysaccharide （LPS） induction， DCs were divided into a blank group， a model group， and Mahuang Xixin Fuzitang groups （2， 4， 8 g·L^-1）. The expression of surface molecules CD80， CD86， and major histocompatibility complex-Ⅱ （MHC-Ⅱ） were detected by flow cytometry. Transwell chamber assay was used to observe cell migration. The levels of chemokine C-C-primitive receptor 7 （CCR7） and chemokine C-X-C-primitive receptor 4 （CXCR4） on the cell surface were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of filamentous actin （F-actin） in the cell microfilament cytoskeleton was detected by immunofluorescence （IF） staining. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA expression levels of Ras homolog family member A （RhoA） and Rho-associated coiled-coil containing protein kinase 1 （ROCK1）. Western blot analysis was performed to detect the protein expression of RhoA and ROCK1. ResultCompared with the blank group， the model group exhibited significantly higher expression levels of CD80， CD86， and MHC-Ⅱ （P<0.01）， a significantly increased number of cells migrating to the lower chamber （P<0.01）， and significantly elevated levels of CCR7 and CXCR4 （P<0.05， P<0.01）. Additionally， F-actin expression was significantly increased （P<0.01）， and both RhoA and ROCK1 mRNA and protein expression levels were significantly higher （P<0.05， P<0.01）. Compared with the model group， treatment with Mahuang Xixin Fuzitang （2， 4， 8 g·L^-1） for 24 hours resulted in significantly lower expression levels of CD80， CD86， and MHC-Ⅱ （P<0.01）， a significantly reduced number of cells migrating to the lower chamber （P<0.05）， and significantly decreased levels of CCR7 and CXCR4 （P<0.05， P<0.01）. Furthermore， F-actin expression was significantly reduced （P<0.01）， and both RhoA and ROCK1 mRNA and protein expression levels were significantly decreased （P<0.05， P<0.01）. ConclusionMahuang Xixin Fuzitang can inhibit the migration of DCs in mice， and its mechanism of action may be related to reducing the activity of the Rho/ROCK signaling pathway， thereby affecting changes in the cell cytoskeleton.

Background::The serum vitamin D level varies widely by population, and studies have linked vitamin D levels with the risk of type 2 diabetes mellitus (T2DM). However, the relationship is inconsistent and the impact of vitamin D on T2DM among East Chinese adults is unclear. The study aimed to investigate the association between serum 25-hydroxyvitamin D (25[OH]D) levels and the risk of T2DM and evaluated whether the association is modified by genetic predisposition.Methods::In the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) cohort, 1862 participants free of T2DM at baseline were included. A weighted genetic risk score was calculated with 28 variants associated with T2DM. Hierarchical logistic models were used to examine the association of serum 25(OH)D and genetic risk with T2DM.Results::After a 5-year follow-up, 132 cases of T2DM were documented. We observed no significant association between quartiles of serum 25(OH)D and T2DM risk after multivariable adjustment (χ 2 = 0.571, Pfor trend = 0.426). Compared to those in the lowest quartile of 25(OH)D, the odds ratios (ORs) (95% confidence interval [CI]) for participants with increased quartiles were 1.29 (0.74-2.25), 1.35 (0.77-2.36), and 1.27 (0.72-2.24), respectively. We observed a positive association of glycated hemoglobin (HbA1c) with 25(OH)D at baseline (β = 1.752, P = 0.001) and after follow-up (β = 1.385, P = 0.003), and a negative association of ln conversion homeostasis model assessment (HOMA)-β with 25(OH)D at baseline (β = -0.982, P = 0.021). There was no significant interaction between 25(OH)D and diabetes genetic predisposition on the risk of T2DM (χ 2 = 2.710, Pfor interaction = 0.100). The lowest OR (95% CI) of T2DM was among participants with low genetic risk and the highest quartile of 25(OH)D (0.17 [0.05–0.62]). Conclusion::Serum 25(OH)D may be irrelevant to the risk of incident T2DM among East Chinese adults regardless of genetic predisposition.

Background::Prenatal and postnatal factors may have joint effects on cardiovascular health, and we aimed to assess the joint association of birth weight and ideal cardiovascular health metrics (ICVHMs) prospectively in adulthood with incident cardiovascular disease (CVD).Methods::In the UK Biobank, 227,833 participants with data on ICVHM components and birth weight and without CVD at baseline were included. The ICVHMs included smoking, body mass index, physical activity, diet information, total cholesterol, blood pressure, and hemoglobin A1c. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women.Results::Over a median follow-up period of 13.0 years (2,831,236 person-years), we documented 17,477 patients with incident CVD. Compared with participants with birth weights of 2.5-4.0 kg, the HRs (95% CIs) of CVD among those with low birth weights was 1.08 (1.00-1.16) in men and 1.23 (1.16-1.31) in women. The association between having a birth weight <2.5 kg and CVD risk in men was more prominent for those aged <50 years than for those of older age ( P for interaction = 0.026). Lower birth weight and non-ideal cardiovascular health metrics were jointly related to an increased risk of CVD. Participants with birth weights <2.5 kg and ICVHMs score 0-1 had the highest risk of incident CVD (HR [95% CI]: 3.93 [3.01-5.13] in men; 4.24 [3.33-5.40] in women). The joint effect (HR [95% CI]: 1.36 [1.17-1.58]) could be decomposed into 24.7% (95% CI: 15.0%-34.4%) for a lower birth weight, 64.7% (95% CI: 56.7%-72.6%) for a lower ICVHM score, and 10.6% (95% CI: 2.7%-18.6%) for their additive interaction in women. Conclusions::Birth weight and ICVHMs were jointly related to CVD risk. Attaining a normal birth weight and ideal ICVHMs may reduce the risk of CVD, and a simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases in women.

Background::Life’s Simple 7, the former construct of cardiovascular health (CVH) has been used to evaluate adverse non-communicable chronic diseases (NCDs). However, some flaws have been recognized in recent years and Life’s Essential 8 has been established. In this study, we aimed to analyze the association between CVH defined by Life’s Essential 8 and risk of 44 common NCDs and further estimate the population attributable fractions (PAFs) of low-moderate CVH scores in the 44 NCDs.Methods::In the UK Biobank, 170,726 participants free of 44 common NCDs at baseline were included. The Life’s Essential 8 composite measure consists of four health behaviours (diet, physical activity, nicotine exposure, and sleep) and four health factors (body mass index, non-high density lipoprotein cholesterol, blood glucose, and blood pressure), and the maximum CVH score was 100 points. CVH score was categorized into low, moderate, and high groups. Participants were followed up for 44 NCDs diagnosis across 10 human system disorders according to the International Classification of Diseases 10th edition (ICD-10) code using linkage to national health records until 2022. Cox proportional hazard models were used in this study. The hazard ratios (HRs) and PAFs of 44 NCDs associated with CVH score were examined.Results::During the median follow-up of 10.85 years, 58, 889 incident NCD cases were documented. Significant linear dose-response associations were found between higher CVH score and lower risk of 25 (56.8%) of 44 NCDs. Low-moderate CVH (<80 points) score accounted for the largest proportion of incident cases in diabetes (PAF: 80.3%), followed by gout (59.6%), sleep disorder (55.6%), chronic liver disease (45.9%), chronic kidney disease (40.9%), ischemic heart disease (40.8%), chronic obstructive pulmonary disease (40.0%), endometrium cancer (35.8%), lung cancer (34.0%), and heart failure (34.0%) as the top 10. Among the eight modifiable factors, overweight/obesity explained the largest number of cases of incident NCDs in endocrine, nutritional, and metabolic diseases (35.4%), digestive system disorders (21.4%), mental and behavioral disorders (12.6%), and cancer (10.3%); however, the PAF of ideal sleep duration ranked first in nervous system (27.5%) and neuropsychiatric disorders (9.9%).Conclusions::Improving CVH score based on Life’s Essential 8 may lower risk of 25 common NCDs. Among CVH metrics, avoiding overweight/obesity may be especially important to prevent new cases of metabolic diseases, NCDs in digestive system, mental and behavioral disorders, and cancer.

[Objective]To elaborate the significance of modulating the spirit and the mechanism of five elements music concrete hypnosis technique,so as to provide new ideas for the diagnosis and treatment of clinical post-stroke depression.[Methods]From the perspective of"modulating the spirit",this paper expounds the significance of five elements music concrete hypnosis technique in"modulating the spirit"by studying ancient and modern literature,explores its mechanism of action,and introduces five elements music concrete hypnosis technique in detail,and finally analyzes it combining with the clinical trial results.[Results]"Those who have the spirit prosper,those who are absent-minded die",modulating the spirit plays an important role in the treatment of clinical diseases,especially in the treatment of psychosomatic diseases.Five elements music concrete hypnosis technique plays a role in regulating the spirit by vibrating viscera,deducing concrete thinking,condensing breath and gathering Qi.The clinical application has achieved satisfactory results.[Conclusion]Five elements music concrete hypnosis technique in the treatment of post-stroke depression fully embodies the thought of"regulating the spirit"of traditional Chinese medicine,and its curative effect is considerable,which is worthy of further exploration and promotion.