Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

With the rapid development of social economy and the continuous improvement of human living standard, the incidence, fatality and recurrence rates of cardiovascular disease (CVD) are increasing year by year, which seriously affects people's life and health. Conventional therapeutic drugs have limited improvement on the disability rate, so the search for new therapeutic drugs and action targets has become one of the hotspots of current research. In recent years, the therapeutic role of the natural compound rosmarinic acid (RA) in CVD has attracted much attention, which is capable of preventing CVD by modulating multiple signalling pathways and exerting physiological activities such as antioxidant, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, as well as anti-coagulation and endothelial function protection. In this paper, the role of RA in the prevention of CVD is systematically sorted out, and its mechanism of action is summarised and analysed, with a view to providing a scientific basis and important support for the in-depth exploration of the prevention value of RA in CVD and its further development as a prevention drug.

Asthma is a chronic inflammatory disease involving multiple inflammatory cells and cytokines. Its pathogenesis is complex, involving various cells and cytokines. Traditional Chinese medicine(TCM) theory suggests that the pathogenesis of asthma is closely related to the dysfunction of internal organs such as the lungs, spleen, and kidneys. In contrast, modern immunological studies have revealed the central role of T helper 1(Th1)/T helper 2(Th2) and T helper 17(Th17)/regulatory T(Treg) cellular immune imbalance in the pathogenesis of asthma. Th1/Th2 imbalance is manifested as hyperfunction of Th2 cells, which promotes the synthesis of immunoglobulin E(IgE) and the activation of eosinophil granulocytes, leading to airway hyperresponsiveness and inflammation.Meanwhile, Th17/Treg imbalance exacerbates the inflammatory response in the airways, further contributing to asthma pathology.Currently, therapeutic strategies for asthma are actively exploring potential targets for regulating the balance of Th1/Th2 and Th17/Treg immune responses. These targets include cytokines, transcription factors, key proteins, and non-coding RNAs. Precisely regulating the expression and function of these targets can effectively modulate the activation and differentiation of immune cells. In recent years,traditional Chinese medicine active ingredients have shown unique potential and prospects in the field of asthma treatment. Based on this, the present study systematically summarizes the efficacy and specific mechanisms of TCM active ingredients in treating asthma by regulating Th1/Th2 and Th17/Treg immune balance through literature review and analysis. These active ingredients, including flavonoids, terpenoids, polysaccharides, alkaloids, and phenolic acids, exert their effects through various mechanisms, such as inhibiting the activation of inflammatory cells, reducing the release of cytokines, and promoting the normal differentiation of immune cells. This study aims to provide a solid foundation for the widespread application and in-depth development of TCM in asthma treatment and to offer new ideas for clinical research and drug development of asthma.
Asthma/genetics* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Th2 Cells/drug effects* ; Th17 Cells/drug effects* ; T-Lymphocytes, Regulatory/drug effects* ; Th1 Cells/drug effects* ; Animals ; Cytokines/immunology* ; Medicine, Chinese Traditional

Objective To investigate the characteristics of changes in hepatitis B surface antigen(HBsAg),hepatitis B virus(HBV)deoxyribonucleic acid(DNA),and alanine aminotransferase(ALT)levels following the cessation of nucleos(t)ide analogues(NAs)therapy in hepatitis B e antigen(HBeAg)-negative chronic hepatitis B(CHB)patients with baseline HBsAg levels<1000 IU/ml.Methods This retrospective cohort study analyzed 73 HBeAg-negative CHB patients treated at the Fifth Medical Centre of Chinese PLA General Hospital from January 2020 to June 2023.Patients were divided into 3 groups according to baseline HBsAg level and discontinuation strategy:HBsAg-negative discontinuation group(n=14),HBsAg-positive discontinuation group(n=25),and HBsAg-positive continuation group(n=34).All patients were followed for 48 weeks.Baseline clinical characteristics and changes in virological and hepatic biochemical indicators during follow-up were compared among the 3 groups.Univariate logistic regression analysis was performed to assess the correlation between clinical indicators and HBV DNA reappearance in HBsAg-positive discontinuation group,and between clinical indicators and HBsAg decline>0.5 log IU/ml in this group.Results There were no significant differences in the baseline levels of gender,age,albumin,and total bilirubin among the 3 groups(P>0.05).The baseline direct bilirubin level was significantly higher in HBsAg-positive discontinuation group than that in other groups(P<0.05),while the lymphocyte counts were significantly higher in HBsAg-negative discontinuation group(P<0.05).During the 48-week follow-up period,the HBV DNA reappearance rate in HBsAg-positive discontinuation group(72.0%)was significantly higher than that in other groups(P<0.001).There was no significant difference in the incidence of ALT elevation among the three groups(P=0.260).The proportion of patients with HBsAg decline>0.5 log IU/ml in HBsAg-positive discontinuation group(24.0%)was significantly higher than that in HBsAg-positive continuation group(5.9%,P<0.05).The proportion of patients with HBsAg increase>0.5 log IU/ml in HBsAg-positive discontinuation group(12.0%)was also significantly higher than that in HBsAg-positive continuation group(0%,P<0.05).Univariate logistic regression analysis revealed no significant association between the analyzed clinical indicators and HBsAg decline(P>0.05).Conclusions Discontinuation of NAs therapy in HBsAg-negative patients demonstrates high safety,with sustained HBsAg negativity post-cessation and low risks of viral relapse and liver function abnormalities.For HBsAg-positive patients,discontinuation may promote HBsAg decline in some individuals but is associated with risks of HBV DNA reappearance and HBsAg elevation.The decision to discontinue therapy should be comprehensively evaluated based on patients'baseline HBsAg levels and clinical characteristics.

Objective To establish a rapid,sensitive,and specific multiplex PCR detection method for the simultaneous detection of Cryptosporidium,Eimeria,and bovine parvovirus.Methods Specific primers targeting the SSU rRNA genes of Cryptosporidium and Eimeria,as well as the VP2 gene of bovine parvovirus were designed and the corresponding recombinant plasmid standards were constructed.To establish the multiplex PCR method,the reaction conditions were optimized using temperature gradient PCR and single-variable control methods.The sensitivity,specificity,reproducibility,and clinical application of the protocol were evaluated.Results The optimal annealing temperature was found to be 60.5℃,and the forward and reverse primer concentrations were determined to be 0.2 μmol/L for Eimeria,and 0.4 μmol/L for Cryptosporidium and bovine parvovirus.The assay demonstrated high sensitivity,with detection limits of 243,260,and 3 110 copies for the recombinant plasmid standards of Cryptosporidium,Eimeria,and bovine parvovirus,respectively.Specificity testing showed no cross-reactivity with ten common bovine pathogens,including Salmonella,bovine viral diarrhea virus,and bovine rotavirus.Consistent intra-and inter-batch results confirmed the strong reproducibility of the method.Clinical application to 81 diarrhea samples from various regions in the Ganzi Prefecture,Sichuan,revealed positivity rates of 18.52%(15/81)for Cryptosporidium,34.57%(28/81)for Eimeria,and 18.52%(15/81)forbovineparvovirus,withamixedinfectionrateof3.7%(3/81).Conclusions Themultiplex PCR method established in this study offers a reliable tool for differential diagnosis and epidemiological investigation of the three common diarrheal pathogens in yaks.

Objective To explore the impact of nurse-led multidisciplinary collaborative nutrition inter-vention on the nutritional indicators in the patients with stroke.Methods A total of 100 patients with stroke admitted in this hospital from January to December 2020 were selected as the study subjects and divided into the observation group and control group by the propensity score matching,50 cases in each group.The control group was given the traditional nutrition intervention,and the observation group was given the nurse-led mul-tidisciplinary cooperative nutrition intervention.The blood,nutritional and biochemical indicators,physique monitoring indicators and nutritional risk indicators were compared between the two groups.Results The levels of total protein(TP),albumin(ALB),hemoglobin(Hb),prealbumin(PAB),body mass index(BMI),upper arm muscle circumference(AMC)and triceps skin fold thickness(TSF)on 21 d after admission in both groups were increased compared with those on 2,15 d after admission,and which on 15 d after admission were higher than those on 2 d after admission(P＜0.05),moreover the above indicators levels on 15,21 d after ad-mission in the observation group were higher than those in the control group,and the differences were statisti-cally significant(P＜0.05).Body mass index(BMI),upper arm circumference(AMC)and triceps skinfold thickness(TSF)in both groups on 21 d of admission were higher than those on 2,15 d of admission(P＜0.05).The nutritional risk screening 2002(NRS2002)score on 21 d after admission in the two groups were decreased compared with those on 2,15 d after admission,while which on 15 d after admission was decreased compared with that on 2 d after admission,moreover the NRS2002 score on 15,21 d after admission in the ob-servation group were lower than those in the control group,and the differences were statistically significant(P＜0.05).Conclusion Giving the nurse-led multidisciplinary cooperative nutrition intervention could im-prove the blood nutritional and biochemical indicators and physique monitoring indicators,and reduce the nu-tritional risk of the patients with stroke.

Objective To investigate the risk factors for diabetic ketoacidosis(DKA)in children/adolescents with type 1 diabetes mellitus(T1DM)and to establish a model for predicting the risk of DKA.Methods A retrospective analysis was performed on 217 children/adolescents with T1DM who were admitted to General Hospital of Ningxia Medical University from January 2018 to December 2021.Among the 217 children/adolescents,169 cases with DKA were included as the DKA group and 48 cases without DKA were included as the non-DKA group.The risk factors for DKA in the children/adolescents with T1DM were analyzed,and a nomogram model was established for predicting the risk of DKA in children/adolescents with T1DM.Results For the 217 children/adolescents with T1DM,the incidence rate of DKA was 77.9%(169/217).The multivariate logistic regression analysis showed that high levels of random blood glucose,hemoglobin A1c(HbA1c),blood ketone body,and triglyceride on admission were closely associated with the development of DKA in the children/adolescents with T1DM(OR=1.156,3.203×1015,20.131,and 9.519 respectively;P<0.05).The nomogram prediction model had a C-statistic of 0.95,with a mean absolute error of 0.004 between the risk of DKA predicted by the nomogram model and the actual risk of DKA,indicating that the model had a good overall prediction ability.Conclusions High levels of random blood glucose,HbA1c,blood ketone body,and triglyceride on admission are closely associated with the development of DKA in children/adolescents with T1DM,and targeted intervention measures should be developed to reduce the risk of DKA.

Objective To develop a matrix metalloproteinase(MMP)-responsive hyaluronic acid(HA)-based controlled-release material for brain-derived neurotrophic factor(BDNF)to provide a novel therapeutic strategy for intervention and repair of traumatic brain injury(TBI).Methods HA was modified with amination,followed by condensation with Suflo-SMCC carboxyl group to form amide,and then linked with glutathione(GSH)to synthesize HA-GSH.The recombinant glutathione S-transferase(GST)-tissue inhibitor of metalloproteinase(TIMP)-BDNF(GST-TIMP-BDNF)expression plasmid was constructed using molecular cloning technique with double enzyme digestion by Bam H Ⅰ and Eco R Ⅰ.The recombinant GST-TIMP-BDNF protein was expressed in the Escherichia coli prokaryotic expression system,and purified by ion exchange chromatography,confirmed by Western blotting.MMP diluents were supplemented with PBS,MMP inhibitor marimastat,and varing concentrations(0.4,0.6,0.8 mg/ml)of GST-TIMP-BDNF or GST-BDNF.MMP-2 activity was analyzed using an MMP activity detection kit to evaluate the inhibitory effect of the recombinant protein on MMP.Primary rat neurons were extracted and cultured to establish an iron death model induced by RSL3.The effect of recombinant protein GST-TIMP-BDNF on neuronal injury was detected by immunofluorescence staining.Results MRI hydrogen spectrum identification confirmed the successful synthesis of HA-GSH.Western blotting results showed the successful expression of the recombinant protein GST-TIMP-BDNF containing the GST tag using the E.coli prokaryotic expression system.MMP activity detection results indicated that the recombinant protein GST-TIMP-BDNF had a superior inhibitory effect on MMP-2 activity compared to GST-BDNF(P<0.05).Immunofluorescence staining results showed a significant increase in fluorescence intensity in rat neurons treated with GST-TIMP-BDNF after RSL3 induction(P<0.05).Conclusion A MMP-responsive HA-based BDNF controlled-release material has been successfully developed,exhibiting a protective effect on neuron damage.

Small ubiquitin-related modifier(SUMOylation)is a dynamic post-translational modification that maintains cardiac function and can protect against a hypertrophic response to cardiac pressure overload.However,the function of SUMOylation after myocardial infarction(MI)and the molecular details of heart cell responses to SUMO1 deficiency have not been determined.In this study,we demonstrated that SUMO1 protein was inconsistently abundant in different cell types and heart regions after MI.However,SUMO1 knockout significantly exacerbated systolic dysfunction and infarct size after myocardial injury.Single-nucleus RNA sequencing revealed the differential role of SUMO1 in regulating heart cells.Among cardiomyocytes,SUMO1 deletion increased the Nppa+Nppb+Ankrd1+cardiomyocyte subcluster pro-portion after MI.In addition,the conversion of fibroblasts to myofibroblasts subclusters was inhibited in SUMO1 knockout mice.Importantly,SUMO1 loss promoted proliferation of endothelial cell subsets with the ability to reconstitute neovascularization and expressed angiogenesis-related genes.Computational analysis of ligand/receptor interactions suggested putative pathways that mediate cardiomyocytes to endothelial cell communication in the myocardium.Mice preinjected with cardiomyocyte-specific AAV-SUMO1,but not the endothelial cell-specific form,and exhibited ameliorated cardiac remodeling following MI.Collectively,our results identified the role of SUMO1 in cardiomyocytes,fibroblasts,and endothelial cells after Ml.These findings provide new insights into SUMO1 involvement in the patho-genesis of MI and reveal novel therapeutic targets.

OBJECTIVE: To detect the body surface temperature of the relevant back-shu points in patients with chronic persistent asthma by infrared thermal imaging technology, and observe the specific changes of the body surface temperature of the relevant back-shu points under the condition of lung disease. METHODS: Forty-five patients with chronic persistent asthma (observation group) and 45 healthy subjects (control group) were selected. The body surface temperature of bilateral Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) were measured by BK-MT02A medical infrared thermography. RESULTS: The body surface temperature of bilateral Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) in the observation group was higher than that in the control group (P<0.01, P<0.05). The body surface temperature of bilateral Feishu (BL 13) and Geshu (BL 17) was higher than that of ipsilateral Pishu (BL 20) and Shenshu (BL 23) in the two groups (P<0.01, P<0.05). There was no statistically significant difference in body surface temperature between ipsilateral Feishu (BL 13) and Geshu (BL 17), between ipsilateral Pishu (BL 20) and Shenshu (BL 23) (P>0.05). CONCLUSION The pathological increase of body surface temperature of Feishu (BL 13), Geshu (BL 17), Pishu (BL 20) and Shenshu (BL 23) in patients with chronic persistent asthma indicates that above acupoints have specificity in reflecting lung diseases. The Feishu (BL 13) and Geshu (BL 17), which have significantly increased body surface temperature, not only provide objective basis for the pathological pathogenesis of "deficiency in origin and excess in symptom" in patients with chronic persistent asthma, but also reflect the different expressions of different acupoints on the same meridian for the lung diseases.
Humans ; Temperature ; Asthma/diagnostic imaging* ; Meridians ; Acupuncture Points ; Acupuncture Therapy/methods*