OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To analyze the clinical value of plasma insulin-like factor 6(INSL6)in predicting the risk of acute aortic syndromes(AAS)and adverse outcomes.Methods A retrospective case-control trial was conducted on 194 AAS patients admitted to Department of Cardiovascular Diseases of Second Affiliated Hospital of Army Medical University between April 2021 and June 2023.Another 194 sex-,age-and BMI-matched individuals without aortic diseases were recruited from the health examination center between December 2021 and January 2024.Their plasma INSL6 level was measured with ELISA,and the general clinical data and results of some laboratory tests were collected and compared between the 2 groups.Spearman correlation analysis was used to assess the relationship between plasma INSL6 and other variables,receiver operating characteristic(ROC)curve was plotted to evaluate the diagnostic efficacy of INSL6 for AAS occurrence,multivariate conditional logistic regression model was utilized to analyze the association between plasma INSL6 and AAS onset,and Kaplan-Meier survival curve and multivariate Cox proportional hazards regression model was applied to analyze the relationship between acute-phase plasma INSL6 level and adverse prognosis in AAS patients.Results The plasma INSL6 level was significantly higher in AAS patients at acute phase than the control individuals[704.40(481.32～1 152.62)vs 141.24(107.60～163.72)pg/mL,P<0.001],but no statistical difference was observed in the level among the patients with different AAS subtypes(aortic dissection,intramural hematoma,and penetrating aortic ulcer).Spearman correlation analysis showed that the plasma INSL6 level was positively correlated with platelet count(r=0.325,P<0.001)and hemoglobin concentration(r=0.186,P=0.009),and negatively with IL-6(r=-0.182,P=0.011),INF-γ(r=-0.283,P<0.001),and D-dimer levels(r=-0.195,P=0.006).Multivariate conditional logistic regression analysis revealed that plasma INSL6 level was independently associated with the occurrence of AAS(OR=28.634,95%CI:7.267～112.820,P<0.001).ROC curve analysis further confirmed that the optimal cutoff value of plasma INSL6 in predicting AAS was 259.425 pg/mL,with a sensitivity of 95.9%and a specificity of 98.5%at this threshold.Kaplan-Meier curve analysis demonstrated that AAS patients with low INSL6 level had significantly lower cumulative survival rates(P=0.020)and event-free survival rates(P=0.004)than those with high INSL6 level(P<0.05).Multivariate COX regression analysis revealed that,after adjusting for sex,age,systolic blood pressure,ST classification,and surgical treatment,acute-phase INSL6 level was independently associated with all-cause mortality(HR:0.999,95%CI:0.999～1.000,P=0.023),AAS-related mortality(HR:0.999,95%CI:0.998～1.000,P=0.012),and composite endpoint events(HR:0.999,95%CI:0.999～1.000,P=0.026)in AAS patients during follow-up.Conclusion Plasma INSL6 level is closely associated with the occurrence and adverse prognosis of AAS,and the indicator is expected to be an effective biomarker for diagnosing AAS and predicting its prognosis.

Objective To investigate the effect of sal-like gene 2(Sall2)gene overexpression on the progression of disease in human superoxide dismutase 1(hSOD1)-G93A mutant amyotrophic lateral sclerosis(ALS)transgenic mice,with the aim of identifying potential therapeutic targets for ALS gene therapy.Methods Differential Sall2 gene were screened through bioinformatics analysis.Forty-eight ALS transgenic mice were selected for this study.AAV-PHP.eB-Sall2 adeno-associated virus with a neuron-specific promoter,human synapsin I(hSyn),was constructed and administered via tail vein injection to six-week-old mice.In parallel,the same litter of ALS mice received an injection of AAV-PHP.eB-GFP.The staining of Sall2 and neuron-specific nuclear protein(NeuN)/GFAP in the spinal cord and cerebral cortex of mice were detected through immunofluorescent double-label staining technology.The survival period,weight changes,exercise ability,and electromyographic changes of the gastrocnemius muscle were detected.The morphological changes in the spinal cord anterior horn neurons were detected through Nissl staining.The effect of Sall2 gene overexpression on the expression of the cell cycle protein E1(cyclin E1)was investigated through Western blotting.Results Bioinformatics analysis showed out that Sall2 was differentially expressed in ALS mice.Compared with ALS mice in the control group,the Sall2 protein expression of ALS mice in the overexpressing Sall2 gene group increased in both the spinal cord and cerebral cortex,and the Sall2 integral absorbance values of Sall2+/NeuN+double-positive cells were higher.The survival time of ALS mice in the Sall2 gene overexpressing group was prolonged,the rate of weight loss was slowed down,the performance in the rotarod and inverted grid tests was improved with longer times,and the positive sharp waves and fibrillation potentials in the gastrocnemius electromyography were reduced.The number of Nissl bodies labeled neurons increased in the spinal cord anterior horn of the Sall2 gene overexpressing mice,and the condition of neuronal damage was improved.Overexpression of the Sall2 gene also reduced the expression of cyclin E1 in both the spinal cord and cerebral cortex of ALS transgenic mice.Conclusion Overexpression of the Sall2 gene can delay disease progression and improve motor performance in ALS transgenic mice,affecting the expression of cyclin E1,thus exerting a therapeutic effect on these mice.

Objective To explore the role of SLIT-ROBO Rho GTPase-activating protein 2(srGAP2)in spinal motor neuron degeneration in amyotrophic lateral sclerosis(ALS).Methods Applied bioinformatics analysis to investigate the expression changes of srGAP2 in the spinal cord of human superoxide dismutase 1(hSOD1)mutant ALS transgenic mice.hSOD1 G93A mutant ALS transgenic mice were selected for animal experimental validation,with littermate wild type(WT)mice serving as the control group.A total of 36 pairs were divided into four groups,namely the pre-onset stage,early-onset stage,mid-onset stage,and late-onset stage.The expression changes and cellular localization of srGAP2 in the spinal cord of ALS mice were detected by Real-time PCR,Western blotting and immunofluorescent double-label staining.The hSOD1G93A mutant NSC34 motor neuron-like cell model was established,and in vitro experiments were carried out to detect the changes in srGAP2 expression,and the effects of srGAP2 over-expression on the viability of hSOD1G93A mutant NSC34 cells and the growth of cell protrusions.Results Bioinformatics analysis revealed abnormally low expression of srGAP2 in the spinal cord of hSOD1 mutant ALS mice.Animal experiments verified that compared with the WT mice,the expression of srGAP2 was reduced at both mRNA level and protein level in the spinal cord of hSOD1G93A mutant ALS transgenic mice at early-onset,mid-onset and late-onset stages.Compared with the WT mice,srGAP2 integral absorbance(IA)values in srGAP2+/NeuN+double-positive cells in the anterior horn of the spinal cord of hSOD1G93A mutant ALS transgenic mice were lower,srGAP2 IA values in srGAP2+/GFAP+double-positive cells were higher;Compared with the hSOD1WT NSC34 cells,the expression of srGAP2 was reduced at both mRNA level and protein level in hSOD1G93A mutant NSC34 cells.Over-expression of srGAP2 elevated the viability of hSOD1G93A mutant NSC34 cells,and up-regulated the expression level of synapse-related protein β Ⅲ-tubulin and growth associated protein 43(GAP43).Conclusion Low expression of srGAP2 is closely associated with the progression of ALS,while over-expression of srGAP2 can promote outgrowth of cell protrusions and exert a protective effect on spinal motor neurons in ALS.

ObjectiveTo improve the quality standard of Yuanhu Zhitong oral liquid in order to strengthen the quality control of this oral liquid. MethodThin layer chromatography（TLC） was used for the qualitative identification of Corydalis Rhizoma and Angelicae Dahuricae Radix in Yuanhu Zhitong oral liquid by taking tetrahydropalmatine， corydaline reference substances and Corydalis Rhizoma reference medicinal materials as reference， and cyclohexane-trichloromethane-methanol（5∶3∶0.5） as developing solvent， Corydalis Rhizoma was identified using GF254 glass thin layer plate under ultraviolet light（365 nm）. And taking petroleum ether（60-90 ℃） -ether-formic acid（10∶10∶1） as developing solvent， Angelicae Dahuricae Radix was identified using a silica gel G TLC plate under ultraviolet light（305 nm）. High performance liquid chromatography（HPLC） was performed on a Waters XSelect HSS T3 column（4.6 mm×250 mm， 5 μm） with acetonitrile（A）-0.1% glacial acetic acid solution（adjusted pH to 6.1 by triethylamine）（B） as the mobile phase for gradient elution（0-10 min， 20%-30%A； 10-25 min， 30%-40%A； 25-40 min， 40%-50%A； 40-60 min， 50%-60%A）， the detection wavelength was set at 280 nm， then the fingerprint of Yuanhu Zhitong oral liquid was established， and the contents of tetrahydropalmatine and corydaline were determined. ResultIn the thin layer chromatograms， the corresponding spots of Yuanhu Zhitong oral liquid， the reference substances and reference medicinal materials were clear， with good separation and strong specificity. A total of 12 common peaks were identified in 10 batches of Yuanhu Zhitong oral liquid samples， and the peaks of berberine hydrochloride， dehydrocorydaline， glaucine， tetrahydropalmatine and corydaline. The similarities between the 10 batches of samples and the control fingerprint were all >0.90. The results of determination showed that the concentrations of corydaline and tetrahydropalmatine had good linearity with paek area in the range of 0.038 6-0.193 0， 0.034 0-0.170 0 g·L^-1， respectively. The methodological investigation was qualified， and the contents of corydaline and tetrahydropalmatine in 10 batches of Yuanhu Zhitong oral liquid samples were 0.077 5-0.142 9、0.126 1-0.178 2 g·L^-1， respectively. ConclusionThe established TLC， fingerprint and determination are simple， specific and reproducible， which can be used to improve the quality control standard of Yuanhu Zhitong oral liquid.

Thrombus is a major factor leading to cardiovascular diseases such as myocardial infarction and stroke. Although fibrinolytic anti-thrombotic drugs have been widely used in clinical practice, they are still limited by narrow therapeutic windows, short half-lives, susceptibility to inactivation, and abnormal bleeding caused by non-targeting. Therefore, it is crucial to effectively deliver thrombolytic agents to the site of thrombus with minimal adverse effects. Based on the long blood circulation and excellent drug-loading properties of human serum albumin (HSA), we employed genetic engineering techniques to insert a functional peptide (P-selectin binding peptide, PBP) which can target the thrombus site to the N-terminus of HSA. The fusion protein was expressed using Pichia pastoris and purified by Ni-chelating affinity chromatography. After being loaded with gold nanoparticles (Au NPs), the fusion protein formed homogeneous and stable nanoparticles (named as PBP-HSA@Au) with a diameter of 17.7 ± 1.0 nm and a zeta potential of -11.3 ± 0.2 mV. Cytotoxicity and hemolysis tests demonstrated the superb biocompatibility of PBP-HSA@Au. Platelet-targeting experiments confirmed the thrombus-targeting ability conferred by the introduction of PBP into PBP-HSA@Au. Upon near-infrared ray (NIR) irradiation, PBP-HSA@Au rapidly converted light energy into heat, thereby disrupting fibrinogen and exhibiting outstanding thrombolytic efficacy. The designed HSA fusion protein delivery system provides a precise, rapid, and drug-free treatment strategy for thrombus therapy. This system is characterized by its simple design, high biocompatibility, and strong clinical applicability. All animal experiments involved in this study were carried out under the protocols approved by the Animal Experiment Ethics Committee of Jiangnan University [JN. No20230915S0301015(423)].

Objective To investigate the effect of varying blood pressure stratification on renal function in the diabetic population.Methods A prospective cohort study was conducted,enrolling 9 489 diabetic patients from a total of 101 510 Kailuan Group employees who underwent health examinations between July 2006 and October 2007.The follow-up period was(8.6±4.0)years.Participants were categorized into four groups based on their baseline blood pressure levels:normal blood pressure(systolic blood pressure<120 mmHg and diastolic blood pressure<80 mmHg),elevated blood pressure(systolic blood pressure 120-130 mmHg and diastolic blood pressure<80 mmHg),stage 1 hypertension(systolic blood pressure 130-140 mmHg and/or diastolic blood pressure 80-90 mmHg),and stage 2 hypertension(systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90 mmHg).The incidence density of chronic kidney disease(CKD)was compared among these groups.A multivariate Cox proportional hazards regression model was employed to assess the effects of different blood pressure levels on renal function in diabetic patients,with the stability of the results confirmed using a multivariate time-dependent Cox proportional hazards model.Sensitivity analysis was conducted after excluding cases of cardiovascular disease(CVD)during follow-up,and cases using antihypertensive and antidiabetic medications at baseline.Results(1)At baseline,stage 1 hypertension patients demonstrated statistically significant higher differences with age and body mass index(BMI)compared to normal blood pressure group(P<0.05).(2)By the end of the follow-up,2 294 cases of CKD were identified,including 1 117 cases of estimated glomerular filtration rate(eGFR)decline and 1 575 cases of urinary protein.The incidences density of CKD,eGFR decline and urinary protein for stage 1 hypertension group were 39.4,16.3 and 25.5 per thousand person-years,respectively,all of which were statistically significant different from normal blood pressure group(log-rank test,P<0.01).(3)Multivariate Cox regression analysis revealed that,compared to the normal blood pressure group,stage 1 hypertension was associated with a 29%increased risk of CKD(HR=1.29,95%CI 1.09-1.52)and a 40%increased risk of eGFR decline(HR=1.40,95%CI 1.08-1.80)in diabetic individuals.Conclusion Stage 1 hypertension significantly increases the risk of CKD and eGFR decline in diabetic individuals,with a particularly notable effect on the risk of eGFR decline.

Objective To study the effect of dinorgestrel combined with levonorgestrel intrauterine birth control system in the treatment of endometriosis(EMs)and its effect on endometrial thickness and hormone levels.Methods EMs patients were selected as the research objects and divided into treatment group and control group according to the cohort method.Patients in the control group were treated with levonorgestrel intrauterine birth control system,while patients in the treatment group were treated with dinorgestrel on the basis of the control group.Compared the efficacy of two groups of patients before and after treatment,use visual analogue scale(VAS)to score pain,calculate endometrial thickness based on menstrual blood to sanitary napkin area,and use radioimmunoassay to measure changes in hormone levels[follicle stimulating hormone(FSH),estradiol(E2),luteinizing hormone(LH),prolactin(PRL),and progesterone(P)]in vivo.Results The control group and the treatment group were enrolled in 40 patients.The total effective rates of treatment in the control group and the treatment group were 75％and 95％,respectively.After treatment,the scores of dysmenorrhea in 2 groups were 3.27±1.04 and 1.36±0.69;the scores of dyspareunia pain were 2.42±0.89 and 1.04±0.55;the scores of abdominal pain in non-menstrual period were 2.17±1.25 and 1.49±1.03,respectively;endometrial thickness were(6.02±1.25)and(3.64±1.04)mm;hemoglobin concentration were(106.58±12.07)and(112.85±12.37)g·L-1;menstrual volume score were 38.41±15.21 and 12.41±4.81;FSH levels were(3.89±2.19)and(2.52±1.30)U·L-1;LH levels were(6.90±2.92)and(8.51±3.72)U·L-1;PRL levels were(367.98±77.99)and(322.01±57.95)μg·L-1;E2 levels were(548.67±79.38)and(504.92±61.31)pmol·L-1;P levels were(17.69±7.38)and(12.23±6.61)nmol·L-1,respectively.Compared with control group,the above indexes in treatment group were statistically significant(all P＜0.05).The adverse drug reactions in the treatment group were mainly vaginal bleeding,fever and vertigo,the adverse drug reactions in the control group were mainly bleeding,fever and vertigo.The total incidence of adverse drug reactions in treatment group and control group was 12.50％and 10.00％,respectively,with no statistically significant difference(P＞0.05).Conclusion The combination of dexamethasone and dexamethasone has a significant therapeutic effect on endometriosis,reducing endometrial thickness and optimizing hormone levels.

Objective To investigate and analyze the distribution of serum cytokeratin 19 fragment antigen 21-1(CYFRA21-1)and squamous cell carcinoma-associated antigen(SCCA)levels in healthy pregnant women during pregnancy and to assess their diagnostic value for cervical cancer in pregnancy.Methods A total of 441 healthy pregnant women and 69 patients with cervical cancer in pregnancy who attended the Obstetrics and Gynecology Hospital of Fudan University from Jan 2021 to May 2024 were selected,and 165 healthy women in the Physical Examination Center of the Obstetrics and Gynecology Hospital of Fudan University were included in the same period as the control group.The healthy pregnant women were divided into 143 in early pregnancy(T1 group),147 in middle pregnancy(T2)and 151 in late pregnancy(T3).Serum CYFRA21-1 and SCCA values were detected and analyzed in all groups.One-way ANOVA,independent samples t-test,Mann-Whitney U-test,Kruskal-Wallis H-test,logistic analysis,and ROC curves were used for comparative analysis.Results The CYFRA21-1 and SCCA values were 1.66(1.19-2.17)ng/mL and 0.8(0.6-1.0)ng/mL in the control group,3.07(2.11-4.14)ng/mL and 0.9(0.7-1.3)ng/mL in the healthy pregnant women group,and were 4.33(2.99-7.60)ng/mL and 1.8(0.9-8.5)ng/mL in the patients with cervical cancer in pregnancy group,respectively.There was a statistically significant difference in the two serum values between every two groups(P<0.05).CYFRA21-1 levels were 3.13(2.46-4.05)ng/mL,1.89(1.50-2.53)ng/mL and 4.19(3.48-5.43)ng/mL in the T1,T2,and T3 groups,respectively;and SCCA levels were 0.9(0.7-1.1)ng/mL,0.7(0.6-1.0)ng/mL and 1.2(0.8-1.7)ng/mL,respectively.The results of T1 and T3 groups were higher than those of the control group(P<0.05);however,there was no statistically significant difference between the results of the T2 group and those of the control group(P>0.05).The areas under the ROC curves for the diagnosis of cervical cancer in pregnancy for CYFRA21-1,SCCA,human epididymis protein 4(HE4),anti-carcinoembryonic antigen(CEA)and joint indicators were 0.684,0.724,0.612,0.791 and 0.913,with sensitivities of 36%,48%,38%,57%and 73%,specificities of 96%,97%,89%,86%and 99%,respectively.The cut-off values of each indicator were 6.05 ng/mL,2.60 ng/mL,51.45 pg/mL and 1.75 ng/mL,respectively.Conclusion Serum CYFRA21-1 and SCCA levels were higher in pregnant women during early and late pregnancy compared with non-pregnant individuals,while they were not statistically different from non-pregnant women during mid-trimester.CYFRA21-1 and SCCA have diagnostic value for patients with cervical cancer during pregnancy.

Aim To investigate the regulatory mecha-nism of prostaglandin E2(PGE2)on the membrane expression of organic anion transporter 1(OAT1)in synoviocytes and the effect of paeoniflorin-6'-O-ben-zene sulfonate(CP-25).Methods Immunofluores-cence was used to detect the effects of CP-25 on the expression of OAT1 and prostaglandin E receptor 4(EP4)in PGE2 stimulated synoviocytes.EP4 agonists(TCS2510)and antagonists(GW627368X)were used to explore the role of EP4 in regulation of OAT1.CP-25 and protein kinase A(PKA)inhibitor H-89 were used to investigate the effects of CP-25 and PKA on OAT1 expression in synoviocytes.Results Membrane expression of EP4 and OAT1 was down-regulated with-in 0～10 min,and thereby up-regulated between 20～60 min in the presence of PGE2 simulation(P＜0.05).CP-25 significantly up-regulated the expres-sions of OAT1 and EP4 in PGE2 stimulated synovio-cytes(P＜0.05).TCS2510 significantly up-regulated the expression of OAT1 in cell membrane of synovio-cytes(P＜0.01).CP-25 up-regulated the expression of OAT1 in PGE2-treated cells,while the effect of CP-25 on expression of OAT1 was significantly inhibited after the together use of GW627368X and H-89.(P＜0.01).Conclusions PGE2-mediated EP4/PKA sig-naling pathway regulates the expression of OAT1 on membranes of synoviocytes.CP-25 can significantly in-crease the membrane expression of OAT1 in synovio-cytes by activating the EP4/PKA signaling pathway.