19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To describe and analyze the epidemiological characteristics of scrub typhus in Huai'an, Jiangsu Province from 2006 to 2024 and explore the long-term incidence trend and distribution of high-risk areas, and to formulate targeted prevention and control strategies. Methods The scrub typhus case report data of Huai'an from 2006 to 2024 in the Chinese Disease Prevention and Control Information System were extracted for descriptive analysis. Results A total of 898 cases of scrub typhus were reported in Huai'an, with an average annual incidence rate of 0.96 per 100 000 from 2006 to 2024. There was a turning point in the incidence trend of scrub typhus in 2011. From 2006 to 2011, the annual percentage change (APC) was 47.09% (95% CI: 7.53 - 859.39), and the upward trend was statistically significant (P < 0.05). From 2012 to 2024, the APC was -2.12% (95% CI: -29.09 - 3.75), and the downward trend was not statistically significant. October and November were the high-incidence months, and the total concentration from 2006 to 2024 was 0.93, indicating that scrub typhus had strict seasonality. The circular distribution method estimated that the peak period of the epidemic was from October 11th to November 25th, and the peak day of incidence was November 3rd. Jinhu County was a high-incidence area. The ratio of male to female cases was 1.03. The age group with the highest reported incidence was 40 to < 80 years old. The occupation with the highest proportion was farmers, accounting for 78.03%. Conclusion From 2006 to 2024, scrub typhus in Huai'an shows a peak every 3 - 4 years. Middle-aged and elderly farmers are the key population at risk, and Jinhu County is a key area. In the future, targeted health education should be carried out to effectively control the prevalence of scrub typhus.

OBJECTIVE: To explore the protective effect of glycosaminoglycans (GAG) on vascular endothelium in patients with sepsis. METHODS: A prospective study was conducted on adult patients with sepsis admitted to the intensive care unit (ICU) of Hangzhou Normal University Affiliated Hospital from December 2022 to December 2023. Patients were randomly divided into conventional treatment group and GAG intervention group. Both groups were treated according to the 2021 Surviving Sepsis Campaign Guidelines. The GAG intervention group was additionally treated with GAG (2 mL of sulodexide intramuscular injection once daily for 7 days) on the basis of conventional treatment. Venous blood was collected from patients at 0, 6, 24, 48, 72 hours and 7 days after enrollment to detect serum vascular endothelial glycocalyx [heparan sulfate (HS) and syndecan-1 (SDC-1)], inflammatory markers [C-reactive protein (CRP), procalcitonin (PCT), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)], and coagulation markers [prothrombin time (PT), activated partial thromboplastin time (APTT), antithrombin-III (AT-III), fibrinogen (Fib), D-Dimer], and to perform acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), and International Society on Thrombosis and Haemostasis (ISTH) scores. The prognosis of patients (length of hospital stay, ICU and 28-day mortality) was observed. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the value of HS in predicting the prognosis of sepsis patients, and the correlation between endothelial glycocalyx degradation products and various clinical indicators was analyzed. RESULTS: A total of 50 adult patients with sepsis meeting the inclusion criteria were enrolled, with 25 in the conventional treatment group and 25 in the GAG intervention group. In terms of degradation products of endothelial glycocalyx, compared to baseline, both groups showed an increasing trend in HS and SDC-1 levels post-treatment. However, the GAG intervention group exhibited significantly lower HS levels at 72 hours and 7 days, as well as lower SDC-1 levels at 6, 24, 48, 72 hours and 7 days compared to the conventional group. Among the surviving patients, the HS levels at 72 hours and SDC-1 levels at 6 hours of treatment in the GAG intervention group were significantly reduced compared to the conventional treatment group. In terms of severity score, compared with before treatment, the GAG intervention group showed a significant decrease in APACHE II, SOFA, and ISTH scores after 7 days of treatment. The SOFA scores of the GAG intervention group after 48 hours and 7 days of treatment were significantly lower than those of the conventional treatment group. In terms of inflammatory indicators, compared with before treatment, the GAG intervention group showed a significant decrease in IL-6 levels after 48 hours of treatment. With the prolongation of treatment time, the CRP levels of both groups of patients showed a significant downward trend, and at 7 days of treatment, the CRP level in the GAG intervention group was significantly lower than that in the conventional treatment group. In terms of coagulation function, with prolonged treatment time, PT and APTT of both groups of patients showed an increasing trend, while Fib showed a decreasing trend. The GAG intervention group showed a significant prolongation of PT after 72 hours of treatment compared to the conventional treatment group. In terms of prognosis, there were no statistically significant differences in ICU and 28-day mortality rates between the two groups. The GAG intervention group had significantly shorter hospital stays than the conventional treatment group. ROC curve analysis showed that HS, CRP, APTT, IL-6, APACHE II, SOFA, and ISTH scores were predictive factors for the prognosis of sepsis patients (all P < 0.05). Compared to a single indicator, the combined detection of multiple indicators has a higher value in predicting the prognosis of sepsis patients [area under the curve (AUC) = 0.911, 95% confidence interval (95%CI) was 0.817-1.000], with a sensitivity of 76.9% and a specificity of 91.9%. Correlation analysis showed that HS was significantly negatively correlated with Fib, PT, TNF-α, IL-6, and PCT (r values were -0.338, -0.396, -0.288, -0.319, and -0.340, all P < 0.05), while HS was significantly positively correlated with D-Dimer and CRP (r values were 0.347 and 0.354, both P < 0.05); SDC-1 was significantly negatively correlated with Fib, PT, APTT, TNF-α, IL-6, and ISTH scores (r values were -0.314, -0.294, -0.408, -0.353, -0.289, -0.287, all P < 0.05). CONCLUSIONS Early glycocalyx degradation can occur in sepsis patients. GAG have a protective effect on,the vascular endothelium, reducing the severity of sepsis and providing organ protection. HS, CRP, APTT, IL-6, APACHE II score, SOFA score, and ISTH score are independent predictive factors for the prognosis of sepsis patients. The combination of HS and the above indicators can significantly improve the accuracy of prediction.
Humans ; Sepsis/blood* ; Glycocalyx/drug effects* ; Glycosaminoglycans/pharmacology* ; Prospective Studies ; Endothelium, Vascular/metabolism* ; Syndecan-1/blood* ; Male ; Female ; C-Reactive Protein/metabolism* ; Interleukin-6/blood* ; Heparitin Sulfate/blood* ; Middle Aged ; Adult ; Tumor Necrosis Factor-alpha/blood* ; Procalcitonin/blood*

OBJECTIVE: Exposure to polycyclic aromatic hydrocarbons (PAHs) or metal(loid)s individually has been associated with neural tube defects (NTDs). However, the impacts of PAH and metal(loid) co-exposure and potential interaction effects on NTD risk remain unclear. We conducted a case-control study in China among population with a high prevalence of NTDs to investigate the combined effects of PAH and metal(loid) exposures on the risk of NTD. METHODS: Cases included 80 women who gave birth to offspring with NTDs, whereas controls were 50 women who delivered infants with no congenital malformations. We analyzed the levels of placental PAHs using gas chromatography and mass spectrometry, PAH-DNA adducts with ³²P-post-labeling method, and metal(loid)s with an inductively coupled plasma mass spectrometer. Unconditional logistic regression was employed to estimate the associations between individual exposures and NTDs. Least absolute shrinkage and selection operator (LASSO) penalized regression models were used to select a subset of exposures, while additive interaction models were used to identify interaction effects. RESULTS: In the single-exposure models, we found that eight PAHs, PAH-DNA adducts, and 28 metal(loid)s were associated with NTDs. Pyrene, selenium, molybdenum, cadmium, uranium, and rubidium were selected through LASSO regression and were statistically associated with NTDs in the multiple-exposure models. Women with high levels of pyrene and molybdenum or pyrene and selenium exhibited significantly increased risk of having offspring with NTDs, indicating that these combinations may have synergistic effects on the risk of NTDs. CONCLUSION Our findings suggest that individual PAHs and metal(loid)s, as well as their interactions, may be associated with the risk of NTDs, which warrants further investigation.
Humans ; Neural Tube Defects/chemically induced* ; Polycyclic Aromatic Hydrocarbons/adverse effects* ; Female ; Case-Control Studies ; China/epidemiology* ; Adult ; Pregnancy ; Environmental Pollutants ; Maternal Exposure/adverse effects* ; Metals/toxicity* ; Young Adult ; Risk Factors

Objective To cultivate glioblastoma U87 stem-like cells(SLCs)and to detect the level of stemness bio-markers,mitochondrial respiratory capacity and the capacity of in vivo tumorigenesis.Methods B-27,growth factors EGF and bFGF was added into DMEM/F-12 culture in serum-free stem cell culture medium for U87 SLCs.Suspended culture of U87 SLCs was suspended using the neuro-sphere formation assay,while adherent culture of U87 SLCs was achieved by coating Matrigel matrix on the culture surface.The mRNA and protein level of stemness biomarkers in culture were detected using real-time quantitative PCR and Western blot.The proportion of CD133+cells in culture was detected by flow cytometry.The changes of cell oxygen consumption rate were detected by Seahorse cell metabo-lism analysis.Cell tumorigenesis ability was verified by subcutaneous tumor transplantation in animals.Results U87 SLCs in stem cell culture medium would grow into typical sphere morphology within one week,and the spheres would continue to grow as the culture process prolongs.At the appropriate concentration of adhesive,U87 SLCs adhered to and grow well in stem cell culture medium.The mRNA transcription of stemness biomarkers such as CD133,nes-tin,OLIG2,CD44,CD15,and integrin α6(ITGA6)was significantly increased as found in both culture methods,and the protein levels of CD133 and nestin were also increased under both methods(P＜0.05).U87 SLCs showed higher mitochondrial reserve respiratory capacity(P＜0.05).U87 SLCs could form larger subcutaneous tumors with fewer inoculated cells(P＜0.05),and grew faster in vivo with stronger tumorigenic ability.Conclusions U87 SLCs have typical stemness characteristics and may function as tumor cell model with higher stemness properties.

Objective To compare the application value of filter membrane method and smear method on the evaluation of disinfection effect of flexible endoscope.Methods 242 flexible endoscopes after cleaning and disinfection from January 2022 to November 2022 were collected as the study subjects,and the disinfection effect of all endoscopes was tested by filter membrane method and smear method.The qualified rate,pathogen detection rate,colony detection and use cost of the two detection methods were compared.Results Among the 242 flexible endoscopes,the total qualified rate of filter membrane method was lower than that of smear method while the total detection rate of pathogenic bacteria and the number of bacterial colony were significantly higher than those of smear method(P<0.05).In the two evaluation methods,the colony count detected by gastroscopy was mainly≤100 cfu/n,and the colony count detected by enteroscopy was mainly≥100 cfu/n(P>0.05).The economic cost and time cost of filter membrane method were higher than those of smear method(P<0.05),and filter membrane method increased the annual depreciation cost of the suction filtration system of 976 yuan.Conclusion Compared with smear method,filter membrane method is more effective in evaluating the disinfection of flexible endoscope,but its economic cost and time cost are also higher.However,in order to build a green environment-friendly hospital,it is necessary to increase the investment of endoscopy center,thus it is recommended to apply filter membrane method.

Objective:To investigate the clinical features and prognosis of male with anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody.Methods:The clinical data of 246 patients with DM and anti-MDA5 autoantibodies hospitalized by Jiangsu Myositis Cooperation Group from 2017 to 2020 were collected and retrospectively analyzed. Chi-square test was performed to compared between counting data groups; Quantitative data were expressed by M ( Q1, Q3), and rank sum test was used for comparison between groups; Single factor survival analysis was performed by Kaplan-Meier method and Log rank test; Cox regression analysis were used for multivariate survival analysis. Results:①The male group had a higher proportion of rash at the sun exposure area [67.1%(47/70) vs 52.8%(93/176), χ2=4.18, P=0.041] and V-sign [50.0%(35/70) vs 30.7%(54/176), χ2=8.09, P=0.004] than the female group. The male group had higher levels of creatine kinase [112(18, 981)U/L vs 57 (13.6, 1 433)U/L, Z=-3.50, P<0.001] and ferritin [1 500 (166, 32 716)ng/ml vs 569 (18, 14 839)ng/ml, Z=-5.85, P<0.001] than the female group. The proportion of ILD [40.0%(28/70) vs 59.7%(105/176), χ2=7.82, P=0.020] patients and the red blood cell sedimentation rate[31.0(4.0, 101.5)mm/1 h vs 43.4(5.0, 126.5)mm/1 h, Z=-2.22, P=0.026] in the male group was lower than that of the female group, but the proportion of rapidly progressive interstitial lung disease (PR-ILD) [47.1%(33/70) vs 31.3%(55/176), χ2=5.51, P=0.019] was higher than that of the female group. ②In male patients with positive anti-MDA5 antibodies,the death group had a shorter course of disease[1.0(1.0, 3.0) month vs 2.5(0.5,84) month, Z=-3.07, P=0.002], the incidence of arthritis [16.7%(4/24) vs 42.2%(19/45), χ2=4.60, P=0.032] were low than those in survival group,while aspartate aminotransferase (AST)[64(22.1, 565)U/L vs 51(14,601)U/L, Z=-2.42, P=0.016], lactate dehydrogenase (LDH) [485(24,1 464)U/L vs 352(170, 1 213)U/L, Z=-3.38, P=0.001], C-reactive protein (CRP) [11.6(2.9, 61.7) mg/L vs 4.95(0.6, 86.4) mg/L, Z=-1.96, P=0.050], and ferritin levels [2 000(681, 7 676) vs 1 125 (166, 32 716)ng/ml, Z=-3.18, P=0.001] were higher than those in the survival group, and RP-ILD [95.8%(23/24) vs 22.2%(10/45), χ2=33.99, P<0.001] occurred at a significantly higher rate. ③Cox regression analysis indicated that the course of disease LDH level, and RP-ILD were related factors for the prognosis of male anti-MDA5 antibodies [ HR (95% CI)=0.203(0.077, 0.534), P=0.001; HR (95% CI)=1.002(1.001, 1.004), P=0.003; HR (95% CI)=95.674 (10.872, 841.904), P<0.001]. Conclusion:The clinical manifestations of male anti-MDA5 antibody-positive patients are different from those of female. The incidence of ILD is low, but the proportion of PR-ILD is high. The course of disease, serum LDH level, and RP-ILD are prognostic factors of male anti-MDA5 antibody-positive patients.