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 explore the current status of H.pylori infection in the natural population of Sanya City,analyze its influencing factors,and provide a reference basis for the prevention and control of H.pylori infection.Methods A total of 677 residents from four districts of Sanya City were selected by overall stratified random sampling method,and were subjected to urea 14C breath test and questionnaire survey to calculate the positive rate of H.pylori in the natural population and analyze the influencing factors of H.pylori infection.Results A total of 606 residents were included,and the number of H.pylori positive detections was 261,with a positive detection rate of 38.5％.Among them,different ethnicity,marital status,smoking,eating vegetables and fruits,and literacy level were associated with H.pylori infection(P＜0.05);gender,age,BMI,alcohol consumption,drinking water source,betel quid chewing,and the number of cohabitants were not significantly associated with H.pylori infection(P＞0.05).Family infection was an independent risk factor for H.pylori infection in the natural population of Sanya City,and Li ethnicity,frequent consumption of fruits and vegetables,and college and higher education level were independent protective factors for H.pylori infection in the natural population of Sanya City.Conclusion The rate of H.pylori infection in the natural population of Sanya City is lower than the national average.Consuming more fruits and vegetables and improving the awareness of hygiene protection are conducive to the prevention of H.pylori infection;and the promotion of the family and related members with the same examination and treatment is important to avoid aggregation of infection within the family.

Objective: To examine the mediating effect of nighttime sleep duration on pain and frailty among elderly patients with comorbidity of chronic diseases, so as to provide insights into frailty control among the elderly. Methods: Demographic information, pain and nighttime sleep duration of the elderly at ages of 60 years and older were collected from the China Health and Retirement Longitudinal Study 2020. Frailty were evaluated using frailty index. The mediating effect of sleep duration for pain and frailty was analyzed using the Process program compiled by HAYSS and colleagues, and the significance of the mediating role was tested using the Bootstrap test. Results: A total of 2 246 elderly patients with comorbidity of chronic diseases were enrolled, including 1 195 males (53.21%) and 1 051 females (46.79%), with a median age of 65.00 (interquartile range, 8.00) years. There were 504 cases with frailty (22.44%), with a median pain score of 0 (interquartile range, 1.00) points, and a mean nighttime sleep duration of (6.44±1.55) hours. Mediating analysis showed that pain affected frailty directly and positively with the effect value of 0.089 (95%CI: 0.066-0.112), and also affected frailty by nighttime sleep duration directly and positively with the effect value of 0.047 (95%CI: 0.036-0.058), with the mediating effect contributed 34.56% of the total effect. Conclusion Pain can directly or indirectly affect frailty among elderly patients with comorbidity of chronic diseases through nighttime sleep duration.

Objective To investigate the classification,concomitant injuries,and their correlations of medial meniscus posterior root(MMPR)injuries through a large-sample analysis,to enhance the comprehensive understanding of MMPR and related injuries.Methods A total of 240 patients with MMPR injuries were divided into 5 types.The distance of the torn end separation and the value of meniscus protrusion of MMPR were measured,and the grading of cartilage injury in the medial tibiofemoral compartment was recorded.The relationships between MMPR injuries and meniscus tear location,tear type,meniscus protrusion,and grading of cartilage injury were analyzed.Results The incidence of MMPR injuries was 2.82％,with females being 3.14 times more affected than males.Medial meniscus tears in type 1 and type 4 MMPR injuries were predominantly located in the posterior horn and posterior root,while there were no statistical differences among types 2,3,and 5.Type 1 MMPR injuries were predominantly oblique tears,types 2,3,and 5 were predominantly radial and complex tears,and type 4 was predominantly complex tears.The incidence of meniscus protrusion was sig-nificantly higher in types 3 and 4 MMPR injuries compared to other types.The value of medial meniscus protrusion was greater in type 4 MMPR than in type 3.In type 3 MMPR injuries,a larger torn end separation distance correlated with a greater value of medial meniscus protrusion.The severity of MMPR injuries correlated positively with the grading of cartilage injury in the medial tibiofemo-ral compartment.Conclusion Females are more prone to MMPR injuries than males.The classification of MMPR injuries correlates with the location and type of medial meniscus tears,as well as medial meniscus protrusion.There is a positive correlation between the torn end separation distance and the value of meniscus protrusion in MMPR injuries.The severity of MMPR injuries correlates with the degree of cartilage injury in the medial tibiofemoral compartment.

This study was aimed at understanding the pollution distribution pattern of avian influenza virus in the environ-ment in poultry related places in Shandong Province,to provide a scientific basis for the prevention,control,prediction,and early warning regarding human infection with avian influenza.From 2020 to 2023,6 523 environmental samples were collected in 16 cities in Shandong Province from four types of poultry-related places.Fluorescence quantitative PCR was used for nucleic acid testing of influenza A virus.Positive samples were further identified for the H5,H7,and H9 subtypes of avian influenza virus.The epidemiological characteristics of avian influenza viruses in the poultry related environment of Shandong Province were described,and inter-rate comparisons were performed with the x2 test.During 2020-2023,6 523 environmental samples were collected,and 1 007 cases positive for avian influenza virus were detected,with a positivity rate of 15.44％.H5,H7,and H9 subtypesand mixed infections were detected.H9 was the main subtype(88.48％)in positive specimens.A significant difference in positivity rates was observed among regions(x2=431.956,P＜0.001),and the highest positivity rate was 28.93％.Significant differences in positivity rates were observed among monitoring sites(x2=304.604,P＜0.001),sample types(x2=109.678,P＜0.001),and quarters(x2=64.963,P＜0.001).The positive detection rate was highest at monitoring sites in urban and rural live poultry markets(20.12％),and the positive detection rate of samples collected by wiping meat cut-ting board surfaces was higher than that of other samples(22.56％).The peak positive detection rate occurred in spring(20.31％).Widespread contamination with avian influenza virus was observed in poultry environments in Shandong Prov-ince.The H9 subtype,the main pathogen,coexisted with H5 and H7 subtypes,thus posing a risk of human infection with avian influenza.Therefore,prevention and control of avian influenza must be strengthened in key seasons,areas,places,and links.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To explore the application effect and safety of general anesthesia with different doses of remimazolam during vascular intervention anesthesia of intracranial aneurysms.Methods Patients with intracranial aneurysms were divided into high,middle and low dose groups according to the random number table method.The venous access was opened after the patients entered the room,and the vital signs were closely monitored.The low,middle and high dose groups were intravenously injected with 0.25,0.30 and 0.35 mg·kg-1remazolam,respectively.After the loss of consciousness,alfentanil and mivacurium chloride were given for anesthesia induction.The anesthetic effect,recovery quality,hemodynamic indexes,cerebral hemodynamic indexes and neurological function indexes before anesthesia induction(T0),at the time of laryngeal mask insertion(T1),embolization(T2),5 min after operation(T3)and 30 min after operation(T4)were compared among the three groups.The incidence of postoperative cerebral vasospasm(CVS),delayed ischemic neurological dysfunction(DIND)and the incidence of adverse drug reactions related to anesthesia were counted.Results The onset times of anesthesia in the high,middle,and low dose groups were(5.03±1.28),(5.17±1.09),and(7.21±1.15)min,respectively;the number of anesthesia rescue interventions were(0.12±0.02),(0.21±0.06),and(1.51±0.23)times,respectively.There was statistically significant difference in the number of rescue interventions between the high and middle dose groups compared to the low dose group(all P＜0.05).The therapeutic efficacy rates of flumazenil in the high,middle,and low dose groups were 18.18％,11.11％and 2.86％,respectively.the mean arterial pressure(MAP)at T2 were(87.06±6.02),(86.85±5.61)and(81.09±5.37)mmHg;the MAP at T4 were(92.05±5.13),(87.57±6.29)and(84.42±5.16)mmHg,respectively.There was statistically significant difference in MAP between the high and low dose groups(all P＜0.05).There were no statistically significant differences in heart rate(HR),oxygen saturation(SpO2),left peak systolic velocity of middle cerebral artery(Vp-MCA),left mean systolic velocity of middle cerebral artery(Vm-MC)and pulsatility index(PI),S100β protein,and neuron-specific enolase(NSE)levels among the three groups at different time points(all P＞0.05).There were no statistically significant differences in the incidence rates of cardiovascular system complications,delayed postoperative cognitive dysfunction,or anesthesia-related adverse reactions between the three groups(all P＞0.05).Conclusion The safety of different doses of remimazolam general anesthesia in the vascular interventional therapy of intracranial aneurysms is high,and the effects on cerebral hemodynamics and neurological function are similar.However,high-dose remimazolam have shorter general anesthesia induction time and less intraoperative anesthesia remedy frequency while the high-dose remimazolam has higher postoperative flumazenil antagonist therapy.