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.

ObjectiveTo analyze the epidemiological distribution and temporal trends of liver cancer incidence among Luzhou residents from 2016‒2022， and to provide a theoretical basis for improving liver cancer prevention and treatment strategies in Luzhou. MethodsData on liver cancer incidence among Luzhou residents from 2016 to 2022 were collected， and the incidence rate， age-specific incidence rate， and annual percentage change （APC） were calculated. A Joinpoint regression model was used to fit a time series segment to the monthly number of new cases in each district and county of Luzhou to explore the trend of liver cancer incidence rate. ResultsThe incidence rate of liver cancer in Luzhou increased from 22.96/10⁵ in 2016 to 32.31/10⁵ in 2022. The incidence rate of liver cancer in men was higher than that in women in both 2016 and 2022， and the incidence rate of liver cancer in men increased from 34.83/10⁵ in 2016 to 47.95/10⁵ in 2022， with an APC of 3.3%； the incidence rate of liver cancer in women increased from 10.50/10⁵ in 2016 to 15.95/10⁵ in 2022， with an APC of 3.0%， and the differences in the change trends were not statistically significant （P>0.05）.The incidence of liver cancer was low in the age group of 0‒<40 years from 2016 to 2022 and increased with age； the incidence of liver cancer in the age group of 55 years and above was increasing at an average annual rate of 16.4%. ConclusionThe overall incidence of liver cancer in Luzhou is on the rise， and the incidence of liver cancer in men is higher than that in women. Middle-aged and elderly men are the key population for liver cancer prevention and treatment， and liver cancer prevention and treatment should be carried out in a targeted manner， taking into account regional development differences.

Objective:To study the predictive values of lung ultrasound (LUS) score and Downes score in selecting respiratory support strategies for newborns with dyspnea.Methods:From September 2021 to July 2022, newborns admitted to our hospital with dyspnea were selected and assigned into the non-invasive respiratory support (N) group, invasive respiratory support (I) group and control (C) group based on the respiratory support strategies on admission. LUS scores and Downes scores at 6, 24, and 48 h after birth were recorded. ROC curves were drawn to determine the predictive values of LUS and Downes scores for respiratory support strategies.Results:A total of 263 cases were enrolled, including 105 cases in N group, 56 cases in I group and 102 cases in C group. The differences of LUS and Downes scores between the three groups at the same timepoint were statistically significant with I group had the highest scores, N group second and C group lowest ( P<0.05). LUS and Downes scores within each group at different timepoints were significantly different ( P<0.05).In all three groups, LUS and Downes scores were decreased with longer duration of treatment. LUS score, Downes score and PaO 2/FiO 2 were positively correlated with each other ( P<0.05). The area under the curve (AUC) of LUS score and Downes score predicting non-invasive respiratory support within 6 h after birth were 0.900 (95% CI 0.861-0.940, P<0.05) and 0.889 (95% CI 0.847-0.931, P<0.05), respectively, with the same cutoff of 2.5. The AUC of the combination of LUS and Downes scores predicting non-invasive respiratory support was 0.944 (95% CI 0.915-0.973, P<0.05). The AUC of LUS score and Downes score predicting invasive respiratory support were 0.979 (95% CI 0.963-0.995, P<0.05) and 0.831 (95% CI 0.760-0.902, P<0.05), respectively, with the same cutoff of 5.5. The AUC of the combination of LUS and Downes scores predicting invasive respiratory support was 0.985 (95% CI 0.972-0.998, P<0.05). Conclusions:Both LUS score and Downes score have certain predictive values for respiratory support strategies in newborns with dyspnea.

Objective To investigate the effects of electroacupuncture on the intestinal NIMA-related kinase 7(NEK7)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathway in mice with Parkinson's disease.Methods According to the randomized number table method,36 C57BL/6 mice were randomly divided into the control group,the model group,and the electroacupuncture group,with 12 mice per group.The Parkinson's disease mouse model was established by gavage of rotenone solution(10 mg/kg)for 28 d.After molding,the electroacupuncture group was stimulated with"Fengfu"(DU17),"Taichong"(LR3),and"Zusanli"(ST36)for 14 d,while the control group and the model group were only treated with immobilization.The motor ability of mice was detected by pole climbing test and hindlimb rating score,the positive expressions of nigral tyrosine hydroxylase(TH)and colon occludin were detected by immunohistochemistry,the histological morphology of colon was observed by hematoxylin-eosin staining,and Western blotting was used to detect the protein expressions of NEK7,NLRP3,Caspase-1,and interleukin-1β(IL-1β).Results Compared with the control group,mice in the model group had lower score on the pole climbing test and a higher hindlimb rating score(P＜0.01);the average optical densities of nigral TH and colon occludin were decreased(P＜0.01);significant inflammatory infiltration was observed in the colonic tissue,and the muscularis propria was thinned;and the protein expressions of NEK7,NLRP3,Caspase-1,and IL-1β in the colonic tissue were elevated(P＜0.01).Compared with the model group,mice in the electroacupuncture group had higher score on the pole climbing test and a lower hindlimb rating score(P＜0.01);the average optical densities of nigral TH and colon occludin were increased(P＜0.01);the degree of inflammatory infiltration of colonic tissues decreased,and the muscularis propria was thickened;and the protein expressions of NEK7,NLRP3,Caspase-1,and IL-1β of colonic tissues were decreased(P＜0.01).Conclusion Electroacupuncture at"Fengfu"(DU17),"Taichong"(LR3),and"Zusanli"(ST36)can improve motor functional impairments in mice with Parkinson's disease,and the mechanism may be through the inhibition of intestinal NEK7/NLRP3 pathway,improving the intestinal barrier damage,relieving the intestinal inflammation,and improving the dopaminergic neuron injury.

Objective To investigate the protective effect of cardamomine(CAR)on anthracycline-induced cardiotoxicity in rats by regulating the pyroptosis mediated by Notch/nuclear factor-κB(NF-κB)signal pathway.Methods The rat model of cardiotoxicity was established by intraperitoneal injection of doxorubicin(DOX).The model rats were randomly divided into DOX group,CAR-L group,CAR-H group and Jagged1 group.Another 10 rats were taken as the control group.The control group and the DOX group were given the same amount of 0.9％NaCl.The CAR-L group and CAR-H group were given 40 and 80 mg·kg-1 CAR by gavage,respectively.The Jagged1 group was given 80 mg·kg-1 CAR+and 25 ng·kg-1 Jagged1 by gavage once a day for 4 weeks.Myocardial injury markers creatine kinase isoenzyme(CK-MB)and troponin Ⅰ(cTn Ⅰ)were detected by kit.The expression of pyroptosis protein Nod-like receptor protein 3(NLRP3)and desquamate D(GSDM-D)were observed by immunohistochemistry.The expression of Notch1 and phosphorylated NF-κB p65(p-NF-κB p65)protein in myocardial tissue was detected by Western blotting.Results The levels of CK-MB in control group,DOX group,CAR-L group,CAR-H group and Jagged1 group were(48.51±5.39),(175.93±13.27),(106.83±9.73),(83.71±8.39)and(126.08±9.74)U·L-1;the levels of cTn Ⅰ were(1.95±0.18),(12.46±1.83),(7.15±0.64),(4.13±0.38)and(8.01±0.78)ng·mL-1;the average optical density of NLRP3 protein were 0.19±0.07,0.36±0.05,0.25±0.05,0.21±0.03 and 0.31±0.06;the average optical density of GSDM-D were 0.18±0.04,0.43±0.06,0.24±0.03,0.19±0.04 and 0.32±0.05.There were significant differences in the above indexes between DOX group and control group(all P＜0.05).There were significant differences in the above indexes between CAR-L group,CAR-H group and DOX group(all P＜0.05),and there were significant differences between CAR-L group and CAR-H group(all P＜0.05).The above indexes in Jagged1 group were significantly different from those in CAR-H group(all P＜0.05).Conclusion CAR can improve myocardial injury in DOX cardiotoxic rats,reduce oxidative stress,inflammatory reaction and pyroptosis,and its mechanism may be related to the inhibition of Notch/NF-κB pathway.

Objective To explore the improve mechanism of ultra-filtration extract from Angelica Sinensis Radix and Hedysari Radix on kidney injury in diabetic kidney disease(DKD)rats.Methods The diabetes model was prepared by intraperitoneal injection of streptozotocin,and then fed with high sugar and high fat diet.The rats with successful DKD were randomly divided into model group,positive control group and experimental-L,-M,-H groups with 8 cases per group.Additionally,selected 8 Wistar rats as the blank group.The experimental-L,-M,-H groups were given 1.5,3.0 and 6.0 g·kg-1 ultra-filtration extract from Angelica Sinensis Radix and Hedysari Radix by gavage,respectively.The positive control group was given 1.75 × 10-3 g·kg-1irbesartan suspension by gavage.The blank and model groups were given equal volume of pure water by gavage.Six groups were administrated once a day for 12 consecutive weeks.The 24 h-urinary total protein were detected by coomassie brilliant blue method.The protein expression levels of nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase-1(HO-1)and andacyl-CoA synthetase long chain family member 4(ACSL4)in kidney tissue were detected by Western blot.Results The 24 h-UTP in the experimental-M,-H groups,positive control group,model group and blank group were(47.70±3.85),(43.57±6.38),(36.80±6.52),(64.34±13.38)and(7.58±3.71)mg;the relative expression levels of Nrf2 protein were 0.86±0.08,0.75±0.06,0.64±0.08,1.09±0.06 and 0.60±0.07;the relative expression levels of HO-1 protein were 0.77±0.04,0.63±0.07,0.47±0.05,1.04±0.06 and 0.34±0.07;the relative expression levels of ACSL4 protein were 0.62±0.07,0.55±0.07,0.46±0.06,1.08±0.07 and 0.30±0.01,respectively.Compared with the model group,the above indexes in the experimental-M,-H groups and positive control group were significantly different(P＜0.05,P＜0.01).Conclusion Ultra-filtration extract from Angelica Sinensis Radix and Hedysari Radix can improve the damage of kidney tissue in DKD rats,and the mechanism may be related to ferroptosis caused by excessive activation of Nrf2/HO-1 signaling pathway.

Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.

Objective To explore the neuroprotective effect of coenzyme Q10 and its possible mechanism in mice with chronic restraint stress(CRS).Methods Mouse models of CRS were treated with intraperitoneal injections of coenzyme Q10 at low,moderate and high doses(50,100 and 200 mg/kg,respectively,n=8),VX765(a caspase-1 specific inhibitor,50 mg/kg,n=8),or fluoxetine(10 mg/kg,n=8)on a daily basis for 4 weeks,and the changes in depression-like behaviors of the mice were assessed by sugar water preference test,forced swimming test and tail suspension test.The expression of glial fibrillary acidic protein(GFAP)in the hippocampus of the mice was detected using immunohistochemistry,and the number of synaptic spines was determined with Golgi staining.Western blotting was performed to detect the changes in the expressions of GFAP and pyroptosis-related proteins in the hippocampus,and the colocalization of neurons and caspase-1 p10 was examined with immunofluorescence assay.Results Compared with the normal control mice,the mouse models of CRS showed significantly reduced sugar water preference and increased immobility time in forced swimming and tail suspension tests(P<0.05),and these depression-like behaviors were obviously improved by treatment with coenzyme Q10,VX765 or FLX.The mouse models showed a significantly decreased positive rate of GFAP and lowered GFAP protein expression in the hippocampus with obviously decreased synaptic spines,enhanced expressions of GSDMD-N,caspase-1 and IL-1β,and increased colocalization of neurons and caspase-1 p10(all P<0.05).All these changes were significantly ameliorated in the mouse models after treatment with Q10.Conclusion Coenzyme Q10 can alleviate depression-like behaviors in mice with CRS by down-regulating the pyroptosis signaling pathway.

Objective To explore the cost structure and influencing factors of high-multiplication cases.Methods Using medical insurance settlement data from a tertiary hospital in Tianjin from April 2023 to March 2024,this study analyzes the characteristics of high-multiplication DRG cases and compares hospitalization costs between high-multiplication and normal-multi-plication patients.The grey relational analysis method is employed to assess the grey correlation between hospitalization costs and various itemized expenses for both groups.Results Significant differences were found between the high-multiplication group and the normal-multiplication group in terms of gender,age,insurance type,length of stay,base points,and all hospitalization costs except for surgical expenses(P＜0.05).Within the cost structure,drug costs from multiple DRG groups showed the strongest correlation with total hospitalization costs.Treatment costs ranked highest in overall grey correlation.Conclusion Enhancing the management of high-multiplication cases is crucial.Future efforts should focus on improving separate payment policies for high-multiplication and special cases,refining clinical pathways,standardizing medical practices,optimizing performance distribution methods,and strengthening operational management to enhance the fine management of medical insurance.

Constipation is a prevalent ailment which might significantly impact the quality of people's life and rise some associated deseases risks. In this study, a chronic constipation mouse model was established using loperamide hydrochloride. Mice were gavaged an Angelica sinensis Cistanche Fiber Compound, comprised of Dang Gui [Angelica sinensis (Oliv.) Diels], Rou Cong Rong (Cistanche deserticola Y.C.Ma), wheat fiber, and low-molecular-weight xylan at high dosage (3.6 g·kg^-1, 30 times the recommended human dose) and low dosage (0.6 g·kg^-1, 5 times the recommended human dose) for 14 days. The study assessed the therapeutic efficacy of the compound by observing fecal morphology, measuring water content, and conducting small intestine motility experiments. Furthermore, enzyme-linked immunosorbent assays (ELISA) were conducted to evaluate the serum levels of gastrointestinal hormones including motilin (MTL), gastrin (GAS), the inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Histopathological examination with H&E staining was employed to evaluate colonic tissue damage. Additionally, Western blot and immunohistochemistry experiments were conducted to examine the expression levels of aquaporin-3 (AQP3) and c-Kit in the colon. The results indicated that the Angelica sinensis Cistanche Fiber Compound could improve fecal morphology, increase fecal water content, enhance small intestinal transit rates in mice. Additionally, there was a significant elevation in the serum levels of gastrointestinal hormones and a notable reduction in the levels of inflammatory factors. The improvement in colonic histopathological damage was accompanied by a marked decrease in the expression of the colonic water channel protein AQP3 and a significant increase in c-Kit expression. These results collectively suggested the presence of a dose-response relationship. These findings indicate that the Angelica sinensis Cistanche Fiber Compound effectively alleviates constipation in mice. Its action is associated with the regulation of colonic water channel protein AQP3 and c-Kit expression, along with the modulation of serum inflammatory factors and gastrointestinal hormones. This experiment was approved by the Animal Experiment Ethics Committee of Jinan University.