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.

Objective To investigate the clinical efficacy of Bushen Yijing Decoction for the treatment of xerophthalmia of kidney yang deficiency type and to observe its effect on serum Th1/Th17 cytokines.Methods From January 2021 to January 2023,a total of 96 patients with xerophthalmia of kidney yang deficiency type were selected as the study objects.According to the treatment methods,the patients were divided into observation group and control group,with 48 cases in each group.The control group was treated with Sodium Hyaluronate Eye Drops externally,and the observation group was given oral use of Bushen Yijing Decoction together with Sodium Hyaluronate Eye Drops externally.The course of treatment for the two groups covered 21 days.The changes of tear film break-up time(BUT),corneal fluorescein staining(FL)score,SchirmerⅠtest(SIT)value,serum Th1/Th17 cytokines,Ocular Surface Disease Index(OSDI)questionnaire scores,and 25-Item National Eye Institute Visual Function Questionnaire(NEI-VFQ-25)score in the two groups were observed before and after treatment.Moreover,the clinical efficacy and incidence of adverse reactions were compared between the two groups.Results(1)After 21 days of treatment,the total effective rate of the observation group was 95.83%(46/48),and that of the control group was 70.83%(34/48).The intergroup comparison(tested by chi-square test)showed that the clinical efficacy of the observation group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the ocular surface function indicators of BUT and SIT values in the two groups were higher and the FL values were lower than those before treatment(P＜0.05).The increase of BUT and SIT values and the decrease of FL values in the observation group were significantly superior to those in the control group(P＜0.01).(3)After treatment,the levels of serum cytokines of interleukin 17(IL-17),tumor necrosis factor alpha(TNF-α)and interferon gamma(IFN-γ)in the two groups were lower than those before treatment(P＜0.05),and the decrease of serum IL-17,TNF-α and IFN-γ levels in the observation group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the questionnaire scores of OSDI in the two groups were lower and the NEI-VFQ-25 scores were higher than those before treatment(P＜0.05).The decrease of OSDI scores and the increase of NEI-VFQ-25 scores in the observation group were significantly superior to those in the control group(P＜0.01).(5)The incidence of adverse reactions in the observation group was 4.17%(2/48),and that in the control group was 8.33%(4/48).There was no significant difference between the two groups(P＞0.05).Conclusion Bushen Yijing Decoction can enhance the clinical efficacy of xerophthalmia of kidney yang deficiency type,and the decoction is effective on alleviating the eye discomforts,improving the ocular surface function of patients,regulating the levels of Th1/Th17 cytokines,and relieving the inflammatory response without inducing severe adverse reactions while with high safety.

Objective To investigate the effect of catalpol(CAT)on necrotic apoptosis in acute myocardial infarction(AMI)rats.Methods Rat AMI model was constructed by ligating the anterior descending branch of the left coronary artery.Sixty SPF grade SD male rats were randomly grouped into sham surgery group(Sham group),AMI model group(Model group),low-dose CAT group(CAT-L group,30 mg·kg-1 CAT),high-dose CAT group(CAT-H group,60 mg·kg-1 CAT),and high-dose CAT+RIP1 activator recombinant RIP1 group(CAT-H+rRIP1 group,60 mg·kg-1 CAT+8 μg·kg-1 rRIP1),12 in each group.CAT was administered by gavage once a day for a total of 4 weeks.Recombinant RIP1 was administered via tail vein injection and the next day for a total of 4 weeks.Sham group and Model group were given equal amounts of physiological saline by gavage and tail vein injection,respectively.The CAT-L group and CAT-H group were injected with physiological saline via the tail vein the next day while receiving gastric lavage.TUNEL staining was applied to observe the apoptosis of rat cardiomyocytes.Western Blot was applied to detect the expression of RIP1/RIP3/MLKL signaling pathway related proteins in rat myocardial tissue.Results The apoptosis rates of myocardial cells in the sham group,model group,CAT-L group,CAT-H group,and CAT-H+rRIP1 group were(4.23±0.63)％,(33.48±3.94)％,(13.50±1.86)％,and(29.62±3.08)％,respectively;the expression levels of RIP1 protein in myocardial tissue were 0.21±0.02,0.86±0.09,0.43±0.04,and 0.72±0.07,respectively;the expression levels of RIP3 protein were 0.30±0.03,0.94±0.09,0.49±0.05,and 0.83±0.08,respectively;the phosphorylation levels of MLKL protein were 0.35±0.04,1.13±0.11,0.64±0.06,and 0.97±0.10,respectively.The above indexes in Model group were compared with those in Sham group,and those in CAT-H group were compared with those in Model group and CAT-H+rRIP1 group,and the differences were statistically significant(all P＜0.05).Conclusion CAT may inhibit necrotic apoptosis of myocardial cells in AMI rats by down-regulating the RIP1/RIP3/MLKL signaling pathway.

Liposome was used as carrier to carry triptolide and ginsenoside Rg3 in the treatment of pancreatic cancer tumor mice. The effects of liposome on the levels of CD4⁺ and CD8⁺ microenvironmental immune factors of pancreatic cancer tumor were investigated, and the tumor inhibitory effect and safety were evaluated. In this study, Pan02 cells were used to construct a tumor-bearing C57BL/6 mouse model. After 14 days of treatment, the changes in tumor volume and body weight of tumor-bearing mice were observed. The results showed that the high and low doses of liposome had significant therapeutic effect on tumor volume in the model group (P < 0.01), and the tumor inhibition rate of high doses of liposome was significantly increased compared with triptolide group (P < 0.05). Immunohistochemistry showed that compared with the model group, the tumor inhibition rate of liposome was significantly increased. The high-dose liposome group can up-regulate the ratio of immune factor CD4⁺/CD8⁺, inhibit the expression of tumor proliferation factor and promote the expression of tumor apoptosis factor, and has a high safety after pathological hematoxylin and eosin staining of liver, spleen, lung and kidney and serum factor detection. Animal welfare and experimental procedures are in accordance with the regulations of the Experimental Animal Ethics Committee of Henan University of Chinese Medicine (approval No.: DWLL202103173). This study provides a new idea for the exploration of immunotherapy for pancreatic cancer.

Objective:To investigate the clinical effect of Alirocumab in reducing low density lipoprotein cholesterol(LDL-C)in patients with coronary heart disease(CHD)and substandard blood lipids and its effect on atheroscle-rotic plaque.Methods:A total of 127 CHD patients with substandard blood lipids who were treated in Shenzhen Longhua District People's Hospital between September 2017 and March 2021 were selected.According to patients re-ceived Alirocumab therapy or not,they were divided into control group(n=81)and combined group(n=46).The control group remained original statin therapeutic regimen,while combined group received additional PCSK9 inhibi-tor Alirocumab injection based on original statin therapeutic regimen,75mg subcutaneously,once every 2 weeks.Both groups were treated for 3 months,then followed up for 12 months.Levels of total cholesterol(TC)and LDL-C,plaque fiber cap thickness,lipid plaque radian,lipid plaque length and minimum lumen cross-sectional area before and after 12-month follow-up,and incidence of adverse reactions and clinical endpoint events were com-pared between two groups.Results:After 12-month follow-up,compared with control group,combined group had significant lower plasma levels of TC[(3.48±1.04)mmol/L vs.(2.29±0.76)mmol/L],LDL-C[(2.08±0.53)mmol/L vs.(1.27±0.41)mmol/L],lipid plaque radian[(107.22±13.29)° vs.(92.65±11.81)°]and lipid plaque length[(5.45±0.89)mm vs.(4.84±0.82)mm],and significant higher plaque fiber cap thickness[(123.60±14.87)μm vs.(131.46±14.29)μm]and minimum lumen cross-sectional area[(2.51±0.37)mm2 vs.(2.69±0.33)mm2](P＜0.01 all).There was no significant difference in incidence rates of adverse reactions(x2=0.428,P=0.513)and clinical endpoint events(x2=0.253,P=0.615)between two groups.Conclusion:Alirocumab can significantly reduce LDL-C level,increase the plaque fiber cap thickness and lumen cross-section-al area,reduce the internal lipid load of plaque and improve the stability of plaque with good safety in CHD patients with substandard blood lipids.

ObjectiveTo explore the role of structural MRI in the diagnosis of spinocerebellar ataxia type 3 （SCA3） and further evaluate its correlation with disease severity and disease duration. MethodsWe prospectively enrolled 81 genetically diagnosed SCA3 patients ［59 symptomatic （sym-SCA3） and 22 pre-symptomatic （pre-SCA3）］ and 35 age- and sex-matched healthy controls （HCs）. MRI structural images （3D T1 MPRAGE） and clinical data of all subjects were collected. Three observers with different radiological experience measured the width of the superior， middle and inferior cerebellar peduncle （SCP， MCP and ICP）， the anterior-posterior diameters of the pons and spinal cord at the levels of the foramen magnum and upper edge of the 3rd-5th cervical vertebra. One observer performed the measurements again 2 months later to assess for the intra- and inter-observer reliability， respectively. One-way ANOVA， rank-sum test， ROC curve and Random Forest were used to evaluate the diagnostic value of the above metrics for SCA3， and the correlation between the metrics and clinical variables was analyzed. ResultsNot depending on the radiological experience， the metrics based on morphological MRI showed high intra- and inter-observer reliability， among which bilateral superior and middle cerebellar peduncles performed best. The diameters of bilateral SCP， MCP， ICP， pons and spinal cord （except spinal cord at the level of the upper edge of the 5th cervical vertebra） decreased successively in HCs， pre-SCA3 and sym-SCA3 with a statistical difference （P<0.017）. ROC analysis revealed that the left MCP had the highest diagnostic value for pre-SCA3 （AUC=0.911）， with sensitivity， specificity and a cut-off value of 85.7%， 95.5% and 10.15 mm， respectively. In contrast， the right SCP had the highest diagnostic value for sym-SCA3 （AUC=0.999）， with sensitivity， specificity and a cut-off value of 100%， 98.3% and 2.62 mm， respectively. The Random Forest model based on the above metrics also had high diagnostic efficiency （AUC= 0.970， specificity=93.1%）， and the left MCP contributed the most. Correlation analysis showed that the above metrics had a significantly or moderately negative correlation with the Scale for the Assessment and Rating of Ataxia （SARA） and disease duration （P<0.05）. ConclusionNot depending on radiological experience， measurements of brain structure based on morphological MRI are reliable， which can help diagnose SCA3 and predict disease severity and duration. The left MCP and the right SCP perform best for predicting pre-SCA3 and sym-SCA3， respectively. Therefore， the structural MRI is recommended for assisting the clinical diagnosis of SCA3.

Sirolimus self-microemulsion-mesoporous silicon sustained release tablets were prepared in order to improve the dissolution of the insoluble drug sirolimus and reduce its side effects. Firstly, sirolimus self-microemulsion was prepared and cured with mesoporous silicon. Secondly, the suitable excipients were selected according to the appearance, hardness and in vitro release rate. The sustained-release tablets with hydroxypropyl methylcellulose (HPMC) as skeleton material were prepared by powder direct pressing method, and the formulation was optimized by central composite design-response surface method to investigate the drug release in vitro. Finally, the pharmacokinetics was carried out in beagle dogs using the commercial sirolimus tablets as references. The final formulation of sustained-release tablets is as follows: 162 mg of sirolimus self-microemulsion-mesoporous silica (1∶1, w/w), 80 mg of HPMC K4M and 80 mg of carboxymethyl starch sodium, the microcrystalline cellulose is 168 mg. The results of in vitro release test showed that the self-made sustained-release tablets released slowly within 12 h, which conformed to the Ritger-Peppas model. The in vivo test results showed that compared with the commercial sirolimus tablets, the C_max of the sustained-release tablets decreased by 49.47%, the T_max of the sustained-release tablets was prolonged by 5.1 times, and the relative bioavailability was 105.81%. Sirolimus self-microemulsion-mesoporous silicon sustained-release tablets have good sustained-release effects in vitro and in vivo, which provides a reference for the solubilization of other insoluble drugs and the research and development of sustained-release preparations. Animal experiments and welfare processes were reviewed and approved by the Animal Ethics Committee of the 900TH Hospital of the Joint Logistics support Force.

Objective:To construct an evaluation index system for the core competence of nurses in intra-hospital transportation of critically ill patients, providing reference for evaluating and cultivating the intra-hospital transportation ability of clinical nurses.Methods:A preliminary evaluation index system for the core competence of nurses in intra-hospital transportation of critically ill patients was established through literature analysis, semi-structured interviews, and research group meetings. From December 2022 to January 2023, the questionnaire consultation was conducted with 18 experts using the Delphi method. Analytic hierarchy process was used to determine the weights of indicators at all levels.Results:A total of two rounds of expert consultation were conducted, and the effective response rate of the questionnaire was 100.00%. The expert authority coefficient was 0.887, and the Kendall harmony coefficient of indicators at all levels in the second round was 0.056 to 0.281. The final evaluation index system for the core competence of nurses in intra-hospital transportation of critically ill patients included three first-level indicators, 14 second-level indicators, and 57 third-level indicators.Conclusions:The evaluation index system for the core competence of nurses in intra-hospital transportation of critically ill patients constructed is scientific and reliable, and can provide reference for evaluating and cultivating the intra-hospital transportation ability of clinical nurses.

Abstract: Objective　To analyze the epidemic characteristics of soil-transmitted helminth (STH) by the spatial epidemiological method in Jiangxi Province. Methods　Surveillance data of STH in Jiangxi Province from 2016 to 2019 were collected for descriptive epidemiological analysis. The space-time permutation distribution of STH infection areas was analyzed with spatial autocorrelation, hotspot analysis methods and retrospective space-time permutation scan statistics. Results　The infection rates of STH were 1.32% (947/71 766), 1.14% (803/70 547), 0.87% (604/69 507) and 0.90% (628/69 620), respectively, and the differences were statistically significant in different years (P<0.01). The rates of hookworm infection were 0.65% (466/71 766), 0.64% (450/70 547), 0.48% (336/69 507) and 0.52% (362/69 620), respectively, and the differences were statistically significant (P<0.01). The infection rates of Ascaris lumbricoides were 0.55% (393/71 766), 0.41% (287/70 547), 0.32% (221/69 507) and 0.32% (225/69 620), respectively, and the differences were statistically significant in different years (P<0.01). The infection rates of Trichuris trichiura were 0.17% (125/71 766), 0.10% (74/70 547), 0.08% (57/69 507) and 0.07% (49/69 620), respectively, and the differences were statistically significant among different years (P<0.01). The results of global spatial autocorrelation analysis showed that there was a spatial autocorrelation index Moran's I value of hookworm infection rate in 2016, Trichuris trichiura infection rate in 2016, 2018 and 2019, with statistical significance (P<0.05). The results of hotspot analysis, SaTScan and FleXScan spatial and temporal scanning analysis showed that there were high-value aggregation regions for each species in each year. Conclusion　The infection rates of STH, hookworm, Ascaris lumbricoides and Trichuris trichiura showed a decreasing trend and space-time clustering from 2016 to 2019. It should be taken into account in the formulation of control strategies.

Malignant tumors are currently seriously endangering human health and life， which has become one of the main causes of death in China. In modern Western medicine， they are mainly tackled by surgery， chemotherapy， and radiotherapy， but the death toll continues to rise year by year. At present， most of the anti-tumor chemotherapeutics used in clinical practice have toxic and side effects， affecting the anti-tumor efficacy and the conditions after treatment. Long-term medication will also induce drug resistance， making the good anti-tumor effect difficult to be achieved. With the vigorous development of traditional Chinese medicine （TCM）， it has played a crucial role in the fight against tumors. It is believed in TCM that "heat toxin" is one of the important causes of tumors. Therefore， the methods of clearing away heat and removing toxin are often emphasized in the treatment of tumors， and the resulting outcomes are satisfactory. There are many Chinese herbs and Chinese herbal compounds classified into the heat-clearing and toxin-removing type. Xihuangwan， a classic heat-clearing prescription， is composed of Calculus Bovis， Moschus， Olibanum， and Myrrh and has the effects of clearing away heat， removing toxin， eliminating edema， and dissipating mass， which is mainly used to treat carbuncle， pustule， scrofula， multiple abscess， and cancer caused by heat-toxin obstruction. In modern clinical practice， it has been employed in patients with lung cancer， breast cancer， gastric cancer， liver cancer， colorectal cancer， and other malignant tumors， especially during the advanced stage， as a routine or adjuvant treatment for alleviating their clinical symptoms and improving their quality of life. The main active components of Xihuangwan are pentacyclic triterpenoids （such as masticinic acids）， volatile oils， steroids （like porcine deoxycholic acid）， and bilirubin， which have been proved effective in anti-tumor. This paper reviewed the prescription source， pharmaceutical research， clinical anti-tumor research， and pharmacological mechanisms of Xihuangwan， which has provided reference for further expanding the anti-tumor applications of Xihuangwan and enhancing its secondary development.