Objective To design and synthesize derivatives of oleanolic acid and ursolic acid, and investigate their anti-hepatitis C virus （HCV） activity along with that of common triterpenoid acids. To explore the structure-activity relationship and provide a reference for the research of anti-HCV drugs derived from natural products through obtaining compounds with higher activity. Methods Oleanolic acid and ursolic acid were directly reacted with corresponding amines using PyBOP as a condensing agent in the presence of DIEA. Alternatively, the target compounds were prepared through PCC oxidation followed by the Baeyer-Villiger reaction catalyzed by m-CPBA. In vitro anti-HCV activity was tested using the HCVcc infection model. Molecular docking was performed by Autodock software to investigate the interaction between the active compounds and HCV NS5B. Results Oleanolic acid, glycyrrhetinic acid, ursolic acid, and asiatic acid all exhibited certain anti-HCV effects. Specifically, oleanolic acid derivatives OA2-OA4, OA6, and OA7, as well as ursolic acid derivatives UA1 and UA2, demonstrated superior anti-HCV activity compared to their parent compounds. Preliminary structure-activity relationship analysis revealed that introducing a bulky group to 28-COOH of oleanolic acid and ursolic acid enhanced their activity. Molecular docking results demonstrated that the active compounds could stably bind to HCV NS5B, thereby exhibiting antiviral activity. Conclusion Pentacyclic triterpenoids possessed anti-HCV effects, and their derivatives coud be synthesized to obtain more active compounds. The anti-HCV mechanism of these compounds may be associated with their inhibition of NS5B.

Objective: To investigate the association between subthreshold depression, psychotic like experiences (PLEs), and their interactions with non suicidal self injury (NSSI) in adolescents from Shandong, so as to provide a reference for the prevention and early intervention of NSSI in adolescents. Methods: A random cluster sampling method was used to select a total of 6 090 adolescents aged 13-22 from two cities along the coast and inland of Shandong Province. Electronic surveys were administered using the SelfInjurious Behavior Questionnaire, Community Assessment of Psychic Experiencepositive 8 items(CAPE-P8), and the Center for Epidemiological Studies Depression Scale(CES-D). The relationship between subthreshold depression, PLEs, and their interaction with NSSI was analyzed using multivariate Logistic regression. Results: The detection rate of NSSI among adolescents was 21.3%. The highest NSSI reporting rate (27.9%) was found in the age group of 13-15 years.The NSSI reporting rates for those detected with subthreshold depression and PLEs were 49.9% and 30.7%, respectively. Multivariate analysis indicated that individuals with subthreshold depression were 3.47 times more likely to engage in NSSI [OR(95%CI)=3.47(2.68-4.50)]. Those identified with PLEs had 5.32 times higher risk of engaging in NSSI than those without such experiences [OR(95%CI)=5.32(4.10-6.89)]. When both subthreshold depression and PLEs coexist, the risk of engaging in NSSI was 18.47 times higher than in individuals with neither condition [OR(95%CI)=18.47(14.75-23.13)] (P<0.01). The relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were 11.44, 0.61, and 2.89, respectively, indicating that the combined interaction of subthreshold depression and PLEs accounted for 61% of adolescent NSSI. Conclusions Subthreshold depression and psychoticlike experiences are associated NSSI in adolescents and exhibit an additive interaction. Alleviating subthreshold depression in adolescents and reducing psychotic experiences may play a positive role in preventing the occurrence of NSSI.

Objective To explore the impact of severe weather on road traffic injuries (RTIs). Methods Relevant literature on the impact of meteorology on the occurrence and resulting casualties of road traffic injuries was searched. Meta-analysis was performed on the included literature using state16.0 software. Results A total of 28 articles were included. The results of meta-analysis showed that heat wave, cloudy day, snowy day, rainy day and other severe weather such as storm had a statistically significant impact on the occurrence of road traffic injuries. Severe weather such as storms had a statistically significant impact on RTIs casualties. Conclusion Heat wave, cloudy day, snowy day, rainy day, storm and other bad weather are independent risk factors for the occurrence of RTIs. Storm is a risk factor for accident casualties. There is not enough evidence to show that low temperature, cold wave and heavy fog are the influencing factors of road traffic accidents.

By sorting out the differences and connections between family doctor teams and specialized disease teams, role competency and mutual collaboration, and introducing the learning health system (LHS) mechanism, a comprehensive operating system for community general practice learning organizations based on LHS was constructed, focusing on five single disease types. The system includes a combination of general and specialized medicine that links three levels of medical institutions, thereby opening up the business cooperation process between professionals in different institutions, and establishing a sustainable collaboration mechanism. This allows medical institutions at three levels to continuously tap the potential of their disciplines, achieve their own ability growth and feel higher work value, and also bring better health solutions to residents, guided by the common goal of "health centered, patient centered".

OBJECTIVE To establish a GC-MS/MS analytical method for the determination of 1-chloroethyl cyclohexyl carbonate in candesartan cilexetil tablets. METHODS The analytical column was DB-5MS(30 m×0.25 mm, 0.25 μm). The column temperature was maintained at 80 ℃, then was raised to 300 ℃ at the rate of 20 ℃·min–1 and was maintained for 5 min. Helium was used as carrier gas, and its flow rate was 1.0 mL·min–1. The detection was achieved in multiple reaction monitoring mode. RESULTS The calibration curve of 1-chloroethyl cyclohexyl carbonate had good linearity in the concentration range of 4.4−437.8 ng·mL–1. The limits of quantification and detection were 4.4 and 2.2 ng·mL–1, respectively. The average recovery was 95.6%(RSD=6.3%, n=9). CONCLUSION This method has satisfactory convenience, good sensitivity and high accuracy, and it is suitable for the determination of 1-chloroethyl cyclohexyl carbonate in candesartan cilexetil tablets.

Objective This study was to develop a"Spleen Deficiency Certificate Scale for County Residents"and test its reliability.It was then developed as an objective tool for Chinese medicine evidence and symptoms for the prevention and control of chronic diseases among county residents.Methods The scale was compiled based on the team's previous foundation.The reliability of the scale was evaluated using internal consistency reliability and split-half reliability,while its validity was evaluated using structural validity,content validity,calibration validity,and discriminant validity.Results The study included 213 adults from Lanxi,of whom 155 were tested for intestinal flora.Seven scale entries were identified:Fatigue,fear of cold,bland mouth,loss of appetite,diarrhea,weak bowel movements,and tooth-marked tongue.In the reliability test,Cronbach's alpha coefficient was 0.828 and McDonald's ω coefficient was 0.825.The"stomach pain"and"bloating"entries did not meet the inclusion requirements and were recommended to be deleted.The Spearman-Brown coefficient was 0.839.The exploratory factor analysis of the two common factors explained 61.6%of the cumulative variance.The calibration validity indicated that the ratio of salivary amylase activity before and after acid stimulation was 0.826±0.253 in the group with spleen deficiency.Significant differences(P<0.05)in the genera Dialister,Shigella,Leuconostoc,Photobacterium,Trabulsiella,and Parvimonas between the spleen deficiency group and the non-spleen deficiency group.Conclusion The Spleen Deficiency Scale for County Residents demonstrates good reliability and validity.

ObjectiveTo investigate the current situation of rehabilitation therapists' work, and analyze the factors related to their career development and transformation. MethodsFrom September, 2022 to January, 2023, 153 rehabilitation therapists in Weifang were investigated with a cross-sectional questionnaire, using general questionnaire, Job Satisfaction Scale for Grassroots Health Technicians, Social Responsibility Scale, Job Role and Identity Inventory, and Employee Turnover Scale. ResultsThe majority of rehabilitation therapists interviewed were male (52.28%), under 35 years old (88.24%), with a bachelor's degree (77.78%), income less than 5 000 yuan a month (46.40%), and less than five years of service (48.36%). The work time was (7.78±0.84) hours a day, (5.39±0.51) days a week. The favorable rate of the physical environment of work was 67.32%, and the favorable rate of the interpersonal relationship environment of work was 80.39%. The score of professional identity was (3.61±0.84), the score of job satisfaction was (3.62±0.97), the score of social responsibility was (3.53±0.79), and the score of turnover was (2.39±1.10). Education level, job satisfaction, and social responsibility were the main factors related to the employee turnover (P < 0.05). ConclusionThe overall educational level of rehabilitation therapists is relatively low, and the human resource structure needs to be optimized. There is a significant difference between academic education and continuing education, and career development needs to be improved. The main factors related to career development and transformation are education level, job satisfaction, and social responsibility.

OBJECTIVE: Current clinical evidence on the effects of home blood pressure telemonitoring (HBPT) on improving blood pressure control comes entirely from developed countries. Thus, we performed this randomized controlled trial to evaluate whether HBPT plus support (patient education and clinician remote hypertension management) improves blood pressure control more than usual care (UC) in the Chinese population. METHODS: This single-center, randomized controlled study was conducted in Beijing, China. Patients aged 30-75 years were eligible for enrolment if they had blood pressure [systolic (SBP) ≥ 140 mmHg and/or diastolic (DBP) ≥ 90 mmHg; or SBP ≥ 130 mmHg and/or DBP ≥ 80 mmHg with diabetes]. We recruited 190 patients randomized to either the HBPT or the UC groups for 12 weeks. The primary endpoints were blood pressure reduction and the proportion of patients achieving the target blood pressure. RESULTS: Totally, 172 patients completed the study, the HBPT plus support group ( n = 84), and the UC group ( n = 88). Patients in the plus support group showed a greater reduction in mean ambulatory blood pressure than those in the UC group. The plus support group had a significantly higher proportion of patients who achieved the target blood pressure and maintained a dipper blood pressure pattern at the 12th week of follow-up. Additionally, the patients in the plus support group showed lower blood pressure variability and higher drug adherence than those in the UC group. CONCLUSION HBPT plus additional support results in greater blood pressure reduction, better blood pressure control, a higher proportion of dipper blood pressure patterns, lower blood pressure variability, and higher drug adherence than UC. The development of telemedicine may be the cornerstone of hypertension management in primary care.
Humans ; Blood Pressure ; Blood Pressure Monitoring, Ambulatory ; Hypertension/therapy* ; Telemedicine/methods* ; Hypotension

ObjectiveTo observe the effect of Qinggan Jianpi Huoxue prescription（QGJPHXP） on the polarization of M1/M2 macrophages in rats with hepatic fibrosis induced by carbon tetrachloride（CCl₄）. MethodA rat hepatic fibrosis model was established by intraperitoneal injection of 40% CCl₄-olive oil suspension twice a week at the dosage of 2.0 mL·kg^-1 for 8 weeks. After the model was successfully established， these rats were randomly divided into the model group， QGJPHXP group（32.084 g·kg^-1） and Biejiajian pills（BJJP） group（0.925 5 g·kg^-1）， with 12 rats in each group. The blank group was injected intraperitoneally with the same amount of olive oil. The rats in the administration groups were given the corresponding solution according to the dose， and the blank and model groups were given the same dose of purified water， once a day. After 4 weeks of continuous administration， the liver tissues of rats were taken and stained with hematoxylin-eosin（HE） and Masson to observe the pathological changes. The serums were collected to detect the alanine aminotransferase（ALT） and aspartate aminotransferase（AST） levels. Interleukin（IL）-6， IL-12， IL-10， IL-1β， transforming growth factor-β₁（TGF-β₁） and tumor necrosis factor-α（TNF-α） levels in liver tissues were measured by enzyme-linked immunosorbent assay（ELISA）. The expression levels of CD86 and CD206 were detected by immunohistochemistry（IHC）. Western blot and real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） were used to detect the protein and mRNA expression levels of inducible nitric oxide synthase（iNOS）， arginase-1（Arg-1）， phosphorylated p38 mitogen-activated protein kinase（p-p38 MAPK）， nuclear transcription factor-κB p65（NF-κB p65） in liver tissues of rats. ResultCompared with the blank group， the hepatic cell plate was irregularly arranged, and local inflammatory cell infiltration and fibrous hyperplasia were observed， while the serum levels of ALT and AST were significantly increased in the model group（P<0.01）， and IL-1β， IL-6， IL-12， TGF-β₁， TNF-α， CD86， CD206， iNOS， p-p38 MAPK，p38 MAPK and NF-κB p65 levels in liver tissues were obviously increased（P<0.05， P<0.01）， while the levels of IL-10 and Arg-1 were obviously decreased（P<0.05， P<0.01）. Compared with the model group， QGJPHXP group reduced the degree of liver cell fibrosis，and serum levels of ALT and AST（P<0.01）， and IL-1β， IL-6， IL-12， TGF-β₁， TNF-α， CD86， iNOS， p-p38 MAPK， p38 MAPK， and NF-κB p65 levels in liver tissues were obviously decreased（P<0.05， P<0.01）， the levels of IL-10， CD206 and Arg-1 were obviously increased in the QGJPHXP group（P<0.05， P<0.01）. ConclusionQGJPHXP has ability to inhibit the activation of pro-inflammatory M1 macrophages， induce the secretion of anti-inflammatory cytokines by M2 macrophages， reduce the release of pro-fibrogenic cytokines， and promote the macrophage polarization of M1 to M2 in liver for tissue repair， thereby serving as an anti-inflammatory and anti-hepatic fibrosis drug.

Objective    To provide experimental data and theoretical support for further studying the maturity of cardiac patches in other in vitro experiments and the safety in other in vivo animal experiments, through standard chemically defined and small molecule-based induction protocol (CDM3) for promoting the differentiation of human induced pluripotent stem cells (hiPSCs) into myocardium, and preliminarily preparing cardiac patches. Methods    After resuscitation, culture and identification of hiPSCs, they were inoculated on the matrigel-coated polycaprolactone (PCL). After 24 hours, the cell growth was observed by DAPI fluorescence under a fluorescence microscope, and the stemness of hiPSCs was identified by OCT4 fluorescence. After fixation, electron microscope scanning was performed to observe the cell morphology on the surface of the patch. On the 1st, 3rd, 5th, and 7th days of culture, the cell viability was determined by CCK-8 method, and the growth curve was drawn to observe the cell growth and proliferation. After co-cultured with matrigel-coated PCL for 24 hours, hiPSCs were divided into a control group and a CDM3 group, and continued to culture for 6 days. On the 8th day, the cell growth was observed by DAPI fluorescence under a fluorescence microscope, and hiPSCs stemness was identified by OCT4 fluorescence, and cTnT and α-actin for cardiomyocyte marker identification. Results    Immunofluorescence of hiPSCs co-cultured with matrigel-coated PCL for 24 hours showed that OCT4 emitted green fluorescence, and hiPSCs remained stemness on matrigel-coated PCL scaffolds. DAPI emitted blue fluorescence: cells grew clonally with uniform cell morphology. Scanning electron microscope showed that hiPSCs adhered and grew on matrigel-coated PCL, the cell outline was clearly visible, and the morphology was normal. The cell viability assay by CCK-8 method showed that hiPSCs proliferated and grew on PCL scaffolds coated with matrigel. After 6 days of culture in the control group and the CDM3 group, immunofluorescence showed that the hiPSCs in the control group highly expressed the stem cell stemness marker OCT4, but did not express the cardiac markers cTnT and α-actin. The CDM3 group obviously expressed the cardiac markers cTnT and α-actin, but did not express the stem cell stemness marker OCT4. Conclusion    hiPSCs can proliferate and grow on matrigel-coated PCL. Under the influence of CDM3, hiPSCs can be differentiated into cardiomyocyte-like cells, and the preliminary preparation of cardiac patch can provide a better treatment method for further clinical treatment of cardiac infarction.