BACKGROUND:Ursolic acid can promote the directed differentiation of bone marrow mesenchymal stem cells into osteoblasts.However,there are few reports on whether ursolic acid has osteogenic effect on human periodontal ligament stem cells. OBJECTIVE:To investigate the effect of ursolic acid on proliferation and osteogenic differentiation of human periodontal ligament stem cells. METHODS:The human periodontal ligament stem cells were isolated and cultured.Passage 3 cells were selected and treated with ordinary medium containing different concentrations(0,1,2,4,6,8 μmol/L)of ursolic acid.After intervention for 1,3,5,7 days,the cell proliferation was detected by CCK-8 assay and the appropriate intervention concentration was screened.Passage 3 human periodontal ligament stem cells were treated with osteogenic induction solution containing 0,1,2,4 μmol/L ursolic acid,respectively.After 7 days of intervention,the mRNA expressions of alkaline phosphatase,Runx2,and osteocalcin were detected by qRT-PCR.After 14 days of intervention,the formation of mineralized nodules was observed by alizarin red staining.Passage 3 human periodontal ligament stem cells were taken and the control group was added with osteogenic induction solution;the ursolic acid group and the antagonist group were added with osteogenic induction solution containing ursolic acid(2 μmol/L)and the bone morphogenetic protein signaling pathway antagonist Noggin,respectively.The ursolic acid+antagonist group was added with osteogenic induction solution containing ursolic acid(2 μmol/L)and Noggin,the inhibitor of bone morphogenetic protein signaling pathway,and cultured for 7 days.qRT-PCR and western blot assay were used to detect the mRNA and protein expressions of bone morphogenetic protein 2,Smad1,osteopontin,and Runx2. RESULTS AND CONCLUSION:(1)1,2,4 μmol/L ursolic acid could promote the proliferation of human periodontal ligament stem cells.6,8 μmol/L ursolic acid could inhibit the proliferation of human periodontal ligament stem cells,and 1,2,4 μmol/L ursolic acid was selected to intervene in subsequent experiments.(2)Compared with 0 μmol/L,1,2,4 μmol/L ursolic acid could promote the expression of alkaline phosphatase,Runx2,and osteocalcin mRNA and the formation of mineralized nodules(P<0.05),and the effect of 2 μmol/L ursolic acid was the most significant.(3)Compared with the control group,the mRNA and protein expressions of bone morphogenetic protein 2,Smad1,osteopontin,and Runx2 in the ursolic acid group were increased(P<0.05),while mRNA and protein expressions of the above indexes were decreased in the antagonist group(P<0.05).Compared with the ursolic acid group,mRNA and protein expressions of above indexes were decreased in ursolic acid+antagonist group(P<0.05).(4)The results indicate that ursolic acid promotes osteogenic differentiation of human periodontal ligament stem cells through bone morphogenetic protein signaling pathway.

OBJECTIVE To predict the in vivo bioequivalence of lenvatinib mesilate capsules and reference preparation by using the parallel artificial membrane permeability analysis. METHODS Based on the biopharmaceutics classification system classification of lenvatinib mesilate and the parallel artificial membrane permeation model, the in vitro dissolution permeation rate test model of lenvatinib mesilate capsules was established, through real-time monitoring of the dissolution and penetration of lenvartinib mesylate capsules and reference preparations in fasting gastric juice, intestinal fluid and postprandial intestinal fluid, the flux and total penetration of drugs through the membrane were calculated. RESULTS In fasting state and fed state, the 90% confidence interval of geometric mean ratio of two key quality parameters (permeation flux and permeation amount) of the preparation A all were in the range of 80.00%−125.00%, the preparation B did not fall into this interval. CONCLUSION This research method can predict the bioequivalence of renvartinib mesylate capsule and reference preparation, and has a certain correlation in vivo and in vitro.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To prepare seven standard strains of 2019 novel coronavirus (2019-nCoV), including wild type (WT) strain, Beta variant, Delta variant, Omicron variants (BA.2, BA.5, BQ.1, XBB.1 branches), which could be used to apply for national standard strains.Methods:According to cytopathic effect (CPE), virus titer, whole-virus-genome-sequencing and detection of mycoplasma, the basic biological characteristics of clonal isolation were determined through plaque purification technology.Results:The CPE was mainly characterized by cell shrinkage and exfoliation in Vero cells after infection with seven 2019-nCoV clonal isolations (WT, Beta, Delta, Omicron, BA.2, BA.5, BQ.1 and XBB.1 branches). The result of mycoplasma detection were negative and titers of the clonal isolation from 2nd to 5th generations were stable at 10 5-10 8 TCID 50/ml; the electron microscope showed that the virions were all round or elliptical, with a diameter between 60 nm and 140 nm. The subtypes of 7 strains were identified by whole-virus-genome-sequencing and phylogenetic analysis, with genomic stability after the fifth successive generations of clonal isolation. Conclusions:The series clonal isolation of 2019-nCoV with typical CPE of coronavirus, clear morphological structure, good viral activity and stable genetic characteristics were prepared, and they could be used to apply for national standard strains.

Objective To investigate the application value of amlodipine atorvastatin calcium tablet(AACT)combined with evidence-based emotional nursing mode(EENM)in elderly patients with hypertension complicated by coronary heart disease(HTN-CHD).Methods HTN-CHD patients admitted to the department of cardiology of The Second Affiliated Hospital of Wenzhou Medical University from June 2021 to June 2023 were selected retrospectively as study subjects.According to the intervention methods,the HTN-CHD patients were divided into the AACT group and the EENM group.Patients in the AACT group were given AACT combined with the usual care intervention,and the EENM group was given EENM on the basis of the AACT group.The changes of psychological status(SDS,SAS,and SPBS),adherence(medication compliance,daily exercise behavior,poor management behavior,and dietary management behavior)and blood pressure[(systolic blood pressure,SBP)and diastolic blood pressure(DBP)]were compared between two groups.The incidence of cardiovascular events in the two groups at 6 months was observed and compared.Results A total of 118 HTN-CHD patients(55 in AACT group and 63 in EENM group)were included in this study.Before the intervention,there was no significant statistical difference in the SDS,SAS,SPBS,medication compliance,daily exercise,poor management,diet management scores,SBP and DBP between AACT and EENM groups(P＞0.05).After the intervention,SDS,SAS,SPBP scores,SBP and DBP of the HTN-CHD patients significantly decreased in both AACT and EENM groups compared with before(P＜0.05).However,the medication compliance behavior score,daily exercise behavior score,bad management behavior score and diet management behavior score increased significantly compared with before(P＜0.05);SDS,SAS,SPBS scores,SBP and DBP of the patients in EENM group decreased more than those in the AACT group(P＜0.05),however,the increase of medication compliance,daily exercise,poor management and diet management behavior scores of the EENM group was higher than that in the AACT group(P＜0.05).Furthermore,the incidence of cardiovascular events was lower in the EENM group than in the AACT group(P＜0.05).Conclusion EENM combined with AACT intervention is beneficial to improve the compliance with HTN-CHD patients,improve the psychological status and blood pressure values,and reduce the incidence of cardiovascular events.

Objective To investigate the clinical effect of ultrasound induction combined with acupunc-ture points and polyethylene glycol 4000 powder for treating constipation in elderly patients with hip fracture. Methods A randomized parallel controlled method was adopted.A total of 100 inpatients meeting the inclu-sion criteria were divided into the control group and treatment group.Fifty cases in the control group were given polyethylene glycol 4000 powder,10 g/d,taking at a draught in 1 h after lunch.Fifty cases in the treat-ment group adopted the ultrasound induction combined with Shenque acupoint and Guanyuan acupoint,which was implemented at 1 h after lunch every day,once a day,30 min each time,and the intensity was appropriate for the patients to tolerate.The two groups were continuously treated for 1 week.The clinical symptoms be-fore and after treatment in the two groups were observed.The constipation score,quality of life score,treat-ment efficacy and safety were compared between before and after treatment.Results There were 3 dropout cases in the control group and 47 cases were finally included.Among them,14 cases were excellently effective,20 cases were effective,13 cases were ineffective,and the total effective rate was 72.34％;there were 2 dropout cases in the treatment group and 48 cases were finally included.Among them,15 cases were excellently effec-tive,18 cases were effective,15 cases were ineffective,and the total effective rate was 68.75％;the total effec-tive rate had no statistical difference between the two groups (P>0.05).The effect onset time of the treat-ment group was earlier than that of the control group with statistical difference (P<0.05).The abdominal symptom dimension and total score in the constipation scores after treatment in the treatment group were lower than those in the control group,and the differences were statistically significant (P<0.05).After treat-ment,the physiological,satisfaction dimension scores and total score in life quality score in the treatment group were lower than those in the control group,and the differences were statistically significant (P<0.05). During the test process,2 cases in the control group had adverse drug reactions,which manifested by mild di-arrhea at the end of the treatment course,and no adverse reactions were found in the treatment group.Conclu-sion The ultrasound induction combined with acupuncture points for treating constipation in elderly patients with hip fracture has equivalence with polyethylene glycol 4000 powder,moreover which has the advantages in the aspects of effect onset time and improvement of abdominal symptoms.

Objective To review the research on the application of clinical decision support system(CDSS)involving nurses in depression both domestically and internationally.Methods 10 Chinese and English databases including PubMed,Web of Science,Scopus,CINAHL,PsycINFO,Embase,Cochrane Library,CNKI,Wanfang Database,and VIP were searched until March,2024.The eligible literature of the application of CDSS involving nurses in depression was selected to analyze the basic characteristics of studies,the functions,characteristics,feasibility,and effectiveness of CDSS.Results Finally,16 English articles involving 13 CDSS were included.This study found that nurses participating in CDSS can improve the degree of depression in patients,but its application in depression management is mainly for screening,and few CDSS can propose personalized depression management programs based on the psychological and social factors of patients.Conclusion The CDSS involving nurses can promote the screening of depression and improve depression in patients,but it fails to propose a personalized depression management program.Future research can develop CDSS based on electronic medical record systems to facilitate nurses'screening for depression and further develop an intelligent management module for CDSS to provide intelligent and personalized management solutions for patients with depression.

Objective:To investigate the application and effectiveness of slit-lamp microscope demonstration combined with supervisory clinical teaching in ophthalmology training for general practice residents.Methods:Sixty general practice residents who underwent ophthalmology training in Fifth Affiliated Hospital of Sun Yat-sen University from March 2021 to March 2023 were randomly assigned to 2 groups. In the traditional teaching group ( n=29), the teaching was primarily led by the instructors, and trainees observed and recorded the clinical findings under their guidance; while in the combined teaching group ( n=31), the trainees received integrated slit-lamp microscope demonstration and supervisory outpatient teaching. Both groups underwent a unified exit examination after the training, with the scores based on knowledge, diagnostic skills, comprehensive evaluation and overall performance. Additionally, satisfaction with the teaching process was assessed through questionnaires completed by both trainees and instructors. Results:There were no significant differences in gender composition, age and initial exam scores between the two groups (all P>0.05). Upon completion of the training, the combined teaching group scored higher in ophthalmology knowledge, outpatient diagnostic skills, and overall performance compared to the traditional teaching group (all P<0.05). Satisfaction scores from both trainees and instructors were also higher in the combined teaching group compared to the traditional teaching group (all P<0.05). Conclusion:The use of slit-lamp microscope demonstration combined with supervisory outpatient teaching can significantly enhance the effectiveness of ophthalmology training for general practice residents.

Objective:To explore the clinical characteristics and genetics of a Chinese patient with Gitelman syndrome (GS) and improve the awareness and diagnosis of GS among clinicians.Methods:Retrospectively analyzed the GS patient's clinical feature, laboratory examination, diagnosis, treatment and literature review admitted to Hebei General Hospital in September 2022.Results:A twelve-year-old boy was admitted to our department due to weakness of lower limbs. Laboratory tests after admission showed hypokalemia, hypomagnesemia, hypocalcemia and metabolic alkalosis. Genetic testing showed tow compound heterozygous mutations in the SLC12A3 gene (c.1456G>A and c.634G>A), which ultimately diagnosed as GS. The patient is on the mend and allowed to leave the hospital after treated by potassium supplement.Conclusion:The rate of leak diagnosis is high. Genetic testing should be undergo earlier if the patients suspected GS.

Objective : To investigate the cross⁃sectional associations of serum interleukin( IL) Ⅳ18 with cartilage volume , cartilage defects , bone marrow lesions ( BML) and biomarkers of cartilage degradation in patients with knee osteoarthritis (OA) , and to provide new ideas and new methods for clinical diagnosis and treatment. Methods: The study included 151 patients with knee OA , a general questionnaire survey was conducted , and the knee strucral was photographed by magnetic resonance imaging (MRI) . The cartilage volume was measured by OsiriX software in 3D⁃FLASH sequence , and cartilage defect and BML were determined in T2⁃weighted sequence. Serum IL-18 and matrix metalloproteinase ( MMP) Ⅳ3 , 13 levels were measured by enzyme⁃linked immunosorbent assay(ELISA) . SPSS software was used for statistical analysis. Results : In multivariable analyses , serum IL⁃18 level was consistent at divided part of joint (femorotibial joint and the patella femoral joint , all P < 0. 05) . Serum IL⁃18 level was positively associated with cartilage defect and BML at media femorotibial area (all P < 0. 01) . Serum IL⁃18 level was positively associated with MMP⁃3 (β = 0. 31 , 95% CI:0. 001 - 0. 010) and MMP⁃13 (β = 0. 86 , 95% CI:0. 08 - 0. 10 , all P < 0. 01) . CI:0. 08 - 0. 10 , all P < 0. 01) . Conclusion Serum IL⁃18 level is negatively associated with cartilage volume and Serum IL⁃18 level is negatively associated with cartilage volume and positively associated with cartilage defect , BML , MMP⁃3 and MMP⁃13 , suggesting IL⁃18 may play a significant role duce the injury of article cartilage in patients with knee OA and delay the progression of disease.