1.Synthesis and in vitro antiviral effects against hepatitis C virus of oleanolic acid and ursolic acid derivatives
Shuwen XIAO ; Heyang ZHOU ; Yongsheng JIN ; Liming QIAO ; Wei ZHENG
Journal of Pharmaceutical Practice and Service 2025;43(10):503-508
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.
2.Standardized Use of the Anti-tumor Drug in 60 Beijing Hospitals in 2024
Juan YANG ; Chengcheng ZHOU ; Jincheng YANG ; Liming SHI ; Sufei ZHENG ; Wenjing YANG
Chinese Hospital Management 2025;45(6):44-48
Objective To investigate the standardized use of anti-tumor drugs in Beijing hospitals in 2024,and put forward relevant policy suggestions on standardizing the use of anti-tumor drugs.Methods In 2024,Beijing Cancer Quality Control Center organized internal medicine and pharmacy experts to conduct a research on the standardized use of anti-tumor drugs in 556 medical records from 60 hospitals.The evaluation content included pathological diagnosis and tumor staging,treatment process and quality control.Results The evaluation of the use of anti-tumor drugs in 60 hospitals in Beijing found that the main problems of non-standardized use of anti-tumor drugs were incomplete or unsigned informed consent forms;incomplete,un-staged or incorrect staging of tumors;lack of adverse reaction evaluation;incomplete records of drug application on the day of treatment;no reasons given for adjustments in drug dosage and administration methods,and incomplete efficacy evaluation.Conclusion It is necessary to strengthen the training and guidance of medical staff,carry out regular quality control inspections,enhance information construction,establish a multi-disciplinary diagnosis and treatment system,and establish a regular follow-up mechanism,so as to further standardize and improve the standard rate of antitumor drug use in hospitals.
3.Progress in 1q21 gain/amplification type multiple myeloma
Jingbo SHI ; Liming YU ; Wei ZHENG ; Siyuan CUI
Chinese Journal of Pathophysiology 2025;41(2):394-402
Multiple myeloma(MM),a common malignancy of plasma cells,remains an incurable disease de-spite significant therapeutic advancements.A defining characteristic of MM is the recurrent occurrence of cytogenetic ab-normalities,particularly the gains of chromosome 1q21(1q21+),which are among the most frequently observed anoma-lies in this condition,affecting approximately 40%of patients with newly diagnosed MM.While numerous studies have identified 1q21+as an independent prognostic marker linked to poor outcomes in MM,its prognostic significance continues to be debated.An increasing number of national and international prognostic stratification systems classify 1q21+as a high-risk factor;however,its predictive value remains contentious.Variations in 1q21 copy numbers significantly impact genomic instability,drug resistance,and the likelihood of early disease progression,highlighting its growing importance in clinical management strategies.Despite the availability of various therapeutic approaches,such as autologous hemato-poietic stem cell transplantation,immunomodulatory drugs,and proteasome inhibitors,the adverse prognostic implica-tions of 1q21+persist unresolved.This review will explore the latest advancements in understanding the 1q21+in MM,fo-cusing on its pathogenesis,prognostic relevance,and implications for clinical management.
4.Prognostic analysis of postoperative adjuvant therapy for hepatocellular carcinoma after con-version therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy: a multicenter study
Kongying LIN ; Jia LIN ; Zisen LAI ; Yongping LAI ; Kui WANG ; Jinhong CHEN ; Zhibo ZHANG ; Jingdong LI ; Sheng TAI ; Shifeng WANG ; Siming ZHENG ; Jianxi ZHANG ; Lu ZHENG ; Kai WANG ; Jiacheng ZHANG ; Jiahui LYU ; Liming HUANG ; Yongyi ZENG
Chinese Journal of Digestive Surgery 2025;24(1):103-112
Objective:To investigate the prognosis of postoperative adjuvant therapy for hepatocellular carcinoma after conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 103 patients with initially unresectable hepatocellular carcinoma (HCC) who were admitted to 11 medical centers in China, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from November 2019 to May 2023 were collected. There were 83 males and 20 females, aged (54±12)years. All 103 patients underwent conversion therapy of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) successfully followed by sequential hepatectomy, of which 72 patients undergoing postoperative adjuvant therapy were divided into the adjuvant therapy group, and 31 patients undergoing postoperative follow-up monitoring were divided into the follow-up monitoring group. Observation indicators: (1) follow-up and postoperative condi-tions; (2) analysis of factors influencing recurrence-free survival time of patients; (3) stratified ana-lysis. Comparison of count data between group was conducted using the chi-square test or Fisher exact probability. The R software was used to draw survival curves, and the Log-rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the Cox proportional hazard model. Results:(1) Follow-up and postoperative conditions. All 103 patients were followed up for 21.0(range, 1.9?47.2)months, with the median recurrence-free survival time of 28.7 months and the 1-, 2-, 3-year recurrence-free survival rates of 68.6%, 55.6%, 41.2%. The median overall survival time of 103 patients was unreached, and the 1-, 2-, 3-year overall survival rates were 90.9%, 82.1%, 69.6%, respectively. The median recurrence-free survival time was 33.1 months in patients of the adjuvant therapy group, with the 1-, 2-year recurrence-free survival rates as 77.2%, 61.5%. The median recurrence-free survival time was 11.1 months in patients of the follow-up monitoring group, with the 1-, 2-year recurrence-free survival rates as 46.6%, 40.8%. There was a significant difference in recurrence-free survival between the two groups of patients ( χ2=5.492, P<0.05). (2) Analysis of factors influencing recurrence-free survival time of patients. Results of multivariate analy-sis showed that pathologic complete response and postoperative adjuvant therapy were independent factors influencing recurrence-free survival time of HCC patients undergoing conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy ( hazard ratio=0.297, 0.492, 95% confidence interval as 0.137?0.647, 0.268?0.903, P<0.05). (3) Stratified analysis. Of the 71 patients with non-pathologic complete response, the median recurrence-free survival time of 48 patients in the adjuvant therapy group was 24.0 months, with the 1-, 2-year recurrence-free survival rates as 67.4%, 48.8%. The median recurrence-free survival time of 23 patients with non-pathological complete response in the follow-up monitoring group was 7.4 months, with the 1-, 2-year recurrence-free survival rates as 35.0%, 26.3%. There was a significant difference in recurrence-free survival between the 48 patients with non-pathologic complete response in the adjuvant therapy group and the 23 patients with non-pathologic complete response in the follow-up monitoring group ( χ2=5.241, P<0.05). Conclusion:For HCC patients with conversion therapy of TKIs and ICIs followed by sequential hepatectomy, postoperative adjuvant therapy, compared to postoperative follow-up monitoring, can prolong the recurrence-free survival time of patients, of whom cases with non-pathologic complete response can benefit from adjuvant therapy.
5.Value of microbiological rapid on-site evaluation in treatment of patients with severe community-acquired pneumonia
Junchen XIONG ; Lihua QIU ; Ning LIU ; Lili SHI ; Liming SUN ; Xiaosheng MENG ; Huade ZHENG ; Jiguang MENG
Chinese Journal of Nosocomiology 2025;35(17):2618-2623
OBJECTIVE To explore the value of microbiological rapid on-site evaluation(M-ROSE)technique in treatment of the patients with severe community-acquired pneumonia(SCAP).METHODS A total of 124 patients with SCAP who were treated in the department of respiratory and critical care medicine of The Fourth Medical Center of Chinese PLA General Hospital from Sep.2023 to Dec.2024 were enrolled in the study and were random-ly divided into the M-ROSE group and the control group in a 1∶1 ratio based on the status of M-ROSE for bron-choalveolar lavage fluid(BALF).The M-ROSE test and conventional etiological test[metagenomic next genera-tion sequencing(mNGS),smear,culture]were performed for the M-ROSE group,and the conventional etiologi-cal test was only carried out for the control group.The baseline data,symptoms and signs,C-reactive protein lev-el,treatment status and outcomes were observed and compared between the two groups of patients.RESULTS A-mong the 62 patients for whom the BALF specimens were detected with M-ROSE,45(72.58%)patients showed the consistent test result for fungi with mNGS,47(75.81%)patients showed the same test result for cocci with mNGS,and 30(48.39%)patients showed the same test result for bacilli with mNGS.The duration of the M-ROSE test was 1.50(1.50,2.00)h,shorter than that of the smear,culture and mNGS(P<0.05).The body temperature returning to the normal and the property,volume of sputum were improved more early in days in the M-ROSE group than in the control group after the anti-infection treatment(P<0.05);the level of inflammatory factor CRP declined more quickly in the M-ROSE group than in the control group(P<0.05);the effective rates of treatment of the M-ROSE group were higher than those of the control group after the hospitalization for 3,5 and 7 days(P<0.05).CONCLUSION The M-ROSE test for BALF may facilitate the rapid etiological diagnosis for the patients with SCAP in early stage,provide guidance for the anti-infection treatment strategies,and accelerate the improvement of symptoms and inflammatory factors;it has certain clinical application value.
6.Current status and influencing factors of oral frailty in elderly diabetic patients
Xiaohui SHANG ; Yifei DU ; Baoli WEN ; Qiming JIA ; Yan ZHENG ; Yu'na HU ; Liming LI
Chinese Journal of Modern Nursing 2025;31(14):1925-1930
Objective:To understand the current status of oral frailty in elderly diabetic patients and analyze its influencing factors.Methods:A convenience sampling method was used to select elderly diabetic patients hospitalized at Henan Cancer Hospital and Henan Provincial People's Hospital from October 2023 to May 2024. The general information questionnaire, Oral Frailty Index-8 (OFI-8) , Short Form of Health Literacy Dental Scale (HeLD-14) , Nutritional Risk Screening 2002 (NRS 2002) , and the Diabetes Distress Scale (DDS) were used to collect data. Binary Logistic regression analysis was used to examine the influencing factors of oral frailty in elderly diabetic patients.Results:A total of 235 questionnaires were distributed, and 220 valid questionnaires were returned, with an effective response rate of 93.62% (220/235) . The incidence of oral frailty in elderly diabetic patients was 46.82% (103/220) . The binary Logistic regression analysis showed that glycated hemoglobin, dry mouth, remaining teeth, nutritional risk, oral health literacy, and diabetes distress were significant influencing factors for the occurrence of oral frailty in elderly diabetic patients ( P<0.05) . Conclusions:The current status of oral frailty in elderly diabetic patients is concerning. Healthcare providers should pay attention to the oral health status of elderly diabetic patients and provide targeted nursing interventions and recommendations based on the influencing factors of oral frailty, in order to reduce its occurrence.
7.Development of a nomogram for predicting pathological complete response after neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer
Ruoxi TIAN ; Xuhua HU ; Hengchang LIU ; Pu CHENG ; Jiyun LI ; Mandula BAO ; Liming ZHAO ; Zhaoxu ZHENG
Chinese Journal of Gastrointestinal Surgery 2025;28(3):304-313
Objective:To construct and validate a predictive model for pathological complete response (pCR) in patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy.Methods:This retrospective observational study included 595 patients with stage T2-4 and (or) N+M0 LARC diagnosed in the Cancer Hospital of Chinese Academy of Medical Sciences and the Fourth Hospital of Hebei Medical University who had no metastases, tolerated neoadjuvant therapy, completed neoadjuvant therapy, and had undergone radical surgery after neoadjuvant therapy. The training set comprised 299 patients admitted to the Cancer Hospital of Chinese Academy of Medical Sciences from 2013 to 2018, the internal validation set 155 patients admitted from 2019 to 2023, and the external validation set 141 patients admitted to the Fourth Hospital of Hebei Medical University from 2013 to 2021. They were divided into pCR group and non-pCR groups according to postoperative pathology. Among the 299 patients in the training set, 247 were in the non-PCR and 52 in the pCR group; among the 155 patients verified internally, 113 were in the non-PCR and 42 in the pCR group; and among the 141 patients validated externally, 132 were in the non-pCR and nine in the pCR group. Logistic regression was used for univariate and multifactorial analysis to explore the factors associated with pCR and construct a nomogram prediction model. Receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA) were used to validate the performance of the predictive model.Results:Univariate and multivariate logistic regression analysis showed that carbohydrate antigen 19-9 ( P=0.040, OR=0.97, 95%CI: 0.93-0.99), neutrophil count ( P<0.001, OR=0.66, 95%CI: 0.52-0.84), tumor T stage: Stage IV ( P=0.011, OR=0.22, 95%CI: 0.07-0.70), tumor N stage: Stage I ( P=0.003, OR=0.22,95%CI:0.08-0.60), Stage II ( P<0.001, OR=0.03, 95%CI: 0.01-0.09) and involvement of mesorectal fascia ( P=0.004, OR=0.09, 95%CI: 0.02-0.47) were independent predictors of pCR. In the training set, the area under the receiver operating characteristic curve of the model was 0.92 (95%CI: 0.87-0.96), whereas in the internal and external validation sets, the AUCs were 0.78 and 0.81, respectively. The calibration curve showed that the prediction model had good prediction efficiency in both the training and verification sets. Decision curve analysis showed that the net benefit of the model was largest when the threshold probability was in the range of 5.2% to 89.7% (in the internal and external validation sets, the threshold probabilities were in the range of 15.7% to 92.3% and 2.2% to 84.1%, respectively). Conclusion:The nomogram model constructed in this study showed efficacy in predicting whether patients with LARC will achieve pCR after receiving neoadjuvant chemoradiotherapy.
8.Standardized Use of the Anti-tumor Drug in 60 Beijing Hospitals in 2024
Juan YANG ; Chengcheng ZHOU ; Jincheng YANG ; Liming SHI ; Sufei ZHENG ; Wenjing YANG
Chinese Hospital Management 2025;45(6):44-48
Objective To investigate the standardized use of anti-tumor drugs in Beijing hospitals in 2024,and put forward relevant policy suggestions on standardizing the use of anti-tumor drugs.Methods In 2024,Beijing Cancer Quality Control Center organized internal medicine and pharmacy experts to conduct a research on the standardized use of anti-tumor drugs in 556 medical records from 60 hospitals.The evaluation content included pathological diagnosis and tumor staging,treatment process and quality control.Results The evaluation of the use of anti-tumor drugs in 60 hospitals in Beijing found that the main problems of non-standardized use of anti-tumor drugs were incomplete or unsigned informed consent forms;incomplete,un-staged or incorrect staging of tumors;lack of adverse reaction evaluation;incomplete records of drug application on the day of treatment;no reasons given for adjustments in drug dosage and administration methods,and incomplete efficacy evaluation.Conclusion It is necessary to strengthen the training and guidance of medical staff,carry out regular quality control inspections,enhance information construction,establish a multi-disciplinary diagnosis and treatment system,and establish a regular follow-up mechanism,so as to further standardize and improve the standard rate of antitumor drug use in hospitals.
9.Spousal correlations of blood lipid based on a family design
Yixin LI ; Huangda GUO ; Hexiang PENG ; Tianjiao HOU ; Hanyu ZHANG ; Yinxi TAN ; Yi ZHENG ; Mengying WANG ; Yiqun WU ; Xueying QIN ; Jin LI ; Ying YE ; Tao WU ; Dafang CHEN ; Yonghua HU ; Liming LI
Journal of Peking University(Health Sciences) 2025;57(3):423-429
Objective:To explore the spousal correlations of total cholesterol(TC),total triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C),and to investigate the reasons behind these spousal correlations.Methods:Participants and data were from the baseline survey of family-based cohort studies in Fangshan,Beijing and Tulou,Fujian.The ori-gin of spousal correlations were explored from perspectives of convergence,assortative mating,social ho-mogamy.Pearson's correlation and generalized linear models(GLM)were used to estimate the spousal correlation.Convergence was assessed by Pearson's correlation between the phenotypic differences be-tween couples and the duration of marriage,with GLM used for further validation.Pearson's correlation of genetic risk scores(GRS)and couple-specific Mendelian randomization(MR)were calculated to assess the genetic correlation and possible causal relationships between spouses.Two-independent-sample t-tests were used to compare GRS consistency across subgroups divided by education attainment,couple-specific MR and Q statistics used to test assortative mating in subgroups and intergroup differences.Results:In the study,342 couples(287 couples from Fangshan and 55 couples from Fujian)were included,with the average age of(64.91±8.76)years.Spousal correlations of TC,TG,HDL-C,and LDL-C showed statistically significant associations both before and after adjusting for covariates,with effect sizes of 0.229(95%CI:0.125-0.327),0.257(95%CI:0.155-0.354),0.179(95%CI:0.074-0.280),and 0.181(95%CI:0.076-0.282).For convergence,for each additional year of marriage,ΔTC increased by 0.016 mmol/L(95%CI:0.001-0.033 mmol/L),and ΔLDL-C increased by 0.017 mmol/L(95%CI:0.002-0.031 mmol/L).For assortative mating,GRS correlations and results of couple specific MR didn't show any statistical significance.For social homogamy,no differences in GRS or assortative mating were found between subgroups stratified by education attainment.Conclusion:The blood lipid in participants exhibit spousal phenotypic correlations,however,no effects of convergence,assortative mating or social homogamy were observed.More independent studies with larger sample sizes are warranted to further validate these findings in the future.

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