1.The effect of rutaecarpine on improving fatty liver and osteoporosis in MAFLD mice
Yu-hao ZHANG ; Yi-ning LI ; Xin-hai JIANG ; Wei-zhi WANG ; Shun-wang LI ; Ren SHENG ; Li-juan LEI ; Yu-yan ZHANG ; Jing-rui WANG ; Xin-wei WEI ; Yan-ni XU ; Yan LIN ; Lin TANG ; Shu-yi SI
Acta Pharmaceutica Sinica 2025;60(1):141-149
Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg-1) and a high dose (15 mg·kg-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D303)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.
2.Diagnostic value of novel inflammatory markers related to routine blood tests in elderly patients with chronic cardiovascular disease complicated with frailty
Xing-Man FAN ; Yan-Yan LI ; Qiong-Yi HE ; Wei-Na LUO ; Xiao-Hua LAN ; Kai-Jie ZHANG ; Meng WANG ; Xiang-Ren KONG ; Hai-Tao ZHANG
Medical Journal of Chinese People's Liberation Army 2025;50(3):301-308
Objective To investigate the diagnostic value of 4 novel inflammatory markers related to routine blood tests,namely neutrophil-to-lymphocyte ratio(NLR),red blood cell distribution width(RDW),hemoglobin-to-RDW ratio(HRR)and systemic immune-inflammation index(SII),in elderly patients with chronic cardiovascular disease(CVD)complicated with frailty.Methods Retrospectively analyze 110 patients with chronic stable CVD who were hospitalized in the cadre ward of cardiovascular medicine at the Air Force Characteristic Medical Center from January 2022 to June 2023.According to the assessment results of the Fried scale,they were divided into three groups:non-frailty group(Fried score=0,n=30),the pre-frailty group(Fried score 1 or 2,n=40)and frailty group(Fried score≥3,n=40).The differences in general information,the impairment rate of daily living activities,miniature nutritional assessment-short form(MNA-SF)scores,mini-mental state examination(MMSE)scores,and the indicators such as NLR,RDW,HRR,and SII among the three groups were compared.Spearman rank correlation was used to analyze the correlation between NLR,RDW,HRR,SII and frailty scores as well as each frailty indicator.Multivariate logistic regression analysis was performed to identify the independent risk factors for frailty in elderly patients with chronic CVD,and the receiver operating characteristic(ROC)curve was used to assess the clinical diagnostic value of NLR and HRR in elderly patients with chronic CVD complicated with frailty.Results Compared with non-frailty group and pre-frailty group,patients in frailty group were older,with higher impaired rates of daily living activities,NLR,RDW,and SII,and lower MNA-SF scores,MMSE scores,and HRR,and differences were statistically significant(P<0.05).Spearman rank correlation analysis showed that the frailty score was positively correlated with NLR(rs=0.354,P<0.001),and RDW(rs=0.448,P<0.001),negatively correlated with HRR(rs=-0.232,P=0.024),and had no significant correlation with SII(rs=0.144,P=0.167).Further analysis of the correlation between the above novel inflammatory markers and the 5 components of frailty showed that NLR was positively correlated with fatigue(rs=0.228,P=0.017),slowed walking speed(rs=0.299,P<0.001),and low physical function(rs=0.319,P<0.001);RDW was positively correlated with decreased grip strength(rs=0.321,P<0.001),slowed walking speed(rs=0.422,P<0.001),and low physical function(rs=0.246,P=0.001);and HRR was negatively correlated with slowed walking speed(rs=-0.230,P=0.025),and low physical function(rs=-0.299,P=0.003).Multivariate logistic regression analysis showed that MNA-SF score(OR=0.577,95%CI 0.342-0.973)was an independent protective factor for pre-frailty in elderly patients with chronic CVD(P<0.05);NLR(OR=7.866,95%CI 1.101-56.185)was an independent risk factor for frailty,while HRR(OR=0.344,95%CI 0.120-0.983)and MNA-SF score(OR=0.292,95%CI 0.146-0.580)were independent protective factors for frailty in elderly CVD patients(P<0.05).The area under the ROC curve of NLR and HRR for diagnosing frailty in elderly patients with chronic CVD were 0.778 and 0.749,respectively.Conclusion NLR and HRR have high clinical diagnostic value for frailty in elderly patients with chronic CVD,and are expected to become effective inflammatory markers for screening elderly patients with chronic CVD complicated with frailty.
3.Establishment and evaluation of a predictive model for spontaneous peritonitis in HBV-related primary liver cancer
Hong-Yan WEI ; Yong-Zhen CHEN ; Ren-Hai TIAN ; Li-Xian CHANG ; Ying-Yuan ZHANG ; Dan-Qing XU ; Chun-Yun LIU ; Li LIU
Medical Journal of Chinese People's Liberation Army 2025;50(8):949-957
Objective To establish and evaluate a nomogram prediction model for spontaneous peritonitis in HBV-related primary liver cancer.Methods A retrospective study was conducted on 1298 patients with HBV-related primary liver cancer hospitalized in the Kunming Third People's Hospital from January 2012 to December 2022.General data and serological indicators were collected,and patients were divided into infection group(n=262)and control group(n=1036)based on the occurrence of spontaneous peritonitis.Univariate and LASSO regression analyses were used to screen variables,followed by binary logistic regression to analyze the influencing factors of spontaneous peritonitis in HBV-related primary liver cancer patients,leading to the establishment of a nomogram prediction model.Finally,the Hosmer-lemeshow(H-L)goodness of fit test,receiver operating characteristic(ROC)curve,calibration curve,decision curve analysis(DCA)and clinical impact curve(CIC)were utilized to evaluate the fit degree,accuracy,calibration,and clinical practicability of the nomogram prediction model.Results Single factor analysis revealed significant differences between infection group and control group in portal vein cancer thrombus(PVTT),Child-Pugh grade,China Liver Cancer Staging(CNLC)stage,alcohol consumption history,smoking history,white blood cell count(WBC),neutrophil count(NE),hemoglobin(Hb),fibrinogen(FIB),abnormal prothrombin(PIVKA-Ⅱ),aspartate aminotransferase(AST),alanine aminotransferase(ALT),total protein(TP),prealbumin(PA),γ-glutamyltransferase(GGT),alkaline phosphatase(ALP),cholinesterase(CHE),total bile acid(TBA),total cholesterol(TC),low density lipoprotein(LDL),creatinine(Cr),HBV DNA,CD3+T cells count,CD4+T cells count,CD8+T cells count,CD4+T cells/CD8+T cells ratio,procalcitonin(PCT),serum amyloid A(SAA),interleukin-6(IL-6),high-sensitivity C-reactive protein(hs-CRP),alpha-fetoprotein(AFP),and IL-4(P<0.05).LASSO regression analysis identified 5 variables:Child-Pugh grade,PVTT,WBC,CHE and hs-CRP.Binary logistic regression analysis indicated that Child-Pugh grade(Grade B:OR=5.780,95%CI 3.271-10.213,P<0.001;Grade C:OR=14.818,95%CI 7.697-28.526,P<0.001),PVTT(OR=2.893,95%CI 2.037-4.108,P<0.001),WBC(OR=1.088,95%CI 1.031-1.148,P=0.002),and hs-CRP(OR=1.005,95%CI 1.001-1.010,P=0.026)were the independent risk factors of spontaneous peritonitis in HBV-related primary liver cancer patients.Using these 4 variables,a nomogram prediction model was constructed and evaluated.The P-value of the H-L goodness of fit test was 0.760.Moreover,the area under ROC curve(AUC)was 0.866,with a sensitivity of 0.870 and a specificity of 0.716.The average absolute error of the calibration curve is 0.022.DCA and CIC analyses demonstrated that the nomogram prediction model possessed some clinical utility.Conclusion The nomogram prediction model for spontaneous peritonitis in HBV-related primary liver cancer patients,constructed using Child-Pugh grade,PVTT,WBC and hs-CRP,exhibits a high fitting degree and accuracy,with the prediction probability highly consistent with the actual occurrence probability,and possesses certain clinical practicability.
4.Quality evaluation of Xinjiang Rehmannia glutinosa and Rehmannia glutinosa based on fingerprint and multi-component quantification combined with chemical pattern recognition.
Pan-Ying REN ; Wei ZHANG ; Xue LIU ; Juan ZHANG ; Cheng-Fu SU ; Hai-Yan GONG ; Chun-Jing YANG ; Jing-Wei LEI ; Su-Qing ZHI ; Cai-Xia XIE
China Journal of Chinese Materia Medica 2025;50(16):4630-4640
The differences in chemical quality characteristics between Xinjiang Rehmannia glutinosa and R. glutinosa were analyzed to provide a theoretical basis for the introduction and quality control of R. glutinosa. In this study, the high performance liquid chromatography(HPLC) fingerprints of 6 batches of Xinjiang R. glutinosa and 10 batches of R. glutinosa samples were established. The content of iridoid glycosides, phenylethanoid glycosides, monosaccharides, oligosaccharides, and polysaccharides in Xinjiang R. glutinosa and R. glutinosa was determined by high performance liquid chromatography-diode array detection(HPLC-DAD), high performance liquid chromatography-evaporative light scattering detection(HPLC-ELSD), and ultraviolet-visible spectroscopy(UV-Vis). The determination results were analyzed with by chemical pattern recognition and entropy weight TOPSIS method. The results showed that there were 19 common peaks in the HPLC fingerprints of the 16 batches of R. glutinosa, and catalpol, aucubin, rehmannioside D, rehmannioside A, hydroxytyrosol, leonuride, salidroside, cistanoside A, and verbascoside were identified. Hierarchical cluster analysis(HCA) and principal component analysis(PCA) showed that Qinyang R. glutinosa, Mengzhou R. glutinosa, and Xinjiang R. glutinosa were grouped into three different categories, and eight common components causing the chemical quality difference between Xinjiang R. glutinosa and R. glutinosa in Mengzhou and Qinyang of Henan province were screened out by orthogonal partial least squares discriminant analysis(OPLS-DA). The results of content determination showed that there were glucose, sucrose, raffinose, stachyose, polysaccharides, and nine glycosides in Xinjiang R. glutinosa and R. glutinosa samples, and the content of catalpol, rehmannioside A, leonuride, cistanoside A, verbascoside, sucrose, and glucose was significantly different between Xinjiang R. glutinosa and R. glutinosa. The analysis with entropy weight TOPSIS method showed that the comprehensive quality of R. glutinosa in Mengzhou and Qinyang of Henan province was better than that of Xinjiang R. glutinosa. In conclusion, the types of main chemical components of R. glutinosa and Xinjiang R. glutinosa were the same, but their content was different. The chemical quality of R. glutinosa was better than Xinjiang R. glutinosa, and other components in R. glutinosa from two producing areas and their effects need further study.
Rehmannia/classification*
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Drugs, Chinese Herbal/chemistry*
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Chromatography, High Pressure Liquid/methods*
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Quality Control
5.Diagnositic value of capsule endoscopy for small intestinal diseases and the influence of prokinetic agents on its operation
Hai-yan WANG ; Miao JIANG ; Shao-ren ZHANG
Fudan University Journal of Medical Sciences 2025;52(6):854-861
Objective To analyze the characteristics of capsule endoscopy(CE)in small intestinal diseases and the effect of prokinetic agents on CE,and to explore the diagnostic value of CE in small intestinal diseases.Methods Clinical data were collected from 332 patients who underwent CE in Jinshan Hospital,Fudan University between May 2020 and Mar 2024,and the etiology and endoscopic characteristics of small intestinal diseases were analyzed.Patients were categorized based on the administration of metoclopramide into the non-use group(Group A)and use group(Group B).Group A was further subdivided based on whether the CE reached the cecum,forming the non-reach group(Group c)and the reach cecum group(Group d).Then we compared the capsule gastric transit time,small intestine transit time,completion rate of the entire small intestine examination,and lesion detection rate across these groups.Additionally,the detection rates of CE were compared with those of colonoscopy,small bowel enteroscopy-CT(SBE-CT),and double-balloon enteroscopy(DBE).Results The most prevalent small intestinal lesions identified were erosions and ulcers,with Crohn's disease(CD)being the primary cause of ulcers,endoscopic ulcers exhibited atypical and diverse presentations,including aphthous and irregular ulcers.In comparison to Group A,Group B demonstrated a shorter small bowel transit time(P<0.05)and a higher lesion detection rate(P<0.05),while no significant difference was observed in the completion rate of the entire small bowel examination.Gastric emptying time and small intestinal transit time were prolonged in Group c compared with Group d(P<0.05).There was no significant difference in the diagnostic rate of terminal ileum lesions between CE and colonoscopy,while the diagnostic rate of CE was higher in patients with terminal ileum lesions under colonoscopy(P<0.05).The diagnostic rate of CE was higher than that of SBE-CT(P<0.05),and the detection rate of CE and DBE was comparable.Conclusion The morphology of small intestinal ulcers varies,and the endoscopic findings are not specific.Metoclopramide administered in real time after capsule ingestion can shorten the intestinal transit time and improve the diagnostic rate of CE.Positive lesions found during colonoscopy should be further evaluated with CE examination,the diagnostic accuracy of CE is higher than that of SBE-CT,CE and DBE have the same diagnostic value for small intestinal diseases.
6.Analysis and suggestions for the FDA drug labeling rules on cardiac safety risk warnings
Wei LIU ; Xiao-qing XING ; Yu-qing REN ; Qian SHEN ; Yue ZHOU ; Nan ZHANG ; Fu-meng LIANG ; Fang-fang WANG ; Hai-yan LI
The Chinese Journal of Clinical Pharmacology 2025;41(2):235-239
Objective To improve and refine the relevant regulations and guiding principles of warnings on drug instructions and labels in China.Methods This paper sorted out the drug instructions of small molecule anti-tumor drugs listed by the U.S.Food and Drug Administration(FDA)from 2005 to 2022,included the drugs mentioned in the QT interval prolongation risk,analyzed the clinical research and QT research results,and sorted out the identification and warning rules of the instructions.Results A total of 35 drugs were included,4 drugs wrote the risk of QT interval prolongation in the black box warning,21 drugs were wrote in the warning and precautions position,6 drugs were wrote in the adverse reaction section,and 2 drugs were only described under clinical pharmacology section.According to the severity of the QT interval prolongation caused by the drug and whether there were serious clinical consequences,they were displayed in the warnings(black box warnings),precautions(warnings and precautions)and adverse reactions in the instructions.Conclusion The aim of this article is to provide a reference for the writing of QT risk warning information of the instructions of domestic drug production enterprises and regulatory departments.It is recommended to clarify the severity of drug safety and the location of the instructions in clinical research,and continue to carry out safety monitoring and update the instructions in time after listing.
7.Diagnositic value of capsule endoscopy for small intestinal diseases and the influence of prokinetic agents on its operation
Hai-yan WANG ; Miao JIANG ; Shao-ren ZHANG
Fudan University Journal of Medical Sciences 2025;52(6):854-861
Objective To analyze the characteristics of capsule endoscopy(CE)in small intestinal diseases and the effect of prokinetic agents on CE,and to explore the diagnostic value of CE in small intestinal diseases.Methods Clinical data were collected from 332 patients who underwent CE in Jinshan Hospital,Fudan University between May 2020 and Mar 2024,and the etiology and endoscopic characteristics of small intestinal diseases were analyzed.Patients were categorized based on the administration of metoclopramide into the non-use group(Group A)and use group(Group B).Group A was further subdivided based on whether the CE reached the cecum,forming the non-reach group(Group c)and the reach cecum group(Group d).Then we compared the capsule gastric transit time,small intestine transit time,completion rate of the entire small intestine examination,and lesion detection rate across these groups.Additionally,the detection rates of CE were compared with those of colonoscopy,small bowel enteroscopy-CT(SBE-CT),and double-balloon enteroscopy(DBE).Results The most prevalent small intestinal lesions identified were erosions and ulcers,with Crohn's disease(CD)being the primary cause of ulcers,endoscopic ulcers exhibited atypical and diverse presentations,including aphthous and irregular ulcers.In comparison to Group A,Group B demonstrated a shorter small bowel transit time(P<0.05)and a higher lesion detection rate(P<0.05),while no significant difference was observed in the completion rate of the entire small bowel examination.Gastric emptying time and small intestinal transit time were prolonged in Group c compared with Group d(P<0.05).There was no significant difference in the diagnostic rate of terminal ileum lesions between CE and colonoscopy,while the diagnostic rate of CE was higher in patients with terminal ileum lesions under colonoscopy(P<0.05).The diagnostic rate of CE was higher than that of SBE-CT(P<0.05),and the detection rate of CE and DBE was comparable.Conclusion The morphology of small intestinal ulcers varies,and the endoscopic findings are not specific.Metoclopramide administered in real time after capsule ingestion can shorten the intestinal transit time and improve the diagnostic rate of CE.Positive lesions found during colonoscopy should be further evaluated with CE examination,the diagnostic accuracy of CE is higher than that of SBE-CT,CE and DBE have the same diagnostic value for small intestinal diseases.
8.Analysis and suggestions for the FDA drug labeling rules on cardiac safety risk warnings
Wei LIU ; Xiao-qing XING ; Yu-qing REN ; Qian SHEN ; Yue ZHOU ; Nan ZHANG ; Fu-meng LIANG ; Fang-fang WANG ; Hai-yan LI
The Chinese Journal of Clinical Pharmacology 2025;41(2):235-239
Objective To improve and refine the relevant regulations and guiding principles of warnings on drug instructions and labels in China.Methods This paper sorted out the drug instructions of small molecule anti-tumor drugs listed by the U.S.Food and Drug Administration(FDA)from 2005 to 2022,included the drugs mentioned in the QT interval prolongation risk,analyzed the clinical research and QT research results,and sorted out the identification and warning rules of the instructions.Results A total of 35 drugs were included,4 drugs wrote the risk of QT interval prolongation in the black box warning,21 drugs were wrote in the warning and precautions position,6 drugs were wrote in the adverse reaction section,and 2 drugs were only described under clinical pharmacology section.According to the severity of the QT interval prolongation caused by the drug and whether there were serious clinical consequences,they were displayed in the warnings(black box warnings),precautions(warnings and precautions)and adverse reactions in the instructions.Conclusion The aim of this article is to provide a reference for the writing of QT risk warning information of the instructions of domestic drug production enterprises and regulatory departments.It is recommended to clarify the severity of drug safety and the location of the instructions in clinical research,and continue to carry out safety monitoring and update the instructions in time after listing.
9.Clinical characterization and prediction modeling of lung cancer patients with high energy metabolism
Jiang-Shan REN ; Jun-Mei JIA ; Ping SUN ; Mei PING ; Qiong-Qiong ZHANG ; Yan-Yan LIU ; He-Ping ZHAO ; Yan CHEN ; Dong-Wen RONG ; Kang WANG ; Hai-Le QIU ; Chen-An LIU ; Yu-Yu FAN ; De-Gang YU
Medical Journal of Chinese People's Liberation Army 2024;49(9):1004-1010
Objective To analyze the clinical characteristics of high energy metabolism in lung cancer patients and its correlation with body composition,nutritional status,and quality of life,and to develop a corresponding risk prediction model.Methods Retrospectively analyzed 132 primary lung cancer patients admitted to the First Hospital of Shanxi Medical University from January 2022 to May 2023,and categorized into high(n=94)and low energy metabolism group(n=38)based on their metabolic status.Differences in clinical data,body composition,Patient Generated Subjective Global Assessment(PG-SGA)scores,and European Organization for Research and treatment of Cancer(EORTC)Quality of Life Questionnaire-Core 30(QLQ-C30)scores were compared between the two groups.Logistic regression was used to identify the risk factors for high energy metabolism in lung cancer patients,and a risk prediction model was established accordingly;the Hosmer-Lemeshow test was used to assess the model fit,and the ROC curve was used to test the predictive efficacy of the model.Results Of the 132 patients with primary lung cancer,94(71.2%)exhibited high energy metabolism.Compared with low energy metabolism group,patients in high-energy metabolism group had a smoking index of 400 or higher,advanced disease staging of stage Ⅲ or Ⅳ,and higher levels of IL-6 level,low adiposity index,low skeletal muscle index,and malnutrition(P<0.05),and lower levels of total protein,albumin,hemoglobin level,and prognostic nutritional index(PNI)(P<0.05).There was no significant difference in age,gender,height,weight,BMI and disease type between the two groups(P>0.05).Logistic regression analysis showed that smoking index≥400,advanced disease stage,IL-6≥3.775 ng/L,and PNI<46.43 were independent risk factors for high energy metabolism in lung cancer patients.The AUC of the ROC curve for the established prediction model of high energy metabolism in lung cancer patients was 0.834(95%CI 0.763-0.904).Conclusion The high energy metabolic risk prediction model of lung cancer patients established in this study has good fit and prediction efficiency.
10.Exploration of potential biomarkers and therapeutic targets for trauma-related acute kidney injury
Peng QI ; Meng-Jie HUANG ; Wei WU ; Xue-Wen REN ; Yong-Zhi ZHAI ; Chen QIU ; Hai-Yan ZHU
Chinese Journal of Traumatology 2024;27(2):97-106
Purpose::Acute kidney injury (AKI) is one of the most common functional injuries observed in trauma patients. However, certain trauma medications may exacerbate renal injury. Therefore, the early detection of trauma-related AKI holds paramount importance in improving trauma prognosis.Methods::Qualified datasets were selected from public databases, and common differentially expressed genes related to trauma-induced AKI and hub genes were identified through enrichment analysis and the establishment of protein-protein interaction (PPI) networks. Additionally, the specificity of these hub genes was investigated using the sepsis dataset and conducted a comprehensive literature review to assess their plausibility. The raw data from both datasets were downloaded using R software (version 4.2.1) and processed with the "affy" package19 for correction and normalization.Results::Our analysis revealed 585 upregulated and 629 downregulated differentially expressed genes in the AKI dataset, along with 586 upregulated and 948 downregulated differentially expressed genes in the trauma dataset. Concurrently, the establishment of the PPI network and subsequent topological analysis highlighted key hub genes, including CD44, CD163, TIMP metallopeptidase inhibitor 1, cytochrome b-245 beta chain, versican, membrane spanning 4-domains A4A, mitogen-activated protein kinase 14, and early growth response 1. Notably, their receiver operating characteristic curves displayed areas exceeding 75%, indicating good diagnostic performance. Moreover, our findings postulated a unique molecular mechanism underlying trauma-related AKI. Conclusion::This study presents an alternative strategy for the early diagnosis and treatment of trauma-related AKI, based on the identification of potential biomarkers and therapeutic targets. Additionally, this study provides theoretical references for elucidating the mechanisms of trauma-related AKI.

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