1.Compound Glycyrrhizin Tablets Ameliorate Liver Injury Induced by Tripterygium Glycosides Tablet by Regulating Cholesterol Metabolism
Xiaotong FU ; Chunyu CAO ; Chun LI ; Chenna LU ; Ting LIU ; Yifei YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):46-55
ObjectiveTo investigate the mechanism of liver injury induced by tripterygium glycosides tablets (TG) and the molecular mechanism of compound glycyrrhizin tablets (CG) in alleviating the abnormalities of cholesterol metabolism caused by TG via cholesterol metabolism. MethodsAccording to the body weights, male Sprague-Dawley (SD) rats were randomly grouped as follows: control (pure water), low-dose TG (TG-L, 189.0 mg·kg-1·d-1), high-dose TG (TG-H, 472.5 mg·kg-1·d-1), TG-L+CG (189.0 mg·kg-1·d-1 TG + 20.25 mg·kg-1·d-1 CG), and TG-H+CG (472.5 mg·kg-1·d-1 TG + 20.25 mg·kg-1·d-1 CG), with 6 rats in each group. Rats were administrated with corresponding drugs once daily for 3 weeks. At the end of the last administration, the mRNA and protein levels of liver X receptor-alpha (LXR-α), low-density lipoprotein receptor (LDLR), adenosine triphosphate-binding cassette transporter A1 (ABCA1), adenosine triphosphate-binding cassette transporter G1 (ABCG1), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase (CYP7A1), cholesterol 12α-hydroxylase (CYP8B1), and sterol 27-hydroxylase (CYP27A1) in the liver tissue were determined by Real-time PCR and Western blotting, respectively. The level of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR), a regulatory enzyme of cholesterol synthesis, was measured by enzyme-linked immunosorbent assay (ELISA). HepG2 cells were used to observe the effect of TG on the cell proliferation in vitro. Specifically, HepG2 cells were grouped as follows: Low-dose TG (TG-l, 15 mg·L-1), medium-dose TG (TG-m, 45 mg·L-1), high-dose TG (TG-h, 135 mg·L-1), fenofibrate (FB, 10 μmol·L-1), CG extract, TG-h+FB (135 mg·L-1 TG + 10 μmol·L-1 FB), TG-m+FB (45 mg·L-1 TG + 10 μmol·L-1 FB), TG-l+FB (15 mg·L-1 TG + 10 μmol·L-1 FB), TG-h+CG (135 mg·L-1 TG + 60 μmol·L-1 CG), TG-m+CG (45 mg·L-1 TG + 60 μmol·L-1 CG), and TG-l+CG (15 mg·L-1 TG + 60 μmol·L-1 CG). The mRNA and protein levels of LXR-α, ABCG1, LDLR, CYP7A1, CYP8B1, and CYP27A1 in HepG2 cells were determined by Real-time PCR and Western blotting, respectively. ResultsThe rat experiment showed that compared with the control group, the TG-H group showed down-regulated mRNA levels of CYP7A1, CYP8B1, and CYP27A1 in the liver tissue (P<0.05, P<0.01), which were up-regulated by the application of CG (P<0.05, P<0.01), and the TG-H+CG group showed up-regulated mRNA level of LDLR (P<0.01). Compared with the control group, the TG-L and TG-H groups showed down-regulated protein levels of LDLR, CYP7A1, and CYP8B1 in the liver tissue (P<0.05, P<0.01). In addition, the protein levels of ABCG1 and LXR-α were down-regulated in the TG-H and TG-L groups, respectively (P<0.05). Compared with TG alone, TG+CG up-regulated the protein levels of ABCG1 and LDLR (P<0.05, P<0.01), and the protein levels of CYP7A1 and CYP8B1 in the TG-H+CG group were up-regulated (P<0.05, P<0.01). The cell experiment showed that compared with the control group, the TG-h group presented up-regulated mRNA level of LXR-α (P<0.01), and the TG-m and TG-h groups showcased down-regulated mRNA levels of LDLR and CYP7A1 (P<0.01) and up-regulated mRNA level of CYP27A1 (P<0.01) in HepG2 cells. The combination of CG with TG restored the above changes (P<0.01). Western blotting results showed that compared with the control group, the TG-m and TG-h groups showed down-regulated protein levels of LXR-α, ABCG1, LDLR, CYP7A1, CYP8B1, and CYP27A1 in HepG2 cells (P<0.01). Compared with the TG-h group, the TG-h+CG group showed up-regulated protein level of LDLR (P<0.05). Compared with the TG-m group, the TG-m+CG group showcased up-regulated protein levels of LDLR, ABCG1, CYP7A1, and CYP27A1 (P<0.05, P<0.01). ConclusionThe administration of TG at 189.0, 472.5 mg·kg-1 for 3 weeks could modulate the signaling pathways associated with cholesterol efflux, endocytosis, and cholesterol biotransformation in hepatocytes, leading to the accumulation of cholesterol and subsequent liver injury in rats. CG could ameliorate the liver injury induced by lipid metabolism disorders caused by TG by up-regulating the expression of LXR-α, LDLR, ABCG1, CYP7A1, CYP8B1, and CYP27A1 to promote cholesterol biotransformation.
2.Improvement effect and mechanism of total flavonoids from Rosa multiflora root on vascular injury in rheumatoid arthritis model rats
Kaiyan LI ; Fei ZHANG ; Ping TIAN ; Dan YANG ; Wei ZHANG ; Xiaoli WANG ; Wanqian TU ; Yifei LIU
China Pharmacy 2024;35(8):931-935
OBJECTIVE To study the improvement effect of total flavonoids from Rosa multiflora root on vascular injury in rheumatoid arthritis (RA) model rats and its potential mechanism. METHODS Female Wistar rats were randomly divided into normal control group, model group, aspirin group (positive control, 30 mg/kg), low-dose and high-dose groups of total flavonoids from R. multiflora root (4.15, 8.30 g/kg, by crude drug), with 10 rats in each group. Except for the normal control group, the RA model was induced in other groups by collagen induction and high-fat diet. After 14 days of modeling, they were given corresponding drug solution/0.5% sodium carboxymethyl cellulose solution intragastrically, once a day, for 36 consecutive days. The total body score, arthritis index (AI) and swollen joint count (SJC) of the rats were evaluated regularly. After the last medication, serum levels of interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule- 1 (VCAM-1) were determined. The pathological morphological changes in the vascular tissue of thoracic aorta were observed; the protein expression of Toll-like receptor 4 (TLR4) and the protein phosphorylation levels of Janus kinase 2 (JAK2) and signal transduction and activator of transcription 3 (STAT3) in vascular tissue of thoracic aorta were measured. RESULTS Compared with the normal control group, serum levels of IL-6, ICAM-1 and VCAM-1, protein expression of TLR4, and the protein phosphorylation levels of JAK2 and STAT3 in vascular tissue of thoracic aorta were increased significantly in model group (P< 0.01). The atherosclerotic plaque (atheroma), cholesterol crystal, lymphocyte infiltration and a small number of unbroken foam cell aggregation could be seen in the vascular tissue of thoracic aorta. Compared with the model group, total body score (except for the low-dose group), AI and SJC were decreased significantly in groups of total flavonoids from R. multiflora root on the 28th day (P<0.05 or P<0.01); total body score,AI and SJC were decreased significantly in low-dose group of total flavonoids from R. multiflora root on the 49th day (P<0.05 or P<0.01); the other quantitative indicators in serum and vascular tissue were significantly reversed in groups of total flavonoids from R. multiflora root (P<0.05 or P<0.01), and pathological damage of vascular tissue was significantly relieved. CONCLUSIONS Total flavonoids from R. multiflora root can significantly improve vascular injury in RA model rats, and its mechanism may be related to reducing the protein expression of TLR4 in vascular tissue and inhibiting the activation of IL-6/JAK2/ STAT3 signaling pathway.
3.Comparative analysis of work-related injury appraisal of 13 cases of occupational brucellosis
Yifei PEI ; Wenwen YUAN ; Lili YANG ; Huajian JU ; Lu HAN
Journal of Environmental and Occupational Medicine 2024;41(4):437-441
Background According to the Classification and Catalogue of Occupational Diseases, brucellosis is one of the notifiable occupational infectious diseases, which occurs from time to time in the occupational population. Objective To compare the work-related injury appraisal process and results of 13 cases of brucellosis at both provincial and municipal levels, analyze and summarize the bias in the practical work of labor capacity identification for occupational diseases such as brucellosis by appraisal management departments and experts, and propose suggestions for optimizing appraisal work. Methods A comparative study was conducted on the objective examination results and labor capacity appraisal conclusions based on the occupational contact history, clinical diagnosis, occupational disease diagnosis staging, and labor capacity appraisal of 13 patients with brucellosis. The reasons for the inconsistency between the initial appraisal conclusion by institutions at the municipal level and the final appraisal conclusion by institutions at the provincial level were compared and analyzed. Results All of the 13 patients with brucellosis applied for municipal-level labor capacity identification after being identified as work-related injuries, 11 of which did not receive a disability level, and 2 were rated as level 10 disability. Four of those who did not receive the disability rate applied for provincial-level labor capacity identification. As a result, 2 cases were maintained original appraisal conclusions, while the other 2 changed the conclusions to level 9 disability and level 10 disability respectively. It was the first time in Shijiangzhuang municipal-level primary labor capacity appraisal and Hebei provincial-level labor capacity re-appraisal that the work-related injury caused by occupational brucellosis was rated as level 9 disability or level 10 disability. Hence, the lessons learned from this comparative analysis are that the degree of target organ damage and (or) organ dysfunction are the direct basis for work-related injury appraisal; an objective and scientific labor capacity identification for occupational brucellosis should base on the each case of disability evaluation, identify the relevant target organ damage and the degree of dysfunction, and rate the disability level after a comprehensive appraisal. Conclusion This analysis would be a guidance to the identification of labor capacity for occupational brucellosis in Hebei Province and the whole country. There is a hysteresis issue in the occupational disease provisions in the national standard GB/T 16180—2014 Standard for identify work ability—Gradation of disability caused by work-related injuries and occupatiaonal diseases. In current situation, appraisal experts should not only search for clauses that directly correspond to the occupational diseases and injuries, but also target conditions not covered in the clauses and conduct assessment based on the characteristics of occupational diseases, with scientific, accurate, and flexible application of the clauses in the standard and appendix, so as to make fair, just, and professional appraisal conclusions.
4.Risk factors for acute pancreatitis in long-term drinking participants: a longitudinal UK Biobank-based study
Jinpeng ZHAO ; Yifei MA ; Qingyong MA ; Zheng WU ; Zheng WANG ; Xue YANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(2):192-199
【Objective】 To examine risk factors for acute pancreatitis (AP) in individuals with chronic alcohol consumption habits. 【Methods】 The study incorporated participants from the initial survey (2006-2010) and subsequent follow-ups (2014+) taken from the UK Biobank database, with the observation period ending on November 30, 2022. During this period, 176 individuals were newly diagnosed with AP, while 59,512 remained unaffected. Vital characteristics of the target population, such as their medical histories, surgical experiences and dietary patterns, were collected during the enrolment phase (2006-2010). The Cox proportional hazard model was employed to ascertain whether these characteristics were potent risk factors for AP. Concurrently, a subgroup from the target population with documented drinking behavior was selected. The multivariate Cox proportional hazard model was utilized to analyze the relationship of the established factors, variances in alcohol consumption, and increased alcohol intake (Δ) with the onset of AP, and whether the additional alcohol intake served as a risk factor. 【Results】 Multivariate analysis revealed that consumption quantity of cooked vegetables inversely correlated with AP risk (HR=0.44, 0.39, 0.42 and 0.41 for one, two, three and four+ tablespoons per day, respectively, as compared to non-consumers). Coffee consumption (2-3 cups per day) also reduced AP risk (HR=0.45 for 2 cups/day; HR=0.39 for 3 cups/day as compared to non-coffee drinkers). However, those with biliary disease without cholecystectomy exhibited a marked increase in AP risk (HR=7.82), which reduced albeit remained elevated for those with biliary disease post-cholecystectomy (HR=2.15). Subgroup analysis showed minimal impact of alcohol intake levels on AP incidence. Yet, increased alcohol consumption (Δ of 1 bottle/week) was linked to a heightened AP risk (HR=1.05, 95% CI:1.02-1.09, P<0.05). 【Conclusion】 Among longstanding alcohol consumers, a diet rich in cooked vegetables and moderate coffee consumption offers protective effects against AP. Conversely, biliary disease (particularly without cholecystectomy) and elevated alcohol intake present considerable risk factors for the development of this condition.
5.Immunogenicity, safety and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years
Dingyan YAO ; Yingping CHEN ; Fan DING ; Xiaosong HU ; Zhenzhen LIANG ; Bo XING ; Yifei CAO ; Tianqi ZHANG ; Xilu WANG ; Yuting LIAO ; Juan YANG ; Huakun LYU
Chinese Journal of Preventive Medicine 2024;58(1):25-32
Objective:To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years.Methods:An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster.Results:The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A′s 44.79 (36.94-54.30) ( P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A′s 15.71 (13.24-18.63) ( P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion:Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).
6.A proteomics research on metabolism-related proteins in female androgenetic alopecia
Ji’an WANG ; Jinran LIN ; Haiyang LI ; Kai YANG ; Chunya NI ; Yue ZHANG ; Zheng LI ; Yifei ZHU ; Qingmei LIU ; Wenyu WU
Chinese Journal of Plastic Surgery 2024;40(1):46-55
Objective:To investigate the metabolism-related proteins and their presence in the plasma of female androgenetic alopecia (FAGA) patients.Methods:From March 2021 to March 2023, FAGA patients aged 18-50 (FAGA group) and healthy women (HC group) were recruited from the Dermatology Outpatient Department of Huashan Hospital. 3 ml of peripheral venous blood was collected from each participant and centrifuged to obtain plasma. Olink proteomics analysis was performed on the collected plasma, differentially expressed proteins were screened with R language, the diagnostic accuracy of the differentially expressed proteins was assessed using receiver operating characteristic (ROC) curve. Gene ontology (GO) analysis was performed on differentially expressed proteins. Immunofluorescence analysis on hair follicles in the parietal region of the FAGA group and the occipital region of the HC group was performed to validate the differentially expressed proteins identified. SPSS 25.0 software was used to analyze the data, with normal distribution metric data represented by Mean±SD. Student’s t-test was used to compare the basic information of two groups of subjects and the relative fluorescence intensity of differentially expressed proteins in hair follicles. Pearson correlation analysis was performed on plasma metabolism-related proteins and the basic information of subjects. P<0.05 indicates a statistically significant difference. Results:Sixty-one cases were included in the FAGA group, with an average age of (33.8±7.4) years and an onset age of (29.5±7.8) years. Among them, 38 cases were mild FAGA, 14 cases were moderate, and 9 cases were severe. Twenty-seven cases were included in the HC group, with an average age of (32.0±7.7) years. There was no statistically significant difference in the basic information (age, body mass index, testosterone, 25-hydroxyvitamin D, uric acid, and ferritin levels) between the two groups of subjects ( P>0.05). Compared to the HC group, the plasma of the FAGA group showed 26 significantly upregulated differentially expressed proteins ( P<0.05), with AHCY and NECTIN2 exhibiting the most significant differences (all P=0.003). The ROC curve evaluation revealed that the area under the curve for AHCY and NECTIN2 was greater than 0.7, indicating good diagnostic accuracy. The GO analysis revealed that the differentially expressed proteins were primarily enriched in the BAT3 complex (cellular component), ubiquitin-dependent ERAD pathway, natural killer cell activation (biological process), as well as ubiquitin protein ligase binding and ubiquitin-specific protease binding (molecular function). Pearson correlation analysis revealed that AHCY ( r=-0.23, P=0.010) and NECTIN2 ( r=-0.31, P=0.033) were negatively correlated with the severity of hair loss in FAGA patients. The results of hair follicle immunofluorescence analysis showed that the relative fluorescence intensity of AHCY and NECTIN2 in the FAGA group was higher than that in the HC group ( P<0.05). In other words, both AHCY and NECTIN2 were upregulated in the FAGA group. Conclusion:Metabolism-related proteins play an important role in FAGA. AHCY and NECTIN2 may serve as early diagnostic biomarkers for FAGA.
7.MiR-4465-modified mesenchymal stem cell-derived small extracellular vesicles inhibit liver fibrosis development via targeting LOXL2 expression
WANG YANJIN ; CHEN YIFEI ; YANG FUJI ; YU XIAOLONG ; CHU YING ; ZHOU JING ; YAN YONGMIN ; XI JIANBO
Journal of Zhejiang University. Science. B 2024;25(7):594-604,中插17-中插21
Liver fibrosis is a significant health burden,marked by the consistent deposition of collagen.Unfortunately,the currently available treatment approaches for this condition are far from optimal.Lysyl oxidase-like protein 2(LOXL2)secreted by hepatic stellate cells(HSCs)is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis.Mesenchymal stem cell-derived small extracellular vesicles(MSC-sEVs)have been proposed as a potential treatment option for chronic liver disorders.Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues.It is currently unclear whether microRNA-4465(miR-4465)can target LOXL2 and inhibit HSC activation.Additionally,it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis.This study explored the effect of miR-4465-modified MSC-sEV(MSC-sEVmiR-4465)on LOXL2 expression and liver fibrosis development.The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC.Moreover,MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro.MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model.MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells.In conclusion,we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2,which might provide a promising therapeutic strategy for liver diseases.
8.Effect of first drainage failure on postoperative prognosis of patients with perihilar cholangiocarci-noma
Aibaidula AILIXIER ; Liang MAO ; Yifei YANG ; Yi WANG ; Lei WANG ; Yudong QIU
Chinese Journal of Hepatobiliary Surgery 2024;30(2):108-113
Objective:To study the effect of first drainage failure on the prognosis of perihilar cholangiocarcinoma (PHCC).Methods:The clinical data of 68 patients with PHCC undergoing surgery in the Department of Pancreatic and Metabolic Surgery of Nanjing Drum Tower Hospital, Affiliated to the Medical School of Nanjing University, from April 2014 to December 2022 were retrospectively analyzed, including 46 males and 22 females, aged (63±9) (range, 39-80) years old. The patients were divided into two groups based on whether the first drainage was successful: successful group ( n=34) and failed group ( n=34). The patient's age, gender, first drainage, complications and other clinical data were collected. Patients were followed up by outpatient or telephone review. Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival comparison. Results:Compared to the successful group, the drainage time [41(28, 52) d vs. 20(14, 28) d], the drainage tube adjustment rate [32.4%(11/34) vs. 0(0/34)], and the incidence of complications after drainage [88.2% (30/34) vs. 0(0/34)] were all increased in the failed group, with the adjustment rate of drainage position decreased [82.4%(28/34) vs. 100%(34/34)] (all P<0.05). Compared to the successful group, the incidence of abdominal infection was higher [70.6%(24/34) vs. 44.1%(15/34)] in the failed group ( P=0.027). The 5-year cumulative survival rates of the failed group and the successful group were 61.4% and 44.1%, respectively ( P>0.05). Conclusion:Compared to the patients of PHCC with first successful drainage, the risk of abdominal infection is increased when first drainage failed, while the incidence of postoperative complications, in-hospital mortality and long-term survival rate are comparable.
9.Characteristics and Regulatory Mechanisms of Cholestatic Liver Injury Caused by Chinese Herbal Medicines
Yun YANG ; Guozhuang ZHANG ; Ting LIU ; Yifei YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):64-71
ObjectiveTo explore the characteristics and regulatory mechanisms of cholestatic liver injury (CLI) caused by traditional Chinese medicine based on data mining, network pharmacology, and molecular docking. MethodChina National Knowledge Infrastructure and PubMed were searched for the relevant literature on CLI caused by traditional Chinese medicine from inception to 2024, and the information was standardized, summarized, and analyzed by cluster analysis. The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP), GeneCards, Online Mendelian Inheritance in Man (OMIM), and DisGeNET were used to retrieve the active ingredients and targets of core medicines. The Venn diagram was established to map the common targets shared by the core medicines and CLI. Cytoscape 3.10.2 was used to construct the protein-protein interaction (PPI) network of the common targets. DAVID was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment of the core targets. Finally, molecular docking was performed by AutoDock Vina. ResultA total of 849 eligible articles were included in this study, from which 64 active ingredients of 39 herbal medicines that can cause cholestasis were counted and categorized according to the 2020 edition of the Pharmacopoeia of the People's Republic of China. The frequency of the medidicnes followed a descending order of heat-clearing medicines, exterior-releasing medicines, blood-activating and stasis-resolving medicines, purgative medicines, phlegm-resolving and cough- and dyspnea-relieving medicines, tonics, wind- and dampness-expelling medicines, interior-warming medicines, urination-promoting and dampness-draining medicines, Qi movement-regulating medicines, hemostatics, toxin-removing, worm-killing, and itch-relieving medicines, astringent medicines, dampness-eliminating medicines, and tranquiling medicines. The cluster analysis revealed that the reports of CLI caused by heat-clearing medicines accounted for the highest proportion of 39.69%. Among the heat-clearing medicines, Gardeniae Fructus (92 articles, accounting for 10.84%), Scutellariae Radix (76 articles, 8.95%), and Sophorae Flavescentis Radix (69 articles, 6.95%) were frequently reported. The core targets of cholestasis induced by Chinese herbal medicines reported to cause CLI mainly included tumor necrosis factor (TNF), peroxisome proliferator activated receptor alpha (PPARA), farnesoid X receptor (FXR), glutamic-pyruvic transaminase 2 (GPT2), superoxide dismutase 1 (SOD1), interferon gamma (IFN-γ), interleukin-6(IL-6), CD36, Apolipoprotein A1(APOA1), Angiotensin converting enzyme(ACE), Cytochrome P450 3A4 enzyme(CYP3A4), Protein kinase B1(Akt1), APOB, albumin(ALB), ATP binding cassette transporter A4(ABCB4), SLC10A1, Estrogen Receptor alpha (ESR1), signal transducer and activator of transcription1(STAT1), β-actin(ACTB), Endothelin 1(EDN1), ABCG2, and peroxisome proliferator activated receptor gamma(PPARG). The signaling pathways involved included bile secretion, ABC transporter, steroid biosynthesis, DNA adducts, drug metabolism, cytochrome P450, peroxisomes, primary bile acid biosynthesis, retinol metabolism, and Toll-like receptor. The molecular docking results showed that the active ingredients (e.g., baicalin and berberine) of the heat-clearing medicines reported by high frequency to cause CLI had high binding affinity to the targets including ABCG2, IFN-γ, EDN1, IL-6 and SOD1, with the binding energy in the range of -13 kcal·mol-1 to -9 kcal·mol-1, and the regulatory pathways were highly correlated with transporters, microvascular function regulation, inflammation, and oxidative stress, which was consistent with the cluster analysis. ConclusionThe available reports about the Chinese herbal medicines causing CLI mainly focused on heat-clearing medicines, and the core targets included ABCG2, IFN-γ, EDN1, IL-6, and SOD1. The regulatory pathways were mainly related to transporters, microvascular function regulation, inflammation, and oxidative stress.
10.Risk factors of postoperative recurrence in patients with primary brain glioma and prediction model construction
Pingping LIU ; Xuefang HE ; Yi ZHANG ; Xu YANG ; Shanshan ZHANG ; Yifei JI
Journal of International Oncology 2024;51(4):193-197
Objective:To investigate the risk factors of postoperative recurrence in patients with primary brain glioma and to construct a prediction model.Methods:A total of 98 patients with primary brain glioma treated by radical surgery in Nanchong Central Hospital from January 2018 to January 2021 were retrospectively included, and were divided into recurrent group (40 cases) and non-recurrent group (58 cases) according to whether there was recurrence or not during the follow-up period. The independent influencing factors for postoperative recurrence in patients with primary brain glioma were evaluated by multivariate logistic regression. Logistic prediction model of postoperative recurrence risk of patients with primary brain glioma was established, and the predictive efficacy of each index was calculated by receiver operator characteristic (ROC) curve.Results:There were statistically significant differences between recurrent group and non-recurrent group in glioma World Health Organization (WHO) grade ( χ2=12.48, P<0.001), isocitrate dehydrogenase (IDH) 1/2 mutation ( χ2=13.24, P<0.001), mean platelet volume (MPV) ( t=5.34, P<0.001), and MPV/platelet count (PLT) ( t=9.73, P<0.001). Multivariate analysis showed that WHO grade Ⅲ-Ⅳ ( OR=8.54, 95% CI: 1.62-44.99, P=0.011), IDH1/2 wild type ( OR=9.08, 95% CI: 1.68-49.19, P=0.010), low MPV ( OR=0.46, 95% CI: 0.21-0.99, P=0.048) and low MPV/PLT ( OR=0.02, 95% CI: 0.01-0.03, P<0.001) were independent risk factors for postoperative recurrence in patients with primary brain glioma. The logistic prediction model based on the above indicators was logit ( P) =11.78+2.15×WHO grade+2.21×IDH1/2 mutation situation-0.78×MPV-200.70×MPV/PLT ( R2=0.785). The ROC curve analysis results showed that WHO grade, IDH1/2 mutation, MPV, MPV/PLT, and logistic prediction model P-value could all be used to predict the risk of postoperative recurrence in patients with primary brain glioma; The areas under the curve were 0.681, 0.684, 0.783, 0.920 and 0.964, respectively. In the area under ROC curve comparison of each indicator, the predictive performance of the logistic regression model P-value was significantly higher than that of other indicators (all P<0.05) . Conclusion:Postoperative recurrence in patients with primary brain glioma may be related to glioma WHO grade, IDH1/2 mutation and platelet related laboratory indexes. The model constructed based on the above indicators can be used to predict the recurrence risk in patients with primary brain glioma after surgery.

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