1.Expression of serpin family E member 1 in gastric cancer and its mechanisms in promoting gastric cancer
Yongyu CHEN ; Yiren HUANG ; Zheyi CHEN ; Bingqian ZHOU ; Shiyu CHEN ; Yingxia ZHENG
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(2):150-160
Objective·To investigate the expression of serpin family E member 1(SERPINE1)in gastric cancer and its potential mechanisms in promoting gastric cancer.Methods·Pan-cancer analysis of SERPINE1 was performed by using the TIMER2.0 online website,and the differences in the expression of SERPINE1 in samples with different tumor stages of gastric cancer were analysed by the clinical data of gastric cancer from The Cancer Genome Atlas(TCGA)database.Survival curves were plotted.Quantitative real-time PCR(qRT-PCR)was used to detect mRNA expression in paired samples of clinical gastric cancer tissues.The small interfering RNA(siRNA)transfection technique was used to knock down the expression of SERPINE1 in MGC-803 and SGC-7901 gastric cancer cell lines,and the migration and invasive abilities of gastric cancer cells were investigated by Transwell and invasion chamber experiments.The effects of SERPINE1 knockdown on the angiogenesis of gastric cancer cells were further explored by the migration assay of human umbilical vein endothelial cells(HUVEC)and tubule formation assay of HUVECs.The Gene Expression Omnibus(GEO)dataset was used for differential gene analysis in high and low expression groups based on the median value of SERPINE1 expression.The differentially expressed genes were further analyzed by Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis and Gene Set Enrichment Analysis(GSEA).qRT-PCR was performed to verify the expression levels of key genes related to epithelial-mesenchymal transition(EMT)and angiogenesis.Results·Bioinformatics analysis showed that SERPINE1 was highly overexpressed in a variety of primary tumour tissues,including gastric cancer.SERPINE1 gene expression increased with increasing tumour stage(P<0.001),and increased expression of SERPINE1 was associated with poor prognosis of gastric cancer(P<0.001).qRT-PCR results showed that SERPINE1 was significantly highly expressed in gastric cancer tissues(P=0.038).After knocking down SERPINE1,gastric cancer cell lines MGC-803 and SGC-7901 cells had decreased migration and invasion(P<0.05).Gastric cancer culture supernatants from the SERPINE1-knockdown gastric cancer cell line reduced angiogenesis in HUVECs(P<0.05).Differential genes in gastric cancer patients in the SERPINE1 high-expression group in the GEO database were enriched in cancer-related pathways such as focal adhesion,extracellular matrix receptor interaction,and angiogenesis-related pathways like angiogenesis and the vascular endothelial growth factor(VEGF)signalling pathway.The expression of SERPINE1 was negatively correlated with cadherin 1(CDH1),and positively correlated with other key genes related to EMT and angiogenesis.Moreover,the expression levels of key genes related to EMT and angiogenesis detected by qRT-PCR in SERPINE1 knockdown gastric cancer cell lines(P<0.05),were consistent with the correlation analysis results mentioned above.Conclusion·SERPINE1 expression is elevated in gastric cancer tissues,which could regulate the expression levels of key genes related to EMT and angiogenesis to promote the migration,invasion and angiogenesis of gastric cancer cells.
2.Study on the safety and pharmacological effect on improving dyspepsia of Shuangshu decoction in rats
Xinyuan CHEN ; Changzhou XIONG ; Jiongfen LI ; Kangyi YU ; Huan XU ; Yingxia WANG ; Dan LIAO ; Junyu TAO ; Ziyi YANG ; Caizhi LIN
China Pharmacy 2025;36(9):1059-1064
OBJECTIVE To study the safety of Shuangshu decoction in rats and its efficacy in improving functional dyspepsia (FD) in rats. METHODS In safety test, 40 rats were divided into blank control group, Shuangshu decoction low-dose, medium- dose and high-dose groups [108, 216, 324 g/(kg·d), calculated by raw medicine, the same applies below]; they were given relevant medicine intragastrically, for continuous 14 days. The mortality and toxic reactions of rats were recorded, and the organ indexes of the liver, kidney, spleen, lung and heart of rats were calculated; the pathological morphological changes in the liver, kidney, spleen, lung, heart, stomach, duodenum, and colon were observed to evaluate the acute toxicity of Shuangshu decoction. Another 40 rats were grouped and administered in the same way for 30 consecutive days. The mortality and toxic reactions of the rats were recorded, and the corresponding organ indexes were calculated. The pathological morphological changes in the corresponding organs were observed, and blood routine and serum biochemical indicators were measured, in order to assess the subacute toxicity of Shuangshu decoction. In pharmacodynamic experiments: 50 rats were divided into blank control group, model group, and Shuangshu decoction low-, medium-, and high-dose groups (9.45, 18.9, 37.8 g/kg), with 10 rats in each group. Except for blank control group, rats in all other groups were used to establish the FD rat model by subcutaneous injection of loperamide (3.5 mg/kg). Rats in each group were administered the corresponding drug solution/normal saline intragastrically, once a day, for 14 consecutive days. After the last medication, fecal moisture content, intestinal propulsion rate, gastric emptying rate and serum level of motilin were all detected, and interstitial cell of Cajal (ICC) ultrastructure of rats was observed in colon tissue. RESULTS The safety experiments showed that no death occurred in each dose group, and no significant difference was found in organ coefficient, routine blood and serum biological index, compared to blank control group (P>0.05); no abnormality was found in organ appearance and pathological sections. The results of the pharmacodynamic experiments showed that, compared with the blank control group, the fecal moisture content, gastric emptying rate, intestinal propulsion rate, and serum motilin levels in the model group were significantly decreased (P<0.05); in the colonic tissue, the mitochondria in the ICC exhibited severe swelling with the disappearance of cristae, and the endoplasmic reticulum was dilated. Compared with model group, the rats in Shuangshu decoction high-dose group showed significant increases in the above quantitative indicators (P< 0.05); additionally, there was a large number of mitochondria in the ICC of the colonic tissue, with clear cristae and regular arrangement. CONCLUSIONS Shuangshu decoction is safe and has a beneficial improving effect on FD rats; its mechanism of action may be related to the regulation of gastrointestinal hormone expression to promote gastric emptying and intestinal propulsion, as well as the repair of mitochondrial structure in ICCs to restore gastrointestinal function.
3.Expression of serpin family E member 1 in gastric cancer and its mechanisms in promoting gastric cancer
Yongyu CHEN ; Yiren HUANG ; Zheyi CHEN ; Bingqian ZHOU ; Shiyu CHEN ; Yingxia ZHENG
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(2):150-160
Objective·To investigate the expression of serpin family E member 1(SERPINE1)in gastric cancer and its potential mechanisms in promoting gastric cancer.Methods·Pan-cancer analysis of SERPINE1 was performed by using the TIMER2.0 online website,and the differences in the expression of SERPINE1 in samples with different tumor stages of gastric cancer were analysed by the clinical data of gastric cancer from The Cancer Genome Atlas(TCGA)database.Survival curves were plotted.Quantitative real-time PCR(qRT-PCR)was used to detect mRNA expression in paired samples of clinical gastric cancer tissues.The small interfering RNA(siRNA)transfection technique was used to knock down the expression of SERPINE1 in MGC-803 and SGC-7901 gastric cancer cell lines,and the migration and invasive abilities of gastric cancer cells were investigated by Transwell and invasion chamber experiments.The effects of SERPINE1 knockdown on the angiogenesis of gastric cancer cells were further explored by the migration assay of human umbilical vein endothelial cells(HUVEC)and tubule formation assay of HUVECs.The Gene Expression Omnibus(GEO)dataset was used for differential gene analysis in high and low expression groups based on the median value of SERPINE1 expression.The differentially expressed genes were further analyzed by Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis and Gene Set Enrichment Analysis(GSEA).qRT-PCR was performed to verify the expression levels of key genes related to epithelial-mesenchymal transition(EMT)and angiogenesis.Results·Bioinformatics analysis showed that SERPINE1 was highly overexpressed in a variety of primary tumour tissues,including gastric cancer.SERPINE1 gene expression increased with increasing tumour stage(P<0.001),and increased expression of SERPINE1 was associated with poor prognosis of gastric cancer(P<0.001).qRT-PCR results showed that SERPINE1 was significantly highly expressed in gastric cancer tissues(P=0.038).After knocking down SERPINE1,gastric cancer cell lines MGC-803 and SGC-7901 cells had decreased migration and invasion(P<0.05).Gastric cancer culture supernatants from the SERPINE1-knockdown gastric cancer cell line reduced angiogenesis in HUVECs(P<0.05).Differential genes in gastric cancer patients in the SERPINE1 high-expression group in the GEO database were enriched in cancer-related pathways such as focal adhesion,extracellular matrix receptor interaction,and angiogenesis-related pathways like angiogenesis and the vascular endothelial growth factor(VEGF)signalling pathway.The expression of SERPINE1 was negatively correlated with cadherin 1(CDH1),and positively correlated with other key genes related to EMT and angiogenesis.Moreover,the expression levels of key genes related to EMT and angiogenesis detected by qRT-PCR in SERPINE1 knockdown gastric cancer cell lines(P<0.05),were consistent with the correlation analysis results mentioned above.Conclusion·SERPINE1 expression is elevated in gastric cancer tissues,which could regulate the expression levels of key genes related to EMT and angiogenesis to promote the migration,invasion and angiogenesis of gastric cancer cells.
4.Clinical characteristics of chronic drug-induced liver injury: a multicenter retrospective cross-sectional study
Hong ZHAO ; Yingxia LIU ; Qing XIE ; Jun LI ; Ming YAN ; Jianming XU ; Jiajun LIU ; Xiaoguang DOU ; Chengwei CHEN ; Yimin MAO ; Wen XIE
Adverse Drug Reactions Journal 2023;25(7):405-412
Objective:To investigate the prevalence, clinical characteristics, risk factors, and prognosis of chronic drug-induced liver injury (DILI).Methods:A multicenter, open, retrospective, non-interventional epidemiological survey was conducted. According to the inclusion criteria, patients with DILI and hospitalized in 308 hospitals in China from January 1, 2012 to December 31, 2014 were enrolled, and medical records of the patients were collected. The patients with DILI were divided into chronic and acute DILI groups. The clinical characteristics, laboratory tests, and prognosis in patients of the 2 groups were compared, and the suspected drugs that induced the liver injury were analyzed. Univariate and multivariate logistic regression analyses were used to analyze the influencing factors of chronic DILI.Results:A total of 25 927 patients were enrolled in the study, including 22 556 (87%) with acute DILI (acute DILI group) and 3 371 (13%) with chronic DILI (chronic DILI group). In the chronic DILI group, there were high proportion of women and the patients were older in age; more patients were with a history of liver disease and the time from medication to DILI was longer; more patients had digestive system symptoms (including loss of appetite, abdominal distension, nausea, vomiting, etc.), fatigue, jaundice, pruritus, liver pain/discomfort, bleeding tendency; the alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and international normalized ratio were higher, while the serum albumin and platelet counts were lower; the proportion of patients with model for end-stage liver disease score ≥ 15 was higher; the all-cause mortality rate and liver disease-related mortality rate were higher, compared with the acute DILI group. The differences above-mentioned were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that male was protective factor [odds ratio ( OR)=0.76, 95% confidence interval ( CI): 0.69-0.83], while previous liver disease history ( OR=2.00, 95% CI: 1.82-2.19) and hypoalbuminemia ( OR=0.96, 95% CI: 0.95-0.96) were independent risk factors for chronic DILI. Conclusions:In the study period, the proportion of chronic DILI among DILI inpatients is 13.0% in the 308 hospitals. Compared with those with acute DILI, more chronic DILI patients were female, and patients with chronic DILI have higher ages, severer conditions, and poorer prognoses; female, previous liver disease history, and hypoalbuminemia are independent risk factors for chronic DILI.
5.Clinical characteristics of chronic drug-induced liver injury: a multicenter retrospective cross-sectional study
Hong ZHAO ; Yingxia LIU ; Qing XIE ; Jun LI ; Ming YAN ; Jianming XU ; Jiajun LIU ; Xiaoguang DOU ; Chengwei CHEN ; Yimin MAO ; Wen XIE
Adverse Drug Reactions Journal 2023;25(7):405-412
Objective:To investigate the prevalence, clinical characteristics, risk factors, and prognosis of chronic drug-induced liver injury (DILI).Methods:A multicenter, open, retrospective, non-interventional epidemiological survey was conducted. According to the inclusion criteria, patients with DILI and hospitalized in 308 hospitals in China from January 1, 2012 to December 31, 2014 were enrolled, and medical records of the patients were collected. The patients with DILI were divided into chronic and acute DILI groups. The clinical characteristics, laboratory tests, and prognosis in patients of the 2 groups were compared, and the suspected drugs that induced the liver injury were analyzed. Univariate and multivariate logistic regression analyses were used to analyze the influencing factors of chronic DILI.Results:A total of 25 927 patients were enrolled in the study, including 22 556 (87%) with acute DILI (acute DILI group) and 3 371 (13%) with chronic DILI (chronic DILI group). In the chronic DILI group, there were high proportion of women and the patients were older in age; more patients were with a history of liver disease and the time from medication to DILI was longer; more patients had digestive system symptoms (including loss of appetite, abdominal distension, nausea, vomiting, etc.), fatigue, jaundice, pruritus, liver pain/discomfort, bleeding tendency; the alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and international normalized ratio were higher, while the serum albumin and platelet counts were lower; the proportion of patients with model for end-stage liver disease score ≥ 15 was higher; the all-cause mortality rate and liver disease-related mortality rate were higher, compared with the acute DILI group. The differences above-mentioned were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that male was protective factor [odds ratio ( OR)=0.76, 95% confidence interval ( CI): 0.69-0.83], while previous liver disease history ( OR=2.00, 95% CI: 1.82-2.19) and hypoalbuminemia ( OR=0.96, 95% CI: 0.95-0.96) were independent risk factors for chronic DILI. Conclusions:In the study period, the proportion of chronic DILI among DILI inpatients is 13.0% in the 308 hospitals. Compared with those with acute DILI, more chronic DILI patients were female, and patients with chronic DILI have higher ages, severer conditions, and poorer prognoses; female, previous liver disease history, and hypoalbuminemia are independent risk factors for chronic DILI.
6.Clinical characteristics of 57 cases of Brucella infection in Shenzhen City
Rongrong ZOU ; Feng CHEN ; Xinran CHEN ; Yingxia LIU ; Jing YUAN
Chinese Journal of Infectious Diseases 2022;40(9):545-550
Objective:To analyze the clinical characteristics of Brucella infection in Shenzhen City, and to provide reference for clinical diagnosis and treatment of patients with Brucella infection. Methods:The clinical characteristics of 57 patients with Brucella infection from January 1, 2018 to December 31, 2020 in The Third People′s Hospital of Shenzhen were retrospectively analyzed. The clinical characteristics of patients with brucellosis and latent Brucella infection, patients with or without comorbidities were compared respectively, and magnetic resonance imaging (MRI) and lumbar puncture examination findings of 57 patients were also analyzed. Statistical analysis was performed using Wilcoxon rank sum test and chi-square test. Results:Among the 57 patients with Brucella infection, 10 cases (17.5%) were latent infections and 47 cases (82.5%) were brucellosis patients. Among brucellosis patients, 91.5%(43/47) had fever and 74.4%(32/43) had maximum body temperature ≥38.1 ℃, 40.4%(19/47) had chills orshivering, 25.5%(12/47) had hyperhidrosis, 17.0%(8/47) had fatigue, 21.3%(10/47) had headache, 23.4%(11/47) had neck/back/low back pain, and 31.9%(15/47) had joint pain. A total of 18 cases (38.3%) had comorbidities. Cases with positive blood cultures in latent infection and brucellosis were seven and 39, respectively. The time from symptom onset to diagnosis was 30.0 (15.0, 67.5) days in 18 patients of brucellosis with comorbidity, which was longer than 20.0 (13.0, 30.0) days in 29 patients without comorbidity. Neck/back/low back pain and joint pain occurred in patients with brucellosis with comorbidity were seven and nine, respectively, and those without comorbidity were four and six, respectively, with statistically significant differences ( Z=-2.00, χ2=3.90 and 4.39, respectively, all P<0.050). Of the 11 brucellosis patients with neck/back/low back pain, six had spondylitis. Of the 15 brucellosis patients with joint pain, six had arthritis. Lumbar puncture examination did not indicate meningitis in six cases of latent infection, while revealed six cases of brucellosis meningitis in 32 brucellosis patients. Fifty-four patients had good outcomes, and three patients were cured after an extended course of treatment. Conclusions:Although patients with latent Brucella infection have no comorbidities, they have a high positive blood culture rate. Active standardized anti- Brucella treatment is recommended. MRI examination of relevant sites is recommended in brucellosis patients with joint, neck/back/low back pain, and lumbar puncture is recommended in brucellosis patients regardless of headache.
7.Clinical efficacy and safety of omalizumab in the treatment of chronic spontaneous urticaria
Yu ZHANG ; Yingxia GAO ; Ningyan GU ; Hong ZHU ; Jingjing CHEN ; Qingjie HU ; Min ZHOU ; Yuanyuan DUAN ; Xu YAO
Chinese Journal of Dermatology 2021;54(7):582-585
Objective:To evaluate the clinical efficacy and safety of omalizumab in the treatment of chronic spontaneous urticaria (CSU) .Methods:Clinical data were collected from 60 patients, who were diagnosed with CSU and received subcutaneous injections of omalizumab at a dose of 300 mg once every 4 weeks for 3 sessions in Hospital of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College from March 2020 to September 2020, and retrospectively analyzed. At weeks 0, 2, 4, 6, 8, 10 and 12, urticaria activity score over 7 days (UAS7) and chronic urticaria quality of life (CU-Q2oL) score were used to evaluate clinical symptoms and quality of life of patients. Changes in the use of other drugs were evaluated before and after the treatment with omalizumab. Paired t test was used to compare UAS7 or CU-Q2oL score before and after treatment. Results:All the 60 CSU patients received 12 weeks of omalizumab treatment. The baseline UAS7 score was 22.37 ± 8.88 points; after one session of the treatment, the UAS7 score dropped to 2.01 ± 5.13 points, reaching the treatment plateau; at week 12, it dropped to 0.6 ± 2.63 points, and 0 point (complete control) in 93.3% of the patients, 1-6 points (favorable control) in 3.3%; the time required for UAS7 score to decrease to 0 point was 22.4 ± 3.2 days. The baseline CU-Q2oL score was 34.10 ± 15.01 points; after one session of the treatment, the CU-Q2oL score dropped to 2.41 ± 7.18 points, reaching the treatment plateau; at week 12, it was 0.56 ± 2.90 points; the time required for CU-Q2oL score to drop to 0 point was 21.15 ± 16.02 days. After the combination treatment with omalizumab, a gradual decrease in dosage or withdrawal of previous therapeutic drugs was realized. At week 12, 39 patients (65%) achieved complete control, and withdrew all therapeutic drugs except omalizumab. During the treatment and follow-up, omalizumab showed good safety, and no adverse reactions were observed.Conclusion:Omalizumab at a dose of 300 mg once every 4 weeks is markedly effective and safe for the treatment of CSU, providing a new treatment option for CSU patients with poor response to traditional therapy.
8.Avian influenza A (H7N9) virus: from low pathogenic to highly pathogenic.
William J LIU ; Haixia XIAO ; Lianpan DAI ; Di LIU ; Jianjun CHEN ; Xiaopeng QI ; Yuhai BI ; Yi SHI ; George F GAO ; Yingxia LIU
Frontiers of Medicine 2021;15(4):507-527
The avian influenza A (H7N9) virus is a zoonotic virus that is closely associated with live poultry markets. It has caused infections in humans in China since 2013. Five waves of the H7N9 influenza epidemic occurred in China between March 2013 and September 2017. H7N9 with low-pathogenicity dominated in the first four waves, whereas highly pathogenic H7N9 influenza emerged in poultry and spread to humans during the fifth wave, causing wide concern. Specialists and officials from China and other countries responded quickly, controlled the epidemic well thus far, and characterized the virus by using new technologies and surveillance tools that were made possible by their preparedness efforts. Here, we review the characteristics of the H7N9 viruses that were identified while controlling the spread of the disease. It was summarized and discussed from the perspectives of molecular epidemiology, clinical features, virulence and pathogenesis, receptor binding, T-cell responses, monoclonal antibody development, vaccine development, and disease burden. These data provide tools for minimizing the future threat of H7N9 and other emerging and re-emerging viruses, such as SARS-CoV-2.
Animals
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COVID-19
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China/epidemiology*
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Humans
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Influenza A Virus, H7N9 Subtype
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Influenza in Birds/epidemiology*
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Influenza, Human/prevention & control*
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Poultry
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SARS-CoV-2
9.Effect of Increasing Efficacy and Decreasing Toxicity of Limax Extract on Cyclophosphamide in the Treatment of Hepatocellular Carcinoma
Tianmin HUANG ; Yingxia YANG ; Hongliang ZHANG ; Lixiu CHEN ; Xiang HUANG ; Jinkui XIE ; Renbin HUANG ; Yufang YANG
China Pharmacy 2021;32(1):17-23
OBJECTIVE:To investigate the effect of increasing efficacy and decreasing toxicity of Limax extract (LE)on cyclophosphamide(CTX)in the treatment of hepatocellular carcinoma. METHODS :The mice were randomly divided into normal group,model group ,CTX group (0.02 g/kg),LE low-dose ,medium-dose and high-dose groups (LEL,LEM,LEH group ,0.6,1.2,2.4 g/kg),CTX+LE low-dose ,medium-dose and high-dose combination groups (CTX+LEL,CTX+LEM,CTX+ LEH group ,the same dose as single drug group ),with 10 huangrenbin518@163.com mice in each group. Except for normal group ,other groups were inoculated with hepatoma cells H 22 in the left ar mpit to establish tumor bearing models. After 24 h of inoculation ,normal group and model group were intragastrically given normal saline , and administration groups were intragastrically given corresponding drugs ,once a day ,for 10 days. On the second day after the last administration ,the general conditions of mice in each group were observed ;the body mass ,thymus index (LI),spleen index (SI)were measured ;the tumor inhibition rate was detected. The effect (q)of combination therapy was evaluated by King ’s formula . The counts of WBC ,RBC and PLT ,serum contents of ALT ,ALT,Scr and BUN were detected in model group ,CTX group and combination groups ,and the contents of MDA,SOD and GSH ,the levels of VEGF ,TNF-α and IL-6 in the tumor tissue were detected by colorimetry and ELISA in above groups. The protein expression of oncogenes (p53,Bcl-2 and Bax )were detected by immunohistochemical method in model group,CTX group and CTX+LEM group. RESULTS :The mice in the model group were in poor spirit and had symptoms of excessive drinking and eating ;although the body weight ,TI and SI were not significantly abnormal compared with normal group (P>0.05),WBC count and AST content were significantly increased ,ALT and BUN contents were significantly decreased (P< 0.05 or P<0.01). Compared with model group ,above symptoms of mice were all improved in administration groups. The tumor weight of administration groups ,TI and SI of CTX group and TI of combination groups were decreased significantly ,but tumor weight of LEL group and LEH group ,TI and SI of LE single groups and combination groups were significantly higher than CTX group;tumor weight of combination groups were significantly lower than CTX group (P<0.05 or P<0.01). The tumor inhibition rates of administration groups were 29.58%-72.08%. The q values of CTX+LEL group ,CTX+LEM group and CTX+LEH group were 1.03,0.97 and 0.86,respectively. Compared with model group ,WBC count ,AST and BUN contents of CTX group ,MDA contents of combination groups ,VEGF,TNF-α and IL-6 levels of administration groups ,the protein expression of Bcl- 2 in CTX group and CTX+LEM group were decreased significantly ;the activities of SOD and GSH of administration groups ,the protein expression of p 53 in CTX+LEM group and Bax in CTX group ,CTX+LEM group were increased significantly (P<0.05 or P< 0.01);WBC counts and AST contents of administration groups ,ALT content of CTX+LEM group ,SOD activity of CTX+LEH group and GSH activity of CTX+LEM group were all significantly higher than those of CTX group ;MDA content of CTX+LEH group,VEGF and TNF-α levels of CTX+LEM group and CTX+LEH group,IL-6 levels of administration groups were all significantly lower than CTX group (P<0.05 or P<0.01). CONCLUSIONS :LE combined with CTX can increase the anti-tumor effect,and LE can reduce the toxicity of CTX induced immunosuppression and bone marrow suppression in mice ,with effect of increasing efficacy and decreasing toxicity. The effect may be related to antioxidant stress ,inhibition of angiogenesis and secretion of inflammatory factors ,and regulation of apoptosis protein expression.
10.Efficacy of antiviral therapy for chronic hepatitis B with nonalcoholic fatty liver disease
Ling QING ; Weiqiang HUANG ; Xiaohe LI ; Feng CHEN ; Yingxia LIU
Journal of Clinical Hepatology 2021;37(9):2075-2080
Objective To investigate the influence of nonalcoholic fatty liver disease (NAFLD) on the antiviral response of patients with chronic hepatitis B (CHB), and to provide a reference for clinical treatment of such patients. Methods A total of 187 patients who attended Shenzhen Third People's Hospital from January 2011 to December 2017 were enrolled and divided into CHB group with 43 patients, NAFLD group with 41 patients, and CHB+NAFLD group with 103 patients. Related indices were measured at enrollment different time points of follow-up, including body height, body weight, alanine aminotransferase (ALT), aspartate aminotransferase, four blood lipid parameters, four indicators of liver fibrosis, aspartate aminotransferase-to-platelet ratio index, HBsAg, HBeAg, anti-HBe, and HBV DNA quantification, and the CHB patients and the CHB+NAFLD patients receiving antiviral therapy were compared in terms of treatment outcome at weeks 12, 24, 48, 72, and 96 of antiviral therapy. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Wilcoxon rank-sum test was used for comparison between two groups; the chi-square test was used for comparison of categorical data between groups. Results Compared with the NAFLD group at baseline, the CHB group and the CHB+NAFLD group had significantly lower platelet count, ALT, gamma-glutamyl transpeptidase (GGT), alkaline phosphatase, and right lobe of liver oblique diameter (all P < 0.05), and compared with the CHB group, the CHB+NAFLD group had significantly higher body mass index, total cholesterol, and triglyceride and a significantly lower spleen thickness (all P < 0.05), while there were no significant differences in the other indicators between the two groups at baseline (all P > 0.05). At week 12 of antiviral therapy, there were no significant differences in liver fibrosis markers and inflammatory indices between the CHB group and the CHB+NAFLD group (all P > 0.05); compared with the CHB+NAFLD group at weeks 24 and 48, the CHB group had significantly greater reductions in ALT ( Z =-2.128 and -3.055, both P < 0.05) and GGT ( Z =-2.025 and -1.631, both P < 0.05); at week 48, the CHB group and the CHB+NAFLD group had a significant reduction in HBV DNA ( Z =-6.445 and -4.415, both P < 0.001), and the CHB group had a significantly greater reduction. The CHB+NAFLD group had a significantly lower HBV DNA clearance rate than the CHB group at different time points of antiviral therapy ( χ 2 =14.237, 13.961, 15.226, 10.462, and 13.030, all P < 0.05). At week 48 of antiviral therapy, the CHB+NAFLD group had a significantly lower HBeAg clearance rate than the CHB group ( χ 2 =5.309, P =0.021), while there was no significant difference between the two groups at week 96 ( χ 2 =0.117, P =0.732). At weeks 24, 48, 72, and 96 of antiviral therapy, the CHB+NAFLD group had a significantly lower ALT normalization rate than the CHB group ( χ 2 =12.049, 5.287, 11.407, and 11.375, all P < 0.05). Conclusion NAFLD reduces the antiviral response of CHB patients and prolongs the duration of antiviral therapy.

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