1.Analysis of Mechanism of Xingpi Capsules in Treatment of Functional Dyspepsia Based on Transcriptomics
Rongxin ZHU ; Mingyue HUANG ; Keyan WANG ; Xiangning LIU ; Yinglan LYU ; Gang WANG ; Fangfang RUI ; Qiong DENG ; Jianteng DONG ; Yong WANG ; Chun LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):164-172
ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia(FD) and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats(7 days old) were randomly divided into the normal group(n=12) and the modeling group(n=48), and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared, the rats in the modeling group were randomly divided into the model group, the low-dose and high-dose groups of Xingpi capsules(0.135, 0.54 g·kg-1) and the domperidone group(3 mg·kg-1), with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water, and rats in the rest of the groups were gavaged with the corresponding medicinal solution, once a day for 7 d. The general survival condition of the rats was observed, and the water intake and food intake of the rats were measured, the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment, the pathological damage of the rat duodenum was examined by hematoxylin-eosin(HE) staining, and the expressions of colonic tight junction protein(Occludin) and zonula occludens protein-1(ZO-1) were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group, and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out. The transcriptomic results were validated by Western blot, immunofluorescence, and real-time fluorescence quantitative polymerase chain reaction(Real-time PCR), and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group, the general survival condition of rats in the model group was poorer, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly reduced(P<0.05), inflammatory infiltration was seen in duodenal pathology, and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced(P<0.01). Compared with the model group, the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly increased(P<0.05), the duodenal pathology showed a decrease in inflammatory infiltration, and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased(P<0.01). Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) through the key genes such as Slc5a1, Abhd6. The validation results showed that compared with the normal group, the phosphorylation levels of PI3K and Akt proteins, the protein expression level of interleukin(IL)-1β, and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3, Slc5a9 and other key genes were significantly increased(P<0.01). Compared with the model group, the phosphorylation levels of PI3K and Akt, the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3 and Slc5a9 were significantly reduced(P<0.05). Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein, and linarionoside A, valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats, its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum, and E-nerolidol, Z-nerolidol, linarionoside A, valerosidatum and senkirkine may be its key active ingredients.
2.Analysis of Mechanism of Xingpi Capsules in Treatment of Functional Dyspepsia Based on Transcriptomics
Rongxin ZHU ; Mingyue HUANG ; Keyan WANG ; Xiangning LIU ; Yinglan LYU ; Gang WANG ; Fangfang RUI ; Qiong DENG ; Jianteng DONG ; Yong WANG ; Chun LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):164-172
ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia(FD) and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats(7 days old) were randomly divided into the normal group(n=12) and the modeling group(n=48), and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared, the rats in the modeling group were randomly divided into the model group, the low-dose and high-dose groups of Xingpi capsules(0.135, 0.54 g·kg-1) and the domperidone group(3 mg·kg-1), with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water, and rats in the rest of the groups were gavaged with the corresponding medicinal solution, once a day for 7 d. The general survival condition of the rats was observed, and the water intake and food intake of the rats were measured, the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment, the pathological damage of the rat duodenum was examined by hematoxylin-eosin(HE) staining, and the expressions of colonic tight junction protein(Occludin) and zonula occludens protein-1(ZO-1) were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group, and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out. The transcriptomic results were validated by Western blot, immunofluorescence, and real-time fluorescence quantitative polymerase chain reaction(Real-time PCR), and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group, the general survival condition of rats in the model group was poorer, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly reduced(P<0.05), inflammatory infiltration was seen in duodenal pathology, and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced(P<0.01). Compared with the model group, the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly increased(P<0.05), the duodenal pathology showed a decrease in inflammatory infiltration, and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased(P<0.01). Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) through the key genes such as Slc5a1, Abhd6. The validation results showed that compared with the normal group, the phosphorylation levels of PI3K and Akt proteins, the protein expression level of interleukin(IL)-1β, and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3, Slc5a9 and other key genes were significantly increased(P<0.01). Compared with the model group, the phosphorylation levels of PI3K and Akt, the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3 and Slc5a9 were significantly reduced(P<0.05). Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein, and linarionoside A, valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats, its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum, and E-nerolidol, Z-nerolidol, linarionoside A, valerosidatum and senkirkine may be its key active ingredients.
3.Exploration on the Mechanism of Aidi Injection in the Treatment of Ovarian Cancer Based on Network Pharmacology and Cell Experiments
Zhimin DENG ; Mali WU ; Fangfang DAI
Journal of Medical Research 2024;53(2):40-46
Objective To explore the key molecular targets and possible mechanisms of Aidi injection in the treatment of ovarian cancer using network pharmacology and cell experiments.Methods TCMSP database was used to screen the active ingredients and tar-gets of Aidi injection,and the abnormal expressed genes of ovarian cancer were screened,and the possible targets of Aidi injection in o-varian cancer were obtained after intersection analysis.Then,protein-protein interaction analysis,drug-compact-target network con-struction and enrichment analysis of possible targets were performed.The target was further screened,and the key genes related to the prognosis of ovarian cancer were experimentally verified.After treated with 50mg/ml Aidi injection,the cell proliferation ability was ob-served by CCK-8 assay,and the expression of core target genes was detected by real-time quantitative polymerase chain reaction.Results A total of 13 possible targets of Aidi injection in ovarian cancer were screened.These targets were mainly enriched in signaling pathways closely related to the occurrence and development of tumors,such as apoptosis,platinum resistance and interleukin-17.Among the 13 genes,claudin 4(CLDN4),secretory leukocyte peptidase inhibitor(SLPI)and baculoviral IAP repeat containing 5(BIRC5)were associated with the prognosis of ovarian cancer.Cell experiments showed that Aidi injection significantly inhibited the proliferation of ovari-an cancer cell,promoted the expression of BIRC5,a protective target of ovarian cancer,while significantly decreased the levels of ovarian cancer risk factors CLDN4 and SLPI.Conclusion Aidi injection may achieve multi-component,multi-target and multi-pathway anti-ovarian cancer and combination chemotherapy by affecting the expression of CLDN4,SLPI and BIRC5.
4.Expression and significance of ubiquitin-specific proteases 20 and hypoxia inducible factor-1α in breast cancer
Lingyu FANG ; Jinghua HU ; Junfeng WEN ; Shiqi HAN ; Yali WANG ; Lulan PU ; Jingjia LI ; Yi YANG ; Shishan DENG ; Lingmi HOU ; Fangfang ZHOU
The Journal of Practical Medicine 2024;40(16):2270-2276
Objective To explore the changes and significane of USP20 and HIF-α expression in breast cancer.Methods Following transfection of shRNA-USP20 lentivirus into breast cancer MDA-MB-231 cells,the gene and protein expression levels of USP20 were detected using fluorescence quantitative PCR and Western Blot.Subsequently,the overexpression of USP20 was observed to determine its effect on HIF-α expression.Similarly,siRNA-USP20 was used to knock down USP20 in breast cancer MDA-MB-231 cells,followed by detection of gene and protein expression levels using fluorescence quantitative PCR and Western Blot.The subsequent changes in HIF-α expression were then examined.Rusults The positive expression rates of USP20 and HIF-α in breast cancer tissues were 69.6%and 46.83%,respectively,while they were negatively expressed in the adjacent normal tissues,with statistically significant differences(P<0.01).The positive expressions of USP20 and HIF-α were predomi-nantly observed in the cytoplasm of breast cancer tissue,with a smaller amount present in the nucleus.There was a significant positive correlation between USP20 and HIF-α in breast cancer.Following transfection of shRNA-USP20 lentivirus into MDA-MB-231 cells,both the protein and gene expression levels of USP20 significantly increased(P<0.01).Over-expression of USP20 did not affect HIF-α mRNA levels but led to a significant increase in HIF-α protein expression(P<0.01).Conversely,siRNA-USP20 interference resulted in a significant decrease in both the protein and gene expression levels of USP20(P<0.01),without affecting HIF-α mRNA levels;however,it caused a notable reduction in HIF-α protein expression(P<0.01).Conclusion The expression of USP20 exhib-ited a significant positive correlation with HIF-α in breast cancer.Overexpression of USP20 led to a substantial increase in HIF-α protein expression,while knock-down of the USP20 gene resulted in a significant decrease in HIF-α protein levels.Therefore,it can be inferred that USP20 may exert its influence on the development of breast cancer through modulation of HIF-α expression,thereby providing crucial experimental evidence for clinical treat-ment,prognosis,and further investigations.
5.Non-contrast CT findings of acute ischemic stroke for predicting early prognosis after mechanical thrombectomy
Jingyao YANG ; Yeyu XIAO ; Qian ZHANG ; Fangfang DENG ; Zhuyin ZHANG ; Jianjun PAN ; Qinghua LUO ; Haiyang DAI
Chinese Journal of Interventional Imaging and Therapy 2024;21(8):457-462
Objective To explore the value of non-contrast CT findings of acute ischemic stroke(AIS)for predicting early prognosis after mechanical thrombectomy.Methods Data of 161 AIS patients from clinical center 1 who underwent mechanical thrombectomy were retrospectively analyzed.The patients were divided into training set(n=113)and internal test set(n=48)at the ratio of 7∶3,while 79 AIS patients who underwent mechanical thrombectomy from clinical center 2 were retrospectively enrolled as external test set.According to the National Institutes of Health stroke scale(NIHSS)scores 7 days after thrombectomy,patients'prognosis were classified as good(<15 points)or poor(≥15 points).Pre-treatment non-contrast CT images of patients were reviewed,and CT findings were comparatively analyzed.Independent predictors of patients'early prognosis after mechanical thrombectomy were obtained with sequential univariate and multivariate logistic regressions,and a predicting model was established and visualized as a nomogram.The receiver operating characteristic curve was drawn,and the distinction was assessed with the area under the curve(AUC),then calibration was assessed with Hosmer-Lemeshow goodness of fit test,and the net benefit was evaluated with decision curve analysis(DCA).Results Alberta stroke program early CT score(ASPECTS),hyperdense middle cerebral artery sign(HMCAS)and basal ganglia calcification were all independent predictors of early prognosis of AIS after mechanical thrombectomy(all P<0.05).The predictive model was established combining the above 3 variables and then visualized as a nomogram to predict prognosis of AIS after mechanical thrombectomy,with AUC of 0.776 in internal test set(χ2=6.052,P=0.417)and 0.800 in external test set(χ2=2.269,P=0.811).DCA showed that the nomogram might provide clinical net benefit within certain threshold probability ranges.Conclusion ASPECTS,HMCAS and basal ganglia calcification were all independent predictors of early prognosis of AIS after mechanical thrombectomy.The nomogram originated from predicting model combining the three could be used to somewhat accurately predict poor early prognosis after mechanical thrombectomy.
6.Association between serum alkaline phosphatase and type 2 diabetes mellitus with nonalcoholic fatty liver disease
Fangfang QIAN ; Meiqing DAI ; Li ZHAO ; Xia DENG ; Ling YANG ; Jue JIA ; Jifang WANG ; Dong WANG ; Guoyue YUAN
Journal of Clinical Hepatology 2023;39(1):83-88
Objective To investigate the association between serum alkaline phosphatase (ALP) and type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD). Methods A total of 599 patients with T2DM who were hospitalized in Department of Endocrinology, Affiliated Hospital of Jiangsu University, from July 2016 to December 2018 were enrolled as subjects. According to the presence or absence of NAFLD, the patients were divided into NAFLD group with 286 patients and non-NAFLD group with 313 patients, and according to the results of abdominal ultrasound, the patients with NAFLD were divided into mild group with 111 patients, moderate group with 105 patients, and severe group with 70 patients. General clinical data were compared between groups. The independent samples t - test was used for comparison of normally distributed continuous data between two groups, and an analysis of variance was used for comparison between three groups; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between three groups; the chi-square test was used for comparison of categorical data between groups. Pearson correlation analysis and Spearman correlation analysis were used to investigate the correlation between ALP and clinical indices, and a logistic regression analysis was used to investigate the influencing factors for NAFLD. Results Compared with the non-NAFLD group, the NAFLD group had significantly higher proportion of patients with history of hypertension ( χ 2 =7.864, P < 0.05), systolic blood pressure ( t =-2.226, P < 0.05), diastolic blood pressure ( t =-3.800, P < 0.05), body mass index (BMI) ( t =-11.842, P < 0.05), waist circumference (WC) ( t =-9.150, P < 0.05), fasting insulin (FINS) ( Z =-6.173, P < 0.05), fasting C-peptide ( t =-5.419, P < 0.05), serum uric acid ( t =-4.957, P < 0.05), low-density lipoprotein cholesterol ( t =-2.702, P < 0.05), triglyceride ( Z =-9.376, P < 0.05), total cholesterol (TC) ( t =-3.016, P < 0.05), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) ( Z =-5.794, P < 0.05), alanine aminotransferase (ALT) ( Z =-6.737, P < 0.05), aspartate aminotransferase (AST) ( Z =-4.389, P < 0.05), gamma-glutamyl transpeptidase (GGT) ( Z =-7.764, P < 0.05), and ALP ( t =-2.833, P < 0.05), as well as significantly lower age ( t =2.184, P < 0.05) and high-density lipoprotein cholesterol ( Z =-5.273, P < 0.05). The severity of NAFLD (mild, moderate or severe) was positively correlated with age ( r s =0.140, P < 0.05), BMI ( r s =0.239, P < 0.05), WC ( r s =0.222, P < 0.05), FINS ( r s =0.191, P < 0.05), HOMA-IR ( r s =0.218, P < 0.05), ALT ( r s =0.188, P < 0.05), AST ( r s =0.279, P < 0.05), GGT ( r s =0.202, P < 0.05), and ALP ( r s =0.361, P < 0.05). In the patients with T2DM and NAFLD, ALP was positively correlated with HbAlc ( r =0.149, P < 0.05), fasting plasma glucose ( r =0.146, P < 0.05), HOMA-IR ( r s =0.132, P < 0.05), TC ( r =0.151, P < 0.05), ALT ( r s =0.210, P < 0.05), AST ( r s =0.192, P < 0.05), and GGT ( r s =0.297, P < 0.05). The logistic regression analysis showed that ALP was an influencing factor for NAFLD in patients with T2DM (odds ratio=1.013, 95% confidence interval: 1.004-1.023, P < 0.05). Conclusion Elevated serum ALP is a risk factor for T2DM with NAFLD and is closely associated with hyperglycemia, insulin resistance, and hyperlipemia, and ALP may play a role in the development and progression of T2DM and NAFLD.
7.Expert consensus on perioperative nursing management of nutrition for elderly patients with hip fractures (version 2023)
Chunhua DENG ; Xiaohua CHEN ; Zhihua YIN ; Yao JIANG ; Xiaoju TAN ; Yaping CHEN ; Junqin DING ; Luo FAN ; Leling FENG ; Yuyun GAN ; Xiaoyan GAO ; Jinli GUO ; Jing HU ; Chen HUANG ; Guiling HUANG ; Tianwen HUANG ; Yingchun HUANG ; Hui JIN ; Yan JIN ; Fangfang LI ; Hui LI ; Hui LIU ; Ping LIU ; Ning NING ; Lingyun SHI ; Guomin SONG ; Yani SUN ; Guangling WANG ; Jie WANG ; Qi WANG ; Xia WANG ; Xiaoyun WANG ; Yi WANG ; Songmei WU ; Jian YANG ; Yumei ZHANG ; Yang ZHOU ; Xiaoyan WANG ; Yuan GAO
Chinese Journal of Trauma 2023;39(5):394-403
Hip fractures are among the most common fractures in the elderly, presenting to be a leading cause of disability and mortality. Surgical treatment is currently the main treatment method for hip fractures. The incidence of perioperative malnutrition is increased after hip fractures in the elderly due to the comorbidities, decreased basal metabolic rate, accelerated protein breakdown, weakened anabolism and surgical stress. However, malnutrition not only increases the incidence of postoperative complications, but also leads to increased mortality, indicating an important role of perioperative nursing management of nutrition for the elderly patients with hip fractures. At present, there still lacks scientific guidance and application standards on perioperative nursing management of nutrition for the elderly patients with hip fractures. Therefore, the Orthopedic Nursing Committee of Chinese Nursing Association and the Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Expert consensus on perioperative nursing management of nutrition for elderly patients with hip fractures ( version 2023) according to evidence-based medical evidences and their clinical experiences. Fourteen recommendations were made from aspects of nutrition screening, nutrition assessment, nutrition diagnosis, nutrition intervention and nutrition monitoring to provide guidance for perioperative nursing management of nutrition in elderly patients with hip fractures.
8.Application of intestinal fluid reinfusion after anterior resection of rectum and preventive ileostomy in patients with low rectal cancer
Ting ZOU ; Fangfang ZHANG ; Mei WANG ; Xin DENG ; Jingfen ZHANG ; Shufen NI
Chinese Journal of Postgraduates of Medicine 2023;46(9):832-837
Objective:To analyze the effect of intestinal fluid reinfusion after anterior resection of rectum and preventive ileostomy in patients with low rectal cancer.Methods:A prospective research method was used, and 60 patients with low rectal cancer in Zhejiang Jinhua Guangfu Tumor Hospital from January 2021 to June 2022 were enrolled. The patients were divided into control group (treated with anterior resection of rectum and preventive ileostomy) and observation group (treated with anterior resection of rectum and preventive ileostomy combined with intestinal fluid infusion) by random number table method with 30 cases each. On the next day and 3 months after surgery, the low anterior resection syndrome (LARS) scale was used to evaluate anal function, the patient-generated subjective global assessment (PG-SGA) method was used to evaluate nutritional status, the stoma-quality of life (stoma-QOL) was used to evaluate the quality of life. The complications were recorded.Results:Both groups of patients were successfully completed the scheduled surgery. There were no statistical differences in LARS score and incidence of LARS on the next day after surgery between the two groups ( P>0.05); the LARS score and incidence of LARS 3 months after surgery in observation group were significantly lower than those in control group: (18.63 ± 3.15) scores vs. (24.90 ± 6.11) scores and 23.33% (7/30) vs. 46.67% (14/30), and there were statistical differences ( P<0.01 or <0.05). There were no statistical differences in PG-SGA score and incidence of malnutrition on the next day after surgery between the two groups ( P>0.05); the PG-SGA score and incidence of malnutrition 3 months after surgery in observation group were significantly lower than those in control group: (3.07 ± 0.82) scores vs. (5.13 ± 1.01) scores and 26.67% (8/30) vs. 46.67% (14/30), and there were statistical differences ( P<0.01 or <0.05). There were no statistical differences in the scores of psychological burden, social interaction, stoma management and daily living of stoma-QOL on the next day after surgery between the two groups ( P>0.05); the scores 3 months after surgery in observation group were significantly higher than those in control group: (27.70 ± 4.28) scores vs. (21.47 ± 5.16) scores, (14.33 ± 2.03) scores vs. (11.90 ± 1.64) scores, (14.87 ± 1.92) scores vs. (11.57 ± 2.38) scores and (15.30 ± 1.03) scores vs. (12.37 ± 2.11) scores, and there were statistical differences ( P<0.01). The incidence of complications in observation group was significantly lower than that in control group: 30.00% (9/30) vs. 60.00% (18/30), and there was statistical difference ( χ2 = 5.45, P<0.05). Conclusions:For the patients with low rectal cancer, the anterior resection of rectum and preventive ileostomy combined with intestinal fluid reinfusion can reduce LARS, improve nutritional status, improve quality of life, and also reduce complications.
9.Effects of plasma exosome⁃derived miR⁃29b⁃3p on myocardial cell inj ury in hypoxia/reoxygenation after sevoflurane postconditioning via targeting IGF1
Fangfang Deng ; Jiyong Li ; Li Zhang ; Gaorui Zou ; Zhijun Chen ; Wei Le
Acta Universitatis Medicinalis Anhui 2023;58(9):1450-1457
Objective :
The purpose of this study was to investigate the effects of plasma exosome⁃derived miR⁃29b⁃3p in myocardial ischemia⁃reperfusion injury ( MIRI) rats on hypoxia/reoxygenation ( H/R) cardiomyocyte after
sevoflurane (SEV) postconditioning through targeting IGF1 .
Methods :
The GEO database was used to screen differentially expressed miRNAs in MIRI , and cardiomyocytes were treated with H/R to construct a MIRI cell model. The expression of miR⁃29b⁃3p and IGF1 in the MIRI cell model post⁃treated with SEV was intervened , and then the survival rate of cardiomyocytes was detected by MTT , apoptosis was detected by flow cytometry , and inflammatory factors (IL⁃1β and TNF⁃α ) in cardiomyocytes in each group were detected by ELISA.
Results :
Compared with Normal group , the expression of miR⁃29b⁃3p in plasma exosomes of MIRI rats was enhanced (P < 0. 05) , and the target⁃binding relationship between miR⁃29b⁃3p and IGF1 was confirmed ( P < 0. 05) . After SEV post⁃treatment , the expression of miR⁃29b⁃3p in H/R⁃stimulated cardiomyocytes decreased , while the expression of IGF1 increased (both P < 0. 05) . Overexpression of miR⁃29b⁃3p in plasma exosomes could significantly inhibit the survival rate of H/R cells after SEV treatment , aggravate apoptosis and inflammatory response , while knockdown of miR⁃29b⁃3p showed a opposite effects (all P < 0. 05) . The rescue experimental data showed that overexpression of IGF1 could partially reverse the effects of overexpression of miR⁃29b⁃3p on H/R cell injury after SEV treatment ( all P <0. 05) .
Conclusion
Plasma exosome⁃derived miR⁃29b⁃3p promotes H/R cardiomyocyte injury after SEV treatment by targeting IGF1 .
10.Liver histopathology and clinical features of autoimmune hepatitis with different antibody statuses
Yuanjiao GAO ; Yanjie LIN ; Liu YANG ; Xiaoyue BI ; Wen DENG ; Tingting JIANG ; Fangfang SUN ; Yao LU ; Lu ZHANG ; Minghui LI ; Yao XIE
Journal of Clinical Hepatology 2022;38(12):2744-2749
Objective To compare clinical and pathological features between autoimmune hepatitis (AIH) patients with positive and negative autoantibodies, and to summarize the experience in diagnosis. Methods A retrospective analysis was performed for the patients who attended Beijing Ditan Hospital from January 2010 to August 2021 and were diagnosed with AIH by liver histopathology, and according to the presence or absence of autoantibodies, they were divided into positive autoantibody group and negative autoantibody group. The two groups were compared in terms of biochemical parameters, immunological features, histopathological features, disease stage, and clinical symptoms and signs. The t -test or the Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data. Results A total of 110 patients were enrolled, among whom 78 (71%) had positive autoantibodies and 32 (29%) had negative autoantibodies. Anti-nuclear antibody (ANA), anti-mitochondrial antibody (AMA), and anti-smooth muscle antibody (ASMA) were the main autoantibodies detected, and of all 110 patients, 74 (67.27%) had positive ANA, 1 (0.91%) had positive AMA, 5 (4.55%) had positive ASMA, and 14 (12.73%) had positive anti-Ro-52 antibody. As for clinical and immunological features, compared with the positive autoantibody group, the negative autoantibody group had significantly lower incidence rates of jaundice of the skin and sclera (21.90% vs 50.00%, χ 2 =7.377, P =0.007) and poor appetite (18.80% vs 41.00%, χ 2 =4.979, P =0.026) and significantly lower median levels of direct bilirubin [7.30(4.05~12.10) μmol/L vs 16.80(6.48~69.75) μmol/L, Z =-2.304, P =0.021], IgG [16.40(13.15~18.05) g/L vs 20.30(16.00~27.15) g/L, Z =-2.715, P =0.007], and GLo [30.60(26.00~34.90) g/L vs 37.30(30.50~42.50) g/L, Z =-3.356, P =0.001]. In terms of liver histopathology, compared with the negative autoantibody group, the positive autoantibody group had a significantly higher proportion of patients with lymphocyte infiltration (91.03% vs 68.75%, χ 2 =6.997, P =0.008) and plasma cell infiltration (82.05% vs 50.00%, χ 2 =11.572, P =0.001); compared with the ANA-negative patients, the ANA-positive patients had significantly higher inflammation grade (G1-G4) (9.46%/16.22%/44.59%/29.73% vs 5.56%/27.78%/63.89%/2.78%, Z =-2.179, P =0.029) and fibrosis degree (S1-S4) (37.84%/25.68%/32.43%/4.05% vs 13.89%/41.67%/30.56%/13.89%, Z =-0.082, P =0.037). Conclusion Compared with AIH patients with positive autoantibodies, AIH patients with negative autoantibodies are mostly in the early stage of the disease and tend to have a low level of IgG, with a relatively high rate of missed diagnosis in clinical practice. Early and active liver biopsy is of particular importance.


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