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 of Predictors to Identify and Screen High Risk Patients With Early Gastric Cancer Submucosal Invasion
Keyan CHEN ; Ye WANG ; Jing ZHANG ; Shigang DING
Chinese Journal of Minimally Invasive Surgery 2024;24(6):401-408
Objective To analyze the clinical,pathological,and endoscopic features of differentiated early gastric cancer,and to study predictors to identify and screen high risk patients with early gastric cancer submucosal infiltration.Methods A total of 172 patients with differentiated early gastric cancer treated by surgical or endoscopic submucosal dissection in our hospital from January 2017 to December 2022 were included,which were divided into the mucosal layer group(144 patients)and submucosal layer group(28 patients)based on postoperative pathology.The clinical,pathological,and white-light endoscopy(WLE)and linked color imaging(LCI)features of the 2 groups were compared.The color difference between the lesion and the surrounding mucosa was evaluated by using the Commission International de L'Eclairage(CIE)L*a*b*system.Indicators with significant differences were included to multifactor logistic stepwise regression analysis(forward method)for the identification and screening of predictors.Results A history of alcohol consumption(P=0.037),a history of smoking(P=0.035),thickening of the gastric wall on enhanced CT(P=0.032),a lesion located in the upper 1/3(P<0.001)or middle 1/3(P=0.009)part of the stomach,depressed macroscopic type(P<0.001),marked margin elevation(P=0.003),presence of fold changes(P=0.006),color difference ≥12.3 under WLE(P=0.003)and≥18.2 under LCI(P=0.002)were associated with submucosal infiltration.Multivariate analysis showed that lesions located in the upper 2/3 portion of the stomach(OR=5.463,95%CI:2.562-11.648,P<0.001),depressed macroscopic type(OR=5.992,95%CI:1.624-22.100,P=0.007),marked margin elevation(OR=4.338,95%CI:1.124-16.747,P=0.033),and color difference ≥18.2 under LCI(OR=4.675,95%CI:1.342-16.288,P=0.015)were independent risk factors for infiltration of submucosal layer of lesions.Conclusion Lesions with depressed macroscopic type,marked elevated margins,located in the upper 2/3 part of the stomach,and having a large color difference from the surrounding mucosa under LCI are high-risk lesions for submucosal infiltration and require more aggressive intervention.
4.A case of diabetes mellitus with glucokinase regulator gene mutation misdiagnosed as type 1 diabetes
Xuefeng LI ; Weiwei CHEN ; Keyan HU ; Shanlong WANG ; Donghui LI ; Huifang PENG ; Qiuhong MA ; Yujin MA ; Hongwei JIANG
Chinese Journal of Endocrinology and Metabolism 2023;39(3):256-260
We report a case of a female teenage with monogenic diabetes mellitus caused by glucokinase regulator (GCKR) gene mutation who presented with diabetic ketosis and misdiagnosed as type 1 diabetes. The patient was treated with insulin for 3 years since diagnosis. The islet function was well preserved, but polycystic ovary syndrome was developed. Whole-exome gene sequencing revealed a GCKR gene c. 69delG heterozygous mutation. After molecular diagnosis, the insulin dosage was gradually reduced to full cessation, and only metformin sustained-release tablets were taken to control blood glucose. It is necessary to regular evaluate islet function of patient with type 1 diabetes, and genetic test is of significance for accurate diagnosis and treatment.
5.Multimodal imaging analysis of acute macular neuroretinopathy in the coronavirus disease 2019 infection
Jiawen FAN ; Nuo TANG ; Yi XUAN ; Jian YU ; Keyan WANG ; Haixiang WU ; Qing CHANG ; Min WANG
Chinese Journal of Ocular Fundus Diseases 2023;39(9):728-734
Objective:To observe the clinical and multimodal imaging features of eyes with acute macular neuroretinopathy (AMN) associated with the coronavirus disease 2019 (COVID-19).Methods:A retrospective study. From December 20, 2022 to January 17, 2023, a total of 29 patients (58 eyes) with COVID-19-associated AMN admitted to Department of Ophthalmology of Eye and ENT Hospital, Shanghai Medical College were included in the study. All the affected eyes underwent the best corrected visual acuity, color fundus photography, infrared fundus photography (IR), short-wavelength autofluorescence (SW-AF), near-infrared autofluorescence (NIL-AF), optical coherence tomography (OCT), and OCT angiography (OCTA). All patients were administered microcirculation-improving oral medication with 12 cases receiving adjunctive low-dose corticosteroid therapy. Follow-ups were conducted 1 to 3 months after the initial diagnosis, with a total of 19 cases (38 eyes) completing the one-month follow-up.Results:Out of the 29 cases, there were 9 males (18 eyes) and 20 females (40 eyes), all of whom experienced bilateral eye involvement. The age of the patients ranged from 12 to 47 years, with an average age of (29.9±9.5) years. The time from the onset of fever to the appearance of ocular symptoms was (2.52±2.01) days. Among the 58 affected eyes, there were 5 cases with retinal cotton wool spots, 2 cases with optic disc edema, and 1 case with parafoveal branch retinal vein occlusion. All affected eyes exhibited deep reddish-brown macular dark spots. IR revealed wedge-shaped, wedge-like, or "petaloid-like" dark areas involving the fovea and parafovea. SW-AF examination showed no obvious abnormality in 39 eyes. Weak autofluorescence dark area were consistent with IR in 19 eyes. NIR-AF examination showed spot-like or flaky self-fluorescent dark areas. OCT examination showed strong reflex lesions spreading vertically upward from the retinal pigment epithelium (RPE) layer in the macular area in the acute stage, showing typical "bean seedling" sign. OCTA revealed reduced blood flow density in the deep capillary plexus (DCP) of 50 eyes. Enface OCT displayed lesion areas that corresponded to the dark areas seen in IR. One month after the initial diagnosis, the condition improved in 18 eyes (47.4%, 18/38). Among the 5 eyes with cotton wool spots, regression of these spots was accompanied by loss of nerve fiber layer in 4 eyes. In cases with optic disc edema, the edema subsided. The "bean sprout" sign disappeared in all affected eyes, and the lesions became localized. The ellipsoid zone and/or interdigitation zone in the lesion areas were discontinuous.Conclusions:COVID-19-related AMN is characterized by distinctive features. IR fundus reveals wedge-shaped, wedge-like, or petaloid dark areas involving the fovea and parafovea. OCT displays strongly reflective lesions with vertical spread above the RPE. OCTA shows reduced blood flow density in the DCP of the retina.
6.Prediction of new atrial fibrillation after off-pump coronary artery bypass grafting based on preoperative heart rate variability: A retrospective study
Yang WANG ; Zongtao YIN ; Hui JIANG ; Dengshun TAO ; Keyan ZHAO ; Jian ZHANG ; Fangran XIN ; Huai LAN ; Wei ZHANG ; Huishan WANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(01):121-125
Objective To study the relationship between preoperative heart rate variability (HRV) and postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass grafting (OPCAB). Methods A retrospective analysis was performed on the clinical data of 290 patients who were admitted to the Department of Cardiovascular Surgery, General Hospital of Northern Theater Command from May to September 2020 and received OPCAB. There were 217 males and 73 females aged 36-80 years. According to the incidence of POAF, the patients were divided into two groups: a non-atrial fibrillation group (208 patients) and an atrial fibrillation group (82 patients). The time domain and frequency domain factors of mean HRV 7 days before operation were calculated: standard deviation of all normal-to-normal intervals (SDNN), root mean square of successive differences, percentage difference between adjacent normal-to-normal intervals that were greater than 50 ms, low frequency power (LF), high frequency power (HF), LF/HF. Results The HRV value of patients without POAF was significantly lower than that of patients with POAF (P<0.05). The median SDNN of the two groups were 78.90 ms and 91.55 ms, respectively. Age (OR=3.630, 95%CI 2.015-6.542, P<0.001), left atrial diameter (OR=1.074, 95%CI 1.000-1.155, P=0.046), and SDNN (OR=1.017, 95%CI 1.002-1.032, P=0.024) were independently associated with the risk of POPAF after OPCAB. Conclusion SDNN may be an independent predictor of POAF after OPCAB.
7.Radiofrequency and ganglion plexus ablation in heart valve surgery: a propensity matching analysis
Zongtao YIN ; Huishan WANG ; Jinsong HAN ; Keyan ZHAO ; Yan JIN ; Yuji ZHANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2021;37(1):18-22
Objective:To evaluate the long-term results of combined ganglion plexus ablation(GPA) during radiofrequency ablation(RF) with long-standing persistent atrial fibrillation(LSP-AF).Methods:This retrospective study sample consisted of 268 patients with LSP-AF underwent valve operations concomitant RF maze Ⅳ procedure. Data were collected prospectively on perioperative outcomes, rhythm status, survival, and clinical events. Propensity score matching conducted by RF and RF+ GPA resulted in 102 patients per group.Results:Independent predictors for rhythm success at 1 year were combined GPA( OR=0.205, P=0.005), smaller left atrium size( OR=1.091, P=0.000); at 5-year and 8-year were a shorter history of AF( OR=1.069, P=0.023; OR=1.066, P=0.030), and smaller left atrium size( OR=1.091, P=0.000; OR=1.086, P=0.000). After matching, RF+ GPA group had significantly higher sinus rhythm(SR) without antiarrhythmic drugs(AADs) at 6 months(91.3% vs. 79.8%, P=0.026), 1-year(90.2% vs. 78.5%, P=0.028), but there were no difference between the two groups at 5-year(64.8% vs. 64.4%, P=0.956), and 8-year(53.3% vs. 50.6%, P=0.711). During the 6 postoperative months, fewer patients in the RF+ GPA group underwent follow-up cardioversions(2.0% vs. 8.8%, P=0.030). Actuarial survival curves did not differ significantly between the 2 groups( HR=1.327, 95% CI 0.4633-3.802, P=0.598). Conclusion:The combination of GPA can be effective at the early postoperative stage for SR restoration in Maze Ⅳ procedures for the treatment of LSP-AF in heart valve surgeries, particularly for lower AADs use and lower cardioversions. However, this effect will gradually diminish after one year.
8.Improving surgical efficacy of proliferative diabetic retinopathy continuously by paying attention to the basis and keeping pace with the times
Chinese Journal of Ocular Fundus Diseases 2021;37(1):5-9
Proliferative diabetic retinopathy (PDR) is one of the most common cause of severe sight impairment in people with diabetes. When PDR develops to a severe stage, vitreoretinal surgery is needed to prevent its aggravation. The surgery for PDR is complicated and difficult. By deeply understanding the pathological mechanism and development law of PDR, and reasonably using various surgical techniques, assisted by emerging surgical equipment and drugs, the surgical efficacy of PDR can be continuously improved, so as to help patients improve or even restore visual function to a greater extent.
9.Long-term outcomes for surgical treatment of long-standing persistent atrial fibrillation using bipolar radiofrequency ablation during concomitant cardiac valve procedures
Zongtao YIN ; Jian ZHANG ; Jinsong HAN ; Keyan ZHAO ; Yan JIN ; Yuji ZHANG ; Huishan WANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2021;37(7):414-417
Objective:To evaluate the long-term results of bipolar radiofrequency(BRF) ablation in restoring sinus rhythm in patients with permanent atrial fibrillation(AF) undergoing surgery for cardiac surgery.Methods:This retrospective study sample consisted of 268 patients with LSP-AF underwent cardiac operations concomitant BRF maze Ⅳ procedure. Data were collected prospectively on perioperative outcomes, rhythm status, survival, and clinical events.Results:15 patients died in the early postoperative period, perioperative mortality rate was 5.5%. The rate of stable sinus rhythm(sSR)was 86.6%, 75.4%, 67.7%, 57.8% in 1, 2, 5, 8 years after operation. Multivariate analysis proved the size of the left atrium( HR=1.073, P<0.001) and duration of AF( HR=1.070, P=0.025) to be an independent predictor of the radiofrequency ablation outcome. Conclusion:Bipolar radiofrequency maze procedure can effectively eliminate AF, maintain long-term of sinus rhythm. Bipolar radiofrequency maze procedure is a safe, easy and effective surgical option for the treatment of AF, with satisfactory long-term results, is worthy of promotion.
10. Preliminary study on the safety of liver transplantation recipients with Rh blood group mismatching
Shaohua SONG ; Yanling WANG ; Hao LIU ; Junfeng DONG ; Keyan SUN ; Jiayong DONG ; Fei TENG ; Wenyuan GUO ; Xiaomin SHI ; Guoshan DING ; Zhiren FU
Chinese Journal of Organ Transplantation 2019;40(9):553-557
Objective:
To explore the safety of liver transplantation recipients with Rh blood group mismatchming.
Methods:
From May 2005 to December 2018, 1 546 cases of liver transplantation in our hospital were retrospectively analyzed. Among these cases, 5 cases of Rh blood group mismatched were Rh(-) recipients receiving Rh(+ ) donor liver. For each Rh blood group mismatched liver transplantation, 5 patients received the same Rh blood group liver allograft were matched according to a certain principle and were defined as Rh-mismatch group and Rh-match group respectively. The serum alanine aminotransferase (ALT), aspartate aminotransferase(AST)and creatinine(SCr)were compared between two groups at Days 7 & 14 post-operation. Serum total bilirubin(TB), gamma-glutamyl transpeptidase(GGT)were compared between two groups at Month 1, 6 & 12 post-operation. Hemoglobin (Hb)were compared between two groups Month 1, 3 & 6 post-operation. The rates of infection, vascular complications and acute rejection was also compared. Indirect antiglobulin test (IAT)was used for detecting the production of anti-RhD antibody in patients in Rh-mismatch group at Month 1, 6 & 12 post-operation.
Results:
At the mentioned time, no significant inter-group difference existed in serum ALT, AST, SCr, TB, GGT and blood Hb levels(all

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