1.Bioinformatics Reveals Mechanism of Xiezhuo Jiedu Precription in Treatment of Ulcerative Colitis by Regulating Autophagy
Xin KANG ; Chaodi SUN ; Jianping LIU ; Jie REN ; Mingmin DU ; Yuan ZHAO ; Xiaomeng LANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):166-173
ObjectiveTo explore the potential mechanism of Xiezhuo Jiedu prescription in regulating autophagy in the treatment of ulcerative colitis (UC) by bioinformatics and animal experiments. MethodsThe differentially expressed genes (DEGs) in the colonic mucosal tissue of UC patients was obtained from the Gene Expression Omnibus (GEO), and those overlapped with autophagy genes were obtained as the differentially expressed autophagy-related genes (DEARGs). DEARGs were imported into Metascape and STRING, respectively, for gene ontology/Kyoto Encyclopedia of Genes and Genomics (GO/KEGG) enrichment analysis and protein-protein interaction (PPI) analysis. Finally, 15 key DEARGs were obtained. The core DEARGs were obtained by least absolute shrinkage and selection operator (LASSO) regression and receiver operating characteristic curve (ROC) analysis. The CIBERSORT deconvolution algorithm was used to analyze the immunoinfiltration of UC patients and the correlations between core DEARGs and immune cells. C57BL/6J mice were assigned into a normal group and a modeling group. The mouse model of UC was established by free drinking of 2.5% dextran sulfate sodium. The modeled mice were assigned into low-, medium-, and high-dose Xiezhuo Jiedu prescription and mesalazine groups according to the random number table method and administrated with corresponding agents by gavage for 7 days. The colonic mucosal morphology was observed by hematoxylin-eosin staining. The protein and mRNA levels of cysteinyl aspartate-specific proteinase 1 (Caspase-1), cathepsin B (CTSB), C-C motif chemokine-2 (CCL2), CXC motif receptor 4 (CXCR4), and hypoxia-inducing factor-1α (HIF-1α) in the colon tissue were determined by Western blot and real-time fluorescence quantitative polymerase chain reaction, respectively. ResultsThe dataset GSE87466 was screened from GEO and interlaced with autophagy genes. After PPI analysis, LASSO regression, and ROC analysis, the core DEARGs (Caspase-1, CCL2, CTSB, and CXCR4) were obtained. The results of immunoinfiltration analysis showed that the counts of NK cells, M0 macrophages, M1 macrophages, and dendritic cells in the colonic mucosal tissue of UC patients had significant differences, and core DEARGs had significant correlations with these immune cells. This result, combined with the prediction results of network pharmacology, suggested that the HIF-1α signaling pathway may play a key role in the regulation of UC by Xiezhuo Jiedu prescription. The animal experiments showed that Xiezhuo Jiedu prescription significantly alleviated colonic mucosal inflammation in UC mice. Compared with the normal group, the model group showed up-regulated protein and mRNA levels of caspase-1, CCL2, CTSB, CXCR4, and HIF-1α, which were down-regulated after treatment with Xiezhuo Jiedu prescription or mesalazine. ConclusionCaspase-1, CCL2, CTSB, and CXCR4 are autophagy genes that are closely related to the onset of UC. Xiezhuo Jiedu prescription can down-regulate the expression of core autophagy genes to alleviate the inflammation in the colonic mucosa of mice.
2.Mechanism of Xiezhuo Jiedu Recipe Regulating Ferroptosis in Treatment of Ulcerative Colitis Based on Bioinformatics and Animal Experiments
Chaodi SUN ; Jianping LIU ; Mingmin DU ; Xin KANG ; Jiancong CUI ; Yuan ZHAO ; Sujie JIA ; Xiaomeng LANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):166-173
ObjectiveThe bioinformatics method was used to screen ferroptosis differential genes (FRGs) closely related to ulcerative colitis (UC), and animal experiments were conducted to verify whether the mechanism of Xiezhuo Jiedu recipe in treating UC is related to the regulation of ferroptosis. MethodThe differentially expressed genes (DEGs) of colonic mucosa tissue of UC patients were obtained from the GEO database, and the intersection of the genes with ferroptosis genes was used to obtain FRGs. The core FRGs were obtained by cluster analysis, minimum absolute contraction and selection operator (LASSO) regression, and receiver operating characteristic curve (ROC) curve analysis. In animal experiments, the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate (DSS). Xiezhuo Jiedu recipe and mesalazine were given by gavage for seven days, and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression levels of E3 ubiquitin ligase (FBXW7), zinc finger protein (ZFP36), solute carrier family 7 member 11 (SLC7A11), and Toll-like receptor 4 (TLR4) in colon tissue. The protein expression levels of FBXW7, ZFP36, SLC7A11, and TLR4 in colon tissue were detected by Western blot. ResultDataset GSE87466 was screened from the GEO database, and its intersections with the ferroptosis gene were analyzed to obtain 21 FRGs. After cluster analysis, LASSO regression, and ROC analysis, core FRGs (FBXW7, ZFP36, SLC7A11, and TLR4) were obtained. Immunoinfiltration analysis showed significant differences in the expression of initial B cells, M1 macrophages, plasma cells, and M2 macrophages in the colonic mucosa tissue of UC mice, and there was a significant correlation between core FRGs and these immune cells. Further animal experiments showed that the colonic mucosa tissue of mice in the model group was disorganized and infiltrated by a large number of inflammatory cells. The inflammation of the colonic mucosa tissue of mice in each group was relieved to varying degrees after treatment with Xiezhuo Jiedu recipe and mesalazine, while the colonic mucosa tissue of mice in the high-dose group of Xiezhuo Jiedu recipe showed almost no inflammatory changes. Compared with the normal group, the protein and mRNA expressions of FBXW7, ZFP36, SLC7A11, and TLR4 in the model group were significantly increased, and the expression of core FRGs in colonic mucosa tissue of mice in all groups was significantly down-regulated after treatment with Xiezhuo Jiedu recipe and mesalazine. ConclusionFBXW7, ZFP36, SLC7A11, and TLR4 are ferroptosis genes closely related to the pathogenesis of UC, and Xiezhuo Jiedu recipe can significantly alleviate colonic mucosa inflammation in mice by down-regulating core ferroptosis genes.
3.Open surgery in the treatment of patients with hilar cholangiocarcinoma: a study on curative efficacy and prognostic factors
Mengkui HAN ; Ping LI ; Mingmin ZHANG ; Wei HUANG ; Siyuan CHANG ; Jin LI ; Ding SUN ; Lei QIN ; Xiaohua YANG
Chinese Journal of Hepatobiliary Surgery 2022;28(11):831-837
Objective:To study the efficacy of different surgical methods in treatment of hilar cholangiocarcinoma (HCCA), and to analyze the factors affecting long-term prognosis of HCCA patients after surgical treatment.Methods:The clinical data of 105 patients who underwent surgical treatment for HCCA at the First Affiliated Hospital of Soochow University from April 2010 to October 2021 were retrospectively analysed. There were 58 males and 47 females, with age (64.2±10.6) years old. Data analysed included surgical treatments, postoperative pathological data, perioperative complications and survival on follow-up. The Kaplan Meier survival curve was plotted, and the log-rank test and Cox proportional hazard model were performed to analyze the key factors affecting long-term prognosis.Results:Of 105 patients, 4 (3.8%) patients died during the perioperative period, and 58 patients (55.2%) developed complications with included 32 (30.5%) patients with pleural effusion and 12 (11.4%) patients with biliary leakage. The follow-up data was available in 85 patients with the overall median survival time of 19 months, and the 1-, 3-, 5-year cumulative survival rates of 58.1%, 27.0% and 24.8% respectively. The 1-, 3-, and 5-year cumulative survival rates for the R 0 resection patients ( n=59) were 69.4%, 36.2%, 27.4%, respectively, which were significantly better than 49.4%, 12.3%, 0% for the R 1/2 resection patients ( n=20), and 0% for the palliative drainage patients ( n=6) (all P<0.05). Univariate analysis and Cox multivariate analysis showed that age ≥70 years ( HR=2.158, 95% CI: 1.175-3.965), preoperative CA19-9 level ≥1 015 U/ml ( HR=1.981, 95% CI: 1.009-3.894), resection margin ( HR=2.587, 95% CI: 1.371-4.881), and lymph node metastasis ( HR=2.308, 95% CI: 1.167-4.567) were independent risk factors for long-term prognosis of HCCA patients (all P<0.05). Conclusions:R 0 resection was an effective way to prolong survival of patients with HCCA. Age, preoperative CA19-9 level, resection margin and lymph node metastasis were related to long-term survival of HCCA patients.
4. Bioequivalence study of buthlphthalide injection in Chinese healthy volunteers
Mingmin CAI ; Huiping WANG ; Mingmin CAI ; Lu TANG ; Qiuyue SUN ; Ting DOU ; Wei QIAN ; Huiping WANG ; Jing SHAO
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(1):70-76
AIM: To establish a method to investigate pharmacokinetics and bioequivalence of buthlphthalide injection. METHODS: An open, randomized, and two-cycle crossover study was conducted in 24 healthy volunteers. Plasma concentrations of buthlphthalide were determined by LC-MS/MS after administering a single dose of reference drug or test drug. Main pharmacokinetic parameters were calculated by Phoenix WinNonlin 6.4 software. RESULTS: For the test drug and the reference drug, the main pharmacokinetic parameters of flurbiprofen were as follows: AUC
5.Current health service demands of new residents in shanghai
Jiahua SHI ; Mingmin HUANG ; Yongmei SUN ; Jiacheng WANG ; Jie GUO ; Yongming QI ; Qiong TANG
Shanghai Journal of Preventive Medicine 2022;34(8):806-811
ObjectiveTo understand the current situation and influencing factors of health service demands of new residents in Shanghai. MethodsFrom July to August 2020, a questionnaire survey was conducted in 1 358 new residents from 36 survey points in 7 districts of the city. The questionnaire included the basic medical insurance coverage in the inflow area, the current situation of medical demand and related influencing factors, and the demands for other health services. Results47.1%(562/1 194)of new residents did not choose to seek timely medical treatment when they were not feeling well. The main reason was that the working hours occupied the medical treatment time. Logistic regression analysis showed that the main factors affecting the medical needs in new residents were the average daily working hours, living area and type of residence, health status, physical examination and physical exercise, and the type of basic medical insurance. The demands of new residents for "health consultation of common diseases and frequently occurring diseases", "health behavior intervention (such as smoking cessation and alcohol restriction)", "medical guidance and publicity", "accidental injury prevention (traffic, work, falling, etc.)" and "maintenance of legitimate rights and interests of health" were 57.1%(682/1 194)、41.3%(493/1 194)、34.9%(417/1 194)、32.2%(385/1 194) and 31.9%(381/1 194), respectively. ConclusionNew residents demands for medical services cannot be met. We should actively improve the working and living conditions of new residents, improve the construction of new residents' health service system, and improve the utilization level of health services.
6.Practice on human genetic resources management using PDCA circle in new drug clinical research
Mingmin SUN ; Tianping LI ; Yi CHAI ; Jun ZHAO
Chinese Journal of Medical Science Research Management 2020;33(3):232-235
Objective:The paper aims to ensure the rational and legal utilization of genetic resources and maintain the national biosafety through the management of human genetic resources in clinical research carried out by medical institutions.Methods:Literature review and survey methods were adopted. Deming Circle, with focus on the four stages from planning, implementation, inspection, and countermeasures, was used to continuously improve the quality of human genetic resources management in the hospital.Results:The concept of hospital human genetic resources management was recognized and the management quality was significantly improved.Conclusions:The PDCA cycle management method is of positive significance to the management of human genetic resources in the clinical research of new drugs in medical institutions, and it is an effective way to improve the management level under current system.
7.Clinical effects on the prevention of alveolar bone absorption by site preservation after tooth extraction due to periodontitis
Junyi SUN ; Mingmin WANG ; Kai DONG ; Chunhui ZHU ; Jin LIU ; Yan DONG ; Ang LI
Journal of Xi'an Jiaotong University(Medical Sciences) 2016;37(3):437-440
Objective To observe the clinical effects on prevention of alveolar bone absorption by site preservation after tooth extraction due to periodontitis.Methods The experimental group consisted of 40 patients with 45 extracted teeth due to periodontitis.The fresh sockets were immediately grafted and filled with Bio-oss collagen and Bio-Gide after minimally invasive tooth extraction,while 40 teeth of control group were only treated with cotton balls bitten tightly over the socket for half an hour.Two groups were observed for changes in alveolar bone density by X-ray and cone beam CT (CBCT)after 6 months.Results There were the wound healing and no infection in extraction site of all patients with or without site preservation operation.The gingiva of extraction site was pink and tough in all groups.The alveolar bone loss in regular extraction patients significantly increased in horizontal and vertical aspects by X-ray and CBCT,while site preservation improved the alveolar bone defects (P<0.05).After site preservation for 6 months,CBCT analysis showed that the density of new alveolar bone markedly enhanced compared with regular extraction group.Conclusion The technique of site preservation after tooth extraction due to periodontitis is a method which can prevent and reduce disuse atrophy absorption of the alveolar ridge so that the height and width of the alveolar bone can meet aesthetic requirements.
8.Effects of electroacupuncture on the expressions of IL-1βand ICAM-1 in bilateral brain tissues of rats with cerebral ischemia/reperfusion injury
Yingzhou SONG ; Linlin SUN ; Yingzhen REN ; Xuhui ZHANG ; Mingmin XU ; Miao YU ; Yu GUO ; Ya TU
Acta Laboratorium Animalis Scientia Sinica 2015;(3):278-284
Objective To explore the variation trends of interleukin-1β( IL-1β) and intercellular adhesion molecule-1 (ICAM-1) in both normal and affected sides of brain tissues in rats with ischemia-reperfusion injury and the therapeutic action of electroacupuncture.Methods The cerebral ischemia-reperfusion model was established with suture embolization in the right middle cerebral artery.The rats were randomly divided into control group, model group and electroacupunture group.Each group was then divided into six subgroups by the time after operation (12 h,24 h,48 h,72 h,96 h,144 h), ten rats in each subgroup. Frozen sections of brain tissues were prepared and the expression of IL-1βand ICAM-1 in brain tissues of both sides were detec-ted by immunohistochemistry.Results The expressions of IL-1βand ICAM-1 showed typical bimodal pattern in both affected is-chemic region and contralateral normal region.In the model group, the peaks of IL-1βin the cerebral ischemic region were at 12 h and 48 h, while in the contralateral normal region the peaks were at 12 h and 144 h, the expression of IL-1βin the ischemic region was significantly higher than that in the contralateral normal region at 48 h (P<0.05), and lower at 96 h and 144 h (P <0.05).In the electroacupuncture group, the expressions of IL-1βin the ipsilateral region were significantly lower than that in the contralateral region at 24 h, 48 h and 144 h (P<0.05).In the model group, the peaks of ICAM-1 in the cerebral ischemic regions were at 24 h and 72 h, while in the contralateral normal regions the peaks were at 24 h and 144 h.In the electroacupunc-ture group, the expressions of ICAM-1 in the ischemic regions were significantly lower than that in the contralateral normal re-gions at all the 12 h, 24 h, 48 h, 72 h and 144 h (P<0.05).Conclusions Our findings suggest that electroacupuncture may inhibit the inflammation of ischemia/reperfusion brain tissue through reducing the expression of IL-1βand ICAM-1 to relieve the cerebral ischemia-reperfusion injury.
9.Application of nanohydroxyapatite/collagen basal bone materials in lumbar posterolateral bone graft fusion:evaluation of pain scores and bone graft fusion effects
Dai LI ; Mingmin YANG ; Yang SUN
Chinese Journal of Tissue Engineering Research 2015;(43):6983-6987
BACKGROUND:Nanohydroxyapatite/colagen basal bone materials have a porous structure which is very close to natural bone. After implanting to the human body, it can be gradualy degraded and absorbed over time to play a strongly guiding and bridging role. OBJECTIVE:To investigate the clinical effect of nanohydroxyapatite/colagen basal bone materials on lumbar posterolateral bone graft fusion. METHODS: Fifty-eight patients with lumbar disease, including 28 males and 30 females, aged 47to81 years were included and were performed lumbar laminectomyvia posterior midline approach, or simultaneously performed discectomy and lumbar posterolateral bone graft fusion between transverse process. The bone graft material was nanohydroxyapatite/colagen basal bone repair material. Pedicle screw system was used to make the internal fixation. Patients were folowed up for 18 months after treatment. Pain relief and bone graft fusion condition were observed. RESULTS AND CONCLUSION: Fifty-eight patients had successfuly completed the treatment. The incisions healed by first intention. The clinical symptoms and signs were significantly improved compared with before treatment. The complications such as infection, screws shifting and loosening, spondylolisthesis and displacement of adjacent vertebral in fixed segments, and the adverse reactions associated with bone graft material were not occurred during the folow-up. At the 1st, 6th, 12th and 18th months after implanting nanohydroxyapatite/colagen basal bone materials, the visual analog scale scores of the lower limbs and waist were al lower than those before implantation (P < 0.05). At the 12thand 18th months of folow-up, the bone graft rates were 84% and 90%, respectively. These results demonstrate that the application of nanohydroxyapatite/colagen basal bone materials in the process of lumbar posterolateral bone graft fusion can ease the symptoms of lower limb pain and lower back pain, which is conducive to bone graft fusion.
10.Nano-hydroxyapatite/polyamide 66 composite for repair of early femoral head necrosis
Mingmin YANG ; Dai LI ; Yang SUN
Chinese Journal of Tissue Engineering Research 2015;(34):5463-5467
BACKGROUND:Nano-hydroxyapatite/polyamide 66 composite has good material-cel interface and three-dimensional porous network structure, and it can also be gradualy degraded over time after implantation in the human body. OBJECTIVE:To explore the effect of nano-hydroxyapatite/polyamide 66 in early repair of femoral head necrosis. METHODS:A retrospective analysis was performed on clinical data of 62 cases of early osteonecrosis of the femoral head, including 32 males and 30 females, aged 34-51 years. These patients were divided into control group (31 cases) and observation group (31 cases) according to treatment methods. Core decompression with nano-hydroxyapatite/polyamide 66 implantation and core decompression with bone graft were respectively performed in the observation and control groups. Incidence of pain in the two groups was compared at 1 day after treatmen; and during the 12-month folow-up, the Harris score of the hip function in the two groups was compared. RESULTS AND CONCLUSION:There was no significant difference in the visual analog scale scores between two groups at 1 day after treatment. The Harris scores in the observation group were significantly higher than those in the control group at 3 and 12 months after treatment (P < 0.05). There was no adverse reaction in the two groups. These findings indicate that nano-hydroxyapatite/polyamide 66 material for repair of early femoral head necrosis has good biocompatibility, and can obtain good effects on limb function recovery.

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