1.Construction and practice of the theory of “turbid toxin pathogenesis” and related prevention and treatment strategies for hepatic encephalopathy in traditional Chinese medicine/Zhuang medicine
Zhipeng WU ; Yuqin ZHANG ; Chun YAO ; Minggang WANG ; Na WANG ; Mengru PENG ; Ningfang MO ; Yaqing ZHENG ; Rongzhen ZHANG ; Dewen MAO
Journal of Clinical Hepatology 2025;41(2):370-374
Hepatic encephalopathy is a difficult and critical disease with rapid progression and limited treatment methods in the field of liver disease, and it is urgently needed to make breakthroughs in its pathogenesis. Selection of appropriate prevention and treatment strategies is of great importance in delaying disease progression and reducing the incidence and mortality rates. This article reviews the theory of “turbid toxin pathogenesis” and related prevention and treatment strategies for hepatic encephalopathy in traditional Chinese medicine/Zhuang medicine, proposes a new theory of “turbid toxin pathogenesis”, analyzes the scientific connotations of “turbid”, “toxin”, and the theory of “turbid toxin pathogenesis”, and constructs the “four-step” prevention and treatment strategies for hepatic encephalopathy, thereby establishing the new clinical prevention and treatment regimen for hepatic encephalopathy represented by “four prescriptions and two techniques” and clarifying the effect mechanism and biological basis of core prescriptions and techniques in the prevention and treatment of hepatic encephalopathy, in order to provide a reference for the prevention and treatment of hepatic encephalopathy.
2.Application of AI software for chromosomal aberration analysis in occupational health surveillance and radiation biological dose estimation
Yingyi PENG ; Qiuying LIU ; Zhifang LIU ; Zongjun ZHANG ; Xiaoyan CHEN ; Kunjie HUANG ; Qiying NONG ; Na ZHAO
China Occupational Medicine 2025;52(2):171-175
Objective To explore the feasibility of applying artificial intelligence (AI) technology in chromosomal aberration (CA) analysis for occupational health surveillance of radiation workers and in biological dose estimation during nuclear emergency responses. Methods Peripheral blood samples from healthy volunteers were irradiated in vitro with X-rays and cobalt-60 (⁶⁰Co) γ rays. Chromosome slides were prepared using an automated harvesting and dropping device. The data training and outcome evaluation of CA analysis was performed on the AI software using chromosome images from occupational medical examination of radiation workers from the current lab or chromosome slides from blood samples irradiated with X-rays. The trained AI software was then used to assist in CA analysis and biological dose estimation among occupational medical examination of radiation workers, with results compared with manual reading and actual exposure doses. Results The trained AI software achieved a CA recognition accuracy of 95.11%. In the occupational health examination of radiation workers, the positive CA detection rate using AI + manual review was 2.25% higher than that in manual reviewing alone. The errors in biological dose estimation for ⁶⁰Co γ rays and X-rays using AI + manual review analysis were 11.86% and 7.33%, respectively, both within the acceptable 20.00% error margin. Conclusion AI + manual review can be effectively applied in CA analysis for occupational health examination and biological dose estimation during nuclear emergencies, significantly improving analysis efficiency.
3.Zingiberis Rhizoma Alleviates Inflammatory Bowel Disease Through Regulating TLR4/MAPK Signaling Pathway in Ly6Chi Monocytes/Macrophages
Yalan LI ; Chonghao ZHANG ; Huachen LIU ; Jialong SU ; Na LI ; Mengyu ZHOU ; Guiying PENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):66-75
ObjectiveTo investigate the potential mechanisms of Zingiberis Rhizoma in treating inflammatory bowel disease (IBD) by integrating network pharmacology with in vitro and in vivo experiments. MethodsTraditional Chinese Medicine Systems Pharmacology Database And Analysis Platform (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID) Database were used to obtain the active component targets of Zingiberis Rhizoma. GeneCards was used to obtain the IBD targets. DAVID was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses on core targets. Cytoscape 3.10.2 was used to establish the "active component-disease target-signaling pathway" interaction network. Mice were randomly assigned to control, model, and Zingiberis Rhizoma (400 mg·kg-1) groups. An IBD model was induced via dextran sulfate sodium (DSS). The colonic tissue was collected post-treatment to assess histology, expression of Ly6C+ monocytes/macrophages, and mRNA levels of Toll-like receptor 4 (TLR4), and inflammatory cytokines. The effect of Zingiberis Rhizoma aqueous extract on RAW264.7 cell viability was evaluated. Furthermore, the effects of the extract at 100, 10, and 1 mg·L-1 on LPS-induced differentiation of RAW264.7 cells into Ly6Chi monocytes/macrophages, mRNA levels of TLR4 and inflammatory cytokines, and protein levels of factors in the TLR4/mitogen-activated protein kinase (MAPK) signaling pathway. ResultsA total of 241 targets were identified for Zingiberis Rhizoma and 6 787 for IBD, with 122 shared targets among Zingiberis Rhizoma, ulcerative colitis (UC), and Crohn's disease (CD). The enrichment analyses yielded 297 GO terms and 88 KEGG pathways. Associations were noted between Zingiberis Rhizoma's active component targets and IBD targets. In vivo experiments: Compared with the control group, the model group showed decreased body weight and disease activity index (DAI)(P<0.01), shortened colon length, damaged mucosal epithelium with inflammatory cell infiltration, raised pathological scores (P<0.05), increased Ly6Chi and Ly6Clo monocytes/macrophages (P<0.05), and up-regulated mRNA levels of TLR4, TNF-α, IL-1β, and IL-6 (P<0.05) and protein levels of TLR4, phosphorylated extracellular signal-regulated protein kinase 1/2 (p-ERK1/2), and phosphorylated p38 MAPK (p-p38 MAPK) (P<0.05). Zingiberis Rhizoma intervention reversed these changes and reduced Ly6Chi monocytes/macrophages (P<0.01). In vitro experiments: compared with the control, LPS increased the proportion and number of Ly6Chi monocytes/macrophages and mRNA levels of TLR4, TNF-α, IL-1β, and IL-6 (P<0.01) and enhanced the expression of TLR4, p-ERK1/2, and p-p38 MAPK (P<0.05). Zingiberis Rhizoma reduced Ly6Chi monocytes/macrophages (P<0.05), down-regulated the mRNA levels of inflammatory cytokines (P<0.05), and suppressed the TLR4/MAPK pathway (P<0.05). ConclusionZingiberis Rhizoma alleviates IBD by suppressing the TLR4/ERK/p38 MAPK signaling pathway and reducing inflammatory cytokine levels in Ly6Chi monocytes/macrophages.
4.Mume Fructus Restores Intestinal Mucosal Epithelial Barrier Through MEK/ERK Signaling Pathway in Mouse Model of Inflammatory Bowel Disease
Huachen LIU ; Chonghao ZHANG ; Yalan LI ; Jie LIU ; Jialong SU ; Na LI ; Shaoshuai LIU ; Qing WANG ; Guiying PENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):76-85
ObjectiveTo clarify the repair effect of Mume Fructus on the intestinal mucosal epithelial barrier in the mouse model of inflammatory bowel disease (IBD) and explore the repair mechanism. MethodsThirty-six male C57BL/6 mice were randomly assigned into six groups: normal, model, low-, medium-, and high-dose (200, 400, and 800 mg·kg-1) Mume Fructus, and sulfasalazine (300 mg·kg-1). Except the normal group, the rest groups had free access to 2% dextran sulfate sodium (DSS) solution for seven days to establish the IBD model, followed by a seven-day drug intervention. The body weight change and disease activity index (DAI) were recorded. After the last administration, spleen and colon tissue samples were collected to analyze the differences in colon length and spleen index. Hematoxylin-eosin staining was used to observe the morphology of the colon tissue. The level of diamine oxidase (DAO) in the serum was measured by the DAO assay kit. Immunohistochemistry was employed to determine the expression of tight junction proteins such as Claudin-1, Occludin, and zonula occludens-1 (ZO-1) in the colon tissue. Real-time PCR was performed to measure the mRNA levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the colon tissue. Finally, Western blot was employed to determine the protein levels of mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinase (ERK), phosphorylated (p)-MEK, and phosphorylated ERK in the colon tissue. ResultsCompared with the normal group, the model group exhibited decreases in body weight and colon length (P<0.01), increases in DAI, spleen index, and serum DAO level (P<0.01), damaged colonic epithelium and goblet cells, and obvious infiltration of inflammatory cells. In addition, the model group exhibited higher positive expression of Claudin-1, Occludin, and ZO-1 (P<0.01), higher mRNA levels of TNF-α and IL-1β (P<0.01), and higher protein levels of p-MEK and p-ERK (P<0.05, P<0.01) than the normal group. However, sulfasalazine and three doses of Mume Fructus markedly decreased the body weight and DAI (P<0.05), recovered the colon length and spleen index, alleviated colon tissue damage, lowered the level of DAO in the serum (P<0.01), and down-regulated the mRNA levels of TNF-α and IL-1β (P<0.01) and the protein levels of p-MEK and p-ERK (P<0.05). Sulfasalazine and low- and medium-dose Mume Fructus increased the positive expression of Occludin, Claudin-1, and ZO-1 (P<0.05, P<0.01). Furthermore, high-dose Mume Fructus elevated the protein expression of Occludin (P<0.05). ConclusionMume Fructus can restore the expression of intestinal epithelial tight junction proteins by inhibiting the phosphorylation of proteins in the MEK/ERK signaling pathway and down-regulating the levels of TNF-α and IL-1β, thus repairing the intestinal mucosal barrier in the mouse model of IBD.
5.Regulatory Effect of Modified Wumeiwan on Th17/Treg Balance and Intestinal Microbiota in Ulcerative Colitis with Dampness-heat Obstruction Syndrome in Human Flora-associated Model
Chonghao ZHANG ; Peiguang MA ; Huachen LIU ; Jialong SU ; Jie LIU ; Yalan LI ; Guichuan XU ; Na LI ; Guiying PENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):86-93
ObjectiveTo investigate the modulating effect of modified Wumeiwan (MWMW) on the ulcerative colitis (UC)-associated intestinal helper T cell 17 (Th17)/regulatory T cell (Treg) balance and intestinal flora by using a human flora-associated model of UC patients with dampness-heat obstruction syndrome, thus providing a new idea for the UC-related research and therapeutic strategies. MethodsThe 24 male C57BL/6J mice were randomized into normal control, model, and MWMW groups (n=8). Model and MWMW groups were first treated with an antibiotic cocktail (vancomycin, 0.1 g·kg-1; neomycin sulfate, 0.2 g·kg-1; ampicillin, 0.2 g·kg-1; metronidazole, 0.2 g·kg-1) for 21 days. At the end of antibiotic treatment, the gavage of fecal microbiota suspension from UC patients with dampness-heat obstruction syndrome was started at a dose of 0.2 mL·d-1 for 19 consecutive days, by which a human flora-associated model of UC was obtained. The MWMW group was administrated daily with MWMW liquid (12.5 g·kg-1), while the normal control and model groups were administrated by gavage with an equal amount of sterile water for 7 consecutive days. The symptoms of dampness-heat obstruction were observed. The colon length and spleen index were measured and calculated, and the proportions of Th17 and Treg cells were detected by flow assay. The intestinal flora was analyzed by 16S rRNA high-throughput sequencing. ResultsCompared with the normal control group, the model group showed shortened colon (P<0.05) and increased spleen index (P<0.01). Compared with the model group, the MWMW group showed prolonged colon (P<0.01) and decreased spleen index (P<0.05). After the intervention of MWMW, the Th17 proportion and Th17/Treg ratio in the colon decreased (P<0.01), and the proportion of Treg cells increased (P<0.05). The number of species and alpha and beta diversity of intestinal flora in mice were regulated by MWMW (P<0.05). In terms of intestinal flora composition, MWMW increased the relative abundance of several phyla (Firmicutes, Proteobacteria, Fusobacteriota, Actinobacteriota, and Gemmatimonadota), the genus Bacteroides, and two species (Bacteroides thetaiotaomicron and B. fragilis) in model mice. Moreover, Spearman's correlation analysis showed that the relative abundance of B. thetaiotaomicron and B. fragilis were negatively correlated with the Th17 level (P<0.05). In addition, the above changes in intestinal flora caused the changes in microbial genes involved in 14 pathways, such as glycolysis, amino acid degradation, inorganic nutrient metabolism, biosynthesis of pyrimidine deoxyribonucleotides, antibiotic resistance, and degradation of polysaccharides. ConclusionsThe human flora-associated model successfully simulated the changes (marked by a decrease in the abundance of Bacteroides) of intestinal flora in UC patients with dampness-heat obstruction syndrome. MWMW can enrich the abundance of beneficial bacteria such as B. thetaiotaomicron and B. fragilis and promote the synergistic intestinal immune modulation with the metabolic functions centered on glycolysis, amino acid metabolism, and nucleotide synthesis through bacterial polysaccharide utilization sites to reduce the Th17/Treg ratio, thereby exerting a protective effect on UC.
6.Predictive efficacy of serum GDF-11 and S100A4 for contrast-induced nephropathy after coronary angiography
Qiang SONG ; Hui SHAO ; Hang XIE ; Hong GUAN ; Na PENG ; Xinming XIE
International Journal of Laboratory Medicine 2024;45(20):2476-2479,2484
Objective lo investigate the predictive value of serum growth differentiation factor 11(GDF-11)and calprotectin A4(S100A4)for contrast-induced nephropathy(CIN)after coronary angiography(CAG).Methods A total of 528 patients who underwent CAG in the First Affiliated Hospital of Xi'an Jiao-tong University from December 2020 to November 2023 were selected as the research objects.According to whether the patients had CIN,they were divided into non-nephropathy group(472 cases)and nephropathy group(56 cases).Enzyme-linked immunosorbent assay was used to detect serum levels of GDF-11 and S100A4.Multivariate Logistic regression analysis was used to explore the influencing factors of CIN after CAG.Receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum GDF-11 and S100A4 for CIN after CAG.Results The serum levels of GDF-11 and S100A4 in nephropathy group were higher than those in non-nephropathy group(P<0.05).The contrast agent dose and postoperative ser-um creatinine level in the nephropathy group were higher than those in the non-nephropathy group(P<0.05).Multivariate Logistic regression analysis showed that contrast agent dose ≥131.84 mL(OR=2.158,95%CI 1.284-3.627),postoperative serum creatinine ≥ 87.57 μmol/L(OR=2.445,95%CI 1.533-3.898),GDF-1 1 ≥4 50.84 ng/mL(OR=2.445,95%CI 1.533-3.898)were the influencing factors of CIN af-ter CAG(P<0.05).The area under the curve(95%CI)of serum GDF-11 and S100A4 for predicting CIN af-ter CAG was 0.861(95%CI 0.810-0.912)and 0.798(95%CI 0.747-0.849),respectively.The optimal cut-off values were 450.84 ng/mL and 86.98 μg/mL,the specificity were 65.89%and 57.62%,and the sensi-tivity were 94.74%and 94.74%,respectively.The area under the curve of the combination of the two was 0.906(95%CI 0.856-0.957),the specificity was 87.09%,and the sensitivity was 84.26%.Conclusion The elevated levels of serum GDF-11 and S100A4 are closely related to the occurrence of CIN in patients after CAG surgery,which can be used as biological indicators to evaluate the occurrence of CIN in patients after CAG surgery,and the combined prediction efficiency of GDF-11 and S100A4 is higher.
7.Clinical study on anti-reflux of conical gastric stump embedding in radical resection of esophageal cancer
Sheng-Kai LIU ; Li-Na CUI ; Jun-Peng LI ; Jun-Jie SHI ; Yan-Ling FAN
Journal of Regional Anatomy and Operative Surgery 2024;33(12):1093-1096
Objective To study the anti-reflux effect of conical gastric stump embedding in radical resection of esophageal cancer.Methods A total of 60 patients who planned to undergo radical resection of esophageal cancer in our hospital from June 2020 to June 2022 were selected as the study objects,and the patients were divided into the observation group and the control group by random number table method,with 30 cases in each group.Patients in both groups underwent laparoscopic radical resection of esophageal cancer and esophagogastric end-to-side mechanical anastomosis.The observation group adopted the conical gastric stump embedding technique after esophagogastric end-to-side mechanical anastomosis.The perioperative related indexes,postoperative complications and gastroesophageal reflux of patients in the two groups were compared.The postoperative anti-reflux effect was evaluated by reflux disease questionnaire(RDQ)score and 24-hour intraesophageal pH monitoring.Results The operation time and digestive tract reconstruction time of patients in the observation group were longer than those in the control group(P<0.05),while there was no statistically significant difference in the amount of intraoperative bleeding,the number of lymph node dissection,the first exhaust time,or the postoperative hospital stay of patients between the two groups(P>0.05).There was no statistically significant difference in the overall incidence of postoperative complications between the two groups(P>0.05).The severity of postoperative gastroesophageal reflux of patients in the observation group was lighter than that in the control group,and the difference was statistically significant(P<0.05).The RDQ score,24-hour reflux frequency,>5 minutes reflux frequency,pH<4 time,and longest reflux time of patients in the observation group was significantly lower/less/shorter than those in the control group(P<0.05).Conclusion The conical gastric stump embedding technique is safe and feasible in the radical resection of esophageal cancer.Although the operation time and digestive tract reconstruction time are slightly prolonged,it does not increase the perioperative risks,which can significantly reduce the occurrence and severity of postoperative gastroesophageal reflux of patients,and achieve a good anti-reflux effect.
8.A case report of cerebral dural arteriovenous fistula with psychiatric and behavioral abnormalities and progressively worsening bilateral thalamic edema
Xiaoxuan DUAN ; Na TANG ; Jian CHEN ; Jingkai LI ; Peng HU ; Xunming JI ; Jiangang DUAN
Chinese Journal of Cerebrovascular Diseases 2024;21(9):616-625
The clinical and imaging manifestations of the dural arteriovenous fistula(DAVF)located in the great cerebral vein area with progressive bilateral thalamic edema lack specificity and are easily confused with a variety of diseases.The authors reported a case presented with psychiatric and behavioral abnormalities,followed by bilateral thalamic lesions.Initially,the diagnosis was considered as a glioma of the thalamus,encephalitis and straight sinus thrombosis,but the clinical and imaging findings progressively worsened.Through multi-modal imaging examinations,a DAVF in the great cerebral vein territory was finally diagnosed.By reporting the case and reviewing the literature,this paper aimed to explore the clinical manifestations and imaging features of the disease to reduce the incidence of misdiagnosis.
9.Sedative effect of ciprofol combined with oxycodone on elderly patients undergoing endoscopic gastric mucosal dissection
Xiaodong ZHANG ; Peng DUAN ; Yingjie SUN ; Qi NA
Journal of China Medical University 2024;53(5):421-426
Objective To investigate the safety and efficacy of ciprofol combined with oxycodone in elderly patients who underwent endoscopic gastric mucosal dissection.Methods A total of 204 elderly patients in the outpatient department of the Northern Theater General Hospital who were to undergo endoscopic gastric mucosal dissection from March 2022 to December 2022 were selected as study participants.They were aged 60-75 years,with a body mass index of 18-30 kg/m2,and ASA grade Ⅱ or Ⅲ,regardless of sex.They were randomly divided into propofol(group P),ciprofol(group C),and ciprofol+oxycodone(group CO)groups,with 68 patients in each group.During anesthesia induction,group P was given propofol(1-1.5 mg/kg);group C,ciprofol(0.2-0.5 mg/kg);and group CO,oxyco-done hydrochloride(0.1-0.2 mg/kg)and ciprofol(0.2-0.5 mg/kg).The injection time of the three groups was>30 s.During anesthesia maintenance,ciprofol[1-1.5 mg/(kg·h)]was continuously injected intravenously in groups C and CO,and propofol[2-5 mg/(kg·h)]was continuously injected intravenously in group P.The modified observer's assessment of alertness/sedation score was evaluated at 3 min after anesthesia induction.If the score was≤1,endoscopy was started.The mean arterial pressure(MAP),heart rate(HR),and blood oxygen saturation(SpO2)at times T0(before drug injection),T1(when eyelash reflex disappeared),T2(when endoscopy began),and T3(when endoscope was withdrawn);visual analogue scale(VAS)scores at 30 min and 1 h after resuscitation;and induction time,recovery time,intravenous pain,respiratory depression,and other adverse reactions were recorded in the three groups.Results There were no significant differences in MAP,HR,and SpO2 at T0 and T3 among the three groups(all P>0.05).At T1 and T2,compared with those in group P,MAP,HR,and SpO2 in groups C and CO were significantly increased(all P<0.05).MAP,HR,and SpO2 in the CO group were slightly lower than those in the C group;however,the differences were not statistically significant(all P>0.05).Compared with that in group P,the incidence of respiratory depression and injection pain in groups C and CO was significantly reduced(P<0.05),but there was no statistically significant difference between groups C and CO(P>0.05).The VAS score at 30 min and 1 h after awakening and inci-dence of body movement in the CO group were lower than those in the P and C groups(all P<0.05);however,there was no statistically significant difference between the P and C groups(all P>0.05).Conclusion Ciprofol combined with oxycodone had definite sedative and analgesic effects in elderly patients undergoing endoscopic gastric mucosal dissection.Compared with the use of propofol or ciprofol alone,with combination therapy,the respiratory cycle is more stable,patients have fewer adverse reactions,and it is worthy of clinical application.
10.Bioinformatics analysis of the impact of immune infiltration in retinal ischemia-reperfusion injury
Wenting WANG ; Na LIANG ; Wenjing HA ; Shaomin PENG
Chinese Journal of Experimental Ophthalmology 2024;42(11):997-1005
Objective:To investigate the potential biomarkers associated with immune cells in retinal ischemia-reperfusion injury (RIRI).Methods:The RIRI gene expression profile dataset GSE20521 was obtained from the Gene Expression Omnibus database, and the differentially expressed genes (DEGs) were screened.The GSE20521 gene set was subjected to Gene Set Enrichment Analysis (GSEA) and Immune Cell Abundance Identifier (ImmuCellAI), yielding information pertaining to enriched pathways and immune cell infiltration.The Weighted Correlation Network Analysis (WGCNA) and Pearson correlation analysis were employed to identify the hub modules and candidate genes exhibiting the strongest correlation with immune infiltration.Subsequently, the protein-protein interaction (PPI) network of candidate genes was constructed, and key genes were screened using CytoHubba plugin.Results:The significant GSEA enrichment pathways in the RIRI group including the interferon-γ (IFN-γ), apoptosis, tumor necrosis factor-α/nuclear factor-κB, IFN-α, complement pathway, interleukin-6 (IL-6)-(signal transducer and activator of transcription 3)(STAT3) and IL2-STAT5 signaling pathways, as well as inflammatory response.Compared with the normal control group, the results of ImmuCellAI evaluation revealed significant increases in the proportions of cDC2 cells, monocyte-derived DC cells, M2 macrophages, and CD8_Tc cells and decreases in the proportions of pDC cells, CD4_T cells, CD4_Tm cells, helper T cells, regulatory T cells, follicular B cells, and eosinophils in the RIRI group (all at P<0.05).A total of 144 DEGs were obtained between the two groups of samples.Taking the intersection of DEGs and hub module genes, 140 candidate genes were obtained.GO analysis showed significant enrichment of positive regulation of cytokine production, leukocyte mediated immunity, wound healing, adaptive immune response, niacinamide adenine dinucleotide phosphate oxidase complex, and chemokine binding, etc.KEGG analysis enriched 50 pathways, including phagosome, pertussis, leishmaniasis tuberculosis, and complement and coagulation cascades.Three key genes were finally obtained, namely Cd68, Tlr2 and Hmox1, which were screened by PPI and different CytoHubba algorithms. Conclusions:The bioinformatics analysis reveals a distinct immune microenvironment in the retina of the RIRI group and normal control group, suggesting a correlation between RIRI and infiltration of multiple immune cell types.

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