1.Thesium chinense Turcz. alleviates antibiotic-associated diarrhea in mice by modulating gut microbiota structure and regulating the EGFR/PI3K/Akt signaling pathway.
Haonan XU ; Fang ZHANG ; Yuying HUANG ; Qisheng YAO ; Yueqin GUAN ; Hao CHEN
Journal of Southern Medical University 2025;45(2):285-295
OBJECTIVES:
To investigate the therapeutic mechanism of Thesium chinense Turcz. (TCT) for antibiotic-associated diarrhea (AAD).
METHODS:
Network pharmacology, KEGG pathway enrichment analysis and molecular docking were used to identify the shared targets and genes of TCT and AAD, the key signaling pathways and the binding between the active components in TCT and the core protein targets. In a Kunming mouse model of AAD established by intragastric administration of lincomycin hydrochloride, the effects of daily gavage of 1% carboxymethyl cellulose sodium or TCT gel solutions at 1.5 g/kg and 3 g/kg (n=10) on body weight and diarrhea were observed. HE staining, ELISA, 16S rRNA sequencing, and Western blotting were used to examine pathologies, expression levels of IL-6 and TNF-α, changes in gut microbiota, and protein expressions of EGFR, p-EGFR, PI3K, p-PI3K, Akt, and p-Akt in the colon tissues of the mice.
RESULTS:
We identified a total of 66 active components of TCT and 68 core targets including EGFR, STAT3 and PIK3CA. KEGG pathway enrichment analysis suggested that the therapeutic effects of TCT was mediated primarily through the PI3K/Akt signaling pathway. Molecular docking showed that EGFR had the highest binding affinity with coniferin, and the EGFR-coniferin complex maintained a stable conformation at 10 ns, whose stability was also confirmed by Gibbs free energy analysis. In the mouse models of AAD, treatment with TCT significantly improved colonic tissue morphology, decreased colonic levels of TNF-α and IL-6, increased gut microbiota diversity, and modulated the relative abundances of the key genera including Lactobacillus and Bacteroides. TCT treatment also markedly reduced protein expressions of p-EGFR, p-PI3K and p-Akt in the colon tissues of the mice.
CONCLUSIONS
TCT can alleviate AAD in mice by modulating gut microbiota composition, regulating the EGFR/PI3K/Akt signaling pathway, and reducing TNF‑α and IL-6 expressions.
Animals
;
Gastrointestinal Microbiome/drug effects*
;
Signal Transduction/drug effects*
;
Mice
;
ErbB Receptors/metabolism*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Diarrhea/drug therapy*
;
Phosphatidylinositol 3-Kinases/metabolism*
;
Anti-Bacterial Agents/adverse effects*
;
Drugs, Chinese Herbal/therapeutic use*
;
Molecular Docking Simulation
2.Recompensation of complications in patients with hepatitis B virus-related decompensated cirrhosis treated with entecavir antiviral therapy.
Ting ZHANG ; You DENG ; Hai Yan KANG ; Hui Ling XIANG ; Yue Min NAN ; Jin Hua HU ; Qing Hua MENG ; Ji Lian FANG ; Jie XU ; Xiao Ming WANG ; Hong ZHAO ; Calvin Q PAN ; Ji Dong JIA ; Xiao Yuan XU ; Wen XIE
Chinese Journal of Hepatology 2023;31(7):692-697
Objective: To analyze the occurrence of recompensation conditions in patients with chronic hepatitis B virus-related decompensated cirrhosis after entecavir antiviral therapy. Methods: Patients with hepatitis B virus-related decompensated cirrhosis with ascites as the initial manifestation were prospectively enrolled. Patients who received entecavir treatment for 120 weeks and were followed up every 24 weeks (including clinical endpoint events, hematological and imaging indicators, and others) were calculated for recompensation rates according to the Baveno VII criteria. Measurement data were compared using the Student t-test or Mann-Whitney U test between groups. Categorical data were compared by the χ (2) test or Fisher's exact probability method between groups. Results: 283 of the 320 enrolled cases completed the 120-week follow-up, and 92.2% (261/283) achieved a virological response (HBV DNA 20 IU/ml). Child-Pugh and MELD scores were significantly improved after treatment (8.33 ± 1.90 vs. 5.77 ± 1.37, t = 12.70, P < 0.001; 13.37 ± 4.44 vs. 10.45 ± 4.58, t = 5.963, P < 0.001). During the 120-week follow-up period, 14 cases died, two received liver transplants, 19 developed hepatocellular cancer, 11 developed gastroesophageal variceal bleeding, and four developed hepatic encephalopathy. 60.4% (171/283) (no decompensation events occurred for 12 months) and 56.2% (159/283) (no decompensation events occurred for 12 months and improved liver function) of the patients had achieved clinical recompensation within 120 weeks. Patients with baseline MELD scores > 15 after active antiviral therapy achieved higher recompensation than patients with baseline MELD scores ≤15 [50/74 (67.6%) vs. 109/209 (52.2%), χ (2) = 5.275, P = 0.029]. Conclusion: Antiviral therapy can significantly improve the prognosis of patients with hepatitis B virus-related decompensated cirrhosis. The majority of patients (56.2%) had achieved recompensation. Patients with severe disease did not have a lower probability of recompensation at baseline than other patients.
Humans
;
Hepatitis B virus/genetics*
;
Hepatitis B, Chronic/drug therapy*
;
Antiviral Agents/adverse effects*
;
Esophageal and Gastric Varices/complications*
;
Liver Cirrhosis/complications*
;
Treatment Outcome
;
Gastrointestinal Hemorrhage/complications*
;
Hepatitis B/drug therapy*
3.Modulation of gut microbiota during alleviation of antibiotic-associated diarrhea with Zingiberis Rhizoma.
Xue-Qiang ZHANG ; Cong-En ZHANG ; Xiao-Hong YU ; Yu-Qing MA ; Meng LI ; Xiao-Ying DUAN ; Zhi-Jie MA
China Journal of Chinese Materia Medica 2022;47(5):1316-1326
This study was aimed to explore the effect of Zingiberis Rhizoma extract on rats with antibiotic-associated diarrhea(AAD), and reveal the modulation of gut microbiota during alleviation of AAD. AAD rat model was successfully established by exposing rats to appropriate antibiotic mixed solution. Peficon(70 mg·kg~(-1)·d~(-1)) was used as positive control, then rats were treated with 200 mg·kg~(-1)·d~(-1) and 400 mg·kg~(-1)·d~(-1) of Zingiberis Rhizoma extract for low and high dosage groups of Zingiberis Rhizoma extract, respectively. The weight changes of the rats were observed, and the degree of diarrhea were evaluated by fecal score, 120 min fecal weight and fecal water content. Colon tissues for histopathological examination were stained with hematoxylin and eosin(HE), and 16 S rRNA sequencing analysis of gut microbiota was performed. The results showed that compared with the model group, the degree of diarrhea, indicated by fecal water content, fecal score, and 120 min fecal weight of positive control group, Zingiberis Rhizoma low-dose group and Zingiberis Rhizoma high-dose group were significantly ameliorated. And the treatment of Zingiberis Rhizoma could significantly improve the pathological condition of colon tissue in AAD rats, especially the high dose of Zingiberis Rhizoma. In addition, 16 S rRNA sequencing analysis of gut microbiota showed that the diversity and abundance of gut microbiota were significantly improved and the reco-very of gut microbiota was accelerated after given high-dose of Zingiberis Rhizoma, while no significant changes of alterations were observed after given Pefikon. Of note, compared with the pefikon group, the abundance and diversity of gut microbiota in Zingi-beris Rhizoma high-dose group were significantly elevated. At the phylum level, the abundance of Firmicutes in AAD rats increased and the abundance of Proteobacteria was decreased after the Zingiberis Rhizoma intervention. At the genus level, the abundance of Bacillus spp., Lachnoclostridium and Escherichia coli-Shigella were decreased, and the abundance of Lactobacillus spp., Trichophyton spp., and Trichophyton spp., etc., were increased. While compared with the AAD model group, there was no significant difference of gut microbiota after given Peficon. The results showed that Zingiberis Rhizoma exerted beneficial health effects against AAD, and positively affected the microbial environment in the gut of rats with AAD.
Animals
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Anti-Bacterial Agents/adverse effects*
;
Diarrhea/drug therapy*
;
Gastrointestinal Microbiome
;
Ginger
;
Plant Extracts
;
Rats
;
Rhizome
4.Practice guidance for the use of terlipressin for liver cirrhosis-related complications (2021).
Chinese Journal of Hepatology 2022;30(8):859-865
Liver cirrhosis is a major global health burden worldwide due to its high risk of morbidity and mortality. Role of terlipressin for the management of liver cirrhosis related complications has been recognized during recent years. This paper aims to develop evidence-based clinical practice guidance on the use of terlipressin for liver cirrhosis related complications. Hepatobiliary Study Group of Chinese Society of Gastroenterology of Chinese Medical Association and Hepatology Committee of Chinese Research Hospital Association have invited gastroenterologists, hepatologists, infectious disease specialists, surgeons, and clinical pharmacists to formulate the clinical practice guidance based on comprehensive literature review and experts' clinical experiences. Overall, 10 major statements regarding efficacy and safety of terlipressin in liver cirrhosis were proposed. Terlipressin can be beneficial for the management of cirrhotic patients with acute variceal bleeding and hepatorenal syndrome (HRS). However, the evidence regarding the use of terlipressin in cirrhotic patients with ascites, post-paracentesis circulatory dysfunction, and bacterial infections and in those undergoing hepatic resection and liver transplantation remains insufficient. Terlipressin-related adverse events, mainly including gastrointestinal symptoms, electrolyte disturbance, and cardiovascular and respiratory adverse events, should be closely monitored. The current clinical practice guidance supports the use of terlipressin for gastroesophageal variceal bleeding and HRS in liver cirrhosis. High-quality studies are needed to further clarify its potential effects in other liver cirrhosis related complications.
Electrolytes
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Esophageal and Gastric Varices/drug therapy*
;
Gastrointestinal Hemorrhage/etiology*
;
Hepatorenal Syndrome/etiology*
;
Humans
;
Liver Cirrhosis/drug therapy*
;
Lypressin/adverse effects*
;
Terlipressin/adverse effects*
;
Vasoconstrictor Agents/adverse effects*
6.Preemptive antiviral therapy with entecavir can reduce acute deterioration of hepatic function following transarterial chemoembolization.
Sun Hong YOO ; Jeong Won JANG ; Jung Hyun KWON ; Seung Min JUNG ; Bohyun JANG ; Jong Young CHOI
Clinical and Molecular Hepatology 2016;22(4):458-465
BACKGROUND/AIMS: Hepatic damage during transarterial chemoembolization (TACE) is a critical complication in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Apart from its role in preventing HBV reactivation, there is some evidence for the benefits of preemptive antiviral therapy in TACE. This study evaluated the effect of preemptive antiviral therapy on acute hepatic deterioration following TACE. METHODS: This retrospective observational study included a prospectively collected cohort of 108 patients with HBV-related HCC who underwent TACE between January 2007 and January 2013. Acute hepatic deterioration following TACE was evaluated. Treatment-related hepatic decompensation was defined as newly developed encephalopathy, ascites, variceal bleeding, elevation of the bilirubin level, prolongation of prothrombin time, or elevation of the Child-Pugh score by ≥2 within 2 weeks following TACE. Univariate and multivariate analyses were conducted to identify factors influencing treatment-related decompensation. Preemptive antiviral therapy involves directing prophylaxis only toward high-risk chronic hepatitis B patients in an attempt to prevent the progression of liver disease. We regarded at least 6 months as a significant duration of preemptive antiviral treatment before diagnosis of HCC. RESULTS: Of the 108 patients, 30 (27.8%) patients received preemptive antiviral therapy. Treatment-related decompensation was observed in 25 (23.1%) patients during the follow-up period. Treatment-related decompensation following TACE was observed more frequently in the nonpreemptive group than in the preemptive group (29.5% vs. 6.7%, P=0.008). In the multivariate analysis, higher serum total bilirubin (Hazard ratio [HR] =3.425, P=0.013), hypoalbuminemia (HR=3.990, P=0.015), and absence of antiviral therapy (HR=7.597, P=0.006) were significantly associated with treatment-related hepatic decompensation. CONCLUSIONS: Our findings suggest that preemptive antiviral therapy significantly reduces the risk of acute hepatic deterioration. Preventing hepatic deterioration during TACE by applying such a preemptive approach may facilitate the continuation of anticancer therapy and thus improve long-term outcomes.
Aged
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Antiviral Agents/*therapeutic use
;
Bilirubin/blood
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Carcinoma, Hepatocellular/*therapy
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Chemoembolization, Therapeutic/*adverse effects
;
Female
;
Gastrointestinal Hemorrhage/etiology
;
Guanine/*analogs & derivatives/therapeutic use
;
Hepatitis B/complications/*drug therapy
;
Humans
;
Hypoalbuminemia/etiology
;
Incidence
;
Liver/physiopathology
;
Liver Diseases/epidemiology/*etiology
;
Liver Neoplasms/*therapy
;
Male
;
Middle Aged
;
Proportional Hazards Models
;
Retrospective Studies
;
Risk Factors
;
Treatment Outcome
7.Moxa salt packets at Zhongwan (CV 12) for cisplatin chemotherapy-induced gastrointestinal reac- tions: a clinical study.
Yahong CAI ; Yuhong WU ; Fuying YE
Chinese Acupuncture & Moxibustion 2016;36(4):405-408
OBJECTIVETo compare the efficacy between moxa salt packets at acupoints combined with tropisetron hydrochloride and single use of tropisetron hydrochloride for cisplatin chemotherapy-induced gastrointestinal reaction.
METHODSSixty patients with malignant tumor who met inclusive criteria and received chemotherapy for the first time were recruited and randomly divided into an observation group and a control group, 30 cases in each one. Between the first days and fifth day into the chemotherapy, the patients in the control group were treated with daily intravenous injection of tropisetron hydrochloride (5 mg), while patients in the observation group, based on the treatment of control group, were treated with moxa salt packets at Zhongwan (CV 12). The nausea and vomiting between the first days and fifth day into the chemotherapy were compared in the two groups, and the occurrence rates of adverse reactions within the first week into chemotherapy were recorded.
RESULTSBetween the second day and fifth day into the chemotherapy, the effective rate for nausea in the observation group was higher than that in the control group (all P < 0.05); between the third day and fifth day into the chemotherapy, the effective rate for vomiting in the observation group was higher than that in the control group (all P < 0.05); one week into the chemotherapy, the occurrence rate of constipation in the observation group was lower than that in the control group (P < 0.05).
CONCLUSIONThe moxa salt packets combined with tropisetron hydrochloride can effectively reduce the cisplatin chemotherapy-induced nausea and vomiting as well as the occurrence rate of delayed-type vomiting, and improve the constipation, which is superior to single use of tropisetron hydrochloride.
Acupuncture Points ; Adult ; Aged ; Antineoplastic Agents ; adverse effects ; Cisplatin ; adverse effects ; Female ; Gastrointestinal Diseases ; etiology ; therapy ; Humans ; Male ; Middle Aged ; Moxibustion ; Nausea ; etiology ; therapy ; Neoplasms ; drug therapy ; Vomiting ; etiology ; therapy
8.Analysis of Risk Factors for Colonic Diverticular Bleeding: A Matched Case-Control Study.
Yuusaku SUGIHARA ; Shin Ei KUDO ; Hideyuki MIYACHI ; Masashi MISAWA ; Shogo OKOSHI ; Hiroyuki OKADA ; Kazuhide YAMAMOTO
Gut and Liver 2016;10(2):244-249
BACKGROUND/AIMS: Diverticular bleeding can occasionally cause massive bleeding that requires urgent colonoscopy (CS) and treatment. The aim of this study was to identify significant risk factors for colonic diverticular hemorrhage. METHODS: Between January 2009 and December 2012, 26,602 patients underwent CS at our institution. One hundred twenty-three patients underwent an urgent CS due to acute lower gastrointestinal hemorrhage. Seventy-two patients were diagnosed with colonic diverticular hemorrhage. One hundred forty-nine age- and sex-matched controls were selected from the patients with nonbleeding diverticula who underwent CS during the same period. The relationship of risk factors to diverticular bleeding was compared between the cases and controls. RESULTS: Uni- and multivariate conditional logistic regression analyses demonstrated that the use of nonsteroidal anti-inflammatory drugs (odds ratio [OR], 14.70; 95% confidence interval [CI], 3.89 to 55.80; p<0.0001), as well as the presence of cerebrovascular disease (OR, 8.66; 95% CI, 2.33 to 32.10; p=0.00126), and hyperuricemia (OR, 15.5; 95% CI, 1.74 to 138.00; p=0.014) remained statistically significant predictors of diverticular bleeding. CONCLUSIONS: Nonsteroidal anti-inflammatory drugs, cerebrovascular disease and hyperuricemia were significant risks for colonic diverticular hemorrhage. The knowledge obtained from this study may provide some insight into the diagnostic process for patients with lower gastrointestinal bleeding.
Adult
;
Aged
;
Aged, 80 and over
;
Anti-Inflammatory Agents, Non-Steroidal/adverse effects
;
Case-Control Studies
;
Cerebrovascular Disorders/complications
;
Colonic Diseases/*etiology/surgery
;
Colonoscopy
;
Diverticulum, Colon/*complications/pathology/surgery
;
Female
;
Gastrointestinal Hemorrhage/*etiology/surgery
;
Humans
;
Hyperuricemia/complications
;
Logistic Models
;
Male
;
Middle Aged
;
Retrospective Studies
;
Risk Factors
9.Fluid Retention Associated with Imatinib Treatment in Patients with Gastrointestinal Stromal Tumor: Quantitative Radiologic Assessment and Implications for Management.
Kyung Won KIM ; Atul B SHINAGARE ; Katherine M KRAJEWSKI ; Junhee PYO ; Sree Harsha TIRUMANI ; Jyothi P JAGANNATHAN ; Nikhil H RAMAIYA
Korean Journal of Radiology 2015;16(2):304-313
OBJECTIVE: We aimed to describe radiologic signs and time-course of imatinib-associated fluid retention (FR) in patients with gastrointestinal stromal tumor (GIST), and its implications for management. MATERIALS AND METHODS: In this Institutional Review Board-approved, retrospective study of 403 patients with GIST treated with imatinib, 15 patients with imaging findings of FR were identified by screening radiology reports, followed by manual confirmation. Subcutaneous edema, ascites, pleural effusion, and pericardial effusion were graded on a four-point scale on CT scans; total score was the sum of these four scores. RESULTS: The most common radiologic sign of FR was subcutaneous edema (15/15, 100%), followed by ascites (12/15, 80%), pleural effusion (11/15, 73%), and pericardial effusion (6/15, 40%) at the time of maximum FR. Two distinct types of FR were observed: 1) acute/progressive FR, characterized by acute aggravation of FR and rapid improvement after management, 2) intermittent/steady FR, characterized by occasional or persistent mild FR. Acute/progressive FR always occurred early after drug initiation/dose escalation (median 1.9 month, range 0.3-4.0 months), while intermittent/steady FR occurred at any time. Compared to intermittent/steady FR, acute/progressive FR was severe (median score, 5 vs. 2.5, p = 0.002), and often required drug-cessation/dose-reduction. CONCLUSION: Two distinct types (acute/progressive and intermittent/steady FR) of imatinib-associated FR are observed and each type requires different management.
Adult
;
Aged
;
Aged, 80 and over
;
Antineoplastic Agents/*adverse effects/therapeutic use
;
Ascites/pathology/radiography
;
Benzamides/*adverse effects/therapeutic use
;
Echocardiography/methods
;
Edema/pathology/radiography
;
Female
;
Gastrointestinal Stromal Tumors/drug therapy/pathology/*radiography
;
Gastrointestinal Tract/pathology/*radiography
;
Heart Failure/radiography
;
Humans
;
Male
;
Middle Aged
;
Molecular Targeted Therapy/*adverse effects
;
Pericardial Effusion/pathology/radiography
;
Peritoneal Neoplasms/diagnosis/radiography/secondary
;
Piperazines/*adverse effects/therapeutic use
;
Pleural Effusion/pathology/radiography
;
Pyrimidines/*adverse effects/therapeutic use
;
Radiology
;
Retrospective Studies
;
Tomography, X-Ray Computed
10.Imatinib mesylate-induced interstitial lung disease in a patient with prior history of Mycobacterium tuberculosis infection.
Na Ri LEE ; Ji Won JANG ; Hee Sun KIM ; Ho Young YHIM
The Korean Journal of Internal Medicine 2015;30(4):550-553
No abstract available.
Adult
;
Antineoplastic Agents/*adverse effects
;
Antitubercular Agents/therapeutic use
;
Biopsy
;
Female
;
Gastrointestinal Stromal Tumors/*drug therapy/pathology/surgery
;
Humans
;
Imatinib Mesylate/*adverse effects
;
Lung Diseases, Interstitial/*chemically induced/diagnosis
;
Mycobacterium tuberculosis/*isolation & purification
;
Protein Kinase Inhibitors/*adverse effects
;
Rectal Neoplasms/*drug therapy/pathology/surgery
;
Tomography, X-Ray Computed
;
Tuberculosis, Pulmonary/diagnosis/drug therapy/*microbiology

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