1.Immunomodulatory effect of short-chain fatty acids in hepatic encephalopathy and its potential diagnostic value
Weiyu CHEN ; Dewen MAO ; Han WANG ; Yang DU ; Wenqian FENG ; Lei FU ; Chun YAO
Journal of Clinical Hepatology 2025;41(5):954-962
Hepatic encephalopathy (HE) is a common complication of severe liver disease in the end stage, and it is urgently needed to improve the rate of effective treatment and clarify the pathogenesis of HE. The liver is a crucial hub for immune regulation, and disruption of immune homeostasis is a key factor in the pathological mechanisms of HE. As the main metabolites of intestinal flora, short-chain fatty acids (SCFAs) play a vital role in the biological processes of both innate and adaptive immunity and can regulate the proliferation and differentiation of immune cells maintain the homeostasis of intestinal microenvironment and the integrity of barrier function. Studies have shown that SCFAs participate in bidirectional and dynamic interactions with the liver-gut-brain axis through immunomodulatory pathways, thereby playing an important role in the diagnosis, treatment, and prognostic evaluation of HE. Starting from the immunoregulatory effect of SCFAs, this article summarizes and analyzes the crosstalk relationship between SCFAs and the liver-gut-brain axis and the significance of SCFAs in the diagnosis and treatment of HE, in order to provide new ideas for optimizing clinical prevention and treatment strategies.
2.Protective mechanism of rhubarb decoction against inflammatory damage of brain tissue in rats with mild hepatic encephalopathy: A study based on the PI3K/AKT/mTOR signaling pathway
Guangfa ZHANG ; Yingying CAI ; Long LIN ; Lei FU ; Fan YAO ; Meng WANG ; Rongzhen ZHANG ; Yueqiao CHEN ; Liangjiang HUANG ; Han WANG ; Yun SU ; Yanmei LAN ; Yingyu LE ; Dewen MAO ; Chun YAO
Journal of Clinical Hepatology 2024;40(2):312-318
ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction (RD) retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy (MHE). MethodsA total of 60 male Sprague-Dawley rats were divided into blank group (CON group with 6 rats) and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks, 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group (MOD group), lactulose group (LT group), low-dose RD group (RD1 group), middle-dose RD group (RD2 group), and high-dose RD group (RD3 group), with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day; the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day; the rats in the RD1, RD2, and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5, 5.0, and 7.5 g/kg, respectively, once a day. After 10 days of treatment, the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects: behavioral status; the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and the level of blood ammonia; pathological changes of liver tissue and brain tissue; the mRNA and protein expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) in brain tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the MOD group, the RD1, RD2, and RD3 groups had a significantly shorter escape latency (all P<0.01), significant reductions in the levels of ALT, AST, IL-1β, IL-6, TNF-α, and blood ammonia (all P<0.05), significant alleviation of the degeneration, necrosis, and inflammation of hepatocytes and brain cells, and significant reductions in the mRNA and protein expression levels of PI3K, AKT, and mTOR in brain tissue (all P<0.05), and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats, possibly by regulating the PI3K/AKT/mTOR signaling pathway.
3.Discussion on the Pathogenesis of Osteonecrosis of the Femoral Head Under the System of Non-uniform Settlement During Bone Resorption and Multidimensional Composite Bowstring Working in Coordination with the Theory of Liver-Kidney and Muscle-Bone Based on the Concept of Liver and Kidney Sharing the Common Source
Gui-Xin ZHANG ; Feng YANG ; Le ZHANG ; Jie LIU ; Zhi-Jian CHEN ; Lei PENG ; En-Long FU ; Shu-Hua LIU ; Chang-De WANG ; Chun-Zhu GONG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(1):239-246
From the perspective of the physiological basis of liver and kidney sharing the common source in traditional Chinese medicine(TCM),and by integrating the theory of kidney dominating bone,liver dominating tendon,and meridian sinew of TCM as well as the bone resorption and collapse theory,and non-uniform settlement theory and lower-limb musculoskeletal bowstring structure theory of modern orthopedics,the pathogenesis of osteonecrosis of the femoral head(ONFH)under the system of non-uniform settlement during bone resorption and multidimensional composite bowstring working in coordination with the theory of liver-kidney and muscle-bone was explored.The key to the TCM pathogenesis of ONFH lies in the deficiency of the liver and kidney,and then the imbalance of kidney yin-yang leads to the disruption of the dynamic balance of bone formation and bone resorption mediated by osteoblasts-osteoclasts,which manifests as the elevated level of bone metabolism and the enhancement of focal bone resorption in the femoral head,and then leads to the necrosis and collapse of the femoral head.It is considered that the kidney dominates bone,liver dominates tendon,and the tendon and bone together constitute the muscle-bone-joint dynamic and static system of the hip joint.The appearance of collapse destroys the originally balanced muscle-bone-joint system.Moreover,the failure of liver blood in the nourishment of muscles and tendons further exacerbates the imbalance of the soft tissues around the hip joint,accelerates the collapse of the muscle-bone-joint dynamic and static system,speeds up the process of femoral head collapse,and ultimately results in irreversible outcomes.Based on the above pathogenesis,the systematic integrative treatment of ONFH should be based on the TCM holistic concept,focuses on the focal improvement of internal and external blood circulation of the femoral head by various approaches,so as to rebuild the coordination of joint function.Moreover,attention should be paid to the physical constitution of the patients,and therapy of tonifying the kidney and regulating the liver can be used to restore the balance between osteogenesis and osteoblastogenesis,and to reconstruct the muscle-bone-joint system,so as to effectively delay or even prevent the occurrence of ONFH.
4.Biological and genetic characteristics of three hypervirulent Klebsiella pneumoniae strains causing liver abscess
Yuqi ZHANG ; Juan WANG ; Lei HAN ; Pu LI ; Wentao MA ; Chun ZHANG ; Yali LI ; Jing YUAN ; Jin’e LEI
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(6):885-894
[Objective] To understand the resistance mechanisms, virulence characteristics, and pathogenicity of hypervirulent Klebsiella pneumoniae (hvKp), which causes pyogenic liver abscess (PLA), and to provide related data for clinical treatment of infection caused by this type of bacteria. [Methods] We collected three strains of Klebsiella pneumoniae isolated from the liver abscess fluid of patients with liver abscesses in various departments of The First Affiliated Hospital of Xi’an Jiaotong University. The hypervirulent phenotypes were determined by the wire test, and drug sensitivity was assessed using the VITEK 2 compact automatic microbiological analyzer. Molecular characteristics such as podocarp serotypes, multi-locus sequence typing (MLST), virulence genes, and drug resistance genes were identified through whole-genome sequencing. Additionally, a mouse infection model was established to evaluate pathogenicity. [Results] The isolates were sticky, with mucous thread pulling length >5 mm, all of which exhibited high viscosity phenotypes. Except 146007, which is a multidrug-resistant bacterium, the other two strains had higher antibiotic sensitivity. Whole genome sequencing revealed that the isolates were of high-virulence type, carrying the toxin plasmid rmpADC/rmpA2, iron uptake system, bacterial hairs, secretion system, and other virulence factors. All the three isolates tested positive for rmpA/rmpA2 combined with iucA/iutA, indicating they could be classified as hvKp. Multiple resistance genes were detected, such as β-lactamase like bla
5.Analysis of causes of bleeding after endoscopic duodenal papillary adenoma resection and establishment of prediction model
Chun-Yan JIN ; Hua YANG ; Lei WANG ; Qin YIN ; Meng-Yun HU ; Xu FANG ; Mu-Han NI
Modern Interventional Diagnosis and Treatment in Gastroenterology 2024;29(4):398-402,406
Objective The causes of bleeding after endoscopic duodenal papilloma resection were analyzed and discussed,and the prediction model of nomogram was established.Methods A total of 233 patients who underwent endoscopic duodenal papilloma resection in our hospital from January 2018 to December 2023 were retrospectively analyzed,and they were divided into bleeding group(n=31 cases)and non-bleeding group(n=202 cases)according to whether postoperative bleeding occurred.The clinical data of the two groups were compared,the independent risk factors for postoperative bleeding were analyzed by multi-factor logistic regression,the risk nomogram prediction model was constructed,and the Bootstrap method was used for 1000 repeated samples to carry out internal verification.Results Anticoagulant drugs(OR=9.063,95%CI:2.132-38.525),lesion diameter ≥2 cm(OR=2.802,95%CI:1.073-7.321),intraoperative fragment resection(OR=27.653,95%CI:3.055~619.174)and pancreatic complications(OR=6.859,95%CI:1.930~24.377)were independent risk factors for postoperative bleeding after endoscopic duodenal papilloma resection(P<0.05).A risk prediction nomogram model was constructed according to the Logistic regression analysis results.The samples were repeatedly sampled 1000 times through Bootstrap method for internal verification.The area under the ROC curve was 0.850,and the 95%CI was 0.780-0.913,indicating good differentiation ability of the model.Calibration curve analysis indicated that the prediction probability of postoperative bleeding predicted by the nomogram prediction model was in good agreement with the actual probability of postoperative bleeding,and Hosmer-Lemeshow showed good goodness of fit(x2=3.304 9,P=0.913 8).Conclusion Taking anticoagulant drugs,lesion diameter ≥2 cm,intraoperative segmentary resection,and postoperative combination of pancreas were independent risk factors for bleeding after endoscopic duodenal papilloma resection.A nomogram prediction model was established to help clinical assessment of postoperative bleeding risk in patients and improve decision-making basis for early prevention.
6.Value of two-dimensional shear wave elastography in diagnosis of liver fibrosis in patients with type 2 diabetes mellitus and non-alcoholic fatty liver
Chun-Ying LIU ; Qing XU ; Fei WANG ; Lei GAO
Chinese Medical Equipment Journal 2024;45(9):73-77
Objective To evaluate the value of two-dimensional shear wave elastography(2D-SWE)in the diagnosis of liver fibrosis in patients with type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease(NAFLD).Methods A total of 100 patients with T2DM complicated with NAFLD from some hospital were selected and was divided into three groups based on the degree of NAFLD including a mild group(38 cases),a moderate group(35 cases)and a severe group(27 cases).The values of liver stiffness measurement(LSM)in different degrees of fatty liver of the three groups were compared;the receiver operating characteristic(ROC)curve was used to evaluate the efficacy of 2D-SWE technique in diagnosing progressive liver fibrosis in T2DM patients with NAFLD.SPSS 26.0 statistical software was used for data analysis.Results The three groups had significant differences in LSM value(P<0.001),and the differences of the LSM values between the mild and moderate groups and between the mild and severe groups were all statistically significant(P<0.001),while the moderate and severe groups had no obvious difference in LSM value(P=0.065),with the LSM value increasing with the aggravation of NAFLD.There were 16 patients with progressive hepatic fibrosis and 84 ones with non-progressive hepatic fibrosis,and the median LSM value of patients with progressive heaptic fibrosis(8.3 kPa)significantly higher than that of patients with non-progressive hepatic fibrosis(5.0 kPa)(P<0.001).The ROC curve showed that the area under the curve(AUC)of 2D-SWE for the diagnosis of progressive liver fibrosis in T2DM patients with moderate and severe fatty liver was 0.896[95%confidence interval(CI):0.819-0.974],and the diagnostic sensitivity and the specificity was 92.3%and 83.7%respectively when the optimal cut-off value was 7.85 kPa.Conclusion The quantitative results of the LSM values measured by 2D-SWE technology differ in patients with different degrees of NAFLD,which can be used for auxiliary diagnosis of the degree of NAFLD and behaves well in diagnosing progressive hepatic fibrosis of patients with type 2 diabetes mellitus complicated with NAFLD.[Chinese Medical Equipment Journal,2024,45(9):73-77]
7.PI3K/Akt pathway-based investigation of total Astragalus saponins on sarcopenia in a rat model of type 2 diabetes mellitus
Lei-Lei MA ; Ji-An LI ; Wen-Xuan XU ; Jing-Ya WANG ; Zhao-Yang TIAN ; Jia-Yu LI ; Ru-Jie HAN ; Xiao-Jin LA ; Chun-Yu TIAN ; Hong CHANG ; Zi-Yang DAI ; Bi-Wei ZHANG
Chinese Traditional Patent Medicine 2024;46(11):3612-3619
AIM To investigate the effects of total Astragalus saponins on the improvement of sarcopenia in a rat model of type 2 diabetes mellitus(T2DM).METHODS The rats were divided into the normal group for a normal feeding and the model group for the feeding of high-sugar and high-fat diet combined with intraperitoneal injection of STZ to establish a T2DM model.The successful model rats were randomly divided into the model group,the metformin group(0.2 g/kg)and the total Astragalus saponins group(80 mg/kg),and given corresponding doses of drugs by gavage.After 12 weeks administration,the rats had their FBG,postprandial blood glucose(PG2h)and wet weight of skeletal muscle measured;their serum levels of INS,C-peptide(C-P),IGF-1,TNF-α and IL-1β detected by ELISA;their morphological changes of skeletal muscle observed by HE staining;their protein expressions of PI3K,p-Akt,mTOR,S6K1,FoxO1 and Murf1 in skeletal muscle detected by Western blot;and their mRNA expressions of Pi3k,Akt and mtor in skeletal muscle detected by RT-qPCR method.RESULTS Compared with the model group,the total Astragalus saponins group displayed decreased levels of FBG,PG2h,OGTT-AUC,HOMA-IR,TNF-α and IL-1β(P<0.01);increased levels of INS,C-P,IGF-1 and wet weight of skeletal muscle(P<0.05,P<0.01);improved skeletal muscle atrophy and increased protein expressions of PI3K,p-Akt,mTOR and S6K1 in skeletal muscle(P<0.05,P<0.01);decreased protein expressions of FoxO1 and Murf1(P<0.05,P<0.01);and increased mRNA expressions of Pi3k,Akt and mtor(P<0.01).CONCLUSION The improvement effects of total Astragalus saponins on sarcopenia in T2DM rats may be associated with the regulation of PI3K/Akt/mTOR and PI3K/Akt/FoxO1 pathways.
8.Safety of high-carbohydrate fluid diet 2 h versus overnight fasting before non-emergency endoscopic retrograde cholangiopancreatography: A single-blind, multicenter, randomized controlled trial
Wenbo MENG ; W. Joseph LEUNG ; Zhenyu WANG ; Qiyong LI ; Leida ZHANG ; Kai ZHANG ; Xuefeng WANG ; Meng WANG ; Qi WANG ; Yingmei SHAO ; Jijun ZHANG ; Ping YUE ; Lei ZHANG ; Kexiang ZHU ; Xiaoliang ZHU ; Hui ZHANG ; Senlin HOU ; Kailin CAI ; Hao SUN ; Ping XUE ; Wei LIU ; Haiping WANG ; Li ZHANG ; Songming DING ; Zhiqing YANG ; Ming ZHANG ; Hao WENG ; Qingyuan WU ; Bendong CHEN ; Tiemin JIANG ; Yingkai WANG ; Lichao ZHANG ; Ke WU ; Xue YANG ; Zilong WEN ; Chun LIU ; Long MIAO ; Zhengfeng WANG ; Jiajia LI ; Xiaowen YAN ; Fangzhao WANG ; Lingen ZHANG ; Mingzhen BAI ; Ningning MI ; Xianzhuo ZHANG ; Wence ZHOU ; Jinqiu YUAN ; Azumi SUZUKI ; Kiyohito TANAKA ; Jiankang LIU ; Ula NUR ; Elisabete WEIDERPASS ; Xun LI
Chinese Medical Journal 2024;137(12):1437-1446
Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.
9.Clinical characteristics of 267 children with eosinophilic gastrointestinal disease:a multicenter study
Chun-Lei ZHAN ; Jie-Yu YOU ; Xiao-Qin LI ; Yong WANG ; Xian-Qin MEI ; Sheng-Hua WAN
Chinese Journal of Contemporary Pediatrics 2024;26(2):139-144
Objective To explore the clinical manifestations,endoscopic findings,histopathological changes,treatment,and prognosis of eosinophilic gastrointestinal disease(EGID)in children,with the aim of enhancing awareness among pediatricians about this condition.Methods Data of 267 children with EGID were prospectively collected from January 2019 to July 2022 at Jiangxi Children's Hospital,Hunan Children's Hospital,and Henan Children's Hospital.The age of onset,symptoms,physical signs,laboratory examination results,endoscopic findings,histopathological changes,and treatment outcomes were observed.Results Among the 267 children with EGID,the majority had mild(164 cases,61.4% )or moderate(96 cases,35.6% )clinical severity.The disease occurred at any age,with a higher prevalence observed in school-age children(178 cases).The main symptoms in infants were vomiting and hematemesis,while in toddlers,vomiting and bloody stools were prominent.Abdominal pain and vomiting were the primary symptoms in preschool and school-age children.Nearly half(49.4% )of the affected children showed elevated platelet counts on hematological examination,but there was no significant difference in platelet counts among children with mild,moderate,and severe EGID(P>0.05).Endoscopic findings in EGID children did not reveal significant specificity,and histopathological examination showed no specific structural damage.Among them,85.0% (227 cases)received acid suppression therapy,34.5% (92 cases)practiced dietary avoidance,20.9% (56 cases)received anti-allergic medication,and a small proportion(24 cases,9.0% )were treated with prednisone.Clinical symptoms were relieved in all patients after treatment,but three cases with peptic ulcers experienced recurrence after drug discontinuation.Conclusions Mild and moderate EGID are more common in children,with no specific endoscopic findings.Dietary avoidance,acid suppression therapy,and anti-allergic medication are the main treatment methods.The prognosis of EGID is generally favorable in children.[Chinese Journal of Contemporary Pediatrics,2024,26(2):139-144]
10.Clinical characteristics and bacterial antimicrobial susceptibility of 42 pa-tients infected with Ralstonia pickettii
Zhen-Kui ZHU ; Ye-Hua LIU ; Ce WANG ; Hong-Zhi YU ; Chun-Lei ZHOU ; Hong MU
Chinese Journal of Infection Control 2024;23(11):1379-1383
Objective To study the clinical characteristics and bacterial antimicrobial susceptibility testing results of patients with clinically isolated Ralstonia pickettii(R.pickettii),and provide basis for the rational use of antimi-crobial agents.Methods Inpatients with R.pickettii infection who were treated at the Tianjin First Central Hospi-tal from January 2014 to December 2023 were analyzed retrospectively.Clinical characteristics and antimicrobial sus-ceptibility testing results were analyzed.Results A total of 80 strains of Ralstonia spp.were isolated over 10-year period,including 42(52.5%)non-repetitive strains of R.pickettii.Among 42 R.pickettii strains,64.3%were isolated from male patients.The strains isolated from sputum,catheter,blood,throat swabs,and drainage fluid specimens accounted for 38.1%,28.6%,19.0%,4.8%,and 2.4%,respectively.The clinical distribution of R.pickettii was highest in the intensive care unit(ICU),with a proportion of 52.4%.The number of infected patients first increased and then decreased with the years,followed by a slight fluctuation.There was no statistically signifi-cant difference in the number of infected patients in each department over the years(P>0.05).R.pickettii had higher susceptibility rates to doxycycline,levofloxacin,ciprofloxacin,and minocycline,susceptibility rates were 78.3%-90.9%,but was completely resistant to compound sulfamethoxazole and cefazolin(100%),it also had higher resistance rates to aztreonam,colistin,cefotetan,tobramycin,amikacin,ceftazidime,and gentamicin(80.0%-97.4%).There was no statistically significant difference in the resistance rates to 21 antimicrobial agents among different years(all P>0.05).Conclusion R.pickettii is mainly from ICU,and the majority of the infected population are adult males.Most strains are isolated from sputum and catheter.R.pickettii presents multidrug re-sistance.Attention should be paid to the changes in the resistance rates of antimicrobial agents,strengthen the dy-namic monitoring of bacterial resistance and guide the rational selection of antimicrobial agents in clinic,implement early and effective treatment to improve the prognosis of the patients.

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