Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was c...Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),antiinfective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed.Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group.Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-αand IL-6 may partake the inflammatory process of DILI.展开更多
Drug-induced liver injury(DILI)is a major problem in the United States,commonly leading to hospital admission.Diagnosing DILI is difficult as it is a diagnosis of exclusion requiring a temporal relationship between dr...Drug-induced liver injury(DILI)is a major problem in the United States,commonly leading to hospital admission.Diagnosing DILI is difficult as it is a diagnosis of exclusion requiring a temporal relationship between drug exposure and liver injury and a thorough work up for other causes.In addition,DILI has a very variable clinical and histologic presentation that can mimic many different etiologies of liver disease.Objective scoring systems can assess the probability that a drug caused the liver injury but liver biopsy findings are not part of the criteria used in these systems.This review will address some of the recent updates to the scoring systems and the role of liver biopsy in the diagnosis of DILI.展开更多
BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations ...BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively.METHODS A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected.The incidence rate,cumulative times,and equally and unequally weighted cumulative effects of excess high-normal ALT levels(ehALT)were measured.Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD.RESULTS A total of 83.13%of participants with MAFLD had normal ALT levels.The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group.Compared with those in the low-normal ALT group,the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651[95%confidence interval(CI):1.199-2.273]and 1.535(95%CI:1.119-2.106)in the third quartile and 1.616(95%CI:1.162-2.246)and 1.580(95%CI:1.155-2.162)in the fourth quartile,respectively.CONCLUSION Most participants with MAFLD had normal ALT levels.Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.展开更多
[Objectives]To investigate the acute toxicity and hepatoprotective effect of Jinchuan formula plum wine extract on mice,determine its safety range,and evaluate its hepatoprotective effect.[Methods]The median lethal do...[Objectives]To investigate the acute toxicity and hepatoprotective effect of Jinchuan formula plum wine extract on mice,determine its safety range,and evaluate its hepatoprotective effect.[Methods]The median lethal dose(LD_(50))was determined by acute toxicity test with the toxic reaction and mortality of mice as indexes.Sixty Kunming mice were randomly divided into 6 groups:normal control group,model group(ConA-induced liver injury model),Jinchuan formula plum wine high,medium and low dose groups(1.0,0.5,0.25 g/kg)and silybin group(0.1 g/kg).The levels of ALT,AST,LDH in serum and TG,VLDL in liver were measured.After HE staining,the pathological changes of liver tissue in mice were observed,and the liver protective effect of Jinchuan formula plum wine extract was analyzed and evaluated.[Results]LD_(50)was 11.18 g/kg,and the 95%confidence limit of LD_(50)was 10.31-12.05 g/kg.The high-dose group of Jinchuan formula plum wine extract could significantly reduce the serum ALT and AST activities of ConA-induced liver injury mice(P<0.05).[Conclusions]Jinchuan formula plum wine extract is relatively safe,and also has a protective effect on liver injury.展开更多
Drug-induced liver injury(DILI)is a rare side effect of drugs caused by all kinds of prescription or over-the-counter chemi-cals,biological agents,traditional Chinese medicine(TCM),natu-ral medicine(NM),health product...Drug-induced liver injury(DILI)is a rare side effect of drugs caused by all kinds of prescription or over-the-counter chemi-cals,biological agents,traditional Chinese medicine(TCM),natu-ral medicine(NM),health products,dietary supplements and their metabolites,and even excipients,which can lead to jaundice,liver failure,or even death.Although it is rare in term of single drug,the occurrence of DILI in all liver injuries is not low due to the wide range of drugs and foods involved.Moreover,there was an increasing trend of incidence of DILI since 2010 worldwide,with Asian regions showing the highest incidence[1].展开更多
Complications of the liver are amongst the world’s worst diseases.Liver fibrosis is the first stage of liver problems,while cirrhosis is the last stage,which can lead to death.The creation of effective anti-fibrotic ...Complications of the liver are amongst the world’s worst diseases.Liver fibrosis is the first stage of liver problems,while cirrhosis is the last stage,which can lead to death.The creation of effective anti-fibrotic drug delivery methods appears critical due to the liver’s metabolic capacity for drugs and the presence of insurmountable physiological impediments in the way of targeting.Recent breakthroughs in anti-fibrotic agents have substantially assisted in fibrosis;nevertheless,the working mechanism of anti-fibrotic medications is not fully understood,and there is a need to design delivery systems that are well-understood and can aid in cirrhosis.Nanotechnology-based delivery systems are regarded to be effective but they have not been adequately researched for liver delivery.As a result,the capability of nanoparticles in hepatic delivery was explored.Another approach is targeted drug delivery,which can considerably improve efficacy if delivery systems are designed to target hepatic stellate cells(HSCs).We have addressed numerous delivery strategies that target HSCs,which can eventually aid in fibrosis.Recently genetics have proved to be useful,and methods for delivering genetic material to the target place have also been investigated where different techniques are depicted.To summarize,this review paper sheds light on themost recent breakthroughs in drug and gene-based nano and targeted delivery systems that have lately shown useful for the treatment of liver fibrosis and cirrhosis.展开更多
BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis...BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.展开更多
In this case, a young female presented with non-specific features such as fever, sore throat, headache and fatigue. She went on to develop epigastric pain, darkening of urine and jaundice, with no resolution of prior ...In this case, a young female presented with non-specific features such as fever, sore throat, headache and fatigue. She went on to develop epigastric pain, darkening of urine and jaundice, with no resolution of prior symptoms. Physical and Laboratory tests confirmed the primary diagnosis of infectious mononucleosis, however, prior history of treatment with multiple drugs led to a diagnosis of DILI as a complication. Appropriate treatment with I.V. antibiotics, hepatoprotective agents, steroids as well as discontinuation of all potential hepatotoxic agents showed significant improvement in patients’ symptoms and overall condition.展开更多
[Objectives]To investigate the protective effect of ethanol extract from sweet potato leaves on liver injury induced by CCl_(4)in mice.[Methods]25 ICR mice were randomly divided into blank group,model group,high-dose ...[Objectives]To investigate the protective effect of ethanol extract from sweet potato leaves on liver injury induced by CCl_(4)in mice.[Methods]25 ICR mice were randomly divided into blank group,model group,high-dose extract group(200 mg/kg),low-dose extract group(100 mg/kg)and positive control group(2 mg/kg colchicine),with 5 mice in each group.All groups except the blank group were given intraperitoneal injection of 20%CCl 4 olive oil solution(2 mL/kg),and the blank group was given the same dose of olive oil solution three times a week.After 4 weeks,each administration group was given the corresponding dose of drugs(10 mL/kg),and the blank group and model group were given the corresponding amount of normal saline for 2 weeks.After the last intragastric administration,fasting was required,but water was allowed,blood was taken from eyeballs,and upper serum was taken by static centrifugation.Serum AST,ALT,CRP,IL-6 and SOD levels were detected by the kit.[Results]Compared with the blank group,the serum AST and ALT levels in the model group were significantly increased;compared with the model group,the ethanol extract of sweet potato leaves could decrease the levels of ALT,AST,CRP,IL-6 and increase the level of SOD in serum.[Conclusions]The ethanol extract of sweet potato leaves had protective effect on the mice with liver injury induced by CCl_(4),and its mechanism may be to protect the liver by lowering enzymes,inhibiting inflammation and antioxidant stress.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a major chronic liver disorder worldwide,and there is no established treatment for this disease.We conducted a network meta-analysis(NMA)to compare existing treatme...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a major chronic liver disorder worldwide,and there is no established treatment for this disease.We conducted a network meta-analysis(NMA)to compare existing treatments,which include four classes of antidiabetic drugs,and examined the optimum treatments for NAFLD.AIM To compare the effectiveness of different treatments for NAFLD.METHODS An NMA was conducted using Stata 14.0(Corporation LLC,College Station,United States)and R(X643.6.3 version)in this study.Eligible randomized controlled trials(RCTs)were searched in the PubMed,Cochrane Library,Embase,Medline and Web of Science databases from database inception to April 2021.Two researchers independently screened the available studies in strict accordance with inclusion and exclusion criteria.The Cochrane Risk of Bias tool was used to evaluate the risk of bias of the included studies.The variables with and without dimensional differences were calculated as the standardized mean difference and weighted mean difference,respectively.An inconsistency model and“nodesplitting”technique were used to test for inconsistency.Funnel plots were used to evaluate publication bias.RESULTS Twenty-two eligible RCTs involving 1377 participants were eventually included in our analysis.Data were pooled using a random-effects model.Our NMA results revealed that glucagon-like peptide-1 receptor agonists(GLP-1RAs)were the most effective treatment,yielding improvements in hepatic fat content(HFC),alanine aminotransferase(ALT),aspartate aminotransferase(AST),serumγ-glutamyl transferase(GGT)and body weight[surface under the cumulative ranking curve(SUCRA)=99.6%,92.6%,82.8%,92.3%and 99.6%,respectively],while thiazolidinediones(TZDs)were the best intervention for reducing the NAFLD activity score(NAS;SUCRA=98.9%).In addition,moderate performance was observed for the sodium glucose cotransporter-2 inhibitors groups(SUCRA=25.1%,66.2%,63.5%,58.2%and 71.9%for HFC,ALT,AST,GGT and body weight,respectively).However,metformin performed poorly according to most indicators(SUCRA=54.5%,0.3%,19.5%,33.7%,57.7%and 44.3%for HFC,NAS,ALT,AST,GGT and body weight,respectively).CONCLUSION GLP-1RAs may be the optimum choice for most patients with NAFLD.However,TZDs are considered the most effective therapies in NAFLD patients with histological disease activity.展开更多
During the outbreak of the coronavirus disease 2019(COVID-19)pandemic,particular interest rose regarding the interaction between metabolic dysfunctionassociated fatty liver disease(MAFLD)and the COVID-19 infection.Sev...During the outbreak of the coronavirus disease 2019(COVID-19)pandemic,particular interest rose regarding the interaction between metabolic dysfunctionassociated fatty liver disease(MAFLD)and the COVID-19 infection.Several studies highlighted the fact that individuals with MAFLD had higher probability of severe acute respiratory syndrome coronavirus 2 infection and more severe adverse clinical outcomes.One of the proposed mechanisms is the inflammatory response pathway,especially the one involving cytokines,such as interleukin 6,which appeared particularly elevated in those patients and was deemed responsible for additional insult to the already damaged liver.This should increase our vigilance in terms of early detection,close follow up and early treatment for individuals with MAFLD and COVID-19 infection.In the direction of early diagnosis,biomarkers such as cytokeratin-18 and scoring systems such as Fibrosis-4 index score are proposed.COVID-19 is a newly described entity,expected to be of concern for the years to come,and MAFLD is a condition with an ever-increasing impact.Delineating the interaction between these two entities should be brought into the focus of research.Reducing morbidity and mortality of patients with COVID-19 and MAFLD should be the ultimate objective,and the optimal way to achieve this is by designing evidence-based prevention and treatment policies.展开更多
This editorial addresses the growing concern of herb-induced liver injury(HILI),focusing on a unique case of Skullcap-induced HILI report.This editorial underscore the significant mortality rate linked to Skullcap-ind...This editorial addresses the growing concern of herb-induced liver injury(HILI),focusing on a unique case of Skullcap-induced HILI report.This editorial underscore the significant mortality rate linked to Skullcap-induced HILI,emphasizing the importance of vigilant monitoring and intervention.As herbal supplement usage rises,collaboration among clinicians and researchers is crucial to comprehend and address the complexities of HILI,particularly those involving Skullcap.展开更多
The sex-based differences between the effects of two novel sugar-based drug candidates,a sulfated polymannuroguluronate(SPMG-911)and an acidic oligosaccharide sugar chain compound(AOSC-971),on the enzymes CYP 1A2,CYP2...The sex-based differences between the effects of two novel sugar-based drug candidates,a sulfated polymannuroguluronate(SPMG-911)and an acidic oligosaccharide sugar chain compound(AOSC-971),on the enzymes CYP 1A2,CYP2E1 and CYP3A4 of Chinese human liver microsome were investigated.The results showed that neither SPMG-911 nor AOSC-971 have any effect on CYP3A4,AOSC-971 induced the CYP 2E1 in men but have no effect on CYP1A2,SPMG-911 inhibit the CYP1A2 also in men but have no effect on CYP2E1.The results are useful for their safety evaluation,as well as for the prediction of inter-drug interactions associated with the two drugs.展开更多
Importance/Objective: Adverse Drug Reactions (ADRs) are unavoidable, but recognizing and addressing ADRs early can improve wellness and prevent permanent injury. We suggest that available medical information and digit...Importance/Objective: Adverse Drug Reactions (ADRs) are unavoidable, but recognizing and addressing ADRs early can improve wellness and prevent permanent injury. We suggest that available medical information and digital/electronic methods could be used to manage this major healthcare problem for individual patients in real time. Methods: We searched the available digital applications and three literature databases using the medical subject heading terms, adverse drug reaction reporting systems or management, filtered by clinical trial or systemic reviews, to detect publications with data about ADR identification and management approaches. We reviewed the reports that had abstract or summary data or proposed or implemented methods or systems with potential to identify or manage ADRs in clinical settings. Results: The vast majority of the 481 reports used retrospectively collected data for groups of patients or were limited to surveying one population group or class of medication. The reports showed potential and definite associations of ADRs for specific drugs and problems, mostly, but not exclusively, for patients in hospitals and nursing homes. No reports described complete methods to collect comprehensive data on ADRs for individual patients in a healthcare system. The digital applications have ADR information, but all are too cumbersome or incomplete for use in active clinical settings. Several studies suggested that providing information about potential ADRs to clinicians can reduce these problems. Conclusion and Relevance: Although investigators and government agencies agree with the need, there is no comprehensive ADR management program in current use. Informing the patient’s healthcare practitioners of potential ADRs at the point of service has the potential for reduction of these complications, which should improve healthcare and reduce unneeded costs.展开更多
Objective:This paper aims to analyze the analgesic effect of ultrasound-guided transversus abdominis plane block(TAPB)combined with non-steroidal anti-inflammatory analgesic drug lornoxicam on abdominal surgery in pat...Objective:This paper aims to analyze the analgesic effect of ultrasound-guided transversus abdominis plane block(TAPB)combined with non-steroidal anti-inflammatory analgesic drug lornoxicam on abdominal surgery in patients with a history of drug addiction.Methods:32 patients aged 18-60 who underwent lower abdominal surgery in the First People's Hospital of Liangshan Yi Autonomous Prefecture and Butuo County People's Hospital of Liangshan Yi Autonomous Prefecture from January 2022 to March 2023 were selected,the patients must have drug abuse history for more than 1 year,with a history of drug withdrawal and relapse.The patients were divided into observation group and control group by the envelope method,with 16 cases in the observation group and 16 cases in the control group.Two groups of patients underwent ultrasound-guided bilateral transversus abdominis plane block after the operation.The observation group was treated with dexmedetomidine hydrochloride 1μg/kg+0.25%ropivacaine hydrochloride 40ml,and the control group was treated with 40ml 0.9%sodium chloride injection,the two groups of patients returned to the ward after operation and given intravenous infusion of lornoxicam for relieving the pain.The visual analogue scale(VAS)score of postoperative pain,the times of rescue analgesia,the time of postoperative anal exhaust,the time of ambulation,nausea and vomiting,withdrawal symptoms,related adverse reactions,and hospitalization days were compared between the two groups.Results:The VAS score of postoperative pain in the observation group was significantly lower than that in the control group,P<0.05.Patients in the observation group used less postoperative rescue analgesics than those in the control group,P<0.05.For postoperative anal exhaust time,the difference between the two groups of patients was relatively small,and the time in the observation group was shorter,P>0.05.The time to get out of bed and the length of hospital stay were not significantly different between the control group and the observation group,P>0.05.The withdrawal symptoms of the patients in the observation group were better,P<0.05,nausea and vomiting,and other adverse reactions were lower in the control group,P<0.05.Conclusion:Ultrasound-guided transversus abdominis plane block combined with lornoxicam can be used to relieve pain in abdominal surgery for patients with drug addiction,which can effectively improve the therapeutic effect of patients and reduce the number of postoperative rescue analgesia.Thus,it has high clinical application value.展开更多
The dynamic changes of liver microsomal drug-metabolizing system (MDMS) andlipoperoxidation were studied in scalded rats. The effects of treatment with vitamin E and silybinwere also evaluated. The results showeed tha...The dynamic changes of liver microsomal drug-metabolizing system (MDMS) andlipoperoxidation were studied in scalded rats. The effects of treatment with vitamin E and silybinwere also evaluated. The results showeed that liver microsomal cytochrome P-450 content, and p-nitroanisole demethylase (P-NOD) and aniline hydroxylase (AH) activity decreased markedlypostburn. On the contrary, liver lipoperoxide and mierosomal lipoperoxidation increased significantlyafter scalding. Both the increase of liver lipoperoxide and mierosomal lipoperoxidation and the de-crease of MDMS activity were prevented by vitamin E and silybin treatments.展开更多
BACKGROUND Although hepatitis B virus infection is the leading cause of chronic liver injury globally,nonalcoholic fatty liver disease(NAFLD)is gradually gaining attention as another major chronic liver disease.The nu...BACKGROUND Although hepatitis B virus infection is the leading cause of chronic liver injury globally,nonalcoholic fatty liver disease(NAFLD)is gradually gaining attention as another major chronic liver disease.The number of patients having chronic hepatitis B(CHB)with concomitant hepatic steatosis has increased.AIM To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB.METHODS Relevant English studies were systematically searched across PubMed,EMBASE,Web of Science,and Cochrane Library until October 2023.Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included.RESULTS Of the 2502 retrieved studies,11 articles were finally included.Biochemical response until 48 wk(OR=0.87,95%CI:0.50–1.53,P=0.000)and 96 wk(OR=0.35,95%CI:0.24–0.53,P=0.24)and virological response until 96 wk(OR=0.80,95%CI:0.43–1.49,P=0.097)were lower in patients with hepatic steatosis than in patients with CHB alone.CONCLUSION Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.展开更多
BACKGROUND Gastric cancer(GC)is the fifth most common type of cancer and has the fourth highest death rate among all cancers.There is a lack of studies examining the impact of liver metastases on the effectiveness of ...BACKGROUND Gastric cancer(GC)is the fifth most common type of cancer and has the fourth highest death rate among all cancers.There is a lack of studies examining the impact of liver metastases on the effectiveness of immunotherapy in individuals diagnosed with GC.AIM To investigate the influence of liver metastases on the effectiveness and safety of immunotherapy in patients with advanced GC.METHODS This retrospective investigation collected clinical data of patients with advanced stomach cancer who had immunotherapy at our hospital from February 2021 to January 2023.The baseline attributes were compared using either the Chi-square test or the Fisher exact probability method.The chi-square test and Kaplan-Meier survival analysis were employed to assess the therapeutic efficacy and survival duration in GC patients with and without liver metastases.RESULTS The analysis comprised 48 patients diagnosed with advanced GC,who were categorized into two groups:A liver metastasis cohort(n=20)and a non-liver metastatic cohort(n=28).Patients with liver metastasis exhibited a more deteriorated physical condition compared to those without liver metastasis.The objective response rates in the cohort with metastasis and the cohort without metastasis were 15.0%and 35.7%(P>0.05),respectively.Similarly,the disease control rates in these two cohorts were 65.0%and 82.1%(P>0.05),respectively.The median progression-free survival was 5.0 months in one group and 11.2 months in the other group,with a hazard ratio of 0.40 and a significance level(P)less than 0.05.The median overall survival was 12.0 months in one group and 19.0 months in the other group,with a significance level(P)greater than 0.05.CONCLUSION Immunotherapy is less effective in GC patients with liver metastases compared to those without liver metastasis.展开更多
Fluphenazine (FP) treatment (50mg/kg bw, ip in saline) 30 min before or 6 or 10 h after CCl4 administration (1 ml/kg ip in olive oil) significantly prevented the liver necrosis produced by the hepatotoxin at 24 h. FP ...Fluphenazine (FP) treatment (50mg/kg bw, ip in saline) 30 min before or 6 or 10 h after CCl4 administration (1 ml/kg ip in olive oil) significantly prevented the liver necrosis produced by the hepatotoxin at 24 h. FP had enhancing effects on the covalent binding of CCl4 reactive metabolites to cellular constituents and on CCl4 induced lipid peroaldation.FP lowered bOdy temperature of the CCl4-poisoned animals during the 24 h observation period. The obtained results are compatible but do not prove the hypothesis that calmodulin (CaM) had participation in late occurring events preceding necrosis. FP lowering action on body temperature, however, might also play a role in the effects of this drug on the onset of CCl4 induced liver necrosis. FP levels in liver tissue as determined by gas chromatography-mass spectrometry evidenced the presence of the drug in amounts suffi cient to inhibit CaM and that suggests that not all preventive effects of FP are due to its indirect actions on the central nervous system via decreased body temperature展开更多
基金funded by The National Key Research and Development Program(2022YFC2603500,2022YFC2603505)Beijing Municipal Health Commission high-level public health technical personnel construction project,discipline leader-03-26+2 种基金Beijing Hospitals Authority Clinical medicine Development of special funding support(XMLX202127)The Digestive Medical Coordinated Development Center of Beijing Hospitals Authority(XXZ0302)The capital health research and development of special(2022-1-2172)。
文摘Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators.Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),antiinfective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed.Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group.Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-αand IL-6 may partake the inflammatory process of DILI.
文摘Drug-induced liver injury(DILI)is a major problem in the United States,commonly leading to hospital admission.Diagnosing DILI is difficult as it is a diagnosis of exclusion requiring a temporal relationship between drug exposure and liver injury and a thorough work up for other causes.In addition,DILI has a very variable clinical and histologic presentation that can mimic many different etiologies of liver disease.Objective scoring systems can assess the probability that a drug caused the liver injury but liver biopsy findings are not part of the criteria used in these systems.This review will address some of the recent updates to the scoring systems and the role of liver biopsy in the diagnosis of DILI.
基金National Natural Science Foundation of China,No.72101236China Postdoctoral Science Foundation,No.2022M722900+1 种基金Collaborative Innovation Project of Zhengzhou City,No.XTCX2023006Nursing Team Project of the First Affiliated Hospital of Zhengzhou University,No.HLKY2023005.
文摘BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively.METHODS A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected.The incidence rate,cumulative times,and equally and unequally weighted cumulative effects of excess high-normal ALT levels(ehALT)were measured.Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD.RESULTS A total of 83.13%of participants with MAFLD had normal ALT levels.The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group.Compared with those in the low-normal ALT group,the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651[95%confidence interval(CI):1.199-2.273]and 1.535(95%CI:1.119-2.106)in the third quartile and 1.616(95%CI:1.162-2.246)and 1.580(95%CI:1.155-2.162)in the fourth quartile,respectively.CONCLUSION Most participants with MAFLD had normal ALT levels.Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.
文摘[Objectives]To investigate the acute toxicity and hepatoprotective effect of Jinchuan formula plum wine extract on mice,determine its safety range,and evaluate its hepatoprotective effect.[Methods]The median lethal dose(LD_(50))was determined by acute toxicity test with the toxic reaction and mortality of mice as indexes.Sixty Kunming mice were randomly divided into 6 groups:normal control group,model group(ConA-induced liver injury model),Jinchuan formula plum wine high,medium and low dose groups(1.0,0.5,0.25 g/kg)and silybin group(0.1 g/kg).The levels of ALT,AST,LDH in serum and TG,VLDL in liver were measured.After HE staining,the pathological changes of liver tissue in mice were observed,and the liver protective effect of Jinchuan formula plum wine extract was analyzed and evaluated.[Results]LD_(50)was 11.18 g/kg,and the 95%confidence limit of LD_(50)was 10.31-12.05 g/kg.The high-dose group of Jinchuan formula plum wine extract could significantly reduce the serum ALT and AST activities of ConA-induced liver injury mice(P<0.05).[Conclusions]Jinchuan formula plum wine extract is relatively safe,and also has a protective effect on liver injury.
基金National Key R&D Pro-gram of China(2022YFC3602000)Zhejiang Provincial Natural Science Foundation of China(LZ22H030001).
文摘Drug-induced liver injury(DILI)is a rare side effect of drugs caused by all kinds of prescription or over-the-counter chemi-cals,biological agents,traditional Chinese medicine(TCM),natu-ral medicine(NM),health products,dietary supplements and their metabolites,and even excipients,which can lead to jaundice,liver failure,or even death.Although it is rare in term of single drug,the occurrence of DILI in all liver injuries is not low due to the wide range of drugs and foods involved.Moreover,there was an increasing trend of incidence of DILI since 2010 worldwide,with Asian regions showing the highest incidence[1].
文摘Complications of the liver are amongst the world’s worst diseases.Liver fibrosis is the first stage of liver problems,while cirrhosis is the last stage,which can lead to death.The creation of effective anti-fibrotic drug delivery methods appears critical due to the liver’s metabolic capacity for drugs and the presence of insurmountable physiological impediments in the way of targeting.Recent breakthroughs in anti-fibrotic agents have substantially assisted in fibrosis;nevertheless,the working mechanism of anti-fibrotic medications is not fully understood,and there is a need to design delivery systems that are well-understood and can aid in cirrhosis.Nanotechnology-based delivery systems are regarded to be effective but they have not been adequately researched for liver delivery.As a result,the capability of nanoparticles in hepatic delivery was explored.Another approach is targeted drug delivery,which can considerably improve efficacy if delivery systems are designed to target hepatic stellate cells(HSCs).We have addressed numerous delivery strategies that target HSCs,which can eventually aid in fibrosis.Recently genetics have proved to be useful,and methods for delivering genetic material to the target place have also been investigated where different techniques are depicted.To summarize,this review paper sheds light on themost recent breakthroughs in drug and gene-based nano and targeted delivery systems that have lately shown useful for the treatment of liver fibrosis and cirrhosis.
基金Supported by Science and Technology Plan Project of Shaoyang City,No.2022GX4139.
文摘BACKGROUND Diabetes and thyroiditis are closely related.They occur in combination and cause significant damage to the body.There is no clear treatment for type-2 diabetes mellitus(T2DM)with Hashimoto's thyroiditis(HT).While single symptomatic drug treatment of the two diseases is less effective,combined drug treatment may improve efficacy.AIM To investigate the effect of a combination of vitamin D,selenium,and hypoglycemic agents in T2DM with HT.METHODS This retrospective study included 150 patients with T2DM and HT treated at The Central Hospital of Shaoyang from March 2020 to February 2023.Fifty patients were assigned to the control group,test group A,and test group B according to different treatment methods.The control group received low-iodine diet guidance and hypoglycemic drug treatment.Test group A received the control treatment plus vitamin D treatment.Test group B received the group A treatment plus selenium.Blood levels of markers of thyroid function[free T3(FT3),thyroid stimulating hormone(TSH),free T4(FT4)],autoantibodies[thyroid peroxidase antibody(TPOAB)and thyroid globulin antibody(TGAB)],blood lipid index[low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triacylglycerol(TG)],blood glucose index[fasting blood glucose(FBG),and hemoglobin A1c(HbA1c)]were measured pre-treatment and 3 and 6 months after treatment.The relationships between serum 25-hydroxyvitamin D3[25(OH)D3]level and each of these indices were analyzed.RESULTS The levels of 25(OH)D3,FT3,FT4,and LDL-C increased in the order of the control group,test group A,and test group B(all P<0.05).The TPOAB,TGAB,TC,TG,FBG,HbA1c,and TSH levels increased in the order of test groups B,A,and the control group(all P<0.05).All the above indices were compared after 3 and 6 months of treatment.Pre-treatment,there was no divergence in serum 25(OH)D3 level,thyroid function-related indexes,autoantibodies level,blood glucose,and blood lipid index between the control group,test groups A and B(all P>0.05).The 25(OH)D3 levels in test groups A and B were negatively correlated with FT4 and TGAB(all P<0.05).CONCLUSION The combination drug treatment for T2DM with HT significantly improved thyroid function,autoantibody,and blood glucose and lipid levels.
文摘In this case, a young female presented with non-specific features such as fever, sore throat, headache and fatigue. She went on to develop epigastric pain, darkening of urine and jaundice, with no resolution of prior symptoms. Physical and Laboratory tests confirmed the primary diagnosis of infectious mononucleosis, however, prior history of treatment with multiple drugs led to a diagnosis of DILI as a complication. Appropriate treatment with I.V. antibiotics, hepatoprotective agents, steroids as well as discontinuation of all potential hepatotoxic agents showed significant improvement in patients’ symptoms and overall condition.
基金Supported by National College Students Innovation and Entrepreneurship Training Program(202110599016)Guangxi Key R&D Project(GuiKeAB 18221095).
文摘[Objectives]To investigate the protective effect of ethanol extract from sweet potato leaves on liver injury induced by CCl_(4)in mice.[Methods]25 ICR mice were randomly divided into blank group,model group,high-dose extract group(200 mg/kg),low-dose extract group(100 mg/kg)and positive control group(2 mg/kg colchicine),with 5 mice in each group.All groups except the blank group were given intraperitoneal injection of 20%CCl 4 olive oil solution(2 mL/kg),and the blank group was given the same dose of olive oil solution three times a week.After 4 weeks,each administration group was given the corresponding dose of drugs(10 mL/kg),and the blank group and model group were given the corresponding amount of normal saline for 2 weeks.After the last intragastric administration,fasting was required,but water was allowed,blood was taken from eyeballs,and upper serum was taken by static centrifugation.Serum AST,ALT,CRP,IL-6 and SOD levels were detected by the kit.[Results]Compared with the blank group,the serum AST and ALT levels in the model group were significantly increased;compared with the model group,the ethanol extract of sweet potato leaves could decrease the levels of ALT,AST,CRP,IL-6 and increase the level of SOD in serum.[Conclusions]The ethanol extract of sweet potato leaves had protective effect on the mice with liver injury induced by CCl_(4),and its mechanism may be to protect the liver by lowering enzymes,inhibiting inflammation and antioxidant stress.
基金Supported by National Natural Science Foundation of China,No.81300702Natural Science Foundation Project of Chongqing CSTC,No.cstc2018jcyjAXO210.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a major chronic liver disorder worldwide,and there is no established treatment for this disease.We conducted a network meta-analysis(NMA)to compare existing treatments,which include four classes of antidiabetic drugs,and examined the optimum treatments for NAFLD.AIM To compare the effectiveness of different treatments for NAFLD.METHODS An NMA was conducted using Stata 14.0(Corporation LLC,College Station,United States)and R(X643.6.3 version)in this study.Eligible randomized controlled trials(RCTs)were searched in the PubMed,Cochrane Library,Embase,Medline and Web of Science databases from database inception to April 2021.Two researchers independently screened the available studies in strict accordance with inclusion and exclusion criteria.The Cochrane Risk of Bias tool was used to evaluate the risk of bias of the included studies.The variables with and without dimensional differences were calculated as the standardized mean difference and weighted mean difference,respectively.An inconsistency model and“nodesplitting”technique were used to test for inconsistency.Funnel plots were used to evaluate publication bias.RESULTS Twenty-two eligible RCTs involving 1377 participants were eventually included in our analysis.Data were pooled using a random-effects model.Our NMA results revealed that glucagon-like peptide-1 receptor agonists(GLP-1RAs)were the most effective treatment,yielding improvements in hepatic fat content(HFC),alanine aminotransferase(ALT),aspartate aminotransferase(AST),serumγ-glutamyl transferase(GGT)and body weight[surface under the cumulative ranking curve(SUCRA)=99.6%,92.6%,82.8%,92.3%and 99.6%,respectively],while thiazolidinediones(TZDs)were the best intervention for reducing the NAFLD activity score(NAS;SUCRA=98.9%).In addition,moderate performance was observed for the sodium glucose cotransporter-2 inhibitors groups(SUCRA=25.1%,66.2%,63.5%,58.2%and 71.9%for HFC,ALT,AST,GGT and body weight,respectively).However,metformin performed poorly according to most indicators(SUCRA=54.5%,0.3%,19.5%,33.7%,57.7%and 44.3%for HFC,NAS,ALT,AST,GGT and body weight,respectively).CONCLUSION GLP-1RAs may be the optimum choice for most patients with NAFLD.However,TZDs are considered the most effective therapies in NAFLD patients with histological disease activity.
文摘During the outbreak of the coronavirus disease 2019(COVID-19)pandemic,particular interest rose regarding the interaction between metabolic dysfunctionassociated fatty liver disease(MAFLD)and the COVID-19 infection.Several studies highlighted the fact that individuals with MAFLD had higher probability of severe acute respiratory syndrome coronavirus 2 infection and more severe adverse clinical outcomes.One of the proposed mechanisms is the inflammatory response pathway,especially the one involving cytokines,such as interleukin 6,which appeared particularly elevated in those patients and was deemed responsible for additional insult to the already damaged liver.This should increase our vigilance in terms of early detection,close follow up and early treatment for individuals with MAFLD and COVID-19 infection.In the direction of early diagnosis,biomarkers such as cytokeratin-18 and scoring systems such as Fibrosis-4 index score are proposed.COVID-19 is a newly described entity,expected to be of concern for the years to come,and MAFLD is a condition with an ever-increasing impact.Delineating the interaction between these two entities should be brought into the focus of research.Reducing morbidity and mortality of patients with COVID-19 and MAFLD should be the ultimate objective,and the optimal way to achieve this is by designing evidence-based prevention and treatment policies.
文摘This editorial addresses the growing concern of herb-induced liver injury(HILI),focusing on a unique case of Skullcap-induced HILI report.This editorial underscore the significant mortality rate linked to Skullcap-induced HILI,emphasizing the importance of vigilant monitoring and intervention.As herbal supplement usage rises,collaboration among clinicians and researchers is crucial to comprehend and address the complexities of HILI,particularly those involving Skullcap.
文摘The sex-based differences between the effects of two novel sugar-based drug candidates,a sulfated polymannuroguluronate(SPMG-911)and an acidic oligosaccharide sugar chain compound(AOSC-971),on the enzymes CYP 1A2,CYP2E1 and CYP3A4 of Chinese human liver microsome were investigated.The results showed that neither SPMG-911 nor AOSC-971 have any effect on CYP3A4,AOSC-971 induced the CYP 2E1 in men but have no effect on CYP1A2,SPMG-911 inhibit the CYP1A2 also in men but have no effect on CYP2E1.The results are useful for their safety evaluation,as well as for the prediction of inter-drug interactions associated with the two drugs.
文摘Importance/Objective: Adverse Drug Reactions (ADRs) are unavoidable, but recognizing and addressing ADRs early can improve wellness and prevent permanent injury. We suggest that available medical information and digital/electronic methods could be used to manage this major healthcare problem for individual patients in real time. Methods: We searched the available digital applications and three literature databases using the medical subject heading terms, adverse drug reaction reporting systems or management, filtered by clinical trial or systemic reviews, to detect publications with data about ADR identification and management approaches. We reviewed the reports that had abstract or summary data or proposed or implemented methods or systems with potential to identify or manage ADRs in clinical settings. Results: The vast majority of the 481 reports used retrospectively collected data for groups of patients or were limited to surveying one population group or class of medication. The reports showed potential and definite associations of ADRs for specific drugs and problems, mostly, but not exclusively, for patients in hospitals and nursing homes. No reports described complete methods to collect comprehensive data on ADRs for individual patients in a healthcare system. The digital applications have ADR information, but all are too cumbersome or incomplete for use in active clinical settings. Several studies suggested that providing information about potential ADRs to clinicians can reduce these problems. Conclusion and Relevance: Although investigators and government agencies agree with the need, there is no comprehensive ADR management program in current use. Informing the patient’s healthcare practitioners of potential ADRs at the point of service has the potential for reduction of these complications, which should improve healthcare and reduce unneeded costs.
基金supported by Liangshan Science and Technology Program(Project number:22ZDYF0100).
文摘Objective:This paper aims to analyze the analgesic effect of ultrasound-guided transversus abdominis plane block(TAPB)combined with non-steroidal anti-inflammatory analgesic drug lornoxicam on abdominal surgery in patients with a history of drug addiction.Methods:32 patients aged 18-60 who underwent lower abdominal surgery in the First People's Hospital of Liangshan Yi Autonomous Prefecture and Butuo County People's Hospital of Liangshan Yi Autonomous Prefecture from January 2022 to March 2023 were selected,the patients must have drug abuse history for more than 1 year,with a history of drug withdrawal and relapse.The patients were divided into observation group and control group by the envelope method,with 16 cases in the observation group and 16 cases in the control group.Two groups of patients underwent ultrasound-guided bilateral transversus abdominis plane block after the operation.The observation group was treated with dexmedetomidine hydrochloride 1μg/kg+0.25%ropivacaine hydrochloride 40ml,and the control group was treated with 40ml 0.9%sodium chloride injection,the two groups of patients returned to the ward after operation and given intravenous infusion of lornoxicam for relieving the pain.The visual analogue scale(VAS)score of postoperative pain,the times of rescue analgesia,the time of postoperative anal exhaust,the time of ambulation,nausea and vomiting,withdrawal symptoms,related adverse reactions,and hospitalization days were compared between the two groups.Results:The VAS score of postoperative pain in the observation group was significantly lower than that in the control group,P<0.05.Patients in the observation group used less postoperative rescue analgesics than those in the control group,P<0.05.For postoperative anal exhaust time,the difference between the two groups of patients was relatively small,and the time in the observation group was shorter,P>0.05.The time to get out of bed and the length of hospital stay were not significantly different between the control group and the observation group,P>0.05.The withdrawal symptoms of the patients in the observation group were better,P<0.05,nausea and vomiting,and other adverse reactions were lower in the control group,P<0.05.Conclusion:Ultrasound-guided transversus abdominis plane block combined with lornoxicam can be used to relieve pain in abdominal surgery for patients with drug addiction,which can effectively improve the therapeutic effect of patients and reduce the number of postoperative rescue analgesia.Thus,it has high clinical application value.
文摘The dynamic changes of liver microsomal drug-metabolizing system (MDMS) andlipoperoxidation were studied in scalded rats. The effects of treatment with vitamin E and silybinwere also evaluated. The results showeed that liver microsomal cytochrome P-450 content, and p-nitroanisole demethylase (P-NOD) and aniline hydroxylase (AH) activity decreased markedlypostburn. On the contrary, liver lipoperoxide and mierosomal lipoperoxidation increased significantlyafter scalding. Both the increase of liver lipoperoxide and mierosomal lipoperoxidation and the de-crease of MDMS activity were prevented by vitamin E and silybin treatments.
文摘BACKGROUND Although hepatitis B virus infection is the leading cause of chronic liver injury globally,nonalcoholic fatty liver disease(NAFLD)is gradually gaining attention as another major chronic liver disease.The number of patients having chronic hepatitis B(CHB)with concomitant hepatic steatosis has increased.AIM To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB.METHODS Relevant English studies were systematically searched across PubMed,EMBASE,Web of Science,and Cochrane Library until October 2023.Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included.RESULTS Of the 2502 retrieved studies,11 articles were finally included.Biochemical response until 48 wk(OR=0.87,95%CI:0.50–1.53,P=0.000)and 96 wk(OR=0.35,95%CI:0.24–0.53,P=0.24)and virological response until 96 wk(OR=0.80,95%CI:0.43–1.49,P=0.097)were lower in patients with hepatic steatosis than in patients with CHB alone.CONCLUSION Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.
基金This study has been reviewed and approved by the Clinical Medical Ethics Committee(Approval No.2021HN26A).
文摘BACKGROUND Gastric cancer(GC)is the fifth most common type of cancer and has the fourth highest death rate among all cancers.There is a lack of studies examining the impact of liver metastases on the effectiveness of immunotherapy in individuals diagnosed with GC.AIM To investigate the influence of liver metastases on the effectiveness and safety of immunotherapy in patients with advanced GC.METHODS This retrospective investigation collected clinical data of patients with advanced stomach cancer who had immunotherapy at our hospital from February 2021 to January 2023.The baseline attributes were compared using either the Chi-square test or the Fisher exact probability method.The chi-square test and Kaplan-Meier survival analysis were employed to assess the therapeutic efficacy and survival duration in GC patients with and without liver metastases.RESULTS The analysis comprised 48 patients diagnosed with advanced GC,who were categorized into two groups:A liver metastasis cohort(n=20)and a non-liver metastatic cohort(n=28).Patients with liver metastasis exhibited a more deteriorated physical condition compared to those without liver metastasis.The objective response rates in the cohort with metastasis and the cohort without metastasis were 15.0%and 35.7%(P>0.05),respectively.Similarly,the disease control rates in these two cohorts were 65.0%and 82.1%(P>0.05),respectively.The median progression-free survival was 5.0 months in one group and 11.2 months in the other group,with a hazard ratio of 0.40 and a significance level(P)less than 0.05.The median overall survival was 12.0 months in one group and 19.0 months in the other group,with a significance level(P)greater than 0.05.CONCLUSION Immunotherapy is less effective in GC patients with liver metastases compared to those without liver metastasis.
文摘Fluphenazine (FP) treatment (50mg/kg bw, ip in saline) 30 min before or 6 or 10 h after CCl4 administration (1 ml/kg ip in olive oil) significantly prevented the liver necrosis produced by the hepatotoxin at 24 h. FP had enhancing effects on the covalent binding of CCl4 reactive metabolites to cellular constituents and on CCl4 induced lipid peroaldation.FP lowered bOdy temperature of the CCl4-poisoned animals during the 24 h observation period. The obtained results are compatible but do not prove the hypothesis that calmodulin (CaM) had participation in late occurring events preceding necrosis. FP lowering action on body temperature, however, might also play a role in the effects of this drug on the onset of CCl4 induced liver necrosis. FP levels in liver tissue as determined by gas chromatography-mass spectrometry evidenced the presence of the drug in amounts suffi cient to inhibit CaM and that suggests that not all preventive effects of FP are due to its indirect actions on the central nervous system via decreased body temperature