AIM To evaluate effect of treatment failure on cag A and vac A genotypes in Helicobacter pylori(H. pylori) isolates from Colombia.METHODS One hundred and seventy-six participants infected with H. pylori from Colombia ...AIM To evaluate effect of treatment failure on cag A and vac A genotypes in Helicobacter pylori(H. pylori) isolates from Colombia.METHODS One hundred and seventy-six participants infected with H. pylori from Colombia were treated during 14 d with the triple-standard therapy. Six weeks later, eradication was evaluated by 13C-Urea breath test. Patients with treatment failure were subjected to endoscopy control; biopsies obtained were used for histopathology and culture. DNA from H. pylori isolates was amplified using primers specific for cag A and vac A genes. The phylogenetic relationships among isolates obtained before and after treatment were established by conglomerate analysis based on random amplified polymorphic DNA(RAPD) fingerprinting.RESULTS Treatment effectiveness was at 74.6%. Of the par-ticipants with treatment failure, 25 accepted subjected to a second endoscopy. Prevalence of posttreatment infection was 64%(16/25) and 40%(10/25) by histology and culture, respectively. Upon comparing the cag A and vac A genotypes found before and after therapy, multiple cag A genotypes(cag A-positive and cag A-negative) were found before treatment; in contrast, cag A-negative genotypes decreased after treatment. vac A s1m1 genotype was highly prevalent in patients before and after therapy. The 3'cag A region was successfully amplified in 95.5%(21/22) of the isolates obtained before and in 81.8%(18/22) of the isolates obtained after treatment. In the isolates obtained from patients with treatment failure, it was found that 72.7%(16/22) presented alterations in the number of EPIYA motifs, compared to isolates found before treatment.CONCLUSION Unsuccessful treatment limits colonization by lowvirulence strains resulting in partial and selective eradication in mixed infections, and acts on the cag A-positive strains inducing genetic rearrangements in cag A variable region that produces a loss or gain of EPIYA repetitions.展开更多
The hepatitis C virus has a high mutation capacity that leads to the emergence of resistance-associated substitutions(RAS).However,the consequence of resistance selection during new direct-acting antiviral drug(DAA)tr...The hepatitis C virus has a high mutation capacity that leads to the emergence of resistance-associated substitutions(RAS).However,the consequence of resistance selection during new direct-acting antiviral drug(DAA)treatment is not necessarily the therapeutic failure.In fact,DAA treatment has shown a high rate(>95%)of sustained virological response even when high baseline RAS prevalence has been reported.In the context of RAS emergence and high rates of sustained viral response,the clinical relevance of variants harboring RAS is still controversial.Therefore,in order to summarize the data available in international guidelines,we have reviewed the clinical utility of testing RAS in the era of new pangenotypic DAA drugs.展开更多
AIM:To assess whether antibiotic resistance varies between the antrum and corpus of the stomach of patients that are either Helicobacter pylori(H.pylori)therapy-naive or pre-treated.METHODS:H.pylori strains were isola...AIM:To assess whether antibiotic resistance varies between the antrum and corpus of the stomach of patients that are either Helicobacter pylori(H.pylori)therapy-naive or pre-treated.METHODS:H.pylori strains were isolated from antrum and corpus biopsies from 66 patients that received a diagnostic gastroduodenoscopy for variant clinical indications.Antimicrobial susceptibility to amoxicillin,clarithromycin,tetracycline,metronidazole,levofloxacin and rifabutin was tested with the E-test method on IsoSensitest agar with 10 vol%defibrinated horse blood.In patients with a different antibiotic susceptibility pattern between the isolates from the antrum and corpus,DNA fingerprinting via random amplified polymorphic DNA analysis was performed to detect differences among DNA patterns of H.pylori isolates.RESULTS:Primary,secondary and tertiary resistance to clarithromycin was 6.9%,53.8%and 83.3%,retrospectively.Metronidazole and levofloxacin resistance also increased according to the number of previous treatments(17.2%,69.2%,83.3%;13.8%,23.1%,33.3%).Tertiary resistance to rifabutin was detected in12.5%of patients.In none of the 66 patients a resistance against amoxicillin or tetracycline was detectable.Discordant antibiotic susceptibility between antrum and corpus isolates for different antibiotics was seen in 15.2%(10/66)of the patients.Two out of those ten patients were naive to any H.pylori antibiotic treatment.The remaining eight patients previously received at least one eradication therapy.DNA fingerprinting analysis revealed no substantial differences among DNA patterns between antrum and corpus isolates in the majority of patients suggesting an infection with a single H.pylori strain.CONCLUSION:Different antibiotic susceptibility between antrum and corpus biopsies is a common phenomenon and a possible explanation for treatment failure.Resistant H.pylori strains may be missed if just one biopsy from one anatomic site of the stomach is taken for H.pylori susceptibility testing.展开更多
AIM:To evaluate the efficacy and safety of tenofovir disoproxil fumarate(TDF) for chronic hepatitis B(CHB) patients after multiple failures.METHODS:A total of 29 CHB patients who had a suboptimal response or developed...AIM:To evaluate the efficacy and safety of tenofovir disoproxil fumarate(TDF) for chronic hepatitis B(CHB) patients after multiple failures.METHODS:A total of 29 CHB patients who had a suboptimal response or developed resistance to two or more previous nucleoside/nucleotide analogue(NA) treatments were included.Study subjects were treated with TDF alone(n = 13) or in combination with lamivudine(LAM,n = 12) or entecavir(ETV,n = 4) for ≥ 6 mo.Complete virologic response(CVR) was defined as an achievement of serum hepatitis B virus(HBV) DNA level ≤ 60 IU/mL by real-time polymerase chain reaction method during treatment.Safety assessment was based on serum creatinine and phosphorus level.Eleven patients had histories of LAM and adefovir dipivoxil(ADV) treatment and 18 patients were exposed to LAM,ADV,and ETV.Twenty-seven patients(93.1%) were hepatitis B e antigen(HBeAg) positive and the mean value of the baseline serum HBV DNA level was 5.5 log IU/mL ± 1.7 log IU/mL.The median treatment duration was 16 mo(range 7 to 29 mo).RESULTS:All the patients had been treated with LAM and developed genotypic and phenotypic resistance to it.Resistance to ADV was present in 7 patients and 10 subjects had a resistance to ETV.One patient had a resistance to both ADV and ETV.The cumulative probabilities of CVR at 12 and 24 mo of TDF containing treatment regimen calculated by the Kaplan Meier method were 86.2% and 96.6%,respectively.Although one patient failed to achieve CVR,serum HBV DNA level decreased by 3.9 log IU/mL from the baseline and the last serum HBV DNA level during treatment was 85 IU/mL,achieving near CVR.No patients in this study showed viral breakthrough or primary non-response during the follow-up period.The cumulative probability of HBeAg clearance in the 27 HBeAg positive patients was 7.4%,12%,and 27% at 6,12,and 18 mo of treatment,respectively.Treatment efficacy of TDF containing regimen was not statistically different according to the presence of specific HBV mutations.History of prior exposure to specific antiviral agents did not make a difference to treatment outcome.Treatment efficacy of TDF was not affected by combination therapy with LAM or ETV.No patient developed renal toxicity and no cases of hypophosphatemia associated with TDF therapy were observed.There were no other adverse events related to TDF therapy observed in the study subjects.CONCLUSION:TDF can be an effective and safe rescue therapy in CHB patients after multiple NA therapy failures.展开更多
Background: Genetic diversity of human immunodeficiency virus affects the treatment and the emergence of resistance. Some subtypes would develop resistance more frequently than others. The aim of this study is to dete...Background: Genetic diversity of human immunodeficiency virus affects the treatment and the emergence of resistance. Some subtypes would develop resistance more frequently than others. The aim of this study is to determine the rate of virological treatment failure and the involvement of genetic diversity and different mutations in this failure in Kinshasa. Methods: Of the 153 Antiretroviral-naive patients who were included in the cohort, 138 patients have been received for the appointment of the 6th month. Clinical parameters were recorded on individual patient charts. The determination of Viral Load (VL) was done at the Laboratory of Molecular Biology. Clinical and biological parameters of the 6th month were compared with those taken at baseline of the cohort to determine the evolution of patients under treatment. Results: At the consultation of the 6th month, 138 patients (90.2%) had returned out of the 153 included. Eighty-one (58.7%) patients were women and 57 (41.3%) men. The age of patients is between 18 and 65 with an average of 37 years. Ten deaths (6.5%) and 5 (3.3%) lost have been reported. One hundred twenty-five patients (90.5%) were in clinical stage 3 and 13 (9.5%) in clinical stage 4. The median CD4 T cells is 560 cells mm3. The median VLs of patients was 0.90 log10 RNA copies/ml. Of the 34 patients in virological failure, 8 (23.5%) are minimal failure, 23 (67.7%) in moderate failure and 3 (8.8%) in severe failure. According to the Pearson’s test, VLs at 6th months were highly correlated with that of inclusion, with V75 and K70 mutations for NRTIs, with V108 mutation for NNRTI well as the virological failure of treatment. Conclusion: Our results confirmed the hypothesis that high Viral Load at the start of the treatment is a poor prognosis for the development of therapy. Transmitted mutations are involved in treatment failure.展开更多
AIM:To report preliminary results of the efficacy and safety of sunitinib in the management of Taiwan Residents gastrointestinal stromal tumors (GIST) patients facing imatinib mesylate (IM) intolerance or failure.METH...AIM:To report preliminary results of the efficacy and safety of sunitinib in the management of Taiwan Residents gastrointestinal stromal tumors (GIST) patients facing imatinib mesylate (IM) intolerance or failure.METHODS:Between 2001 and May 2010,199 Taiwan Residents patients with metastatic GIST were treated at Chang Gung Memorial Hospital.Among them,23 (11.6%) patients receiving sunitinib were investigated.RESULTS:Sixteen male and 7 female patients with a median age of 59 years (range:24-83 years) received sunitinib.Twenty-two GIST patients changed to sunitinib because of IM failure and 1 because of intolerance.The median duration of sunitinib administration was 6.0 mo (range:2-29 mo).The clinical benefit was 65.2% [2 complete response (CR),4 partial response (PR),and 9 stationary disease (SD);15/23].In 12 patients harboring mutations of the kit gene at exon 11,the clinical benefit rate (CR,PR,and SD) was 75.0% and 6 patients with tumors containing kit exon 9 mutations had a clinical benefit of 50.0% (not significant,P=0.344).The progression free survival (PFS) and overall survival (OS) did not differ between patients whose GISTs had wild type,KIT exon 9,or KIT exon 11 mutations.Hand-foot syndrome was the most common cause of grade Ⅲ adverse effect (26.1%),followed by anemia (17.4%),and neutropenia (13.0%).During the median 7.5-mo follow-up after sunitinib use,the median PFS and OS of these 23 GIST patients after sunitinib treatment were 8.4 and 14.1 mo,respectively.CONCLUSION:Sunitinib appears to be an effective treatment for Taiwan Residents with IM-resistant/intolerant GISTs and induced a sustained clinical benefit in more than 50% of Taiwan Residents advanced GIST patients.展开更多
AIM To describe factors associated with treatment failure and frequency of resistance-associated substitutions(RAS).METHODS Human immunodeficiency virus(HIV)/hepatitis C virus(HCV) coinfected patients starting a first...AIM To describe factors associated with treatment failure and frequency of resistance-associated substitutions(RAS).METHODS Human immunodeficiency virus(HIV)/hepatitis C virus(HCV) coinfected patients starting a first direct-acting antiviral(DAA) regimen before February 2016 and included in the French ANRS CO13 HEPAVIH cohort were eligible. Failure was defined as:(1) non-response [HCV-RNA remained detectable during treatment, at end of treatment(EOT)]; and(2) relapse(HCVRNA suppressed at EOT but detectable thereafter). Sequencing analysis was performed to describe prevalence of drug class-specific RAS. Factors associated with failure were determined using logistic regression models.RESULTS Among 559 patients, 77% had suppressed plasma HIV-RNA < 50 copies/mL at DAA treatment initiation, 41% were cirrhotic, and 68% were HCV treatmentexperienced. Virological treatment failures occurred in 22 patients and were mainly relapses(17, 77%) then undefined failures(3, 14%) and non-responses(2, 9%). Mean treatment duration was 16 wk overall. Posttreatment NS3, NS5 A or NS5 B RAS were detected in 10/14 patients with samples available for sequencing analysis. After adjustment for age, sex, ribavirin use, HCV genotype and treatment duration, low platelet count was the only factor significantly associated with a higher risk of failure(OR: 6.5; 95%CI: 1.8-22.6). CONCLUSION Only 3.9% HIV-HCV coinfected patients failed DAA regimens and RAS were found in 70% of those failing. Low platelet count was independently associated with virological failure.展开更多
Background:To evaluate the clinical efficacy of oral administration of Chinese medicines with warming Yang effects and Western medicine in the treatment of heart failure caused by dilated cardiomyopathy.Methods:Seven ...Background:To evaluate the clinical efficacy of oral administration of Chinese medicines with warming Yang effects and Western medicine in the treatment of heart failure caused by dilated cardiomyopathy.Methods:Seven databases including Chinese National Knowledge Infrastructure,Weipu database,Wanfang database,China Biomedical Literature Service System,Cochrane library,PubMed,and Embase were searched.The search date was from established to October 2019.Randomized clinical trials of dilated cardiomyopathy patients with heart failure under the combination treatment of Chinese medicines with warming Yang effects and Western medicine were included.We then assessed the methodological quality of included literatures,extracted valid data and conducted systematically evaluation according to the Cochrane systematic review method.Outcome index included clinical efficacy,left ventricular ejection fraction,and brain natriuretic peptide.Results:Meta-analysis results showed that the clinical effective rate was higher in the combination group than that in the control group(RR=1.24,95%CI(1.14,1.34),P<0.01).In addition,the combination group could improve left ventricular ejection fraction compared with the control group(Std.MD=0.85,95%CI(0.69,1.01),P<0.01).However,the meta-analysis of brain natriuretic peptide levels showed that the included literatures have higher heterogeneity and the meta-analysis results were unstable.So the results of brain natriuretic peptide were abandoned.Conclusion:Oral administration of Chinese medicines with warming Yang effects combined with Western medicine is better than Western medicine alone in improving clinical effect and left ventricular ejection fraction,but it is not clear whether brain natriuretic peptide can be improved.Because the quality of the included studies is not high and inconsistent outcome index,more standardized and rigorous randomized double-blind controlled trials are needed to validate and guide clinical use.展开更多
Background:Acute liver failure(ALF)is an unpredictable and life-threatening critical illness.The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which ...Background:Acute liver failure(ALF)is an unpredictable and life-threatening critical illness.The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which may lead to multiple organ failure.Methods:Animals were divided into 3 groups,normal,thioacetamide(TAA,ALF model)and TAA+AGK2.Cultured L02 cells were divided into 5 groups,normal,TAA,TAA+mitofusin 2(MFN2)-siRNA,TAA+AGK2,and TAA+AGK2+MFN2-siRNA groups.The liver histology was evaluated with hematoxylin and eosin staining,inositol-requiring enzyme 1(IRE1),activating transcription factor 6β(ATF6β),protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)and phosphorylated-PERK(p-PERK).C/EBP homologous protein(CHOP),reactive oxygen species(ROS),MFN2 and glutathione peroxidase 4(GPX4)were measured with Western blotting,and cell viability and liver chemistry were also measured.Mitochondriaassociated endoplasmic reticulum membranes(MAMs)were measured by immunofluorescence.Results:The liver tissue in the ALF group had massive inflammatory cell infiltration and hepatocytes necrosis,which were reduced by AGK2 pre-treatment.In comparison to the normal group,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+in the TAA-induced ALF model group were significantly increased,which were decreased by AGK2 pre-treatment.The levels of MFN2 and GPX4 were decreased in TAA-induced mice compared with the normal group,which were enhanced by AGK2 pretreatment.Compared with the TAA-induced L02 cell,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+were further increased and levels of MFN2 and GPX4 were decreased in the MFN2-siRNA group.AGK2 pre-treatment decreased the apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+and enhanced the protein expression of MFN2 and GPX4 in MFN2-siRNA treated L02 cell.Immunofluorescence observation showed that level of MAMs was promoted in the AGK2 pre-treatment group when compared with the TAA-induced group in both mice and L02 cells.Conclusions:The data suggested that AGK2 pre-treatment had hepatoprotective role in TAA-induced ALF via upregulating the expression of MFN2 and then inhibiting PERK and ferroptosis pathway in ALF.展开更多
BACKGROUND The increased expression of G3BP1 was positively correlated with the prognosis of liver failure.AIM To investigate the effect of G3BP1 on the prognosis of acute liver failure(ALF)and acute-on-chronic liver ...BACKGROUND The increased expression of G3BP1 was positively correlated with the prognosis of liver failure.AIM To investigate the effect of G3BP1 on the prognosis of acute liver failure(ALF)and acute-on-chronic liver failure(ACLF)after the treatment of artificial liver support system(ALSS).METHODS A total of 244 patients with ALF and ACLF were enrolled in this study.The levels of G3BP1 on admission and at discharge were detected.The validation set of 514 patients was collected to verify the predicted effect of G3BP1 and the viability of prognosis.RESULTS This study was shown that lactate dehydrogenase(LDH),alpha-fetoprotein(AFP)and prothrombin time were closely related to the prognosis of patients.After the ALSS treatment,the patient’amount of decreased G3BP1 index in difference of G3BP1 between the value of discharge and admission(difG3BP1)<0 group had a nearly 10-fold increased risk of progression compared with the amount of increased G3BP1 index.The subgroup analysis showed that the difG3BP1<0 group had a higher risk of progression,regardless of model for end-stage liver disease high-risk or low-risk group.At the same time,compared with the inflam matory marks[tumor necrosis factor-α,interleukin(IL)-1βand IL-18],G3BP1 had higher discrimination and was more stable in the model analysis and validation set.When combined with AFP and LDH,concordance index was respectively 0.84 and 0.8 in training and validation cohorts.CONCLUSION This study indicated that G3BP1 could predict the prognosis of ALF or ACLF patients treated with ALSS.The combination of G3BP1,AFP and LDH could accurately evaluate the disease condition and predict the clinical endpoint of patients.展开更多
In Mexico, digitalis was known since the 16th century and was used to treat patients with bloating, and it was not until the 20th century that it began to be used as a medicine for heart failure. In conjunction with d...In Mexico, digitalis was known since the 16th century and was used to treat patients with bloating, and it was not until the 20th century that it began to be used as a medicine for heart failure. In conjunction with diuretics. Digitalis was later used in combination individualized with the new medications, for this purpose and research has shown that the combination of medications on an individualized basis is what is currently successfully available for the medical treatment of heart failure.展开更多
Objective: To compare the clinical efficacy of conventional Western medicine combined with Qiliqiangxin capsule and western medicine alone in the treatment of chronic heart failure, and to prove that Qiliqiangxin caps...Objective: To compare the clinical efficacy of conventional Western medicine combined with Qiliqiangxin capsule and western medicine alone in the treatment of chronic heart failure, and to prove that Qiliqiangxin capsule combined treatment has more advantages, providing reference for clinical decision-making in the treatment of chronic heart failure. Methods: Randomized controlled trials (RCTs) of conventional Western medicine treatment and Western medicine combined with Qiliqiangxin capsule in the treatment of chronic heart failure were searched in databases such as PubMed, Embase, Webofscience, CNKI, WanFang, VIP, and CBM. The bias risk assessment was conducted using the RCT tool recommended by Cochrane, and then the meta-analysis was performed using RevMan5.4 and Stata17 software. Compare the efficacy evaluation of cardiac function, left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), cardiac stroke output (SV), 6-minute walking test (6MWT), and N-terminal proBNP in the conventional western medicine combined with Qiliqiangxin capsule group (hereinafter referred to as the treatment group) and the conventional western medicine group (hereinafter referred to as the control group). Results: A total of 20 RCTs meeting the criteria were included, including 2953 patients, including 1508 in the treatment group and 1445 in the control group. The results of meta-analysis showed that the treatment group had significantly better cardiac function evaluation, LVEF, LVEDD, SV, 6MWT, and NT-proBNP improvement than the control group. Its central functional efficacy evaluation (OR=2.09,95% CI: 1.71-2.55, P<0.001), LVEF (WMD=7.05,95% CI: 5.30-8.79, P<0.00001), LVEDD (WMD=6.73, 95% CI: 3.18-10.29, P=0.0002), SV (WMD=6.73, 95% CI: 3.18-10.29, P=0.0002), 6MWT (SMD=0.70,95% CI: 0.54-0.87, P<0.00001), NT-proBNP (SMD=-1.95,95% CI: -2.5 2 to 1.38 (P<0.0001), with statistically significant differences. Conclusion: Conventional western medicine combined with Qiliqiangxin capsule can significantly improve the clinical efficacy of heart failure, improve LVEF, LVEDD, SV, and NT-proBNP index, and improve exercise tolerance. It is worth using for reference in the treatment.展开更多
Background:The aim of this study is to investigate the mechanism of action underlying the therapeutic effects of the national patent Chinese medicine compound“Qiangxinhuoli prescription(QXHLF)”on chronic heart failu...Background:The aim of this study is to investigate the mechanism of action underlying the therapeutic effects of the national patent Chinese medicine compound“Qiangxinhuoli prescription(QXHLF)”on chronic heart failure(CHF).Methods:In vitro,the H 9 C 2 cell model was induced by ANGII,and cell proliferation and related protein expression were detected by Cell Counting Kit-8 and Western blot.In vivo,A rat model of CHF was prepared by ligation of the left anterior descending coronary artery.The effects of QXHLF on cardiac function in CHF rats were evaluated by cardiac index,hemodynamic changes,enzyme-linked immunosorbent assay,hematoxylin-eosin staining,immunohistochemistry,Western blot and RT-PCR.The expression of pro-apoptotic factors and anti-apoptotic factors,as well as TGFβ1,p-p38,TAK 1 mRNA,and protein,were detected.Results:In vitro,QXHLF has a significant inhibitory effect on the proliferation of H 9 C 2 cells.QXHLF can reduce the expression levels of TAK 1,TGFβ1,p-p38,Caspase3 and BAX proteins in H 9 C 2 cells,and increase the expression level of BCL 2 protein.In vivo,QXHLF has the potential to increase left ventricular systolic pressure,m aximum rate of change in left ventricular pressure while decreasing left ventricular end diastolic pressure,and inhibiting the serum levels of brain natriuretic peptide.Moreover,QXHLF exhibits significant improvements in the pathological alterations of myocardial cells and fibers in CHF rats,leading to enhanced myocardial tissue morphology and notable advantages in combating myocardial fibrosis.QXHLF can reduce the levels of BAX and Caspase3 and up-regulate the expression of BCL 2,thereby inhibiting cardiomyocyte apoptosis.Furthermore,QXHLF demonstrates inhibitory effects on the mRNA and protein expression levels of TGFβ1,TAK 1,and p-p38 in the heart tissue of the CHF rat model.Conclusion:These findings indicate that QXHLF has a therapeutic effect on CHF by inhibiting the p38-MAPK signaling pathway,reducing myocardial fibrosis,preventing apoptosis,inhibiting cell proliferation,and restoring myocardial injury.展开更多
Objective:To explore the clinical effect of a non-invasive ventilator combined with conventional therapy in the treatment of patients with chronic obstructive pulmonary disease(COPD)combined with respiratory failure.M...Objective:To explore the clinical effect of a non-invasive ventilator combined with conventional therapy in the treatment of patients with chronic obstructive pulmonary disease(COPD)combined with respiratory failure.Methods:68 patients with COPD combined with respiratory failure treated in our hospital from September 2021 to October 2023 were selected as the research subjects.Using the random number table method,they were divided into a control group and an experimental group of 34 cases each.The control group received conventional symptomatic treatment,and the experimental group received non-invasive ventilator treatment based on the control group.The clinical effects,blood gas indicators(partial pressure of carbon dioxide(PaCO_(2)),partial pressure of oxygen(PaO_(2)),arterial oxygen saturation(SaO_(2))),lung function(forced expiratory volume in 1 second(FEV1),forced vital capacity(FVC),6 min walking distance),complications,and inflammatory factor levels(c-reactive protein(CRP),interleukin-6(IL-6),neutrophil-to-lymphocyte ratio(NLR))of the two groups of patients were observed.Results:(1)The clinical efficacy of the patients in the experimental group(33/97.06%)was more significant as compared with the control group(25/73.53%)(P<0.05);(2)After treatment,the clinical efficacy of the two groups of patients in terms of FEV1,FEV1/FVC,6-minute walking distance,PaO_(2)and SaO_(2)all increased in the experimental group as compared to that of the control group(P<0.05);(3)After treatment,the PaCO_(2),CRP,IL-6,and NLR of the two groups of patients decreased,and the decrease in the experimental group was higher than that of the control group(P<0.05);(4)The patients’complication rate in the experimental group(2/5.88%)was lower as compared to that of the control group(9/26.46%)(P<0.05).Conclusion:Non-invasive ventilators combined with conventional therapy achieved good clinical results in treating patients with COPD and respiratory failure.展开更多
BACKGROUND Heart failure(HF),a common cardiovascular condition,is characterized by significant morbidity and mortality.While traditional Chinese medicine(TCM)is often used as a complementary approach in HF management,...BACKGROUND Heart failure(HF),a common cardiovascular condition,is characterized by significant morbidity and mortality.While traditional Chinese medicine(TCM)is often used as a complementary approach in HF management,systematic evalua-tions of its impact on clinical outcomes,TCM syndrome scores,and B-type natriuretic peptide(BNP)levels are lacking.This study fills this gap through a comprehensive analysis of randomized controlled trials(RCTs)focusing on TCM for HF treatment.It encompasses an assessment of methodological quality,a meta-analysis,and an evaluation of evidence quality based on established standards.The results offer crucial insights into the potential advantages and constraints of TCM in HF management.RCTs on TCM for HF treatment published since the establishment of the database were searched in four Chinese and English databases,including China National Knowledge Infrastructure,Wanfang,VIP Information Chinese Science and Technology Journal,and PubMed.Methodological quality was assessed for the included studies with the Cochrane risk-of-bias assessment tool,and the meta-analysis and publication bias assessment was performed with the RevMan5.3 software.Finally,the quality of evidence was rated according to the GRADE criteria.RESULTS A total of 1098 RCTs were initially retrieved.After screening,16 RCTs were finally included in our study,which were published between 2020 and 2023.These RCTs involved 1660 HF patients,including 832 in the TCM group[TCM combined with conventional Western medicine(CMW)treatment]and 828 in the CWM group(CWM treatment).The course of treatments varied from 1 wk to 3 months.TCM syndrome differentiation was analyzed in 11 of the included RCTs.In all included RCTs,outcome indicators included comprehensive clinical outcomes,TCM syndrome scores,and BNP levels.The meta-analysis results showed significant differences between the TCM and CWM groups in terms of comprehensive clinical outcomes[risk ratio=-0.54;95%confidence interval(CI)=-0.61,-0.47;P<0.00001],TCM syndrome scores[weighted mean difference(WMD)=-142.07;95%CI=-147.56,-136.57;P<0.00001],and BNP levels(WMD=-142.07;95%CI=-147.56,-136.57;P<0.00001).According to the GRADE criteria,RCTs where"TCM improves clinical comprehensive outcomes"were rated as low-quality evidence,and RCTs where"TCM reduces TCM syndrome scores"or"TCM decreases BNP levels"were rated as medium-quality evidence.CONCLUSION TCM combined with CWM treatment effectively improves comprehensive clinical outcomes and diminishes TCM syndrome scores and BNP levels in HF patients.Given the low and medium quality of the included RCTs,the application of these results should be cautious.展开更多
Despite the extensive studies conducted on the effectiveness of microwave treatment as a novel rock preconditioning method,there is yet to find reliable data on the rock failure mechanisms due to microwave heating.In ...Despite the extensive studies conducted on the effectiveness of microwave treatment as a novel rock preconditioning method,there is yet to find reliable data on the rock failure mechanisms due to microwave heating.In addition,there is no significant discussion on the energy efficiency of the method as one of the important factors among the mining and geotechnical engineers in the industry.This study presents a novel experimental method to evaluate two main rock failure mechanisms due to microwave treatment without applying any mechanical forces,i.e.distributed and concentrated heating.The result shows that the existence of a small and concentrated fraction of a strong microwave absorbing mineral will change the failure mechanism from the distributed heating to the concentrated heating,which can increase the weakening over microwave efficiency(WOME)by more than 10 folds.This observation is further investigated using the developed coupled numerical model.It is shown that at the same input energy,the existence of microwave absorbing minerals can cause major heat concentration inside the rock and increase the maximum temperature by up to three times.展开更多
BACKGROUND Heart failure(HF),an end-stage manifestation of various cardiac diseases,poses an enormous economic and health burden on society.Vericiguat may be an effective drug in the treatment of HF.AIM To explore by ...BACKGROUND Heart failure(HF),an end-stage manifestation of various cardiac diseases,poses an enormous economic and health burden on society.Vericiguat may be an effective drug in the treatment of HF.AIM To explore by meta-analysis the efficacy and safety of Vericiguat in treating chronic heart failure.METHODS Databases,including PubMed,EMBASE,Web of Science,and Cochrane Library,were searched to collect all published randomized controlled trials(RCTs)on Vericiguat treatment of chronic heart failure from the earliest electronic records to those published in March 2023.Two investigators independently screened the literature according to inclusion and exclusion criteria,evaluated the quality of the studies,and extracted valid data before conducting a meta-analysis using RevMan5.4.RESULTS Four RCTs with 5919 patients were included,and the meta-analysis showed that treatment with 10 mg Vericiguat reduced the incidence of the primary endpoint(a composite of cardiovascular mortality and first heart-failure-related hospital-ization)in patients with chronic heart failure compared to placebo[relative risk(RR)=0.91,95%confidence interval(CI):0.85–0.98,P=0.01],and reduced the incidence of heart-failure-related hospitalization(RR=0.92,95%CI:0.84–1.00,P=0.05).However,for the incidence of cardiovascular and all-cause death,there were no significant differences between the Vericiguat and placebo groups.In addition,the two groups did not show significant differences in blood pressure,heart rate,and Kansas Cardiomyopathy Questionnaire physical limitation score.In terms of safety,10 mg Vericiguat did not increase the risk of adverse effects in patients with chronic heart failure.Vericiguat may increase the risk of symp-tomatic hypotension(RR=1.17,95%CI:0.98–1.39,P=0.08)and syncope(RR=1.18,95%CI:0.90–1.55,P=0.24),but not significantly.CONCLUSION Vericiguat(10 mg)was more effective than placebo in treating patients with chronic heart failure and had a better safety profile.展开更多
[Objectives] To investigate the clinical efficacy of intermittent levosimendan in the treatment of acute heart failure. [Methods] 100 patients diagnosed with acute heart failure and hospitalized in the internal medici...[Objectives] To investigate the clinical efficacy of intermittent levosimendan in the treatment of acute heart failure. [Methods] 100 patients diagnosed with acute heart failure and hospitalized in the internal medicine-cardiovascular department in The First People s Hospital of Yulin from January 2019 to February 2020 were randomly divided into two groups, 50 cases in each group. Both groups were treated with conventional anti-heart failure drugs. The control group was given levosimendan once, and the observation group was given levosimendan three times, with an interval of one month. The creatinine (Cr) level, serum NT proBNP, left ventricular ejection fraction (LVEF) and left ventricular end diastolic diameter (LVEDD) were observed at 48 h before and after treatment and one month and two months after treatment in both groups. [Results] Compared with before treatment, the levels of NT-proBNP decreased in the two groups at 48 h after treatment, and the difference was statistically significant ( P <0.05). The Cr level of the control group did not change significantly before and after treatment, and the Cr level of the observation group decreased at one and two months after treatment compared with before treatment, with statistically significant differences ( P <0.05). Compared with before treatment, NT-proBNP and LVEDD decreased and LVEF increased at one and two months after treatment, and the differences were statistically significant ( P <0.05). There were no obvious adverse reactions in the two groups of patients during the treatment. [Conclusions] Repetitive use of levosimendan in the treatment of acute heart failure could significantly improve the renal function, cardiac contractility and cardiac function of patients, and with the passage of time, the treatment effect was improved, which is worthy of clinical promotion.展开更多
Objective:To evaluate the efficacy of emergency ventilator therapy in severe acute left heart failure.Methods:A total of 75 patients with severe acute left ventricular heart failure who were admitted to the hospital f...Objective:To evaluate the efficacy of emergency ventilator therapy in severe acute left heart failure.Methods:A total of 75 patients with severe acute left ventricular heart failure who were admitted to the hospital from July 2020 to July 2023 were randomly divided into two groups.Group A received additional emergency ventilator treatment,and group B received conventional treatment.The efficacy was compared.Results:The curative effect of patients with severe acute left heart failure in group A was higher than that in group B(P<0.05);all blood gas indicators in group A were better than those in group B(P<0.05);all vital signs indicators in group A were better than those in group B(P<0.05);group A was more satisfied with the treatment of severe acute left ventricular heart failure than group B(P<0.05).Conclusion:Patients with severe acute left heart failure who receive emergency ventilator treatment can stabilize vital signs,improve blood oxygen supply,and enhance curative effect.展开更多
BACKGROUND Heart failure(HF)is a global health problem characterized by impaired heart function.Cardiac remodeling and cell death contribute to the development of HF.Although treatments such as digoxin and angiotensin...BACKGROUND Heart failure(HF)is a global health problem characterized by impaired heart function.Cardiac remodeling and cell death contribute to the development of HF.Although treatments such as digoxin and angiotensin receptor blocker drugs have been used,their effectiveness in reducing mortality is uncertain.Researchers are exploring the use of adipose-derived mesenchymal stem cell(ADMSC)exosomes(Exos)as a potential therapy for HF.These vesicles,secreted by cells,may aid in tissue repair and regulation of inflammation and immune responses.However,further investigation is needed to understand the specific role of these vesicles in HF treatment.AIM To investigate the mechanism of extracellular vesicles produced by ADMSC s in the treatment of HF.METHODS Exogenous surface markers of ADMSCs were found,and ADMSCs were cultured.RESULTS The identification of surface markers showed that the surface markers CD44 and CD29 of adipose-derived stem cells(ADSCs)were well expressed,while the surface markers CD45 and CD34 of ADSCs were negative,so the cultured cells were considered ADSCs.Western blotting detected the Exo surface marker protein,which expressed CD63 protein but did not express calnexin protein,indicating that ADSC-derived Exos were successfully extracted.CONCLUSION The secretion of MSCs from adipose tissue can increase ATP levels,block cardiomyocyte apoptosis,and enhance the heart function of animals susceptible to HF.The inhibition of Bax,caspase-3 and p53 protein expression may be related to this process.展开更多
文摘AIM To evaluate effect of treatment failure on cag A and vac A genotypes in Helicobacter pylori(H. pylori) isolates from Colombia.METHODS One hundred and seventy-six participants infected with H. pylori from Colombia were treated during 14 d with the triple-standard therapy. Six weeks later, eradication was evaluated by 13C-Urea breath test. Patients with treatment failure were subjected to endoscopy control; biopsies obtained were used for histopathology and culture. DNA from H. pylori isolates was amplified using primers specific for cag A and vac A genes. The phylogenetic relationships among isolates obtained before and after treatment were established by conglomerate analysis based on random amplified polymorphic DNA(RAPD) fingerprinting.RESULTS Treatment effectiveness was at 74.6%. Of the par-ticipants with treatment failure, 25 accepted subjected to a second endoscopy. Prevalence of posttreatment infection was 64%(16/25) and 40%(10/25) by histology and culture, respectively. Upon comparing the cag A and vac A genotypes found before and after therapy, multiple cag A genotypes(cag A-positive and cag A-negative) were found before treatment; in contrast, cag A-negative genotypes decreased after treatment. vac A s1m1 genotype was highly prevalent in patients before and after therapy. The 3'cag A region was successfully amplified in 95.5%(21/22) of the isolates obtained before and in 81.8%(18/22) of the isolates obtained after treatment. In the isolates obtained from patients with treatment failure, it was found that 72.7%(16/22) presented alterations in the number of EPIYA motifs, compared to isolates found before treatment.CONCLUSION Unsuccessful treatment limits colonization by lowvirulence strains resulting in partial and selective eradication in mixed infections, and acts on the cag A-positive strains inducing genetic rearrangements in cag A variable region that produces a loss or gain of EPIYA repetitions.
文摘The hepatitis C virus has a high mutation capacity that leads to the emergence of resistance-associated substitutions(RAS).However,the consequence of resistance selection during new direct-acting antiviral drug(DAA)treatment is not necessarily the therapeutic failure.In fact,DAA treatment has shown a high rate(>95%)of sustained virological response even when high baseline RAS prevalence has been reported.In the context of RAS emergence and high rates of sustained viral response,the clinical relevance of variants harboring RAS is still controversial.Therefore,in order to summarize the data available in international guidelines,we have reviewed the clinical utility of testing RAS in the era of new pangenotypic DAA drugs.
基金Supported by In part supported by a grant from the BMBF,BMBF-0315905D in the frame of ERA-NET Patho Geno Mics
文摘AIM:To assess whether antibiotic resistance varies between the antrum and corpus of the stomach of patients that are either Helicobacter pylori(H.pylori)therapy-naive or pre-treated.METHODS:H.pylori strains were isolated from antrum and corpus biopsies from 66 patients that received a diagnostic gastroduodenoscopy for variant clinical indications.Antimicrobial susceptibility to amoxicillin,clarithromycin,tetracycline,metronidazole,levofloxacin and rifabutin was tested with the E-test method on IsoSensitest agar with 10 vol%defibrinated horse blood.In patients with a different antibiotic susceptibility pattern between the isolates from the antrum and corpus,DNA fingerprinting via random amplified polymorphic DNA analysis was performed to detect differences among DNA patterns of H.pylori isolates.RESULTS:Primary,secondary and tertiary resistance to clarithromycin was 6.9%,53.8%and 83.3%,retrospectively.Metronidazole and levofloxacin resistance also increased according to the number of previous treatments(17.2%,69.2%,83.3%;13.8%,23.1%,33.3%).Tertiary resistance to rifabutin was detected in12.5%of patients.In none of the 66 patients a resistance against amoxicillin or tetracycline was detectable.Discordant antibiotic susceptibility between antrum and corpus isolates for different antibiotics was seen in 15.2%(10/66)of the patients.Two out of those ten patients were naive to any H.pylori antibiotic treatment.The remaining eight patients previously received at least one eradication therapy.DNA fingerprinting analysis revealed no substantial differences among DNA patterns between antrum and corpus isolates in the majority of patients suggesting an infection with a single H.pylori strain.CONCLUSION:Different antibiotic susceptibility between antrum and corpus biopsies is a common phenomenon and a possible explanation for treatment failure.Resistant H.pylori strains may be missed if just one biopsy from one anatomic site of the stomach is taken for H.pylori susceptibility testing.
文摘AIM:To evaluate the efficacy and safety of tenofovir disoproxil fumarate(TDF) for chronic hepatitis B(CHB) patients after multiple failures.METHODS:A total of 29 CHB patients who had a suboptimal response or developed resistance to two or more previous nucleoside/nucleotide analogue(NA) treatments were included.Study subjects were treated with TDF alone(n = 13) or in combination with lamivudine(LAM,n = 12) or entecavir(ETV,n = 4) for ≥ 6 mo.Complete virologic response(CVR) was defined as an achievement of serum hepatitis B virus(HBV) DNA level ≤ 60 IU/mL by real-time polymerase chain reaction method during treatment.Safety assessment was based on serum creatinine and phosphorus level.Eleven patients had histories of LAM and adefovir dipivoxil(ADV) treatment and 18 patients were exposed to LAM,ADV,and ETV.Twenty-seven patients(93.1%) were hepatitis B e antigen(HBeAg) positive and the mean value of the baseline serum HBV DNA level was 5.5 log IU/mL ± 1.7 log IU/mL.The median treatment duration was 16 mo(range 7 to 29 mo).RESULTS:All the patients had been treated with LAM and developed genotypic and phenotypic resistance to it.Resistance to ADV was present in 7 patients and 10 subjects had a resistance to ETV.One patient had a resistance to both ADV and ETV.The cumulative probabilities of CVR at 12 and 24 mo of TDF containing treatment regimen calculated by the Kaplan Meier method were 86.2% and 96.6%,respectively.Although one patient failed to achieve CVR,serum HBV DNA level decreased by 3.9 log IU/mL from the baseline and the last serum HBV DNA level during treatment was 85 IU/mL,achieving near CVR.No patients in this study showed viral breakthrough or primary non-response during the follow-up period.The cumulative probability of HBeAg clearance in the 27 HBeAg positive patients was 7.4%,12%,and 27% at 6,12,and 18 mo of treatment,respectively.Treatment efficacy of TDF containing regimen was not statistically different according to the presence of specific HBV mutations.History of prior exposure to specific antiviral agents did not make a difference to treatment outcome.Treatment efficacy of TDF was not affected by combination therapy with LAM or ETV.No patient developed renal toxicity and no cases of hypophosphatemia associated with TDF therapy were observed.There were no other adverse events related to TDF therapy observed in the study subjects.CONCLUSION:TDF can be an effective and safe rescue therapy in CHB patients after multiple NA therapy failures.
文摘Background: Genetic diversity of human immunodeficiency virus affects the treatment and the emergence of resistance. Some subtypes would develop resistance more frequently than others. The aim of this study is to determine the rate of virological treatment failure and the involvement of genetic diversity and different mutations in this failure in Kinshasa. Methods: Of the 153 Antiretroviral-naive patients who were included in the cohort, 138 patients have been received for the appointment of the 6th month. Clinical parameters were recorded on individual patient charts. The determination of Viral Load (VL) was done at the Laboratory of Molecular Biology. Clinical and biological parameters of the 6th month were compared with those taken at baseline of the cohort to determine the evolution of patients under treatment. Results: At the consultation of the 6th month, 138 patients (90.2%) had returned out of the 153 included. Eighty-one (58.7%) patients were women and 57 (41.3%) men. The age of patients is between 18 and 65 with an average of 37 years. Ten deaths (6.5%) and 5 (3.3%) lost have been reported. One hundred twenty-five patients (90.5%) were in clinical stage 3 and 13 (9.5%) in clinical stage 4. The median CD4 T cells is 560 cells mm3. The median VLs of patients was 0.90 log10 RNA copies/ml. Of the 34 patients in virological failure, 8 (23.5%) are minimal failure, 23 (67.7%) in moderate failure and 3 (8.8%) in severe failure. According to the Pearson’s test, VLs at 6th months were highly correlated with that of inclusion, with V75 and K70 mutations for NRTIs, with V108 mutation for NNRTI well as the virological failure of treatment. Conclusion: Our results confirmed the hypothesis that high Viral Load at the start of the treatment is a poor prognosis for the development of therapy. Transmitted mutations are involved in treatment failure.
基金Supported by Chang Gung Medical Research Program 380711 Grant to Dr. Yeh CN
文摘AIM:To report preliminary results of the efficacy and safety of sunitinib in the management of Taiwan Residents gastrointestinal stromal tumors (GIST) patients facing imatinib mesylate (IM) intolerance or failure.METHODS:Between 2001 and May 2010,199 Taiwan Residents patients with metastatic GIST were treated at Chang Gung Memorial Hospital.Among them,23 (11.6%) patients receiving sunitinib were investigated.RESULTS:Sixteen male and 7 female patients with a median age of 59 years (range:24-83 years) received sunitinib.Twenty-two GIST patients changed to sunitinib because of IM failure and 1 because of intolerance.The median duration of sunitinib administration was 6.0 mo (range:2-29 mo).The clinical benefit was 65.2% [2 complete response (CR),4 partial response (PR),and 9 stationary disease (SD);15/23].In 12 patients harboring mutations of the kit gene at exon 11,the clinical benefit rate (CR,PR,and SD) was 75.0% and 6 patients with tumors containing kit exon 9 mutations had a clinical benefit of 50.0% (not significant,P=0.344).The progression free survival (PFS) and overall survival (OS) did not differ between patients whose GISTs had wild type,KIT exon 9,or KIT exon 11 mutations.Hand-foot syndrome was the most common cause of grade Ⅲ adverse effect (26.1%),followed by anemia (17.4%),and neutropenia (13.0%).During the median 7.5-mo follow-up after sunitinib use,the median PFS and OS of these 23 GIST patients after sunitinib treatment were 8.4 and 14.1 mo,respectively.CONCLUSION:Sunitinib appears to be an effective treatment for Taiwan Residents with IM-resistant/intolerant GISTs and induced a sustained clinical benefit in more than 50% of Taiwan Residents advanced GIST patients.
基金Supported by Inserm-ANRS(French National Institute for Health and Medical Research-ANRS/France REcherche Nord and Sud Sida-hiv Hépatites)
文摘AIM To describe factors associated with treatment failure and frequency of resistance-associated substitutions(RAS).METHODS Human immunodeficiency virus(HIV)/hepatitis C virus(HCV) coinfected patients starting a first direct-acting antiviral(DAA) regimen before February 2016 and included in the French ANRS CO13 HEPAVIH cohort were eligible. Failure was defined as:(1) non-response [HCV-RNA remained detectable during treatment, at end of treatment(EOT)]; and(2) relapse(HCVRNA suppressed at EOT but detectable thereafter). Sequencing analysis was performed to describe prevalence of drug class-specific RAS. Factors associated with failure were determined using logistic regression models.RESULTS Among 559 patients, 77% had suppressed plasma HIV-RNA < 50 copies/mL at DAA treatment initiation, 41% were cirrhotic, and 68% were HCV treatmentexperienced. Virological treatment failures occurred in 22 patients and were mainly relapses(17, 77%) then undefined failures(3, 14%) and non-responses(2, 9%). Mean treatment duration was 16 wk overall. Posttreatment NS3, NS5 A or NS5 B RAS were detected in 10/14 patients with samples available for sequencing analysis. After adjustment for age, sex, ribavirin use, HCV genotype and treatment duration, low platelet count was the only factor significantly associated with a higher risk of failure(OR: 6.5; 95%CI: 1.8-22.6). CONCLUSION Only 3.9% HIV-HCV coinfected patients failed DAA regimens and RAS were found in 70% of those failing. Low platelet count was independently associated with virological failure.
文摘Background:To evaluate the clinical efficacy of oral administration of Chinese medicines with warming Yang effects and Western medicine in the treatment of heart failure caused by dilated cardiomyopathy.Methods:Seven databases including Chinese National Knowledge Infrastructure,Weipu database,Wanfang database,China Biomedical Literature Service System,Cochrane library,PubMed,and Embase were searched.The search date was from established to October 2019.Randomized clinical trials of dilated cardiomyopathy patients with heart failure under the combination treatment of Chinese medicines with warming Yang effects and Western medicine were included.We then assessed the methodological quality of included literatures,extracted valid data and conducted systematically evaluation according to the Cochrane systematic review method.Outcome index included clinical efficacy,left ventricular ejection fraction,and brain natriuretic peptide.Results:Meta-analysis results showed that the clinical effective rate was higher in the combination group than that in the control group(RR=1.24,95%CI(1.14,1.34),P<0.01).In addition,the combination group could improve left ventricular ejection fraction compared with the control group(Std.MD=0.85,95%CI(0.69,1.01),P<0.01).However,the meta-analysis of brain natriuretic peptide levels showed that the included literatures have higher heterogeneity and the meta-analysis results were unstable.So the results of brain natriuretic peptide were abandoned.Conclusion:Oral administration of Chinese medicines with warming Yang effects combined with Western medicine is better than Western medicine alone in improving clinical effect and left ventricular ejection fraction,but it is not clear whether brain natriuretic peptide can be improved.Because the quality of the included studies is not high and inconsistent outcome index,more standardized and rigorous randomized double-blind controlled trials are needed to validate and guide clinical use.
基金supported by the grant from the National Natural Science Foundation of China (82070609)
文摘Background:Acute liver failure(ALF)is an unpredictable and life-threatening critical illness.The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which may lead to multiple organ failure.Methods:Animals were divided into 3 groups,normal,thioacetamide(TAA,ALF model)and TAA+AGK2.Cultured L02 cells were divided into 5 groups,normal,TAA,TAA+mitofusin 2(MFN2)-siRNA,TAA+AGK2,and TAA+AGK2+MFN2-siRNA groups.The liver histology was evaluated with hematoxylin and eosin staining,inositol-requiring enzyme 1(IRE1),activating transcription factor 6β(ATF6β),protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)and phosphorylated-PERK(p-PERK).C/EBP homologous protein(CHOP),reactive oxygen species(ROS),MFN2 and glutathione peroxidase 4(GPX4)were measured with Western blotting,and cell viability and liver chemistry were also measured.Mitochondriaassociated endoplasmic reticulum membranes(MAMs)were measured by immunofluorescence.Results:The liver tissue in the ALF group had massive inflammatory cell infiltration and hepatocytes necrosis,which were reduced by AGK2 pre-treatment.In comparison to the normal group,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+in the TAA-induced ALF model group were significantly increased,which were decreased by AGK2 pre-treatment.The levels of MFN2 and GPX4 were decreased in TAA-induced mice compared with the normal group,which were enhanced by AGK2 pretreatment.Compared with the TAA-induced L02 cell,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+were further increased and levels of MFN2 and GPX4 were decreased in the MFN2-siRNA group.AGK2 pre-treatment decreased the apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+and enhanced the protein expression of MFN2 and GPX4 in MFN2-siRNA treated L02 cell.Immunofluorescence observation showed that level of MAMs was promoted in the AGK2 pre-treatment group when compared with the TAA-induced group in both mice and L02 cells.Conclusions:The data suggested that AGK2 pre-treatment had hepatoprotective role in TAA-induced ALF via upregulating the expression of MFN2 and then inhibiting PERK and ferroptosis pathway in ALF.
文摘BACKGROUND The increased expression of G3BP1 was positively correlated with the prognosis of liver failure.AIM To investigate the effect of G3BP1 on the prognosis of acute liver failure(ALF)and acute-on-chronic liver failure(ACLF)after the treatment of artificial liver support system(ALSS).METHODS A total of 244 patients with ALF and ACLF were enrolled in this study.The levels of G3BP1 on admission and at discharge were detected.The validation set of 514 patients was collected to verify the predicted effect of G3BP1 and the viability of prognosis.RESULTS This study was shown that lactate dehydrogenase(LDH),alpha-fetoprotein(AFP)and prothrombin time were closely related to the prognosis of patients.After the ALSS treatment,the patient’amount of decreased G3BP1 index in difference of G3BP1 between the value of discharge and admission(difG3BP1)<0 group had a nearly 10-fold increased risk of progression compared with the amount of increased G3BP1 index.The subgroup analysis showed that the difG3BP1<0 group had a higher risk of progression,regardless of model for end-stage liver disease high-risk or low-risk group.At the same time,compared with the inflam matory marks[tumor necrosis factor-α,interleukin(IL)-1βand IL-18],G3BP1 had higher discrimination and was more stable in the model analysis and validation set.When combined with AFP and LDH,concordance index was respectively 0.84 and 0.8 in training and validation cohorts.CONCLUSION This study indicated that G3BP1 could predict the prognosis of ALF or ACLF patients treated with ALSS.The combination of G3BP1,AFP and LDH could accurately evaluate the disease condition and predict the clinical endpoint of patients.
文摘In Mexico, digitalis was known since the 16th century and was used to treat patients with bloating, and it was not until the 20th century that it began to be used as a medicine for heart failure. In conjunction with diuretics. Digitalis was later used in combination individualized with the new medications, for this purpose and research has shown that the combination of medications on an individualized basis is what is currently successfully available for the medical treatment of heart failure.
基金National Natural Science Foundation of China Regional Science Foundation Project(No.82160887)General Project of Guangxi Natural Science Foundation(No.2021GXNSFAA220111)Guangxi Natural Science Foundation Project Youth Science Foundation Project(No.2021GXNSFBA196018)。
文摘Objective: To compare the clinical efficacy of conventional Western medicine combined with Qiliqiangxin capsule and western medicine alone in the treatment of chronic heart failure, and to prove that Qiliqiangxin capsule combined treatment has more advantages, providing reference for clinical decision-making in the treatment of chronic heart failure. Methods: Randomized controlled trials (RCTs) of conventional Western medicine treatment and Western medicine combined with Qiliqiangxin capsule in the treatment of chronic heart failure were searched in databases such as PubMed, Embase, Webofscience, CNKI, WanFang, VIP, and CBM. The bias risk assessment was conducted using the RCT tool recommended by Cochrane, and then the meta-analysis was performed using RevMan5.4 and Stata17 software. Compare the efficacy evaluation of cardiac function, left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), cardiac stroke output (SV), 6-minute walking test (6MWT), and N-terminal proBNP in the conventional western medicine combined with Qiliqiangxin capsule group (hereinafter referred to as the treatment group) and the conventional western medicine group (hereinafter referred to as the control group). Results: A total of 20 RCTs meeting the criteria were included, including 2953 patients, including 1508 in the treatment group and 1445 in the control group. The results of meta-analysis showed that the treatment group had significantly better cardiac function evaluation, LVEF, LVEDD, SV, 6MWT, and NT-proBNP improvement than the control group. Its central functional efficacy evaluation (OR=2.09,95% CI: 1.71-2.55, P<0.001), LVEF (WMD=7.05,95% CI: 5.30-8.79, P<0.00001), LVEDD (WMD=6.73, 95% CI: 3.18-10.29, P=0.0002), SV (WMD=6.73, 95% CI: 3.18-10.29, P=0.0002), 6MWT (SMD=0.70,95% CI: 0.54-0.87, P<0.00001), NT-proBNP (SMD=-1.95,95% CI: -2.5 2 to 1.38 (P<0.0001), with statistically significant differences. Conclusion: Conventional western medicine combined with Qiliqiangxin capsule can significantly improve the clinical efficacy of heart failure, improve LVEF, LVEDD, SV, and NT-proBNP index, and improve exercise tolerance. It is worth using for reference in the treatment.
基金the Science and Technology Research Project of the Education Department of Jilin Province(No.JJKH20220862KJ)the Jilin Province higher education teaching reform research topic(No.20224BRFI7U003M)National Natural Science Foundation of China(No.82074324).
文摘Background:The aim of this study is to investigate the mechanism of action underlying the therapeutic effects of the national patent Chinese medicine compound“Qiangxinhuoli prescription(QXHLF)”on chronic heart failure(CHF).Methods:In vitro,the H 9 C 2 cell model was induced by ANGII,and cell proliferation and related protein expression were detected by Cell Counting Kit-8 and Western blot.In vivo,A rat model of CHF was prepared by ligation of the left anterior descending coronary artery.The effects of QXHLF on cardiac function in CHF rats were evaluated by cardiac index,hemodynamic changes,enzyme-linked immunosorbent assay,hematoxylin-eosin staining,immunohistochemistry,Western blot and RT-PCR.The expression of pro-apoptotic factors and anti-apoptotic factors,as well as TGFβ1,p-p38,TAK 1 mRNA,and protein,were detected.Results:In vitro,QXHLF has a significant inhibitory effect on the proliferation of H 9 C 2 cells.QXHLF can reduce the expression levels of TAK 1,TGFβ1,p-p38,Caspase3 and BAX proteins in H 9 C 2 cells,and increase the expression level of BCL 2 protein.In vivo,QXHLF has the potential to increase left ventricular systolic pressure,m aximum rate of change in left ventricular pressure while decreasing left ventricular end diastolic pressure,and inhibiting the serum levels of brain natriuretic peptide.Moreover,QXHLF exhibits significant improvements in the pathological alterations of myocardial cells and fibers in CHF rats,leading to enhanced myocardial tissue morphology and notable advantages in combating myocardial fibrosis.QXHLF can reduce the levels of BAX and Caspase3 and up-regulate the expression of BCL 2,thereby inhibiting cardiomyocyte apoptosis.Furthermore,QXHLF demonstrates inhibitory effects on the mRNA and protein expression levels of TGFβ1,TAK 1,and p-p38 in the heart tissue of the CHF rat model.Conclusion:These findings indicate that QXHLF has a therapeutic effect on CHF by inhibiting the p38-MAPK signaling pathway,reducing myocardial fibrosis,preventing apoptosis,inhibiting cell proliferation,and restoring myocardial injury.
文摘Objective:To explore the clinical effect of a non-invasive ventilator combined with conventional therapy in the treatment of patients with chronic obstructive pulmonary disease(COPD)combined with respiratory failure.Methods:68 patients with COPD combined with respiratory failure treated in our hospital from September 2021 to October 2023 were selected as the research subjects.Using the random number table method,they were divided into a control group and an experimental group of 34 cases each.The control group received conventional symptomatic treatment,and the experimental group received non-invasive ventilator treatment based on the control group.The clinical effects,blood gas indicators(partial pressure of carbon dioxide(PaCO_(2)),partial pressure of oxygen(PaO_(2)),arterial oxygen saturation(SaO_(2))),lung function(forced expiratory volume in 1 second(FEV1),forced vital capacity(FVC),6 min walking distance),complications,and inflammatory factor levels(c-reactive protein(CRP),interleukin-6(IL-6),neutrophil-to-lymphocyte ratio(NLR))of the two groups of patients were observed.Results:(1)The clinical efficacy of the patients in the experimental group(33/97.06%)was more significant as compared with the control group(25/73.53%)(P<0.05);(2)After treatment,the clinical efficacy of the two groups of patients in terms of FEV1,FEV1/FVC,6-minute walking distance,PaO_(2)and SaO_(2)all increased in the experimental group as compared to that of the control group(P<0.05);(3)After treatment,the PaCO_(2),CRP,IL-6,and NLR of the two groups of patients decreased,and the decrease in the experimental group was higher than that of the control group(P<0.05);(4)The patients’complication rate in the experimental group(2/5.88%)was lower as compared to that of the control group(9/26.46%)(P<0.05).Conclusion:Non-invasive ventilators combined with conventional therapy achieved good clinical results in treating patients with COPD and respiratory failure.
文摘BACKGROUND Heart failure(HF),a common cardiovascular condition,is characterized by significant morbidity and mortality.While traditional Chinese medicine(TCM)is often used as a complementary approach in HF management,systematic evalua-tions of its impact on clinical outcomes,TCM syndrome scores,and B-type natriuretic peptide(BNP)levels are lacking.This study fills this gap through a comprehensive analysis of randomized controlled trials(RCTs)focusing on TCM for HF treatment.It encompasses an assessment of methodological quality,a meta-analysis,and an evaluation of evidence quality based on established standards.The results offer crucial insights into the potential advantages and constraints of TCM in HF management.RCTs on TCM for HF treatment published since the establishment of the database were searched in four Chinese and English databases,including China National Knowledge Infrastructure,Wanfang,VIP Information Chinese Science and Technology Journal,and PubMed.Methodological quality was assessed for the included studies with the Cochrane risk-of-bias assessment tool,and the meta-analysis and publication bias assessment was performed with the RevMan5.3 software.Finally,the quality of evidence was rated according to the GRADE criteria.RESULTS A total of 1098 RCTs were initially retrieved.After screening,16 RCTs were finally included in our study,which were published between 2020 and 2023.These RCTs involved 1660 HF patients,including 832 in the TCM group[TCM combined with conventional Western medicine(CMW)treatment]and 828 in the CWM group(CWM treatment).The course of treatments varied from 1 wk to 3 months.TCM syndrome differentiation was analyzed in 11 of the included RCTs.In all included RCTs,outcome indicators included comprehensive clinical outcomes,TCM syndrome scores,and BNP levels.The meta-analysis results showed significant differences between the TCM and CWM groups in terms of comprehensive clinical outcomes[risk ratio=-0.54;95%confidence interval(CI)=-0.61,-0.47;P<0.00001],TCM syndrome scores[weighted mean difference(WMD)=-142.07;95%CI=-147.56,-136.57;P<0.00001],and BNP levels(WMD=-142.07;95%CI=-147.56,-136.57;P<0.00001).According to the GRADE criteria,RCTs where"TCM improves clinical comprehensive outcomes"were rated as low-quality evidence,and RCTs where"TCM reduces TCM syndrome scores"or"TCM decreases BNP levels"were rated as medium-quality evidence.CONCLUSION TCM combined with CWM treatment effectively improves comprehensive clinical outcomes and diminishes TCM syndrome scores and BNP levels in HF patients.Given the low and medium quality of the included RCTs,the application of these results should be cautious.
基金The authors extend their appreciation to the Deputyship for Research&Innovation,Ministry of Education in Saudi Arabia,for funding this research work through the project number(IFPRC036-135-2020)and King Abdulaziz University,DSR,Jeddah,Saudi Arabia.
文摘Despite the extensive studies conducted on the effectiveness of microwave treatment as a novel rock preconditioning method,there is yet to find reliable data on the rock failure mechanisms due to microwave heating.In addition,there is no significant discussion on the energy efficiency of the method as one of the important factors among the mining and geotechnical engineers in the industry.This study presents a novel experimental method to evaluate two main rock failure mechanisms due to microwave treatment without applying any mechanical forces,i.e.distributed and concentrated heating.The result shows that the existence of a small and concentrated fraction of a strong microwave absorbing mineral will change the failure mechanism from the distributed heating to the concentrated heating,which can increase the weakening over microwave efficiency(WOME)by more than 10 folds.This observation is further investigated using the developed coupled numerical model.It is shown that at the same input energy,the existence of microwave absorbing minerals can cause major heat concentration inside the rock and increase the maximum temperature by up to three times.
基金Key Research and Development projects in Jiangxi Province,No.20223BBG71010National Natural Science Foundation of China,No.81960058.
文摘BACKGROUND Heart failure(HF),an end-stage manifestation of various cardiac diseases,poses an enormous economic and health burden on society.Vericiguat may be an effective drug in the treatment of HF.AIM To explore by meta-analysis the efficacy and safety of Vericiguat in treating chronic heart failure.METHODS Databases,including PubMed,EMBASE,Web of Science,and Cochrane Library,were searched to collect all published randomized controlled trials(RCTs)on Vericiguat treatment of chronic heart failure from the earliest electronic records to those published in March 2023.Two investigators independently screened the literature according to inclusion and exclusion criteria,evaluated the quality of the studies,and extracted valid data before conducting a meta-analysis using RevMan5.4.RESULTS Four RCTs with 5919 patients were included,and the meta-analysis showed that treatment with 10 mg Vericiguat reduced the incidence of the primary endpoint(a composite of cardiovascular mortality and first heart-failure-related hospital-ization)in patients with chronic heart failure compared to placebo[relative risk(RR)=0.91,95%confidence interval(CI):0.85–0.98,P=0.01],and reduced the incidence of heart-failure-related hospitalization(RR=0.92,95%CI:0.84–1.00,P=0.05).However,for the incidence of cardiovascular and all-cause death,there were no significant differences between the Vericiguat and placebo groups.In addition,the two groups did not show significant differences in blood pressure,heart rate,and Kansas Cardiomyopathy Questionnaire physical limitation score.In terms of safety,10 mg Vericiguat did not increase the risk of adverse effects in patients with chronic heart failure.Vericiguat may increase the risk of symp-tomatic hypotension(RR=1.17,95%CI:0.98–1.39,P=0.08)and syncope(RR=1.18,95%CI:0.90–1.55,P=0.24),but not significantly.CONCLUSION Vericiguat(10 mg)was more effective than placebo in treating patients with chronic heart failure and had a better safety profile.
基金Supported by Scientific Research and Technology Development Program of Yulin City(20204031).
文摘[Objectives] To investigate the clinical efficacy of intermittent levosimendan in the treatment of acute heart failure. [Methods] 100 patients diagnosed with acute heart failure and hospitalized in the internal medicine-cardiovascular department in The First People s Hospital of Yulin from January 2019 to February 2020 were randomly divided into two groups, 50 cases in each group. Both groups were treated with conventional anti-heart failure drugs. The control group was given levosimendan once, and the observation group was given levosimendan three times, with an interval of one month. The creatinine (Cr) level, serum NT proBNP, left ventricular ejection fraction (LVEF) and left ventricular end diastolic diameter (LVEDD) were observed at 48 h before and after treatment and one month and two months after treatment in both groups. [Results] Compared with before treatment, the levels of NT-proBNP decreased in the two groups at 48 h after treatment, and the difference was statistically significant ( P <0.05). The Cr level of the control group did not change significantly before and after treatment, and the Cr level of the observation group decreased at one and two months after treatment compared with before treatment, with statistically significant differences ( P <0.05). Compared with before treatment, NT-proBNP and LVEDD decreased and LVEF increased at one and two months after treatment, and the differences were statistically significant ( P <0.05). There were no obvious adverse reactions in the two groups of patients during the treatment. [Conclusions] Repetitive use of levosimendan in the treatment of acute heart failure could significantly improve the renal function, cardiac contractility and cardiac function of patients, and with the passage of time, the treatment effect was improved, which is worthy of clinical promotion.
文摘Objective:To evaluate the efficacy of emergency ventilator therapy in severe acute left heart failure.Methods:A total of 75 patients with severe acute left ventricular heart failure who were admitted to the hospital from July 2020 to July 2023 were randomly divided into two groups.Group A received additional emergency ventilator treatment,and group B received conventional treatment.The efficacy was compared.Results:The curative effect of patients with severe acute left heart failure in group A was higher than that in group B(P<0.05);all blood gas indicators in group A were better than those in group B(P<0.05);all vital signs indicators in group A were better than those in group B(P<0.05);group A was more satisfied with the treatment of severe acute left ventricular heart failure than group B(P<0.05).Conclusion:Patients with severe acute left heart failure who receive emergency ventilator treatment can stabilize vital signs,improve blood oxygen supply,and enhance curative effect.
文摘BACKGROUND Heart failure(HF)is a global health problem characterized by impaired heart function.Cardiac remodeling and cell death contribute to the development of HF.Although treatments such as digoxin and angiotensin receptor blocker drugs have been used,their effectiveness in reducing mortality is uncertain.Researchers are exploring the use of adipose-derived mesenchymal stem cell(ADMSC)exosomes(Exos)as a potential therapy for HF.These vesicles,secreted by cells,may aid in tissue repair and regulation of inflammation and immune responses.However,further investigation is needed to understand the specific role of these vesicles in HF treatment.AIM To investigate the mechanism of extracellular vesicles produced by ADMSC s in the treatment of HF.METHODS Exogenous surface markers of ADMSCs were found,and ADMSCs were cultured.RESULTS The identification of surface markers showed that the surface markers CD44 and CD29 of adipose-derived stem cells(ADSCs)were well expressed,while the surface markers CD45 and CD34 of ADSCs were negative,so the cultured cells were considered ADSCs.Western blotting detected the Exo surface marker protein,which expressed CD63 protein but did not express calnexin protein,indicating that ADSC-derived Exos were successfully extracted.CONCLUSION The secretion of MSCs from adipose tissue can increase ATP levels,block cardiomyocyte apoptosis,and enhance the heart function of animals susceptible to HF.The inhibition of Bax,caspase-3 and p53 protein expression may be related to this process.
