2024 Vol. 42, No. 10
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2024, 42(10): 411-418.
doi: 10.12206/j.issn.2097-2024.202403049
Abstract:
Metabolic dysfunction-associated steatotic liver disease （MASLD） is the most prevalent chronic liver disease globally, encompassing the entire spectrum of fatty liver pathogenesis. It progresses from simple steatosis to metabolic-associated steatohepatitis （MASH）, involving injury and inflammation, with or without fibrosis, ultimately leading to cirrhosis and hepatocellular carcinoma, which affects approximately a quarter of the world's population. Liver biopsy remains the gold standard for differentiating MASH from steatosis and assessing advanced fibrosis. However, its limitations, including costliness, invasiveness, and sampling bias, have spurred the development of noninvasive diagnostic techniques. In addition, there are no FDA-approved drugs for the treatment of MASLD. Enumerating noninvasive diagnostic markers that have the potential to replace liver biopsy were summarized, and the current treatment options for MASLD were discussed, with clinical trials designed to evaluate the efficacy and safety of single agents or combination therapies to halt or reverse disease progression, which could provide new insights for the clinical diagnosis and treatment of MASLD.
Metabolic dysfunction-associated steatotic liver disease （MASLD） is the most prevalent chronic liver disease globally, encompassing the entire spectrum of fatty liver pathogenesis. It progresses from simple steatosis to metabolic-associated steatohepatitis （MASH）, involving injury and inflammation, with or without fibrosis, ultimately leading to cirrhosis and hepatocellular carcinoma, which affects approximately a quarter of the world's population. Liver biopsy remains the gold standard for differentiating MASH from steatosis and assessing advanced fibrosis. However, its limitations, including costliness, invasiveness, and sampling bias, have spurred the development of noninvasive diagnostic techniques. In addition, there are no FDA-approved drugs for the treatment of MASLD. Enumerating noninvasive diagnostic markers that have the potential to replace liver biopsy were summarized, and the current treatment options for MASLD were discussed, with clinical trials designed to evaluate the efficacy and safety of single agents or combination therapies to halt or reverse disease progression, which could provide new insights for the clinical diagnosis and treatment of MASLD.
2024, 42(10): 419-425.
doi: 10.12206/j.issn.2097-2024.202405005
Abstract:
Carbapenem-resistant Enterobacteriaceae （CRE） is an increasingly serious threat to human health worldwide. CRE usually carries multiple drug resistance genes, which limit the selection of therapeutic drugs, prolong treatment time, require higher treatment costs and greater treatment risks. The epidemiology, resistance mechanisms, current resistance status of CRE and the latest therapeutic drugs for CRE were summarized in this papoer, which provide a basis for the rational use of antibiotics in clinical prevention and treatment of drug-resistant bacterial infections.
Carbapenem-resistant Enterobacteriaceae （CRE） is an increasingly serious threat to human health worldwide. CRE usually carries multiple drug resistance genes, which limit the selection of therapeutic drugs, prolong treatment time, require higher treatment costs and greater treatment risks. The epidemiology, resistance mechanisms, current resistance status of CRE and the latest therapeutic drugs for CRE were summarized in this papoer, which provide a basis for the rational use of antibiotics in clinical prevention and treatment of drug-resistant bacterial infections.
2024, 42(10): 426-432.
doi: 10.12206/j.issn.2097-2024.202206072
Abstract:
Objective To investigate the anti-fatigue effect of PTR-SeNPs in vivo by measuring the muscle relative length of hindlimb, load-bearing swimming time as well as serum and liver indexes of mice. Methods 48 male C57/BL6 mice were randomly assigned into 4 groups with 12 mice in each group, including vehicle control group （control group）, swimming training exercise group （EC group） with vehicle treatment, swimming training exercise with low dose of PTR-SeNPs group （LPTR-SeNPs） and high dose of PTR-SeNPs group （HPTR-SeNPs）. The mice were intragastrically administrated with normal saline in both control group and EC group, as well as 2.5 and 10 μmol/（kg·bw） PTR-SeNPs in LHPTR-SeNPs group, respectively, once per day for consecutively 21 days. After swimming training exercise, the muscle structures in the hind limb of mice were examined by magnetic resonance imaging. Furthermore, the burdened swimming time was measured, the serum content of blood lactic acid （BLA）, urea nitrogen （BUN）, alanine aminotransferase （ALT）, glutamic oxalate aminotransferase （AST） and lactate dehydrogenase （LDH）, as well as the hepatic level of glycogen （HG）, malondialdehyde （MDA） and activity of catalase （CAT） and superoxide dismutase （SOD） were determined. Results Compared with the control group, the serum contents of BLA, BUN, ALT, AST and LDH in EC group （P<0.05 or P<0.01） and hepatic CAT in HPTR-SeNPs group （P<0.01） were significantly increased. The muscle relative length of hind limbs and the burdened swimming time were extended by HPTR-SeNPs markedly （P<0.05）. There was no significant difference in MDA level in LHPTR-SeNPs group. Compared with EC group, the burdened swimming time of mice was significantly prolonged （P<0.01）, the contents of BLA and BUN were obviously decreased in the HPTR-SeNPs group （P<0.05 or P<0.01）, the level of HG was significantly increased in the LHPTR-SeNPs groups （P<0.05 or P<0.01）, the serum content of ALT, AST and LDH were markedly decreased in the HPTR-SeNPs group （P<0.05 or P<0.01）. Hepatic SOD activity was remarkably increased in LPTR-SeNPs group （P<0.05）, the level of CAT was evidently increased （P<0.01） and AST was decreased （P<0.05） in the HPTR-SeNPs group. Conclusion PTR-SeNPs could improve the liver physiological function, increase glycogen storage, reduce the accumulation of metabolites and enhance the body’s antioxidant capacity to ameliorate fatigue significantly, which could present the potential to be developed into health care products or drugs.
2024, 42(10): 433-438, 444.
doi: 10.12206/j.issn.2097-2024.202310049
Abstract:
Objective Pulmonary oxygen poisoning resulting from hyperbaric oxygen, frequently occurs in specialized operations, without any current effective prevention or treatment measures. To elucidate the impact and mechanism of neostigmine （NEO） in combination with anisodamine （ANI） （neoscopolamine） on pulmonary oxygen toxicity. Methods The animal model of pulmonary oxygen poisoning was established. C57BL/6 mice were exposed to 2.5 ATA 99.9% oxygen for 6 h. The control group mice were injected with normal saline ip, while the treatment group mice received injections of ANI （25 mg/kg, ip）and NEO （50 μg/kg, ip）. Lung tissues were collected and stained with HE to observe any pathological injuries after exposure. Evans blue stain was utilized to identify lung permeability, wet/dry lung ratio, and protein concentration in the bronchoalveolar lavage fluid （BALF） to assess the lung injury’s severity. The modifications in inflammatory factors, oxidative stress indicators, and iron content in lung tissue were assessed. Results The results showed that the 2.5 ATA 99.9% oxygen-exposed group experienced a significant worsening of lung injury, as well as increased lung permeability, lung wet/dry ratio, and protein content in alveolar lavage fluid when compared to the control group. Moreover, mRNA levels of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, and IFN-γ in the lung tissue of the model group were significantly elevated, while the levels of anti-inflammatory cytokines IL-4 and TGF-β were significantly reduced. The oxidative index MDA also significantly increased, while the antioxidant index GSH significantly decreased. Additionally, the expression of GPX4, a marker of ferroptosis, increased with an increase in iron content. Neoscopolamine treatment successfully reversed those effects. Conclusion The combined use of ANI and NEO had a protective effect on pulmonary oxygen poisoning. Neoscopolamine may inhibit inflammation and oxidative stress by activating the cholinergic anti-inflammatory pathway, thereby reducing the content of free iron in lung tissue and finally inhibiting cell ferroptosis.
2024, 42(10): 439-444.
doi: 10.12206/j.issn.2097-2024.202309059
Abstract:
Objective To analyze the current status of anti-bacterial activity of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli clinically isolated from hospitalized patients, detect their related resistance genes, and provide reference for the clinical treatment of carbapenem resistant Enterobacteria （CRE） infections and the rational use of antibiotics. Methods A total of 400 non-repetitive isolates of Klebsiella pneumoniae and Escherichia coli isolated from clinical specimens of Punan Branch of Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2022 to December were collected. The minimum inhibitory concentrations of these strains against commonly used antibiotics were determined by the broth microdilution method. The carbapenemase and related resistance genes of CRE were detected by drug resistance phenotype testing and PCR. Results Among the 400 strains, 51 strains were identified as CRE, accounting for 12.75%. Among these, 49 strains produced carbapenemases, with 41 strains （80.39%） being CR Klebsiella pneumoniae and 10 strains （19.61%） being CR Escherichia coli. Among the CRE strains, 34 strains （66.67%） carried blaKPC, 13 strains （25.49%） carried blaNDM, and 2 strains （3.92%） carried blaOXA-48. Conclusion Compared with other commonly used antibiotics, colistin and tigecycline exhibited good in vitro antibacterial activity against carbapenemase-producing Klebsiella pneumoniae and Escherichia coli. In addition, there was good concordance between drug resistance phenotype testing and genotyping. Clinical microbiology laboratories could continuously monitor the drug resistance phenotype and genotype of CRE and develop appropriate treatment plans based on actual conditions.
2024, 42(10): 445-450.
doi: 10.12206/j.issn.2097-2024.202403057
Abstract:
Objective To explore the risk signals of adverse events （ADE） in the use of exenatide microspheres by the FDA adverse event reporting system （FAERS）, and provide reference for clinical rational drug use and drug safety. Methods With exenatide microspheres as the target drug, the search keywords were Exenatide Microspheres for Injection, LY05006 , AC 2993 LAR and Bydureon. SAS software was used to extract the ADE report data from January 2, 2012 to March 31, 2023 in the FAERS database and the duplicates were removed. Data mining of exenatide microspheres-related ADE reports was performed by the reporting odds ratio method and the comprehensive standard method. Results A total of 27 248 exenatide microspheres-related ADE reports were retrieved, involving 27 SOCs, of which 4 719 were severe ADE reports. The reporting personnel were mainly consumers （18 435 cases, 67.66%）, the United States was the mainly reporting country （26 295 cases, 96.50%）. A total of 163 ADE risk signals were obtained by reporting odds ratio method and comprehensive standard method, including new adverse reactions such as abnormal blood cholesterol, elevated lipase and mixed hyperlipidemia. Conclusion Based on the FAERS database, the post-marketing ADE of exenatide microspheres was mined and analyzed, which could provide reference for clinical medication safety and improvement of patients' medication compliance.
2024, 42(10): 451-456.
doi: 10.12206/j.issn.2097-2024.202310044
Abstract:
Objective To systematically evaluate the efficacy and safety of nivolumab in the treatment of non-small cell lung cancer. Methods PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure（CNKI）, Weipu Chinese Science and Technology Journal Database, Wanfang Medical Database were searched for articles published from the establishment of the database to March 2023. Published randomized controlled clirical trials of nivolumab in the treatment of patients with non-small cell lung cancer were selected, overall survival, progression-free survival, and adverse reaction rate as outcome indicators were used. A meta-analysis using STATA version 13.1 statistical software was conducted. Results A total of 8 phase Ⅲ randomized controlled trials involving 4945 subjects were included. Compared with the traditional chemotherapy group, patients in the nivolumab group had significantly reduced risk of death in terms of overall survival （HR=0.73, 95%CI=0.65-0.82, P<0.05）, and in terms of progression-free survival, nivolumab significantly reduced the risk of recurrence compared with the traditional chemotherapy group （HR=0.74, 95% CI=0.63-0.88, P<0.05）. In terms of safety, there was no significant difference between the nivolumab group and the traditional chemotherapy group for diarrhea, but the incidence of nausea, neutropenia, anemia, decreased appetite, and fatigue in the nivolumab group was lower than that in the traditional chemotherapy group. However, it should be worth noting that the incidence of immune-related adverse events such as rash was higher in the nivolumab group than in the traditional chemotherapy group, and the difference was statistically significant （OR=3.85, 95%CI=2.05-6.25, P<0.05）. Conclusion Compared to traditional chemotherapy, the efficacy and safety of nivolumab in the treatment of non-small cell lung cancer were better, but the risk of immune-related adverse events increased.
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