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An elderly female melanoma patient who experienced severe liver injury after treatment with pembrolizumab and axitinib,which improved with glucocorticoid therapy.Through medication analysis and adverse reaction scale evaluated,it was considered that severe liver injury was more closely related to the immune checkpoint inhibitor,pembrolizumab.After a comprehensive analysis of the relationship between liver injury and immunotherapy,as well as the benefits and risks of immunotherapy for patients,immunotherapy was rechallenged 40 days after discontinuation of pembrolizumab.Restarting treatment with pembrolizumab after immune-mediated hepatitis poses a risk of recurrence of hepatotoxicity.After reviewing related literature,it had been found that the incidence of severe hepatotoxicity caused by rechallenging treatment was low,and the overall safety was controllable.Pembrolizumab had brought therapeutic benefits to patients,with no further immune-mediated liver injury of 5 cycles medication.This case can provide a reference for rechallenging immunotherapy after immune-mediated hepatitis.
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Objective To analyze the predictive value of serum levels of procalcitonin(PCT)and cytokines on the prognosis of patients with COVID-19 at admission.Methods From November 2022 to February 2023,patients diagnosed with COVID-19 who were admitted to Beijing Chest Hospital were enrolled.Chemiluminescence was used to detect serum PCT levels,and flow microsphere array was used to detect serum cytokines IL-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-17A,IL-17F,IL-22,TNF-α,TNF-β,IFN-γ level.ICU admission,mechanical ventilation and in-hospital death were defined as poor prognosis.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.After excluding patients with bacterial infection,the relationship between serum PCT and cytokine levels at admission and the prognosis of COVID-19 patients was analyzed.Results A total of 176 patients with complete data were included,including 134 in the PCT-normal group and 42 in the PCT-elevated group,with a median age of 71.50 years and 71.59%males.Patients in the PCT elevated-group had significantly higher rates of ICU admission(38.41%vs.13.11%,P<0.05),mechanical ventilation(76.92%vs.24.59%,P<0.001)and in-hospital mortality(38.46%vs.6.56%,P<0.001)were significantly higher than those in the PCT-normal group.Serum levels of cytokines IL-6(7.40 pg/mL vs.4.78 pg/mL,P = 0.033 4)and IL-8(10.97 pg/mL vs.5.92 pg/mL,P<0.001)were significantly higher in patients with poor prognosis than in those with good prognosis.The area under the curve for PCT,IL-6,and IL-8 to predict poor prognosis in COVID-19 patients was 0.687,0.660,and 0.746,respectively;sensitivity was 52.78%,55.17%,and 72.41%,respectively;and specificity was 81.58%,74.19%,and 74.19%,respectively,as calculated from the ROC curve.When PCT,IL-6 and IL-8 jointly predict the prognosis of COVID-19 patients,the area under the curve is 0.764,the sensitivity is 70.00%,and the specificity is 80.00%.Conclusion Serum PCT and cytokines IL-6 and IL-8 could be used as predictive markers for poor prognosis in patients with COVID-19.
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OBJECTIVE To investigate the effects of matrine (MT) on steatosis Chang Liver cell model induced by oleic acid (OA) and its possible mechanism. METHODS Chang Liver cells were divided into blank group, model group and MT low-dose, medium-dose group and high-dose groups (0.1, 0.5, 1.0 mmol/L). Except for blank group, the other groups were treated with 1.0 mmol/L OA for 24 h to establish steatosis model, and MT groups were given corresponding concentrations of drugs for 24 h. The activities of steatosis Chang Liver cells were observed; the morphologies of intracellular lipid droplets were observed and lipid content was also determined. The contents of liver function indexes [alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP)], as well as mRNA and protein expressions of farnesoid X receptor (FXR), cytochrome P450 7A1 (CYP7A1) and fibroblast growth factor 19 (FGF19) were all detected. RESULTS OA and MT had no significant effect on the activity of Chang Liver cells. After OA treatment, orange lipid droplets formed in cytoplasm; compared with blank group, relative lipid content and the levels of liver function indexes were increased significantly, while the mRNA and protein expressions of FXR, CYP7A1 and FGF19 were down-regulated significantly (P<0.05). After treatment of low, medium and high concentrations of MT, above indexes were all reversed significantly (P<0.05). CONCLUSIONS MT could significantly improve the lipid content and liver function indexes of steatosis Chang Liver cells induced by OA though regulating FXR/CYP7A1/ FGF19 signaling pathway.
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Objective To investigate the effects of Akkermansia muciniphila (AKK) on azomethane-oxide (AOM)/glucan sodium sulfate (DSS)-induced inflammatory colorectal cancer mouse model and intestinal stem cells. Methods AOM/DSS-induced mouse models of inflammatory-associated colorectal cancer were randomly divided into three groups, namely, model, AKK and aspirin groups, based on different administration of drugs by gavage. The tumor number, size, distribution, and burden were observed 10 weeks after intervention. Immunohistochemical method was used to analyze the expressions of Ki67 and Lgr5 proteins, which are utilized to characterize tumor malignancy and stem cells. The mRNA expressions of Lgr5, CD133, Nanog, and ALDH1 were detected by qRT-PCR. Results Compared with those of the model group, the tumor number, size, and burden of the AKK group were significantly reduced (P < 0.01). The expressions of Ki67 and Lgr5 in the AKK group of tumor tissues were significantly decreased (P < 0.05), and the mRNA expressions of CD133, Nanog and ALDH1 were significantly down-regulated. Conclusion AKK is effective against AOM/DSS-induced colitis-associated colorectal cancer in mice, and its mechanism of action may be closely related to colorectal stem cell activity.
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Zn2+ is required for the activity of many mitochondrial proteins, which regulate mitochondrial dynamics, apoptosis and mitophagy. However, it is not understood how the proper mitochondrial Zn2+ level is achieved to maintain mitochondrial homeostasis. Using Caenorhabditis elegans, we reveal here that a pair of mitochondrion-localized transporters controls the mitochondrial level of Zn2+. We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn2+ exporter. Loss of SLC-30A9 leads to mitochondrial Zn2+ accumulation, which damages mitochondria, impairs animal development and shortens the life span. We further identify SLC-25A25/SCaMC-2 as an important regulator of mitochondrial Zn2+ import. Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn2+ accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9. Moreover, we reveal that the endoplasmic reticulum contains the Zn2+ pool from which mitochondrial Zn2+ is imported. These findings establish the molecular basis for controlling the correct mitochondrial Zn2+ levels for normal mitochondrial structure and functions.
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Animales , Caenorhabditis elegans/metabolismo , Proteínas de Transporte de Catión/genética , Homeostasis , Mitocondrias/metabolismo , Zinc/metabolismoRESUMEN
Objective@#To understand the impact of violent video games exposure, self control level and coping style on aggressive behavior of junior high school students in Shanghai, and provide a basis for future interventions to effectively reduce adolescents aggressive behavior.@*Methods@#Cluster sampling was used to select 1 886 students of 4 public middle schools in Shanghai from May to June 2019. The data was collected included Violent Video Game Use Habits Questionnaire, Buss & Perry aggression questionnaire, Adolescent Self Control Dual System Scale and Simple Coping Style Questionnaire.@*Results@#According to the potential profile analysis, the level of aggressive behavior of junior school students in Shanghai could be divided into four groups, which was low aggressive group,middle aggressive group one, middle aggressive group two and high aggressive group according to level of aggregate. After controlling for gender and age, multivariate Logistic regression showed that exposure to violent video games, impulse system and negative response were risk factors for aggressive behavior( P <0.05); using low aggressive group as control group,the OR of violent video games in other three groups were 1.26, 1.30 and 1.70 respectively. The OR of impulse system were 2.96 , 4.40 and 6.84 respectively. The OR of negative response were 1.17, 1.42 and 1.74 respectively. Positive response was a protective factor( P <0.05). Using low aggressive group as control group, the OR of positive in other three groups were 0.82, 0.52 and 0.49 respectively.@*Conclusion@#Violent video game exposure, impulsive system and negative coping style can increase the level of aggressive behavior of junior high school students, while positive coping style can reduce the level of aggression of junior middle school students.
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Objective@#To study the protective effect of N-acetylcysteine on acute lung injury induced by PFIB inhalation and its mechanism.@*Methods@#Survival experiment: 48 male ICR (CD-1) mice were randomly divided into 4 groups, i. e., PFIB control group, NAC prevention group, NAC treatment group, and NAC prevention + treatment group, each group contains 12 animals. The mice of PFIB C group were exposed to PFIB without any treatment. The mice of NAC P group were exposed to PFIB 30min after NAC administration. The mice of NAC T group were exposed to PFIB 1h before NAC administration, The mice of NAC P+T group were administrated with NAC twice (30 min before and 1h after PFIB inhalation) . 150 mg/kg NAC was given by each time. The 7 days survival rate of mice after lethal dose PFIB exposure was observed. 18 male Wistar rats were randomly divided into 3 groups i.e., normal control group (N-C) , PFIB control group (PFIB-C) and NAC prevention group (NAC-P) , with each group contains 6 animals in the second experiment. The rats of N-C group received no treatment. The rats of NAC-P group and PFIB-C group were exposed to PFIB 30min after treatment of NAC (420 mg/Kg, i.p.) and saline, respectively. The respiratory functions of animals were tested before and 24 h after PFIB inhalation. The arterial blood gas was analyzed after rats were anesthetized 24 hours post sublethal dose PFIB exposure. Then samples of BALF, plasma and lung tissue were collected. Wet lung/body weight ratio, protein and phospholipid content in BALF, and T-SOD, GSH, GSH-Px in plasma and lung tissue were measured. The expression of Peroxiredoxin 2 was detected by Westernblot assay.@*Results@#NAC prevention can significantly improve the survival of mice exposed to a lethal dose PFIB while NAC treatment is ineffective. Severe lung edema was observed in rats 24 h after PFIB exposure. Compared to N-C group, the wet lung/body weight ratio, protein and phospholipid content in BALF, and respiratory rate of PFIB control group all increased significantly (P<0.01) . The arterial oxygen partial pressure (PaO2) reduced significantly (P<0.05) . The GSH-Px activity in lung tissue reduced significantly (P<0.01) while the expression of Peroxiredoxin 2 increased significantly (P<0.01) . NAC prophylaxis significantly reduced the wet lung/body weight ratio, protein and phospholipid content in BALF, respiratory rate of rats exposed to PFIB (P<0.01) . Compared with PFIB-C group, the PaO2 (P<0.05) and the activity of GSH-Px (P<0.01) and the expression of Peroxiredoxin 2 in lung tissue (P<0.01) were increased significantly.@*Conclusion@#Acute lung injury induced by PFIB inhalation is related to oxidative stress caused by the stimulation to lung. induced and pulmonary subjected to stimulate the generation of exposure, NAC prevention can regulation of the redox system in lung tissue and protect target organ of the treated animals effectively.
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Objective To investigate the distribution pattern and antimicrobial resistance of the clinical isolates of pathogen.Methods The identification and dug susceptibility tests of the isolates from 2013 to 2015 were performed by using VITEK2-compact system.The susceptibilities of isolates to antimicrobial agents were analyzed with WHONET 5.6 software.Results A Total of 2 991(90.4%) gram-negative bacteria and 317(9.6%) gram-positive bacteria were isolated.Among all of the isolates,the top three pathogens were Klebsiella pneumonia,followed by Pseudomonas aeruginosa and Acinetobacter baumannii.The detection rates of extended-spectrum beta-lactamase(ESBLs)-producing Escherichia coli were 40.4%,48.2% and 38.3% respectively in the three consecutive years,while the detection rates of the ESBLs-producing Klebsiella pneumonia were 16.9%,8.4% and 11.6% respectively.No Escherichia coli resistant to impenem were detected.The resistant rate to impenem of Klebsiella pneumonia was 1.6%.The detection rates of methicillin resistant Staphylococcus aureus(MRSA) and methicillin resistant coagulase-negative staphylococci(MRCNS) in the three years were 53.8%,54.3%,42.9% and 84.5%,82.7%,85.9% respectively.No Staphylococci isolates resistant to linezolid and tigecycline were found.Enterococcus isolates were sensitive to gentamicine,linezolid,tigecycline and vancomycin.Conclusion Carbapenems could remain the best antimicrobials against Enterobacteriaccae.Lnezolid and tigecycline could be effective antimicrobials against Staphylococci isolates.The detection rates of Klebsiella pneumonia and Acinetobacter baumannii increased year by year.The monitoring of drug resistance should be strengthened to control the emergence and spread of multidrug resistant pathogen.
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The performances and characteristics of the functional electrospinning nanofibers were introduced in the field of protection against biological and chemical warfare agents, whose present situation, prospects and advantages were summarized. It's suggested that the functional nanofibers might contribute to increasing the protection ability of the textile against the biological and chemical agents. The difficulty and future trends of the functional nanofibers were analyzed also.
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Acute lung injury ( ALI) is a type of pulmonary excessive inflammation with high morbidity and mortality.It can be induced by multiple causes.There are currently no successful therapeutic or preventive measures because the patho-genesis of ALI has not been completely clarified.Many studies have shown that the activation of complement 5a (C5a) and its receptors is necessary in the process of ALI.Drug development targeting on C5a and its receptors may bring new hope to the treatment of ALI.In this article, the experimental evidence and possible mechanisms are summarized to reveal the rela-tionship between C5a and ALI.
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To investigate the protective effects of scutellarin benzyl ester on neonatal rats' cardiomyocytes injured by ischemia and its anti-apoptosis mechanism.
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OBJECTIVE To inquire into the risk factors of uremia patients with fungus infection and search for the effective methods to prevent and control it.METHODS All the cases of the 82 uremia patients with fungus infection in the clinic of our hospital were analyzed.RESULTS The sites of the fungus infection were intestines and stomach,blood vessel,respiratory tract,oral cavity,reproductive tract,skin soft tissue and urinary tract.The common fungus infection was Candida albicans,about 60.61 per cent.The risk factors of uremia patients with fungus infection were the old age,several underlying diseases,hypoimmunity,not using medicine properly during the treatment and invasive operation.CONCLUSIONS The effective methods to prevent and control fungus infection are as the follows: to improve the staff′s awareness of the danger of fungus infection,be strict to the rules of hospital isolation and sterilization,and be try to reduce invasive operation.We should strengthen the cleaning of the wards and the crew's hands,strengthen the monitoring of quality and pay more attention to the primary treatment.We should use the medicine properly,especially the use of antibiotics,immune suppressants and hormones,and pay attention to result of culture from the microbiological laboratory.We should cure the underlying diseases actively and improve the suffers′ immunity function.