Analysis of the influencing factors and clinical related characteristics of pulmonary tuberculosis in patients with type 2 diabetes mellitus

BACKGROUND In China,the prevalence of type 2 diabetes mellitus(T2DM)among diabetic patients is estimated to be between 90%-95%.Additionally,China is among the 22 countries burdened by a high number of tuberculosis cases,with approximately 4.5 million individuals affected by active tuberculosis.Notably,T2DM poses a significant risk factor for the development of tuberculosis,as evidenced by the increased incidence of T2DM coexisting with pulmonary tuberculosis(T2DMPTB),which has risen from 19.3%to 24.1%.It is evident that these two diseases are intricately interconnected and mutually reinforcing in nature.AIM To elucidate the clinical features of individuals diagnosed with both T2DM and tuberculosis(T2DM-PTB),as well as to investigate the potential risk factors associated with active tuberculosis in patients with T2DM.METHODS T2DM-PTB patients who visited our hospital between January 2020 and January 2023 were selected as the observation group,Simple DM patients presenting to our hospital in the same period were the control group,Controls and case groups were matched 1:2 according to the principle of the same sex,age difference(±3)years and disease duration difference(±5)years,patients were investigated for general demographic characteristics,diabetes-related characteristics,body immune status,lifestyle and behavioral habits,univariate and multivariate analysis of the data using conditional logistic regression,calculate the odds ratio(OR)values and 95%CI of OR values.RESULTS A total of 315 study subjects were included in this study,including 105 subjects in the observation group and 210 subjects in the control group.Comparison of the results of both anthropometric and biochemical measures showed that the constitution index,systolic blood pressure,diastolic blood pressure and lymphocyte count were significantly lower in the case group,while fasting blood glucose and high-density lipoprotein cholesterol levels were significantly higher than those in the control group.The results of univariate analysis showed that poor glucose control,hypoproteinemia,lymphopenia,TB contact history,high infection,smoking and alcohol consumption were positively associated with PTB in T2DM patients;married,history of hypertension,treatment of oral hypoglycemic drugs plus insulin,overweight,obesity and regular exercise were negatively associated with PTB in T2DM patients.Results of multivariate stepwise regression analysis found lymphopenia(OR=17.75,95%CI:3.40-92.74),smoking(OR=12.25,95%CI:2.53-59.37),history of TB contact(OR=6.56,95%CI:1.23-35.03)and poor glycemic control(OR=3.37,95%CI:1.11-10.25)was associated with an increased risk of developing PTB in patients with T2DM,While being overweight(OR=0.23,95%CI:0.08-0.72)and obesity(OR=0.11,95%CI:0.02-0.72)was associated with a reduced risk of developing PTB in patients with T2DM.CONCLUSION T2DM-PTB patients are prone to worse glycemic control,higher infection frequency,and a higher proportion of people smoking,drinking alcohol,and lack of exercise.Lymphopenia,smoking,history of TB exposure,poor glycemic control were independent risk factors for T2DM-PTB,and overweight and obesity were associated with reduced risk of concurrent PTB in patients with T2DM.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Targeting nuclear factor erythroid 2-related factor 2-regulated ferroptosis to treat nervous system diseases

By critically examining the work,we conducted a comprehensive bibliometric analysis on the role of nuclear factor erythroid 2-related factor 2(NRF2)in nervous system diseases.We also proposed suggestions for future bibliometric studies,including the integration of multiple websites,analytical tools,and analytical approaches,The findings presented provide compelling evidence that ferroptosis is closely associated with the therapeutic challenges of nervous system diseases.Targeted modulation of NRF2 to regulate ferroptosis holds substantial potential for effectively treating these diseases.Future NRF2-related research should not only focus on discovering new drugs but also on designing rational drug delivery systems.In particular,nanocarriers offer substantial potential for facilitating the clinical translation of NRF2 research and addressing existing issues related to NRF2-related drugs.

Prevalence and Risk Factors of Stroke in Inpatients with Type 2 Diabetes Mellitus in China

Objective The prevalence and the cluster characteristics of risk factors of stroke were assessed in a Chinese diabetic population.Methods Clinical data of 30693 inpatients who were diagnosed with type 2 diabetes mellitus(T2DM)and admitted between 2013 and 2018 were retrospectively analyzed.The age-standardized prevalence of stroke was estimated using the 2010 Chinese population census data,and risk factors were analyzed by multiple imputation and regression.Results The crude and standardized prevalence rates of stroke in patients with T2DM were 34.4%and 21.5%,respectively,and 85.2%of the stroke patients had ischemic stroke.Nearly half of the patients who experienced stroke had clusters of more than 4 risk factors.Compared with no-risk-factor clustering,the risk of stroke significantly increased 3-4 times in the presence of more than 4 risk-factor clusters(P<0.001).Hypertension was the most common major risk factor for ischemic stroke[odds ratio(OR),2.34;95%confidence interval(CI),2.18-2.50]and hemorrhagic stroke(OR,3.68;95%CI 2.95-4.59;P<0.001).Moreover,a 1-standard-deviation increase in fasting blood glucose(FBG)was significantly negatively correlated with ischemic stroke risk,and the same change in FBG was significantly associated with an 8%increased risk of hemorrhagic stroke.Conclusion The prevalence of stroke in patients with T2DM is rather high,and the clustering of risk factors is associated with the development of stroke in T2DM patients.Risk factors differ in different stroke subtypes.Identifying risk factors for a specific high-risk group is necessary.

Frequency of the C677T Polymorphism of MTHFR, G20210A of Prothrombin and R506Q of Factor V Leiden in Type 2 Diabetics in Abidjan

In Africa, the prevalence of diabetes is escalating and remains a concern due to the numerous complications it causes. Vascular damage associated with diabetes leads to a prothrombotic state observed in diabetic individuals. Diabetes is a complex and multifactorial disease involving genetic components. With the aim of preventing complications and contributing to an efficient management of diabetes, we investigated genes likely to lead to a risk of thrombosis, in particular the C677T of MTHFR, G20210A of prothrombin, and R506Q of factor V Leiden in type 2 diabetics in Abidjan receiving ambulatory care. A descriptive cross-sectional study was carried out on consenting type 2 diabetic patients. Mutation detection was carried out using the PCR-RFLP method employing restriction enzymes. Hemostasis tests (fibrinogen, D-dimers, fibrin monomers, and von Willebrand factor) were performed using citrate tubes on the Stage? Star Max automated system. Plasminogen activator inhibitor was assayed by ELISA method, and biochemical parameters were determined using the COBAS C311. The study population consisted of 45 diabetic patients, 51.1% of whom presented vascular complications, mainly neuropathy. Disturbances in hemostasis parameters were observed, with 15.5% of patients showing an increase in fibrin monomers. Mutation analysis revealed an absence of factor V mutation (factor V Leiden) and of G20210A mutation of the prothrombin gene. However, 15.6% of subjects had a heterozygous C677T mutation of MTHFR, with 57% of them being anemic. The exploration of biological and genetic factors associated with thrombotic risk is of significant interest in the optimal management of African type 2 diabetics.

Prognostic significance of oligodendrocyte transcription factor 2 expression in glioma patients:A systematic review and metaanalys

BACKGROUND Gliomas are the most common primary central nervous system neoplasm.Despite recent advances in the diagnosis and treatment of gliomas,patient prognosis remains dismal.Therefore,it is imperative to identify novel diagnostic biomarkers and therapeutic targets of glioma to effectively improve treatment outcomes.AIM To investigate the association between oligodendrocyte transcription factor 2(Olig2)expression and the outcomes of glioma patients.METHODS The PubMed,Embase,Cochrane Library,and China National Knowledge Infrastructure databases were searched for studies(published up to October 2023)that investigated the relationship between Olig2 expression and prognosis of glioma patients.The quality of the studies was assessed using the Newcastle Ottawa Scale.Data analyses were performed using Stata Version 12.0 software.RESULTS A total of 1205 glioma patients from six studies were included in the metaanalysis.High Olig2 expression was associated with better outcomes in glioma patients[hazard ratio(HR):0.81;95%(confidence interval)CI:0.51-1.27;P=0.000].Furthermore,the results of subgroup meta-analysis showed that high expression of Olig2 was associated with poor overall survival in European patients(HR:1.34;95%CI:0.79-2.27)and better prognosis in Asian patients(HR:0.43;95%CI:0.22-0.84).The sensitivity analysis showed that no single study had a significant effect on pooled HR,and there was also no indication of publication bias according to the Egger’s and Begger’s P value test or funnel plot test.CONCLUSION High Olig2 expression may have a positive impact on the prognosis of glioma patients,and should be investigated further as a prognostic biomarker and therapeutic target for glioma.

Research Progress on Self-Efficacy Level of Patients with Type 2 Diabetes Mellitus and Its Influencing Factors

Self-efficacy plays an important role in the management of type 2 diabetes mellitus (T2DM) patients, and it runs through the whole process of diabetes treatment, which is conducive to controlling and delaying the occurrence and development of complications, as well as improving the quality of life of patients. This paper mainly describes the concept of self-efficacy, the current situation of self-efficacy of diabetic patients at home and abroad, the functional aspects and their influencing factors, so as to take relevant measures on how to improve self-efficacy. It aims to provide a theoretical basis for the development of self-efficacy interventions for patients with type 2 diabetes mellitus.

Interleukin-1 receptor associated kinase 2 is a functional downstream regulator of complement factor D that controls mitochondrial fitness in diabetic cardiomyopathy

Diabetic cardiomyopathy is a disorder of the cardiac muscle that affects patients with diabetes.The exact mechanisms underlying diabetic cardiomyopathy are mostly unknown,but several factors have been implicated in the pathogenesis of the disease and its progression towards heart failure,including endothelial dysfunction,autonomic neuropathy,metabolic alterations,oxidative stress,and alterations in ion homeostasis,especially calcium transients[1].In Military Medical Research,Jiang et al.[2]sought to determine the functional role of complement factor D(Adipsin)in the pathophysiology of diabetic cardiomyopathy.

Refining the Factors Affecting N_(2)O Emissions from Upland Soils with and without Nitrogen Fertilizer Application at a Global Scale

Nitrous oxide(N_(2)O)is a long-lived greenhouse gas that mainly originates from agricultural soils.More and more studies have explored the sources,influencing factors and effective mitigation measures of N_(2)O in recent decades.However,the hierarchy of factors influencing N_(2)O emissions from agricultural soils at the global scale remains unclear.In this study,we carry out correlation and structural equation modeling analysis on a global N_(2)O emission dataset to explore the hierarchy of influencing factors affecting N_(2)O emissions from the nitrogen(N)and non-N fertilized upland farming systems,in terms of climatic factors,soil properties,and agricultural practices.Our results show that the average N_(2)O emission intensity in the N fertilized soils(17.83 g N ha^(-1)d^(-1))was significantly greater than that in the non-N fertilized soils(5.34 g N ha^(−1) d^(−1))(p<0.001).Climate factors and agricultural practices are the most important influencing factors on N_(2)O emission in non-N and N fertilized upland soils,respectively.For different climatic zones,without fertilizer,the primary influence factors on soil N_(2)O emissions are soil physical properties in subtropical monsoon zone,whereas climatic factors are key in the temperate zones.With fertilizer,the primary influence factors for subtropical monsoon and temperate continental zones are soil physical properties,while agricultural measures are the main factors in the temperate monsoon zone.Deploying enhanced agricultural practices,such as reduced N fertilizer rate combined with the addition of nitrification and urease inhibitors can potentially mitigate N_(2)O emissions by more than 60%in upland farming systems.

Inetetamab combined with S-1 and oxaliplatin as first-line treatment for human epidermal growth factor receptor 2-positive gastric cancer

BACKGROUND Patients with human epidermal growth factor receptor 2(HER2)-positive advanced gastric cancer have poor outcomes.Trastuzumab combined with chemotherapy is the first-line standard treatment for HER2-positive advanced gastric cancer.Inetetamab is a novel anti-HER2 drug,and its efficacy and safety in gastric cancer have not yet been reported.AIM To evaluate the efficacy and safety of the S-1 plus oxaliplatin(SOX)regimen combined with inetetamab as a first-line treatment for HER2-positive advanced gastric cancer.METHODS Thirty-eight patients with HER2-positive advanced gastric cancer or gastroeso-phageal junction adenocarcinoma were randomly divided into two groups:One group received inetetamab combined with the SOX regimen,and the other group received trastuzumab combined with the SOX regimen.After 4-6 cycles,patients with stable disease received maintenance therapy.The primary endpoints were progression-free survival(PFS)and overall survival(OS),and the secondary endpoints were the objective response rate,disease control rate,and adverse events(AEs).RESULTS Thirty-seven patients completed the trial,with 18 patients in the inetetamab group and 19 patients in the trastuzumab group.In the inetetamab group,the median PFS was 8.5 months,whereas it was 7.3 months in the trastuzumab group(P=0.046);this difference was significant.The median OS in the inetetamab group vs the trastuzumab group was 15.4 months vs 14.3 months(P=0.33),and the objective response rate was 50%vs 42%(P=0.63),respectively;these differences were not significant.Common AEs included leukopenia,thrombocytopenia,nausea,and vomiting.The incidence rates of grade≥3 AEs were 56%in the inetetamab group and 47%in the trastuzumab group(P=0.63),with no significant difference.CONCLUSION In the first-line treatment of HER2-positive advanced gastric cancer,inetetamab and trastuzumab showed comparable efficacy.The inetetamab group showed superior PFS,and both groups had good safety.

BIRC3 induces the phosphoinositide 3-kinase-Akt pathway activation to promote trastuzumab resistance in human epidermal growth factor receptor 2-positive gastric cancer

BACKGROUND Trastuzumab-targeted therapy is currently the standard of care for advanced human epidermal growth factor receptor 2(HER2)-positive gastric cancer.However,the emergence of resistance to trastuzumab poses significant challenges.AIM To identify the key genes associated with trastuzumab resistance.These results provide a basis for the development of interventions to address drug resistance and improve patient outcomes.METHODS High-throughput sequencing and bioinformatics were used to identify the differentially expressed pivotal gene BIRC3 and delineate its potential function and pathway regulation.Tumor samples were collected from patients with HER2-positive gastric cancer to evaluate the correlation between BIRC3 expression and trastuzumab resistance.We established gastric cancer cell lines with both highly expressed and suppressed levels of BIRC3,followed by comprehensive in vitro and in vivo experiments to confirm the involvement of BIRC3 in trastuzumab resistance and to elucidate its underlying mechanisms.RESULTS In patients with HER2-positive gastric cancer,there is a significant correlation between elevated BIRC3 expression in tumor tissues and higher T stage,tumor node metastasis stage,as well as poor overall survival and progressionfree survival.BIRC3 is highly expressed in trastuzumab-resistant gastric cancer cell lines,where it inhibits tumor cell apoptosis and enhances trastuzumab resistance by promoting the phosphorylation and activation of the phosphoinositide 3-kinase-Akt(PI3K-AKT)pathway in HER2-positive gastric cancer cells,both in vivo and in vitro.CONCLUSION This study revealed a robust association between high BIRC3 expression and an unfavorable prognosis in patients with HER2-positive gastric cancer.Thus,the high expression of BIRC3 stimulated PI3K-AKT phosphorylation and activation,stimulating the proliferation of HER2-positive tumor cells and suppressing apoptosis,ultimately leading to trastuzumab resistance.

Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer

Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy resistance.Human epidermal growth factor receptor 2(HER2)is one of the most important targets in targeted therapy for gastric cancer.Trastuzumab combined with chemotherapy has been used as the first-line treatment for advanced gastric cancer.The safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been verified.However,monoclonal antibodies,due to their large molecular weight,inability to penetrate the blood-brain barrier,and drug resistance,lead to decreased therapeutic efficacy,so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric cancer.Small-molecule tyrosine kinase inhibitors,such as lapatinib and pyrrotinib,have the advantages of small molecular weight,penetrating the blood-brain barrier and high oral bioavailability,and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the future.Antibo-drug conjugate,such as T-DM1 and T-DXd,can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing,and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as trastuzumab.Therefore,after more detailed stratification of gastric cancer patients,various gastric cancer drugs targeting HER2 are expected to play a more significant role.

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

BACKGROUND Gastrointestinal stromal tumors(GISTs)are typical gastrointestinal tract neoplasms.Imatinib is the first-line therapy for GIST patients.Drug resistance limits the long-term effectiveness of imatinib.The regulatory effect of insulin-like growth factor 2(IGF2)has been confirmed in various cancers and is related to resistance to chemotherapy and a worse prognosis.AIM To further investigate the mechanism of IGF2 specific to GISTs.METHODS IGF2 was screened and analyzed using Gene Expression Omnibus(GEO:GSE225819)data.After IGF2 knockdown or overexpression by transfection,the phenotypes(proliferation,migration,invasion,apoptosis)of GIST cells were characterized by cell counting kit 8,Transwell,and flow cytometry assays.We used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition(EMT)-associated proteins.We injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of GIST.RESULTS Data from the GEO indicated that IGF2 expression is high in GISTs,associated with liver metastasis,and closely related to drug resistance.GIST cells with high expression of IGF2 had increased proliferation and migration,invasiveness and EMT.Knockdown of IGF2 significantly inhibited those activities.In addition,OEIGF2 promoted GIST metastasis in vivo in nude mice.IGF2 activated IGF1R signaling in GIST cells,and IGF2/IGF1R-mediated glycolysis was required for GIST with liver metastasis.GIST cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib resistance.Moreover,2-deoxy-D-glucose(a glycolysis inhibitor)treatment reversed IGF2 overexpressionmediated imatinib resistance in GISTs.CONCLUSION IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.

Inetetamab combined with tegafur as second-line treatment for human epidermal growth factor receptor-2-positive gastric cancer: A case report

BACKGROUND Human epidermal growth factor receptor-2(HER-2)plays a vital role in tumor cell proliferation and metastasis.However,the prognosis of HER2-positive gastric cancer is poor.Inetetamab,a novel anti-HER2 targeting drug independently developed in China,exhibits more potent antibody-dependent cell-mediated cytotoxicity than trastuzumab,which is administered as the first-line treatment for HER2-positive gastric cancer in combination with chemotherapy.In this case,the efficacy and safety of inetetamab combined with tegafur was investigated as a second-line treatment for HER2-positive gastric cancer.CASE SUMMARY A 52-year-old male patient with HER2-positive gastric cancer presented with abdominal distension,poor appetite,and fatigue two years after receiving six cycles of oxaliplatin combined with tegafur as first-line treatment after surgery,followed by tegafur monotherapy for six months.The patient was diagnosed with postoperative recurrence of gastric adenocarcinoma.He received 17 cycles of a combination of inetetamab,an innovative domestically developed anti-HER2 monoclonal antibody,and tegafur chemotherapy as the second-line treatment(inetetamab 200 mg on day 1,every 3 wk combined with tegafur twice daily on days 1–14,every 3 wk).Evaluation of the efficacy of the second-line treatment revealed that the patient achieved a stable condition and progression-free survival of 17 months.He tolerated the treatment well without exhibiting any grade 3-4 adverse events.CONCLUSION Inetetamab combined with chemotherapy for the treatment of metastatic HER2-positive gastric cancer demonstrates significant survival benefits and acceptable safety.

Study on the Influencing Factors of L2 Reading Ability and Its Regulation Strategies

This paper takes college students as research subjects to investigate the factors affecting L2 Reading ability and their regulation strategies through scale surveys.The findings are as follows:(1)Linguistic factors have significant impacts on L2 Reading ability,and the influence of non-linguistic factors,such as non-intellectual factors and cultural background knowledge,is also important;and(2)flexible use of reading regulation strategies according to the learning conditions(such as the information extraction strategy,the metacognitive reading regulation strategy,and the interactive reading strategy)can effectively improve learners’L2 Reading ability.The findings of this study have important theoretical and practical value for improving L2 learners’Reading ability.

Human epidermal growth factor receptor 2 expression level and combined positive score can evaluate efficacy of advanced gastric cancer

BACKGROUND Although treatment options for gastric cancer(GC)continue to advance,the overall prognosis for patients with GC remains poor.At present,the predictors of treatment efficacy remain controversial except for high microsatellite instability.AIM To develop methods to identify groups of patients with GC who would benefit the most from receiving the combination of a programmed cell death protein 1(PD-1)inhibitor and chemotherapy.METHODS We acquired data from 63 patients with human epidermal growth factor receptor 2(HER2)-negative GC with a histological diagnosis of GC at the Cancer Hospital,Chinese Academy of Medical Sciences between November 2020 and October 2022.All of the patients screened received a PD-1 inhibitor combined with chemotherapy as the first-line treatment.RESULTS As of July 1,2023,the objective response rate was 61.9%,and the disease control rate was 96.8%.The median progression-free survival(mPFS)for all patients was 6.3 months.The median overall survival was not achieved.Survival analysis showed that patients with a combined positive score(CPS)≥1 exhibited an extended trend in progression-free survival(PFS)when compared to patients with a CPS of 0 after receiving a PD-1 inhibitor combined with oxaliplatin and tegafur as the first-line treatment.PFS exhibited a trend for prolongation as the expression level of HER2 increased.Based on PFS,we divided patients into two groups:A treatment group with excellent efficacy and a treatment group with poor efficacy.The mPFS of the excellent efficacy group was 8 months,with a mPFS of 9.1 months after excluding a cohort of patients who received interrupted therapy due to surgery.The mPFS was 4.5 months in patients in the group with poor efficacy who did not receive surgery.Using good/poor efficacy as the endpoint of our study,univariate analysis revealed that both CPS score(P=0.004)and HER2 expression level(P=0.015)were both factors that exerted significant influence on the efficacy of treatment the combination of a PD-1 inhibitor and chemotherapy in patients with advanced GC(AGC).Finally,multivariate analysis confirmed that CPS score was a significant influencing factor.CONCLUSION CPS score and HER2 expression both impacted the efficacy of immunotherapy combined with chemotherapy in AGC patients who were non-positive for HER2.

姜酮通过激活Nrf2/HO-1信号通路减轻OGD/R后氧化应激损伤对HT22细胞凋亡的抑制作用

目的:探讨姜酮对氧糖剥夺/复糖复氧(OGD/R)后小鼠海马神经元HT22细胞的保护作用,阐明其相关作用机制。方法:培养HT22细胞,设置不同OGD/R时间梯度,建立OGD/R细胞损伤模型。HT22细胞分为对照组、OGD/R组、OGD/R+1μmol·L^(-1)姜酮组、OGD/R+10μmol·L^(-1)姜酮、OGD/R+100μmol·L^(-1)姜酮组和OGD/R+0.2%二甲亚枫(DMSO)组,CCK-8法检测各组细胞活性并计算各组细胞存活率,确定姜酮最适药物浓度。细胞分为对照组、OGD/R组、OGD/R+姜酮组和OGD/R+姜酮+核因子E2相关因子2(Nrf2)抑制剂(ML385)组,OGD/R+姜酮组细胞经姜酮给药处理4 h后予以OGD 8 h和复糖复氧8 h处理,OGD/R+姜酮+ML385组细胞在姜酮给药前予以10μmol·L^(-1)ML385预处理6 h,CCK-8法检测各组细胞活性,Western blotting法检测各组细胞中Nrf2、血红素加氧酶1(HO-1)、B细胞淋巴瘤2(Bcl-2)和Bcl-2相关X蛋白(Bax)蛋白表达水平,酶联免疫吸附试验(ELISA)法检测各组细胞培养上清中超氧化物歧化酶(SOD)活性和丙二醛(MDA)水平。结果:与对照组比较,HT22细胞经OGD 8 h和复糖复糖8 h处理后细胞存活率低于50%,以OGD 8 h和复糖复糖8 h建立HT22细胞OGD/R模型。与OGD/R组比较,OGD/R+不同剂量姜酮组细胞存活率均不同程度升高,其中OGD/R+100μmol·L^(-1)姜酮组细胞存活率升高最明显(P<0.01),故选用100μmol·L^(-1)姜酮用于后续实验。与对照组比较,OGD/R组细胞活性明显降低(P<0.01),细胞中Nrf2、HO-1和Bax蛋白表达水平明显升高(P<0.01),Bcl-2蛋白表达水平明显降低(P<0.05),细胞培养上清中SOD活性明显降低(P<0.01),MDA水平明显升高(P<0.01);与OGD/R组比较,OGD/R+姜酮组细胞活性明显升高(P<0.01),细胞中Nrf2、HO-1和Bcl-2蛋白表达水平明显升高(P<0.05或P<0.01),Bax蛋白表达水平明显降低(P<0.05),细胞培养上清中SOD活性明显升高(P<0.01),MDA水平明显降低(P<0.01);与OGD/R+姜酮组比较,OGD/R+姜酮+ML385组细胞活性明显降低(P<0.01),细胞中Nrf2、HO-1和Bcl-2蛋白表达水平明显降低(P<0.01),Bax蛋白表达水平明显升高(P<0.01),细胞培养上清中SOD活性明显降低(P<0.01),MDA水平明显升高(P<0.05)。结论:姜酮可通过激活Nrf2/HO-1信号通路减轻OGD/R后氧化应激损伤对HT22细胞凋亡的抑制作用。

槲皮素预处理ALI大鼠肺组织损伤、炎症/氧化应激反应、铁死亡及Nrf2/HO-1信号通路激活情况观察

目的观察槲皮素灌胃预处理的LPS诱导急性肺损伤(ALI)大鼠肺组织损伤、炎症反应、氧化应激反应、铁死亡及Nrf2/HO-1信号通路激活情况,以探讨槲皮素对ALI的预防作用及机制。方法24只SD大鼠分为槲皮素低、中、高剂量组和阳性对照组(地塞米松)、模型组、正常对照组。槲皮素低、中、高剂量组以25、50、100 mg/kg槲皮素灌胃,1次/天,连续7 d;槲皮素灌胃处理的第4天在大鼠气管内滴注5 mg/kg LPS;阳性对照组以地塞米松1.04 mg/kg灌胃,其余处理同槲皮素组;模型组以生理盐水灌胃,1次/天,连续7天,其余处理同槲皮素组;正常对照组以生理盐水连续灌胃7 d。末次灌注给药后,观察各组肺组织损伤(肺功能及肺组织病理改变、纤维组织阳性表达率、肺泡上皮细胞凋亡率)、炎症反应(肺泡灌洗液TNF-α、IL-6、IL-1β)、氧化应激反应(肺泡灌洗液SOD、GSH、MDA,肺组织ROS)、铁死亡(Fe^(2+)水平)及Nrf2/HO-1信号通路激活[肺组织核因子红细胞2相关因子2(Nfr2)、血红素加氧酶1(HO-1)、超氧化物歧化酶2(SOD2)、过氧化氢酶(CAT)蛋白]情况。结果与正常对照组比较,模型组PaCO_(2)水平升高,PaO_(2)、SaO_(2)水平降低(P均<0.01);肺组织可见肺泡上皮细胞变性坏死,纤维组织阳性表达率高;肺泡上皮细胞凋亡率高;肺泡灌洗液中TNF-α、IL-6、IL-1β水平均升高,SOD、GSH水平降低,MDA水平升高,肺组织ROS表达水平升高,肺泡灌洗液中Fe^(2+)水平升高(P均<0.05)。与模型组相比,槲皮素中、高剂量组和阳性对照组中PaCO_(2)均降低(P均<0.05),槲皮素高剂量组PaO_(2)和SaO_(2)水平升高(P均<0.05);槲皮素高剂量组与阳性对照组肺组织炎性浸润与纤维增生明显减少,肺泡恢复正常生理结构;槲皮素低、中、高剂量组和阳性对照组肺纤维组织阳性表达率均下降(P均<0.05),其中槲皮素高剂量组肺纤维组织阳性表达率最低;槲皮素低、中、高剂量组和阳性对照组肺泡上皮细胞凋亡率均降低(P均<0.01);槲皮素低、中、高剂量组和阳性对照组肺泡灌洗液中TNF-α、IL-6、IL-1β水平均降低、SOD、GSH水平升高、MDA水平降低,肺组织ROS表达水平降低(P均<0.01),肺泡灌洗液中Fe^(2+)水平降低。与正常对照组比较,模型组肺组织中CAT、HO-1、Nrf2、SOD2蛋白表达水平低(P均<0.01);与模型组比较,槲皮素中、高剂量组和阳性对照组肺组织中CAT、HO-1、Nrf2、SOD2蛋白表达水平高(P均<0.05)。结论槲皮素灌胃预处理的ALI大鼠肺组织损伤、炎症反应、氧化应激反应、铁死亡情况减轻,Nfr2/HO-1信号通路激活;槲皮素灌胃预处理可预防LPS诱导的大鼠ALI,可能通过抑制炎症反应、氧化应激反应及铁死亡而起作用;槲皮素可能通过上调Nfr2/HO-1信号通路而抑制炎症反应、氧化应激反应及铁死亡;50、100 mg/kg槲皮素均对LPS诱导的大鼠ALI起预防作用,以100 mg/kg槲皮素的作用效果更佳。

能源资源开发区域大气CO_(2)时空变化及影响因素分析

分析能源资源开发区域大气碳浓度的时空变化和影响因素,对于探索“碳达峰”“碳中和”背景下能源资源开发高质量发展路径至关重要。新疆维吾尔自治区是我国重要的能源和战略资源基地,本文面向新疆维吾尔自治区的能源资源开发现状,采集并预处理了2015—2021年轨道碳观测卫星-2(Orbiting Carbon Observatory-2,OCO-2)二氧化碳L3数据产品,分析研究区大气碳浓度的时间变化趋势和空间分布格局,构建深度森林回归模型,并分析各影响因素对碳浓度时空变化的驱动作用。结果表明:(1)新疆维吾尔自治区、准噶尔盆地、吐哈盆地和塔里木盆地XCO_(2)浓度在2015—2021年均呈周期性上升趋势,增长率呈“先减后增”,且季节变化趋势呈现明显的“春季高冬季低”;(2)在春、秋和冬季,新疆XCO_(2)浓度空间格局呈现“北高南低”的趋势,在盆地区域及能源资源开发区域出现XCO_(2)高浓度积聚现象,夏季则呈现“北低南高”趋势;(3)地形起伏、风场流速、NDVI、地表温度、降水量、10 mV风、10 mU风和能源开发强度对区域XCO_(2)浓度时空分布有显著影响,各因素呈现明显的空间异质性和显著差异。研究结果有助于理解能源资源开采区域的大气碳浓度时空演变机制,在国家碳减排目标的实现、指导碳中和策略、追踪碳减排效果等方面具有深远意义。

BMAL1减轻H_(2)O_(2)诱导的心肌细胞损伤机制研究

目的探讨脑和肌肉组织芳香烃受体核转运蛋白的类似蛋白1(BMAL1)通过核因子E2相关因子2(NRF2)调节活性氧(ROS)/NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎症小体通路对过氧化氢(H_(2)O_(2))诱导的心肌细胞损伤的影响。方法体外培养H9c2细胞和BMAL1稳定过表达的H9c2细胞,建立H_(2)O_(2)诱导的H9c2细胞损伤模型,并将细胞分为对照(Control)组、H_(2)O_(2)组、BMAL1过表达(BMAL1-OE)组、BMAL1过表达+H_(2)O_(2)(BMAL1-OE+H_(2)O_(2))组、BMAL1过表达+NRF2抑制剂(BMAL1-OE+ML385)组、BMAL1过表达+NRF2抑制剂+H_(2)O_(2)(BMAL1-OE+ML385+H_(2)O_(2))组。采用CCK-8法检测细胞活力,荧光探针2’,7’-二氯荧光素二乙酸酯检测ROS生成,Western blot检测BMAL1、NRF2和NLRP3蛋白表达,酶联免疫吸附试验法检测白细胞介素(IL)-1β释放。结果与Control组相比,H_(2)O_(2)组H9c2心肌细胞活力减弱,ROS生成增多,BMAL1和NRF2蛋白表达水平降低,NLRP3蛋白表达水平升高,IL-1β释放增多(P<0.05);与H_(2)O_(2)组相比,BMAL1-OE+H_(2)O_(2)组H9c2心肌细胞活力升高,ROS生成减少,BMAL1和NRF2蛋白表达水平升高,NLRP3蛋白表达水平降低,IL-1β释放减少(P<0.05)。与BMAL1-OE+H_(2)O_(2)组相比,BMAL1-OE+ML385+H_(2)O_(2)组H9c2心肌细胞活力减弱,ROS生成增多,NLRP3蛋白表达水平升高,IL-1β释放增多(P<0.05)。结论BMAL1可减轻H_(2)O_(2)诱导的H9c2心肌细胞损伤,其机制可能与NRF2调节ROS/NLRP3炎症小体通路有关。