Challenges in managing ST elevation myocardial infarction during the COVID-19 pandemic

BACKGROUND Coronavirus disease 2019(COVID-19)may contribute to delayed presentations of acute myocardial infarction.Delayed presentation with late reperfusion is often associated with an increased risk of mechanical complications and adverse outcomes.Inherent delays are possible as every patient who is acutely sick is being considered a potential case or a career of COVID-19.Also,standardized personal protective equipment precautions are established for all members of the team,regardless of pending COVID-19 testing which might further add to delays.AIM To compare performance measures and clinical outcomes of all patients who presented to our facility with ST elevation myocardial infarction(STEMI)during the COVID-19 pandemic to same time cohort from 2019.METHODS All patients who presented to our facility with STEMI during the pandemic were compared to a matched cohort during the same time period in 2019.STEMI with unknown time of symptom onset and inpatient STEMI patients were excluded.Primary outcome was major adverse cardiac events(MACE)in-hospital and up to 14 d after STEMI,including death,myocardial infarction,cardiac arrest,or stroke.Significant differences among groups for continuous variables were tested through ANOVA,using SYSTAT,version 13.Chi-square tests of association were used to compare patient characteristics among groups using SYSTAT.Relative risk scores and associated tests for significance were calculated for discrete variables using MedCalc(MedCalc Software,Ostend,Belgium).RESULTS There was a significantly longer time interval from symptom onset to first medical contact(FMC)in the COVID-19 group(P<0.02).Time to first electrocardiogram,door-to-balloon time,and FMC to balloon time were not significantly affected.The right coronary artery was the most common culprit for STEMI in both the cohorts.Over 60%of patients had one or more obstructive(>50%)lesion(s)remote from the culprit site.In-hospital and 14 d MACE were more prevalent in the COVID-19 group(P<0.01 and P<0.001).CONCLUSION This single academic center study in the United States suggests that there is a delay in patients with STEMI seeking medical attention during the COVID-19 pandemic which could be translating into worse clinical outcomes.

Epidemiological Clinical Profile of Chronic Kidney Disease in Adults under 50 at the University Hospital of Brazzaville

Introduction: Chronic Kidney Disease (CKD) is a major global public health problem. In Congo, we have very few studies on it. Patients and Methods: We carried out an analytical cross-sectional study with retrospective data collection including patients aged 18 to 49 years, hospitalized for CKD in the nephrology department of University Hospital of Brazzaville, during the period from January 1, 2016 to August 31, 2020. The variables considered were socio-demographic, clinical, paraclinical, therapeutic and evolutionary. The statistical test used was Pearson’s chi-square test. Results: CKD in those under 50 represented 21.1% of admissions and 35.6% of CKD. The mean age was 35.9 ± 8.4 years. There was a male predominance with a sex ratio of 1.27. Hypertension was the most common comorbidity (49.2%), followed by HIV (13.6%) and diabetes mellitus (13.2%). Stage 5 CKD was most prevalent (82.7%). Indeterminate kidney disease was in the order of 55.9%. The low socioeconomic level (74.9% of cases) hampered the achievement of dialysis in 66.3% of patients for whom this treatment was indicated. Failure to perform dialysis significantly influenced the occurrence of death (p-value = 0.005). Conclusion: CKD is common among people under 50 and more affects males with a high mortality rate due to lack of access to dialysis. The main causes are hypertension and HIV.

小檗碱抗肿瘤作用与Wnt/-βcaten in信号转导关系

目的证明小檗碱抗肿瘤作用机制可能与信号转导过程的调控有关。方法采用细胞增殖抑制和Hoechst 33258染色凋亡实验比较小檗碱和黄连总碱对人结肠癌HCT116和SW480细胞的作用。利用Tcf-4报告基因研究小檗碱对肿瘤细胞的信号转导影响。结果小檗碱在5—40mg·L^-1浓度范围内呈浓度依赖性和时间依赖性抑制人结肠癌HCT116和SW480细胞的增殖；小檗碱（20mg·L^-1）处理72h后的HCT116和SW480细胞出现明显凋亡；相当于小檗碱浓度的黄连总碱有类似于小檗碱的作用。20—40mg·L^-1小檗碱和黄连总碱均能明显抑制β—catenin／Tcf介导的转录活性。结论黄连总碱的抗肿瘤作用可能与其主要成分小檗碱有关；其抗肿瘤作用机制至少与抑制Wnt／β-catenin信号通路有关。

人工关节磨损钛微粒诱导破骨的分子生物学机制

背景:通过对人工关节无菌性松动发病机制的深入研究已证实,单核巨噬细胞、成纤维细胞、成骨细胞等在磨损微粒刺激下会产生大量炎性破骨细胞因子,导致假体周围骨溶解。另有研究发现细菌内毒素在人工关节无菌性松动中可能起重要作用。目的:分析人工关节磨损钛微粒诱导溶骨的分子生物学机制。设计、时间及地点:对比观察实验,于2004/2008在武汉大学人民医院和田纳西州立大学医学中心完成。材料:IC-21巨噬细胞购自ATCC TIB-186 American Type Culture Collection,钛微粒购自Alfa Aesar Company,细菌内毒素购自Sigma。方法:IC-21巨噬细胞分别与清洁钛微粒、细菌内毒素结合钛微粒和细菌内毒素联合培养,作为清洁钛微粒组、细菌内毒素结合钛微粒组及细菌内毒素组,与单纯IC-21巨噬细胞组作为对照。主要观察指标:每组分别在培养4,8,16,32h各时点取巨噬细胞,分别用反转录聚合酶链反应技术和电泳迁移率变动分析法,分别检测核激活因子受体mRNA、骨保护素mRNA表达及核转录因子κBDNA的结合活性。结果:与对照组比较,细菌内毒素结合钛微粒组和清洁钛微粒组IC-21巨噬细胞培养4h时核激活因子受体mRNA表达开始增加,之后逐渐升高(P<0.01);培养8h时骨保护素mRNA表达轻度增高,随后恢复到对照组水平。细菌内毒素组未检测到核激活因子受体mRNA表达,培养4h时骨保护素mRNA表达轻度一过性增加。细菌内毒素组和细菌内毒素结合钛微粒组培养4h即可发现核转录因子κBDNA结合活性较清洁钛颗粒组显著增高(P<0.01),在培养8h达到高峰,并在随后的32h中维持在较高活性。清洁钛颗粒组培养16,32h检测到核转录因子κBDNA结合活性轻度增高,显著高于对照组(P<0.05)。结论:清洁钛微粒和细菌内毒素具有不同的诱导溶骨的作用机制。清洁钛微粒可能通过核激活因子受体/骨保护素信号途径,启动溶骨反应过程;细菌内毒素则启动核转录因子κB/破骨性细胞因子信号通路,诱导溶骨。两种机制在人工关节松动过程中同时发生,并协同作用。

Inflammatory bowel disease:Efficient remission maintenance is crucial for cost containment

The inflammatory bowel diseases(IBD) are chronicincurable inflammatory disorders of the gut. Some 10% run a downhill course, requiring emergency medical support and often surgery; another small subset are monogenic, and, threatening pediatric patients, are the challenge of these days. The majority of the IBDs, however, are polygenic low-penetrance diseases, running a lifetime waxing-and-waning course. The prevalent trend is towards a slow worsening and steady cost increase. Each and all drugs of the available arsenal exhibit strengths and weaknesses: Mesalamines are chiefly effectively for mildmoderate colitis, and do not work in Crohn's; steroids do not control some 40% of the ulcerative colitis cases, and are not indicated for Crohn's; thiopurines are effective in the maintenance of the IBDs but do not prevent relapses on withdrawal; biologics are still being used empirically(not monitored) causing further increase of their cost over that of hospitalization. Against all these caveats, two simple rules still hold true: Strict adherence maintenance and avoidance of colitogenic drugs. This matter is expanded in this minireview.

Distribution and drug resistance of pathogens isolated from 4142 blood cultures

Objective:To investigate the distribution and drug resistance of pathogens isolated from 4142 blood cultures, and provide a scientific foundation for guiding clinical rational use of antimicrobial agents for bloodstream infections.Methods: Blood cultures obtained from 4142 inpatients and outpatients who were hospitalized from Jan 2015 to Dec 2016. The culture was detected by automatic BACT/ALERT 3D blood culture system of biomerieux. Bacteria isolated from positive blood cultures were further identified, and the drug susceptibility tests were conducted by VITEK-2 Compact automatic microbial analysis system and ATB Expression microbial analysis system. The drug susceptibility results were evaluated according to CLSI 2014 standard. Statistical analysis was performed by using WHONET 5.6 software. Results:A total of 396 unique strains were isolated from 4142 blood cultures, and the positive rate is 9.6%. Among the positive blood cultures, 194 (49.0%) strains were identified as Gram-positive, 185 (46.7%) strains were identified as Gram-negative, and 17(4.3%) strains were identified as fungi. The coagulase-negative Staphylococcus were the most frequently detectable (29.2%), followed by Escherichia coli (18.4%), Klebsiella pneumonia (7.3%), Staphylococcus aureus (5.1%), Acinetobacter baumannii(5.1%), and Enterococcus genera (5.1%). The incidences of methicillin resistant coagulase negative staphylococcus (MRCNS) and methicillin resistant staphylococcus aureus (MRSA) were 81.9% and 50.0% respectively. However, vancomycin resistant staphylococcus and enterococcus were not detected. The prevalence of extended spectrumβ lactamases (ESBLs) in E. coli and K. pneumoniae were 56.2% and 37.9%, respectively. All the E. coli strains were sensitive to amikacin, piperacillin/tazobactam, imipenem and meropenem, and the sensitive rate of K. pneumoniae strains to imipenem and meropenem were 93.1% and 89.7%, respectively.Conclusions MRCNS stains were the most frequently detected pathogens in blood cultures in the present study. The characteristic of drug resistance for the pathogens indicated that monitoring of imipenem and meropenem resistant K. pneumoniae should be underlined to prevent nosocomial outbreak. Fungi bloodstream infections of ward such as ICU and department of hemopathology should be enhanced monitored.

Novel therapeutic evaluation biomarkers of lipid metabolism targets in uncomplicated pulmonary tuberculosis patients

Currently,the management of pulmonary tuberculosis(TB)lacks potent medications and accurate efficacy evaluation biomarkers.In view of the fact that the host lipids are the important energy source of Mycobacterium tuberculosis(Mtb),UPLC-MS/MS based on lipid metabolism was used to monitor the plasma lipid spectrum of TB patients from the initial diagnosis to cured.The analysis showed that TB patients presented aberrant metabolism of phospholipids,glycerides,and sphingolipids.Upon the treatment,the abnormal expression of Cer(d18:1/24:0),CerP(d18:1/20:3),LPE(0:0/22:0),LPA(0:0/16:0),and LPA(0:0/18:0)in TB patients were gradually normalized,indicating that the intervention of lipid metabolism could block energy metabolism and inhibit the cell wall synthesis of Mtb.Furthermore,the increase in ceramide(Cer)levels could promote autophagosome-lysosome fusion.LPA(0:0/16:0)and LPA(0:0/18:0)had a great potential in the early diagnosis(both sensitivity and specificity were 100%)and efficacy evaluation(both sensitivity and specificity were 100%)of TB,indicating that the above lipid metabolites could be used as potential biomarkers for TB.

我国成年人单纯性收缩期高血压患病率调查

目的评估我国成年人单纯性收缩期高血压的患病率及其人群分布。方法亚洲国际心血管病合作研究(InterASIA)于2000至2001年进行,应用多阶段抽样方法选择15540名35～74岁成年人为代表性样本,分析单纯性收缩期高血压和其他亚型高血压的患病率。应用标准问卷调查高血压病史及其治疗情况。血压值为休息5min后3次坐位血压测量值的平均值。未接受抗高血压治疗的个体通过以下标准确定高血压亚型单纯性收缩期高血压为收缩压≥140mmHg(1mmHg=0133kPa),舒张期血压<90mmHg;单纯性舒张期高血压为收缩压<140mmHg,舒张压≥90mmHg,而收缩期和舒张期联合性高血压为收缩压≥140mmHg,舒张压≥90mmHg。结果15540名35～74岁成年人样本中,76%(1181人)患有单纯性收缩期高血压,74%(1150人)患有收缩期和舒张期联合性高血压,而44%(683人)患有单纯性舒张期高血压。收缩期高血压的患病率随着年龄的增长而增加,且老年女性比老年男性更为常见。南方与北方地区的单纯性收缩期高血压患病率没有明显差异;农村单纯性收缩期高血压患病率高于城市。结论我国收缩期高血压患病率较高,应引起重视。

Repairing skull defects in children with nano-hap/collagen composites: A clinical report of thirteen cases

Objective:To evaluate the clinical results of repairing skull defects with biomimetic bone(nano-hap/collagen composites,NHACs)in children.Methods:Thirteen children with skull defects were treated with NHACs in our hospital.The NHACs molded with the help of a 3D printer were used in the operations.Results:All 13 operations were successful,and patients recovered without infection.Only one patient suffered from subcutaneous hydrops post-operation.The implanted NHACs remained fixed well after 1 year,and their CT HU values raised gradually.Skull shapes of children developed normally.Recovery of neurological and cognitive function was significant.Conclusions:NHAC,chosen to repair skull defects in children,can coexist with normal skull and reduce the negative effects on growth and development.NHAC could be a good choice for children with skull defects.

Potential medicinal plants involved in inhibiting 3CL^(pro) activity:A practical alternate approach to combating COVID-19

At present,a variety of vaccines have been approved,and existing antiviral drugs are being tested to find an effective treatment for coronavirus disease 2019(COVID-19).However,no standardized treatment has yet been approved by the World Health Organization.The virally encoded chymotrypsin-like protease(3CL^(pro))from severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which facilitates the replication of SARS-CoV in the host cells,is one potential pharmacological target for the development of antiSARS drugs.Online search engines,such as Web of Science,Google Scholar,Scopus and PubMed,were used to retrieve data on the traditional uses of medicinal plants and their inhibitory effects against the SARS-CoV 3CL^(pro).Various pure compounds,including polyphenols,terpenoids,chalcones,alkaloids,biflavonoids,flavanones,anthraquinones and glycosides,have shown potent inhibition of SARS-CoV-2 3CL^(pro) activity with 50% inhibitory concentration(IC_(50))values ranging from 2-44μg/mL.Interestingly,most of these active compounds,including xanthoangelol E(isolated from Angelica keiskei),dieckol 1(isolated from Ecklonia cava),amentoflavone(isolated from Torreya nucifera),celastrol,pristimerin,tingenone and iguesterin(isolated from Tripterygium regelii),tannic acid(isolated from Camellia sinensis),and theaflavin-3,3’-digallate,3-isotheaflav1in-3 gallate and dihydrotanshinone I(isolated from Salvia miltiorrhiza),had IC_(50)values of less than 15μg/mL.Kinetic mechanistic studies of several active compounds revealed that their mode of inhibition was dose-dependent and competitive,with K_(i)values ranging from 2.4-43.8μmol/L.Given the significance of plant-based compounds and the many promising results obtained,there is still need to explore the phytochemical and mechanistic potentials of plants and their products.These medicinal plants could serve as an effective inexpensive nutraceutical for the general public to help manage COVID-19.

Prognostic value of lactate transporter SLC16A1 and SLC16A3 as oncoimmunological biomarkers associating tumor metabolism and immune evasion in glioma

Background:Hypoxic microenvironment is immunosuppressive and protu-morigenic,and elevated lactate is an intermediary in the modulation of immune responses.However,as critical lactate transporters,the role of SLC16A1 and SLC16A3 in immune infiltration and evasion of glioma is not fully elucidated.Methods:Gene expression in low‐and high‐grade glioma(LGG and GBM)was evaluated with TCGA database.The TISIDB,TIMER and CIBERSORT databases were utilized for the analysis of the correlation between SLC16A1 or SLC16A3 and immunocyte infiltration as well as immune checkpoints.Results:Compared with normal tissues,a significant increase of both SLC16A1 and SLC16A3 was found in LGG and GBM,and closely related to the poor prognosis only in LGG.Cancer SEA indicated that SLC16A1 was involved in hypoxia while SLC16A3 contributed to metastasis and inflamma-tion in glioma.The SLC16A3 expression was significantly correlated with neutrophil activation by GO analysis.TISCH showed the distribution of SLC16A1 on glioma cells and SLC16A3 on immune cells,which was correlated to tumor‐associated macrophages and neutrophils that are immunosuppressive.SLC16A1 and SLC16A3 were identified to tightly interacted with diverse immune checkpoints(especially PD1,PD‐L1,PD‐L2,Tim‐3)and immunosuppressive factors(TGF‐βand IL‐10)in glioma.Furthermore,SLC16A3 had a positive correlation to activation markers of tumor‐associated neutrophils and chemokines such as CCL2,CCL22,CXCR2,CXCR4 in LGG and CCL7,CCL20 CXCL8 in GBM,which could enhance infiltration of immunosuppressive cells to the tumor microenvironment.Conclusion:In general,our results suggest that SLC16A1 and SLC16A3 act as a bridge between tumor metabolism and immunity by promoting immuno-suppressive cell infiltration,which contributes to immune evasion and a worse prognosis in glioma.Targeting SLC16A1 and SLC16A3 may provide novel therapeutic strategy for immunotherapy in glioma.

Malignant transformation and treatment of cystic mixed germ cell tumor

Objective:The authors report an extremely unusual presentation and management of a children pineal mixed germ cell tumor mainly composed of immature teratoma,aiming to summarize main theraptic points by literature review.Methods:A cystic lesion located in the rear of third ventricle in a child was detected3 years ago with no other therapy performed except for a ventriculo-peritoneal shunt.During the following 3 years,intermitted regular brain MRI demonstrated no evidence of lesion aggrandizement.However from 20 days before admission to our institute the patient began to present acutely with exacerbating clinical symptoms meanwhile brain MRI showed signs of abrupt revulsions of initial lesion without any incentive cause.Neurological examination revealed a significant rising of serum tumor marker level.Then surgical resection was performed immediately after admission which was followed by correlative two-course chemotherapy.Results:Postoperative brain MRI demonstrated totally removing of the lesion in rear of third ventricle.Serum tumor marker level decreased remarkably after surgery and declined to normal level after two-course chemotherapy.No obvious neurological deficit occurred except for short-term memory difficulty which gradually recovered within two weeks.Soon after the second course chemotherapy the patient was currently asymptomatic and returned to school.Conclusions:(1)To ensure definitive diagnosis and proper therapecutic protocols benefit from grasping clinical features of mixed germ cell tumor.(2)Overall preoperative investigation including serum tumor marker level is as critical as neurological imaging examination.(3)Surgical excision is confirmed to be the key modality of treatment.With the regarding of mixed germ cell tumor,never highlight total resection too much.(4)Postoperative adjuvant chemotherapy is recommended as further intensive treatment to improve the prognosis of mix germ cell tumor.