Clinical characteristics of 82 death cases with COVID-19

BackgroundA recently developing pneumonia caused by SARS-CoV-2 was originated in Wuhan, China, and has quickly spread across the world. We reported the clinical characteristics of 82 death cases with COVID-19 in a single center. MethodsClinical data on 82 death cases laboratory-confirmed as SARS-CoV-2 infection were obtained from a Wuhan local hospitals electronic medical records according to previously designed standardized data collection forms. ResultsAll patients were local residents of Wuhan, and the great proportion of them were diagnosed as severe illness when admitted. Most of the death cases were male (65.9%). More than half of dead patients were older than 60 years (80.5%) and the median age was 72.5 years. The bulk of death cases had comorbidity (76.8%), including hypertension (56.1%), heart disease (20.7%), diabetes (18.3%), cerebrovascular disease (12.2%), and cancer (7.3%). Respiratory failure remained the leading cause of death (69.5%), following by sepsis syndrome/MOF (28.0%), cardiac failure (14.6%), hemorrhage (6.1%), and renal failure (3.7%). Furthermore, respiratory, cardiac, hemorrhage, hepatic, and renal damage were found in 100%, 89%, 80.5%, 78.0%, and 31.7% of patients, respectively. On the admission, lymphopenia (89.2%), neutrophilia (74.3%), and thrombocytopenia (24.3%) were usually observed. Most patients had a high neutrophil-to-lymphocyte ratio of >5 (94.5%), high systemic immune-inflammation index of >500 (89.2%), increased C-reactive protein level (100%), lactate dehydrogenase (93.2%), and D-dimer (97.1%). A high level of IL-6 (>10 pg/ml) was observed in all detected patients. Median time from initial symptom to death was 15 days (IQR 11-20), and a significant association between aspartate aminotransferase (p=0.002), alanine aminotransferase (p=0.037) and time from initial symptom to death were interestingly observed. ConclusionOlder males with comorbidities are more likely to develop severe disease, even die from SARS-CoV-2 infection. Respiratory failure is the main cause of COVID-19, but either virus itself or cytokine release storm mediated damage to other organ including cardiac, renal, hepatic, and hemorrhage should be taken seriously as well. FundingNo founding. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSAs the seventh member of enveloped RNA coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV)-2 causes a cluster of severe respiratory disease which is similar to another two fatal coronavirus infection caused by SARS-CoV and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). Through searching PubMed and the China National knowledge infrastructure databases up to February 20, 2020, no published article focusing on hospitalized dead patients was identified. Added value of this studyWe conducted a single-center investigation involving 82 hospitalized death patients with COVID-19 and focused on their epidemiological and clinical characteristics. 66 of 82 (80.5%) of patients were older than 60 years and the median age was 72.5 years. The bulk of death cases had comorbidity (76.8%). Respiratory failure remained the leading cause of death, following by sepsis syndrome/MOF, cardiac failure, hemorrhage, and renal failure. Most patients had a high neutrophil-to-lymphocyte ratio, high systemic immune-inflammation index, and increased levels of proinflammatory cytokines. Implications of all the available evidenceSARS-CoV-2 causes a cluster of severe respiratory illness which is similar to another two fatal coronavirus infection caused by SARS-CoV and MERS-CoV. Death is more likely to occur in older male patients with comorbidity. Infected patients might develop acute respiratory distress and respiratory failure which was the leading cause of death, but damages of other organs and systems, including cardiac, hemorrhage, hepatic, and renal also contribute to the death. These damages might be attributable to indirect cytokines storm initiated by immune system and direct attack from SARS-CoV-2 itself.

Introduction and reflections of the British pediatrician training model / 中华医学教育探索杂志

This paper introduces pediatrician training model in Britain, from medical students to consults, including its step-by-step training methods, multi angle multi-level evaluation methods, and em-phasis on the professionism and clinical competence. Through the comparison of the current pediatrician training model in China, this paper provides a reference for Chinese pediatrician training model in future.

Fourth branchial pouch sinus of children: from diagnosis to techniques and technology of surgical operation / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To clarify the correct diagnostic methods of FBPS of children, and to explore techniques and technology of surgical operation aim to complete excision of sinus tract and preservation of the recurrent laryngeal nerve through analyzing the clinical characteristics and the characteristics of open neck surgery in FBPS of children.@*METHOD@#Clinical materials of 6 children FBPS with internal pyriform sinus were retrospectively analyzed, and literatures were studied to explore the appropriate surgical management of children FBPS; lesions of 6 patients were completely dissected by open neck surgery with the help of di-direction catheterization revealing the tract of fistula, and the openings of the fistula to pyriform apex were cauterized by monopolar coagulation at the end of the procedure; all 6 cases were with systematic endoscopic follow-up.@*RESULT@#All cases of 6 children patients were cured by open neck surgery, no recurrence of clinical symptoms were observed during a mean follow-up of 14 months (1-3 years); 2 cases were diagnosed with an "anatomical" relapse (persistence of the sinus tract orifice without clinical symptoms) at the follow-up endoscopy(at 3 and 4 months after surgery); all 6 cases had no complication of laryngeal paralysis.@*CONCLUSION@#The children patients presenting recurrent acute suppurative thyroiditis and deep neck abscess of anterior area in the lower part of neck, especially locating left neck, should be considered as the diagnosis of FBPS. also the same as confirmed by enhanced neck CT scan and direct laryngoscopy. Patients with identification of internal pyriform sinus and Betz fold by direct laryngoscopy, and with identification of fistula which passes through the cricothyroid membrane beneath the superior laryngeal nerve can be confirmed FBPS. Completely dissection of sinus tract by open neck surgery was the effective management of children FBPS and di direction catheterization aids to reveal and identify the tract of fistula. Resection of the posterior part of the thyroid cartilage ala can be useful to aid exposure and preservation of the recurrent laryngeal nerve; but co-excision of a portion of the upper of the thyroid gland aids to the entire dissection of lesions. In addition, cauterizing the opening of the fistula to pyriform apex may be useful to obliterate the internal opening of pyriform sinus.

The protective effect of APPL1 on high glucose or cytokines-induced pancreatic β-cell apoptosis and dysfunction / 中华内分泌代谢杂志

Objective To determine the role of APPL1,an adaptor protein,played in pancreatic β-cell.Methods APPL1 was overexpressed in INS-1 cells with adenovirus encoding APPL1.Western blot was conducted to measure protein cxprcssion.Propidium iodide/Hoechst staining was used to determine the cell apoptosis.Insulin secretion was measured by ELISA.Results Exposure of INS-1 cells to 20 mmol/L glucose or 30U/ml interleukin-1 β plus 20 ng/ml TNF-α 48 h induced β-cell apoptosis (P＜0.01) and impaired 2 h glucosestimulated insulin secretion (P＜ 0.01).Overexpression of APPL1 in INS-1 decreased cell apoptosis by 34.16％-42.79％ (P＜0.01) and increased glucose-induced insulin secretion by 1.39-2.20 folds compared with control groups (P＜0.05).Conclusion APPL1 decreases β-cell apoptosis and increases glucose-stimulated insulin secretion,and thus protects β-cell against high glucose or cytokines-induced dysfunction.

Clinical research for treatment of angina with autologous bone marrow mononuclear cell transplantation / 中国医师进修杂志

Objective To evaluate the safety and efficacy of transplantation of autologous bone marrow mononuclear cell (BMMNC) for angina.Methods Fifteen patients who had suffered from unstable angina were selected to receive intraeoronary transplantation immediately following percutaneous coronary intervention (PCI) with BMMNC (BMMNC group).Sixteen patients who had suffered from unstable angina only received treatment of regular medicine and PCI (non-BMMNC group).Two-D echocardiography,singlephoton emission computed tomography (SPECT) imaging and Holter monitoring electrocardiogram were checked up before and 6 months after the procedure.The complications of myocardial infarction,arrhythmia etc,efficacy for angina were evaluated during the procedure and 3,6 months after the procedure.Results The intracoronary injection of BMMNC did not result in myocardial infarction and arrhythmia during the transplantation.Efficacy parameters including nitroglycerine usage per week,exercise time 3 months after the procedure showed that BMMNC group were better than non-BMMNC group (P <0.05).Efficacy parameters including angina frequency per week,nitroglycerine usage per week,exercise time,and Canadian Cardiovascular Society class 6 months after the procedure showed that BMMNC group were better than nonBMMNC group[(12.6 ± 9.3) times/week vs.(18.0 ± 16.3) times/week,(-4.1 ± 14.7) mg/week vs.(4.8 ± 37.9)mg/week,(2.5±1.3)min vs.(2.0 ± 2.1) min, (-1.4 ± 1.0) grades vs.(-0.8 ± 1.7) grades](P＜0.05).Conclusion Intracoronary transplantation of autologous BMMNC is safe and efficient for angina.

Pharmacokinetics of cantide, an antisense oligonucleotide, and its metabolites in rhesus monkeys / 药学学报

To study the pharmacokinetics of cantide, an antisense oligonucleotide, and its metabolites after iv gtt administration in rhesus monkeys, a dual solid phase extraction pretreatment method coupling with non-gel sieving capillary electrophoresis analysis method was used for determination of cantide and its metabolites in plasma and their pharmacokinetic parameters were calculated. The pharmacokinetic behavior of cantide and its metabolites (M1 and M2) after iv gtt administration (8, 16 and 24 mg kg(-1)) in rhesus monkeys were investigated. After iv gtt administration of cantide to rhesus monkeys, cantide in plasma was eliminated rapidly and the terminal elimination half-life (t1/2) was 57.91-77.97 min, the correlation coefficients (r) to the dose of Cmax AUC(o-inf) and AUC(0-t) of the prototype was 0.9918, 0.9568 and 0.9773, respectively. The metabolites of cantide reached the Cmax following cantide immediately and the Cmax of metabolites were lower than that of the prototype. The CL(S) of cantide and its metabolites (M1 and M2) were 1.60-2.19, 5.92-8.58 and 6.07-8.78 mL min(-1) kg(-1), respectively. So, it is concluded that the Cmax of cantide and its metabolites increased with the dose, which is the same as their AUC(0-inf) and AUC(0-t). The CL(S) of metabolites were higher than that of the prototype. The MRT and t1/2 of metabolites in the high dose group increased obviously.

Repair potential of heat-treated rat bone marrow mesenchymal stem cells in infarcted myocardium / 中华器官移植杂志

Objective To study the effects of heat shock treatment of rat bone marrow mesenehymal stem cells(MSCs),the apoptosis ratio of treated-cells under low serum condition and the treated-cells transplantation on left ventricular function in rats with myocardiaIinfarction.Methods MSC8 were heat-treated under 42℃for 30 min,then the heat shock protein-70(HSP-70)was detected bv Western blot.The apoptosis ratio of heat-treated MSCs under low serum condition was tested by Annexin kit.The treated-MSCs labeled with Dil were transplanted into infarcted myocardium and 8 weeks later,the cardiac function of rats in each group was evaluated by echocardiography and cardiac catheterization.Results The immunophenotype of heat-treated MSCs did not vary,Western blot confirmed a higher level expression of HSP-70 in the treated-MSCs group as compared with that in the control group.The early apoptosis ratio was lower in treated-MSCs measured by flow cytometry with annexin staining than that of MSCs when cultured with low serum medium.After 8 weeks,LVEF,LVSP,+dp/dtmax,and-dp/dtmax were significantly higher,and the LVEDP was significantly lowar in heat-treated MSCs transplantation group than that in the control group.Conclusions Heat shock pretreatment of MSCs enhances the tolerance of MSCs to low serum medium,whereas does not lcad to the change of the cell immunophenotype.Transplantation of heattreated MSCs might improve the cardiac function in a rat myocardialinfarction model.

Effects of Huoxue Qianyang Formula on expressions of proto-oncogenes c-fos and c-myc in spontaneous hypertensive rats with ventricular hypertrophy / 中西医结合学报

OBJECTIVE: To explore the possible mechanism of Huoxue Qianyang Formula (HXQYF), a compound traditional Chinese herbal medicine, in reversing the left ventricular hypertrophy (LVH) of spontaneous hypertensive rats (SHRs) by analyzing the expressions of mRNAs and proteins of proto-oncogenes c-fos and c-myc in left ventricular muscle. METHODS: The experimental study was carried out in SHRs, the sex- and age-matched Wistar-Kyoto (WKY) rats were served as normal control (n=5, normal saline 10 ml/kg daily). Twenty-five SHRs were randomly divided into five groups: untreated group (n=5, normal saline 10 ml/kg daily), high-dose HXQYF-treated group (n=5, 0.84 g/ml HXQYF, 10 ml/kg daily), medium-dose HXQYF-treated group (n=5, 0.42 g/ml HXQYF, 10 ml/kg daily), low-dose HXQYF-treated group (n=5, 0.21 g/ml HXQYF, 10 ml/kg daily) and cilazapril-treated group (n=5, 1 mg/ml cilazapril, 10 ml/kg daily). The drugs were intragastrically administered once daily for 14 weeks. The expressions of mRNAs and proteins of proto-oncogenes c-fos and c-myc in left ventricular muscle were detected separately by in situ hybridization histochemical method and immunohistochemical method. RESULTS: Compared with the normal control group, the expressions of mRNAs and proteins of proto-oncogenes c-fos and c-myc in left ventricular muscle were significantly increased in untreated group (P<0.01). After treatment, the expressions of c-fos and c-myc mRNAs in left ventricular muscle in HXQYF-treated groups were significantly down-regulated as compared with those of the untreated group (P<0.05). The expressions of c-myc protein were also significantly decreased in high- and medium-dose HXQYF-treated groups as compared with the untreated group (P<0.05), but it had no significant effects in protein expression of c-fos in the three HXQYF-treated groups. CONCLUSION: HXQYF can inhibit the expression of c-myc in ventricular hypertrophy tissue, which may be the mechanism in treating LVH of hypertension.

Evaluation of regional left ventricular diastolic function in patients with myocardial infarction by the curve of ventricular wall motion / 中国医师进修杂志

Objective To detect the curve of ventricular wall motion features of regional wall abnor-malities in patients with coronary artery disease during each diastolic period, and its possibility to evaluate re-gional left ventricular diastolic function. Methods Fifty-four patients with anterior myocardial infarction (MI group) and 78 normal subjects (NOR group) underwent Doppler tissue imaging, which were performed in 2-chamber-view by the tracing technology of ventrieular wall motion synchronously. Isovolumic relax-ation period, rapid flow period, slow filling phase, atrial systole period were measured. Results In NOR group, distant value of 76 patients (97.44%) showed a gradually decreasing positive value from the apex to middle and from middle to base of left ventricle. While in MI group, such rules disappeared, 52 patients (96.30%) were negative in infarction area. In isevolumic relaxation period in NOR group, 76 patients (97.44%) showed palliative downward wave, but in MI group, 27 patients (50.00%) showed palliative downward wave(P<0.05). In rapid flow period, both NOR and MI group showed downward and steep waves,but in MI group, the gradient rule disappeared and distance of ventricular wall motion was negative in infarc-tion area. In slow filling phase, compared with NOR group, which had horizontal wave, MI group had no obvi-ously horizontal waves. Conclusion Regional myocardial ischemia and infarction can cause significant ab-normalities of regional ventricular wall motion in active diastolic phase, and it can be evaluated quantitatively and synchronously with high sensitivity by the curve of ventricular wall motion which has the potential value in regional left ventricular diastolic function.

Evaluation of Regional Left Ventricular Cardiocyte Viability and Diastolic Function by Strain Curves in Patients with Myocardial Infarction / 中国康复理论与实践

@#Objective To detect the strain features of regional wall abnormalities in patients with coronary artery disease during each diastolic period, and its possibility to evaluate regional left ventricular cardiocyte viability and diastolic function.Methods 54 patients with anterior myocardial infarction (MI group) and 78 normal subjects (NOR group) underwent Doppler tissue imaging, which were performed in 2-chamber-view by strain curves synchronously.Results In the NOR group, strain value of 66 cases (84.62%) showed an gradually increasing negative value from the apex to base to middle of left ventricle, while in the MI group, there were 9 cases (16.67%) with such a trend. IR phase: in the NOR group, 564 segments (90.38%) were upward wave bands, but in the MI group, there were 123 segments (28.47%) having such waves ( P<0.05). RF phase: in the NOR group, 576 segments (92.31%) were upward and steep wave bands, but in the MI group, the number of upward waves were obviously less (102 segments,23.61%) ( P<0.01). SF period: compared with the NOR group, which was horizontal, the MI group had upward wave bands ( P<0.05).Conclusion Regional myocardial ischemia and infarction can cause significant regional diastolic wall abnormalities of strain value in active diastolic phase. Regional diastolic wall motion abnormalities can be evaluated quantitatively and synchronously with high sensitivity by strain curve which has the potential value in cardiocyte viability and diastolic function.