Kinetic Characteristics of Neutralizing Antibody Responses Vary among Patients with COVID-19 / 生物医学与环境科学（英文）

Objective@#The coronavirus disease 2019 (COVID-19) pandemic continues to present a major challenge to public health. Vaccine development requires an understanding of the kinetics of neutralizing antibody (NAb) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).@*Methods@#In total, 605 serum samples from 125 COVID-19 patients (from January 1 to March 14, 2020) varying in age, sex, severity of symptoms, and presence of underlying diseases were collected, and antibody titers were measured using a micro-neutralization assay with wild-type SARS-CoV-2.@*Results@#NAbs were detectable approximately 10 days post-onset (dpo) of symptoms and peaked at approximately 20 dpo. The NAb levels were slightly higher in young males and severe cases, while no significant difference was observed for the other classifications. In follow-up cases, the NAb titer had increased or stabilized in 18 cases, whereas it had decreased in 26 cases, and in one case NAbs were undetectable at the end of our observation. Although a decreasing trend in NAb titer was observed in many cases, the NAb level was generally still protective.@*Conclusion@#We demonstrated that NAb levels vary among all categories of COVID-19 patients. Long-term studies are needed to determine the longevity and protective efficiency of NAbs induced by SARS-CoV-2.

Initial implantation experience and short-term follow-up results of implanting leadless intracardiac transcatheter pacing system / 中华心血管病杂志

Objective: To explore the utility and safety of leadless intracardiac transcatheter pacing system. Methods: The study was a prospective observational study. Patients underwent Micra transcatheter pacing system in Beijing Anzhen hospital from December 2019 to January 2020 were enrolled. The baseline characteristics, platelet count, hemoglobin, anticoagulation and/or antiplatelet therapy, mean procedural time, average fluoroscopy time, number of deployment and electrical parameters (threshold, R-wave amplitude, impedance) were recorded. Ultrasonography of bilateral femoral and iliac veins was performed in all patients. Patients were followed including access site complication, adverse event and device evaluation at implant, hospital discharge, 1 and 3 months post-implant. R-wave≥5 mV, impedance between 400 and 1 500 Ω and threshold increase≤1.5 V than implant is considered a stable parameter. Femoral access site complications included hematoma, hemorrhage, pseudoaneurysm, and arteriovenous fistula. Adverse events included dislodgement, cardiac effusion/perforation and infection. Left ventricular end diastolic diameter and ejection fraction before and at 1 month after implant were reported. Results: Five patients were enrolled and pacemaker implantation was successful in all 5 patients. Patients were all males and the average age was (78.4±8.4) years. 2 patients received aspirin and clopidogrel therapy, 1 patient suffered from anemia and thrombocytopenia occurred in 1 patient. No stenosis, occlusion and vascular malformation of bilateral femoral and iliac veins was observed. The mean implant time was (39.6±1.7) minutes. The average fluoroscopy time was (9.2±1.3) minutes and the number of deployment was (1.40±0.55). Electrical parameters(threshold, R-Wave amplitude and impedance) were as follows: (0.40±0.10) V/0.24 ms, (10.80±3.72) mV and (822.00±162.23) Ω at implant; (0.45±0.07) V/0.24 ms, (13.04±2.41) mV, and (748.0±91.5) Ω at discharge, (0.40±0.06) V/0.24 ms, (14.26±4.11) mV, and (700.0±91.7) Ω at 1 month post-implant and (0.39±0.05) V/0.24 ms, 14.40±3.97 mV, and (682.0±96.0) Ω at 3 months post-implant, respectively. Threshold increase was ≤1.5 V compared to that during implantation, electrical parameters were acceptable and stable. There was no difference in LVEDD [(44.00±5.24) mm vs. (44.00±5.34) mm,P=1.000] and EF [(62.00±3.39)% vs. (62.20±3.56)%, P=0.861] before and 1 month post-implant. No incidence of access site complications, cardiac effusion/perforation, dislodgment or infections occurred during the 3 months. Conclusions: The leadless transcatheter pacemaker implantation performed in our study archived a high implant success rate and favorable safety profile as well as associated with low and stable pacing thresholds. The long-term safety and benefit of leadless pacemaker need to be evaluated in future clinical studies.

Elevated Levels of Very Low-density Lipoprotein Cholesterol Independently Associated with In-stent Restenosis in Diabetic Patients after Drug-eluting Stent Implantation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>High rate of in-stent restenosis (ISR) remained an unsolved clinical problem in clinical practice, especially among patients with diabetes mellitus (DM). Diabetic patients often had hypertriglyceridemia with elevated levels of very low-density lipoprotein cholesterol (VLDL-C). Increasing evidence suggested that VLDL-C was known as a significant risk factor for atherosclerosis and had been recommended as a treatment target by current dyslipidemia guidelines. However, the role of VLDL-C in the occurrence and development of ISR in coronary artery disease (CAD) patients with DM had not been studied. The aim of this study was to evaluate the association between the elevated levels of VLDL-C and the risk of ISR in CAD patients with DM.</p><p><b>METHODS</b>A total of 1390 diabetic patients, who underwent coronary drug-eluting stent (DES) implantation at Beijing Anzhen Hospital and followed up by angiography within 6-24 months, were consecutively enrolled. Patients' demographic and clinical characteristics, including age, gender, CAD risk factors, family history, life style, medical history, and coronary angiographic information, were collected carefully at baseline percutaneous coronary intervention and follow-up angiography. Multivariate Cox's proportional hazards regression modeling using the step-wise method (entry, 0.05; removal, 0.05) was used to determine the independent risk associated with ISR in diabetic patients.</p><p><b>RESULTS</b>Finally, 1206 of patients were included in this study. ISR occurred in 132/1206 diabetic patients (10.9%) by follow-up angiography. Patients with ISR had elevated median serum VLDL-C levels compared with those without ISR (0.65 mmol/L vs. 0.52 mmol/L, P = 0.030). The multivariate regression analysis showed that VLDL-C was significantly associated with the risk of ISR in diabetic CAD patients (hazard ratio [HR] = 1.15, 95% confidence interval [CI]: 1.03-1.29, P = 0.017). The HR for the risk of ISR associated with VLDL-C level ≥0.52 mmol/L was 3.01 (95% CI: 1.24-7.34, P = 0.015).</p><p><b>CONCLUSION</b>The elevated level of serum VLDL-C was a significant and independent risk factor for ISR in diabetic CAD patients after coronary DES implantation.</p>

Heart rate distribution and predictors of resting heart rate after initiation of beta-blocker treatment in patients with coronary artery disease: REsults of Sympathetic Evaluation And Research of China (RESEARCH) study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The importance of heart rate as secondary prevention strategies for patients with coronary artery disease (CAD) is emphasized by multiple guidelines. However, limited information is available on the heart rate distribution and the change patterns of resting heart rate when initiating beta-blocker therapy among Chinese patients with CAD.</p><p><b>METHODS</b>The REsults of Sympathetic Evaluation And Research of China (RESEARCH) study is a multi-centre, prospective, observational study involving 147 centers in 23 cities across China. All eligible beta-blocker naive patients were prescribed with metroprolol succinate. Initial dosage and target heart rate were selected at the discretion of their physicians in charge according to their usual institutional practice. The heart rate distribution and the change patterns of resting heart rate after initiation of beta-blocker therapy were observed.</p><p><b>RESULTS</b>The majority of patients (63.6%) were prescribed with 47.5 mg metroprolol succinate. At baseline, there were only 17.4% of patients whose heart rate was less than 70 beats per minute, and the proportion reached 42.5% and 79.1%, one month and two months after initiation of beta-blockers, respectively. Multivariate linear regression analysis showed that baseline heart rate (B = 0.900, SE = 0.006, t = 141.787, P < 0.0001) and the dosage (B = -0.007, SE = 0.002, t = -3.242, P = 0.001) were independent predictors of resting heart rate 2 months after beta-blocker therapy.</p><p><b>CONCLUSIONS</b>Resting heart rate is not optimally controlled in a broadly representative cohort of Chinese outpatients with CAD even after initiation of β-blocker therapy, and baseline heart rate and the dosage of beta-blocker are both independent predictors of resting heart rate after β-blocker therapy.</p>

Hepatitis B virus (HBV) mutation in enhancer I (HBV Enh I)/X-promoter and the relationship between chronic HBV-related disease spectrum / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>To investigate the hepatitis B virus (HBV) mutation in the Enhancer I (HBV Enh I)/X-promoter and to analysis the relationship between chronic HBV-related disease spectrum.</p><p><b>METHODS</b>275 patients were enrolled in this study, including 100 cases of chronic hepatitis B (CHB), 74 cases of liver cirrhosis (LC), 101 cases of hepatocellular carcinoma (HCC), grouping by different HBV genotypes, using semi-nested PCR amplification of HBV Enh I/X-promoter and sequencing DNA, the mutations were determined by alignment to HBV reference sequence, the data was compared by chi2 test and analyzed by multivariate logistic regression.</p><p><b>RESULTS</b>(1) Genotyping results: 61.48% (158/257) were infected with HBV genotype B, including 70 cases of CHB, 36 cases of LC and 52 cases of HCC; 38.52% (117/257) were infected with HBV genotype C, including 30 cases of CHB, 38 cases of LC and 49 cases of HCC. (2) In the patients were infected with HBV genotype B, A1123Y mutation in LC was significantly higher than in CHB (30.56% vs. 8.58%, chi2 = 8.533, P = 0.005, A = 4.693, 95% CI [1.567-14.056]), HCC was significantly higher than in CHB (28.85% vs. 8.58%, chi2 = 8.607, P = 0.003, A = 4.324,95% CI [1.544-2.109]); A1317G mutation in HCC was significantly higher than in CHB (30.77% vs. 7.14%, chi2 = 11.687, P = 0.001, A = 5.778, 95% CI [1.955-17.076]). In the patients were infected with HBV genotype C, T1323C mutation in HCC was significantly higher than in CHB (30.61% vs. 6.67%, chi2 = 6.318, P = 0.12, A = 6.176, 95% CI [1.301-29.331]). (3) Multivariate regression analyses showed that A1317G (OR = 5.706, 95% CI [1.770-18.837], P = 0.004) and T1323C (A = 5.810, 95% CI [1.114-30.306], P = 0.037) mutation were risk factors for HCC.</p><p><b>CONCLUSION</b>HBV Enh I/X-promoter mutations were associated with the development of LC and HCC, the mutations can help to predict the occurrence of LC and HCC.</p>

Epidemiological analysis of brucellosis in Hebei province from 2006 to 2010 / 中国地方病学杂志

ObjectiveBy analyzing the epidemiological characteristics and trends of brucellosis in Hebei province,provide a scientific basis for the formulation of strategies for effective prevention and control of the disease.MethodsUsing the descriptive epidemiological method,data of the “China information system for disease control and prevention” from 2006 to 2010 were statistically analyzed.ResultsThere were 13 632 reported cases from 2006 to 2010 in Hebei province,no death,the annual incidence rates reported were 3.4068/10 million,3.4851/10 million,4.5701/10 million,4.6045/10 million,and 3.5582/10 million,respectively.Eleven counties throughout the province had reported cases.The cases were found intensively in Zhangjiakou,Chengde,Baoding,Handan and Shijiazhuang,which accounting for 90.02％ (12 271/13 632) of the total cases.The disease was found each month throughout the year,and showed a seasonal cycle with peak period in spring and summer.The disease was most commonly found in 25 - 65 age people,which accounting for 84.57％(11 529/13 632).The incidence in male was higher than that of female,and male to female ratio was about 3.56:1.00.Vocational high risk population was farmers,accounting for 91.15％ of the total cases(12 425/13 632).ConclusionsBrucellosis epidemic in Hebei province is relatively serious,and the epidemic range has expand each year,even highly active in some particular areas.To control the outbreak of brucellosis,departments cooperation between health and animal husbandry should be strengthened; management of source of infection should be strengthened; health education and behavior intervention should be carried out thoroughly and deeply for high-risk groups.

Recombinant lentivirus-mediated gene transfer of NT4-p53(N15)-Ant inhibits the growth of hepatocellular carcinoma cells in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To construct a recombinant lentivirus vector containing fusion gene NT4-p53(N15)-Ant and transfer it into HepG2 cancer cells for gene therapy.</p><p><b>METHODS</b>The gene of p53(N15)-Ant was obtained by T-vector method. After restriction enzyme digestion, the interest gene of p53(N15)-Ant was inserted in pBV220/NT4 vector and fusion gene of NT4-p53(N15)-Ant was subcloned into the plasmid of lentivirus and cotransferred into HEK-293 cells with helper plasmid. The recombinant lentivirus was produced by homologous recombination of the above mentioned two plasmids in HEK-293 cells and its titer was measured by plaque-forming. The expression of LV. NT4-p53-Ant in transfected HepG2 cells was finally confirmed by reverse transcription polymerase chain reaction (RT-PCR) procedure. The effect of LV. NT4-p53(N15)-Ant on HepG2 cells was measured by a colorimetric 3-[4,5-dimethyl thiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The inhibition effect on HepG2 cells of LV. NT4-p53(N15)-Ant and its potential mechanism was detected by light microscopy, electron microscopy, MTT, LDH-release assay and annexin V-PI double staining.</p><p><b>RESULTS</b>The gene of p53(N15)-Ant was confirmed by restriction enzyme digestion and DNA sequencing. High titer of the recombinant lentivirus was obtained by homologous recombination in HEK-293 cell lines (1 x 10(11) pfu/ml), and the expression of NT4-p53(N15)-Ant gene in HepG2 cells was confirmed by RT-PCR. The viability of HepG2 cells was decreased to 83.4%, 46.9% and 33.9%, at 24 h, 48 h and 72 h, respectively, after infection by LV. NT4-p53(N15)-Ant. Compared with the LV. EGFP control group, there were significant differences (P < 0.01). The LDH level in HepG2 cells infected by LV. NT4-p53(N15)-Ant at 48 h, 72 h and 96 h after infection was 682 IU/L, 815 IU/L and 979 IU/L, respectively, significantly increased than that in the LV. EGFP group (P < 0.01), indicating the cell membrane destruction.</p><p><b>CONCLUSION</b>The recombinant lentivirus vector encoding gene NT4-p53(N15)-Ant is successfully constructed in this experiment by molecular cloning and recombination in vitro techniques, and the results suggested that this fusion gene has an anti-tumor effect, which provides the basis for further research on recombinant adenovirus for cancer gene therapy.</p>

Effects of upstream tirofiban versus downstream tirofiban on platelet aggregation and clinical outcomes in patients with high-risk acute coronary syndromes undergoing percutaneous coronary interventions / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the effects of upstream versus downstream application of tirofiban on platelet aggregation and clinical outcomes (major adverse cardiovascular event, MACE) in patients with high-risk non-ST-segment elevation acute coronary syndromes (NSTE-ACS) undergoing percutaneous coronary intervention (PCI).</p><p><b>METHODS</b>From July 2006 to July 2007, 160 high-risk NSTE-ACS patients undergoing PCI were randomized to receive upstream (4-6 h prior PCI) tirofiban and downstream (immediately prior to PCI) tirofiban. Platelet aggregation inhibition was determined at admission, before coronary angiography and after PCI. Incidences of MACE at 1, 3, 7, 30 and 180 days after PCI were compared. The incidences of bleeding complications and thrombocytopenia during tirofiban treatments were recorded.</p><p><b>RESULTS</b>The extent of platelet aggregation inhibition post tirofiban was significantly greater in upstream tirofiban than that in downstream tirofiban group (8% vs. 42%, P<0.05). The incidences of MACE at various time points were similar between the two groups (all P>0.05). Aging, hypertension and type-2 diabetes were independent risk factors of MACE. The incidences of major and minor bleeding complications as well as mild thrombocytopenia during tirofiban treatments were similar between the two groups (2.5% vs. 1.3%, 1.3% vs. 1.3% and 1.3% vs. 1.3%, respectively; all P>0.05).</p><p><b>CONCLUSION</b>On top of aspirin and clopidogrel, upstream application of tirofiban is associated with increased platelet aggregation inhibition but the incidences of MACE up to 180 days post tirofiban are similar in the upstream and downstream tirofiban treated patients with high-risk NSTE-ACS after PCI. Aging, hypertension and type-2 diabetes were independent risk factors of MACE in these patients.</p>

Effects of upstream tirofiban versus downstream tirofiban on myocardial damage and 180-day clinical outcomes in high-risk acute coronary syndromes patients undergoing percutaneous coronary interventions / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>For patients with moderate to high-risk acute coronary syndromes (ACS) who undergo early, invasive treatment strategies, current guidelines recommend the usage of glycoprotein (GP) IIb/IIIa inhibitors as an upstream treatment for a coronary care unit or as an downstream provisional treatment for selected patients who are undergoing percutaneous coronary intervention (PCI). The relative advantage of either strategy is unknown. The purpose of this study was to evaluate the effects of upstream tirofiban versus the effects of downstream tirofiban on myocardial damage and 180-day major adverse cardiovascular events (MACE) after PCI in high-risk non-ST-segment elevation ACS (NSTE-ACS) undergoing PCI.</p><p><b>METHODS</b>From July 2006 to July 2007, 160 high-risk NSTE-ACS undergoing PCI were randomized to receive upstream (within 4 - 6 hours before coronary angiography) tirofiban or downstream (the guidewire crossing the lesion) tirofiban, to evaluate the extent of myocardial damage after PCI by quantitatively and qualitatively analyzing the value of cardiac troponin I (cTnI) as well as MB isoenzyme of creatine kinase (CK-MB) before and after PCI. The incidences of 24-hour, 3-day, 7-day, 30-day and 180-day MACE after PCI were followed up and the rates of bleeding complications and thrombocytopenia during tirofiban administration were recorded.</p><p><b>RESULTS</b>The peak release and cumulative release of cTnI levels within 48 hours after PCI were significantly lower with upstream tirofiban than downstream tirofiban (0.45 vs 0.63 and 0.32 vs 0.43, respectively; P < 0.05). Post-procedural cTnI elevation within 48 hours was significantly less frequent among patients who received the upstream tirofiban than those who received the downstream tirofiban (66.3% vs 87.5%, P < 0.05). The peak and cumulative release of CK-MB levels as well as post-procedural CK-MB elevation within 48 hours after PCI were not significantly different between the two groups (16 vs 14 , 5 vs 3 and 26.3% vs 36.3%, respectively; P > 0.05). The incidences of 24-hour, 3-day, and 7-day MACE after PCI were the same between the two groups (0 vs 0, 0 vs 0 and 1.25% vs 1.25%, respectively). Although the incidences of 30-day and 180-day MACE after PCI were not statistically different between the two groups, the incidences were consistently lower with upstream tirofiban (3.75% vs 6.25% and 12.99% vs 16.67%; P > 0.05). Aging (OR = 1.164, P < 0.001), hypertension (OR = 4.165, P = 0.037) and type 2 diabetes (OR = 13.628, P < 0.001) were independent risk factors of MACE. The timing of administrating the tirofiban (OR = 2.416, P = 0.153) plays an extensive role in the incidence of MACE. The incidences of major and minor bleeding complications as well as mild thrombocytopenia during the administration of tirofiban were similar between the two groups (2.50% vs 1.25%, 1.25% vs 1.25% and 1.25% vs 1.25%, respectively; P > 0.05).</p><p><b>CONCLUSIONS</b>Based on the pretreatment with aspirin and clopidogrel, upstream tirofiban was associated with attenuated minor myocardial damage and the tendency of reducing incidences of 180-day MACE after PCI among high-risk NSTE-ACS patients undergoing PCI. Aging, hypertension and type 2 diabetes were independent risk factors of MACE in high-risk NSTE-ACS patients undergoing PCI associated with tirofiban.</p>

Epidemiological survey of primary palmar hyperhidrosis in adolescents / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Despite recent advances in recognition and treatment of primary palmar hyperhidrosis (PPH), the epidemiological survey has hardly been conducted. The aim of this study was to investigate the prevalence and epidemiological characteristics of primary PPH among adolescents in three cities of southeast China.</p><p><b>METHODS</b>Stratified-cluster sampling was carried out and cross-sectional epidemiological survey by questionnaire was applied among 33 000 college and high school students.</p><p><b>RESULTS</b>The prevalence rate of PPH was 4.36% affecting both sexes equally. Prevalence rate of severe PPH was 0.27%. The average age of onset was 12.27 +/- 2.12 years. The peak age of onset was 6 - 16 years, accounting for 97.2% of PPH population. Positive family history was found in 17.9% PPH cases. Besides palms, axillae and soles can be also affected.</p><p><b>CONCLUSIONS</b>PPH affects a larger group of individual than previously reported. More measures should be taken to enhance the recognition, diagnosis, and treatment of PPH.</p>

Expression and clinical significance of matrix metalloproteinase in gastric stromal tumor / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the expression and clinical significance of matrix metalloproteinase (MMP) in gastric stromal tumor (GST).</p><p><b>METHODS</b>MMP-2 and MMP-9 expression were determined by immunohistochemistry in tumor tissues in 44 patients with GST, and their relationship with clinicopathologic factors of the neoplasm was also investigated.</p><p><b>RESULTS</b>MMP-2 and MMP-9 were expressed in the cytoplasm in 84.1% (37/44) and 81.8% (36/44) of tumors, respectively. The positive rates of MMP-2 and MMP-9 increased significantly in parallel to the increase in tumor malignancy (P < 0.05) and associated with pattern of tumor growth, tumor size, and centre necrosis (P < 0.05). In addition, there was a statistically significant positive correlation between the expression of the two markers in GST (r = 0.6523, P < 0.05). Furthermore, the 5-year postoperative survival rates of patients with positive expressions of MMP-2 and MMP-9 were significantly lower than those of patients with negative expressions of the two markers (P < 0.05).</p><p><b>CONCLUSION</b>Over expression of MMP-2 and MMP-9 can be served as objective markers to judge the malignant degree and, to predict the prognosis of patients with GST.</p>

Adenovirus-mediated killing of hepatocellular carcinoma HepG2 cells by heterogeneous fusion gene NT4p53(N15)Ant / 南方医科大学学报

<p><b>UNLABELLED</b>OBJECTIVE To construct a recombinant adenovirus Ad.NT4p53(N15)Ant and explore its cytotoxic effect against hepatocellular carcinoma HepG2 cells in vitro.</p><p><b>METHODS</b>The recombinant adenovirus containing the fusion gene of neurotrophin 4 (NT4)signal peptide, N-terminal residues (12-26) of p53 and 17 amino acid Drosophila homeobox protein Antennapedia (Ant) was constructed by gene cloning protocol. The effect of this fusion gene on HepG2 cells was evaluated by MTT assay, PI staining and flow cytometry.</p><p><b>RESULTS</b>The fusion gene Ad.NT4p53(N15)Ant was successfully constructed, as verified by restriction endonuclease digestion and PCR. Ad.NT4p53(N15)Ant could strongly suppress the growth of HepG2 cells (with a growth inhibition rate of 63.3% 48 h after infection) without affecting NIH-3T3 cells. Flow cytometry showed that Ad.NT4p53(N15)Ant could induce obvious apoptosis of HepG2 cells.</p><p><b>CONCLUSION</b>The recombinant adenovirus containing NT4p53(N15)Ant fusion gene can inhibit the growth the of HepG2 cells in vitro partially by inducing cell apoptosis.</p>