Use of Thread-hanging Microwave Antenna to Assist in Precise Puncture of Lung Nodule and Influencing Factors / 肿瘤防治研究

Objective To explore a precise method with a microwave antenna for puncture of pulmonary nodules and analyze phenomena that affect the puncture results. Methods Clinical data of 107 cases with solitary malignant pulmonary nodules were collected, and the mean length of pulmonary nodules was 13.6±0.6 mm in CT axial position. A thread-hanging method was used to assist the puncture of pulmonary nodules. The procedure was successful when the needle was not withdrawn and inserted into the central region of the nodule. The success rate and complications of the pulmonary procedure were recorded. The incidence of the following phenomena were also documented: needle coercing, needle slipping, needle tip pushing, pulmonary nodule prolapsing, radial nodule deformation, nodular masking, and radial movement distance of needle tip. Results In all of 107 cases evaluated, the antenna puncture was successful in 101 cases (94.4%) but failed in 6 cases (5.6%). Pneumothorax and pulmonary hemorrhage occurred in 23 (21.5%) and 19 cases (17.8%), respectively. The following phenomena occurred: needle coercing in 9 cases (8.4%), needle slipping in 6 cases (5.6%), needle tip pushing in 19 cases (17.8%), pulmonary nodule prolapsing in 15 cases (14%), radial nodule deformation in 14 cases (13.1%), and nodular masking in 5 cases (4.7%). The mean radial adjusting distance of needle tip was 0.7±0.4 cm. Conclusion The thread-hanging method can assist in the accurate puncture of microwave antenna for pulmonary nodules. We should focus and deal with phenomena that may occur and affect the result of puncture.

An Update on Impacts of Epigallocatechin Gallate Co-administration in Modulating Pharmacokinetics of Statins, Calcium Channel Blockers, and Beta-blockers.

Brewed green tea, green tea extract, and its primary active compound, epigallocatechin gallate, may interact with drugs and alter the drug's therapeutic effectiveness, ultimately leading to therapeutic failure or drug overdose. Several isolated reports have claimed that epigallocatechin gallate is the main active ingredient that causes these effects. While a few studies aimed to uncover evidence of epigallocatechin gallate-drug interactions, no study has thoroughly and collectively reviewed them. Epigallocatechin gallate is a potential cardioprotective agent used by many patients with cardiovascular diseases as a complementary medicine alongside conventional modern medications, either with or without the knowledge of their physicians. Therefore, this review focuses on the impact of concurrent epigallocatechin gallate supplementation on pharmacokinetics and pharmacodynamics of several commonly used cardiovascular drugs (statins, beta-blockers, and calcium channel blockers). The PubMed index was searched for key words related to this review, without year limit, and the results were analyzed for interactions of cardiovascular drugs with epigallocatechin gallate. This review concludes that epigallocatechin gallate increases systemic circulation of several statins (simvastatin, fluvastatin, rosuvastatin) and calcium channel blockers (verapamil), but decreases the bioavailability of beta-blockers (nadolol, atenolol, bisoprolol). Further studies on its clinical significance in affecting drug efficacy are required.

Prevention and treatment of postoperative complications of esophageal cancer / 中华胃肠外科杂志

Surgery is the primary treatment for esophageal cancer, but the postoperative complication rate remains high. Therefore, it is important to prevent and manage postoperative complications to improve prognosis. Common perioperative complications of esophageal cancer include anastomotic leakage, gastrointestinal tracheal fistula, chylothorax, and recurrent laryngeal nerve injury. Respiratory and circulatory system complications, such as pulmonary infection, are also quite common. These surgery-related complications are independent risk factors for cardiopulmonary complications. Complications, such as long-term anastomotic stenosis, gastroesophageal reflux, and malnutrition are also common after esophageal cancer surgery. By effectively reducing postoperative complications, the morbidity and mortality of patients can be reduced, and their quality of life can be improved.

Value of postoperative radiotherapy and analysis of prognostic factors in early-stage neuroendocrine carcinoma of cervix / 中华妇产科杂志

Objective: To evaluate the effect of postoperative radiotherapy and high-risk pathological factors on the prognosis of early-stage neuroendocrine carcinoma of cervix (NECC). Methods: A single-center retrospective cohort study of early-stage NECC in Peking Union Medical College Hospital from January 2011 to April 2022 were enrolled. The patients were treated with radical hysterectomy±adjuvant treatment. They were divided into postoperative non-radiation group and postoperative radiation group. The possible postoperative recurrence risk factors identified by univariate analysis were assessed using multivariate logistic regression. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Sixty-two cases were included in the study, including 33 cases in postoperative non-radiation group and 29 cases in postoperative radiation group. (2) The median follow-up time was 37 months (ranged 12-116 months), with 23 cases (37%) experienced recurrences. There were 7 cases (11%) pelvic recurrences and 20 cases (32%) distant recurrences, in which including 4 cases (6%) both pelvic and distant recurrences. Compared with postoperative non-radiation group, the postoperative radiation group had a lower pelvic recurrence rate (18% vs 3%; P=0.074) but without statistic difference, a slightly elevated distant recurrence rate (24% vs 41%; P=0.150) and overall recurrence rate (33% vs 41%; P=0.513) without statistically significances. Univariate analysis showed that lymph-vascular space invasion and the depth of cervical stromal invasion≥1/2 were risk factors for postoperative recurrence (all P<0.05). Multivariate analysis showed lymph-vascular space invasion was an independent predictor for postoperative recurrence (OR=23.03, 95%CI: 3.55-149.39, P=0.001). (3) During the follow-up period, 18 cases (29%, 18/62) died with tumor, with 10 cases (30%, 10/33) in postoperative non-radiation group and 8 cases (28%, 8/29) in postoperative radiation group, without significant difference (P=0.814). The postoperative 3-year and 5-year survival rate was 79.2%, 60.8%. The depth of cervical stromal invasion≥1/2 was more common in postoperative radiation group (27% vs 64%; P=0.011), and postoperative radiation in such patients showed an extended trend in PFS (32.3 vs 53.9 months) and OS (39.4 vs 73.4 months) but without statistic differences (P=0.704, P=0.371). Compared with postoperative non-radiation group, the postoperative radiation did not improve PFS (54.5 vs 37.3 months; P=0.860) and OS (56.2 vs 62.4 months; P=0.550) in patients with lymph-vascular space invasion. Conclusions: Postoperative radiation in early-stage NECC patients has a trend to reduce pelvic recurrence but not appear to decrease distant recurrence and overall recurrence, and has not improved mortality. For patients with the depth of cervical stromal invasion≥1/2, postoperative radiation has a trend of prolonging OS and PFS but without statistic difference. Lymph-vascular space invasion is an independent predictor for postoperative recurrence, but postoperative radiation in such patients does not seem to have any survival benefits.

Efficacy and safety of tenofovir alafenamide fumarate in treatment of chronic hepatitis B patients aged ≥60 years in Qingdao, China / 临床肝胆病杂志

Objective To investigate the application value of tenofovir alafenamide fumarate (TAF) in elderly patients with chronic hepatitis B (CHB) and its influence on bones and kidneys. Methods A total of 36 CHB patients, aged ≥60 years, who received TAF antiviral therapy in Qingdao Municipal Hospital, The Affiliated Hospital of Qingdao University, Qingdao Sixth People's Hospital, Chengyang People's Hospital, and Jimo People's Hospital from June 2021 to October 2022 were enrolled in this study, and all patients received TAF (25 mg/d) antiviral therapy. Related data were collected at baseline and weeks 24 and 48 of treatment, including virological indicators, biochemical parameters, urinary protein electrophoresis indices, transient elastography (FibroScan), and bone mineral density. Virological indicators included high-sensitivity HBV DNA quantification; biochemical parameters included total bilirubin, direct bilirubin (DBil), indirect bilirubin (IBil), alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, total bile acid (TBA), glucose, blood urea nitrogen, creatinine, estimated glomerular filtration rate, and cystatin C (Cys C); urinary protein electrophoresis indices included urinary β2 microglobulin (β2-MG), urinary retinol (URBP), and urinary α1 microspherin (α1-MG). The paired t -test was used for comparison of normally distributed continuous data before and after treatment, and the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment; the chi-square test or the Fisher's exact test was used for comparison of categorical data. Results A total of 36 CHB patients completed 24 weeks of follow-up. The complete virological response rate after 24 weeks of treatment was higher than that at baseline [83.3% (30/36) vs 77.8% (28/36), χ 2 =0.36, P =0.55], and there were significant reductions in DBil ( t =-2.42, P =0.02) and Cys C ( t =-4.34, P 0.05). Conclusion TAF has a good antiviral effect in CHB patients aged ≥60 years and can help more CHB patients achieve complete virological response, without causing damage to the kidney, and it can also improve bone mineral density and liver fibrosis degree.

Bisphenol A is a carcinogen that induces lipid accumulation, peroxisome proliferator­activated receptor­Î³ expression and liver disease.

Bisphenol (BP) A is an exogenous endocrine disruptor that mimics hormones closely associated with health complications, e.g., obesity and cancers. The present study aimed to evaluate the effects of BPA on human liver cells and tissue. The peroxisome proliferator-activated receptor (PPAR)-γ expression profile across tumour samples and paired normal tissue was first analysed using GEPIA. Subsequently, BPA-treated liver THLE-2 cell viability was evaluated using an MTT assay. Clusterin, PPARα and PPARγ gene expression in BPA-treated THLE-2 cells was assessed using GEPIA before validating the gene expression using real-time PCR and analysing overall survival using TCGA data in GEPIA. Cytoplasmic lipid accumulation was examined in BPA-treated THLE-2 cells using Oil Red O staining, and liver tissue was examined using haematoxylin and eosin staining. Finally, cytochrome P450 (CYP) gene expression was assessed in BPA-treated THLE-2 cells using real-time PCR. PPARγ is likely the primary nuclear receptor protein involved in lipid accumulation in THLE-2 cells following BPA treatment and is associated with liver disease. THLE-2 cells exposed to BPA showed a decrease in viability and lipid accumulation after 48 h treatment. Higher PPARγ gene expression was significantly associated with survival of patients with liver cancer, with an average survival time of <80 months. Haematoxylin and eosin-stained sections showed notable disruption of the liver architecture in tissue exposed to BPA. Downregulated CYP1A1 and CYP1B1 gene expression implied that BPA-treated THLE-2 cells decreased capacity for carcinogen metabolism, while upregulated CYP2S1 gene expression exerted minimal cytotoxicity. The present study revealed that BPA served as a carcinogen, enhanced tumorigenesis susceptibility and may induce other types of liver disease.

Medicolegal aspects of non-rapid eye movement parasomnias

INTRODUCTION@#In a subset of adults with non-rapid eye movement (NREM) parasomnias, clinical variants might be violent in nature and can potentially result in unintentional but considerable harm. As such, there is substantial interest on the forensic ramifications of these sleep behaviours.@*METHODS@#This review examined the diagnostic criteria for parasomnias established in the context of international classification systems; medicolegal case reports; legal frameworks; and court cases in and outside of Singapore, to provide an overview of the implications of NREM parasomnias.@*RESULTS@#Violent or injurious behaviours that occurred in the context of somnambulism, otherwise known as sleepwalking, have challenged traditional legal theories of criminal culpability. Yet little has changed in the application of sleep science to criminal responsibility. In Singapore, the defence of somnambulism has hitherto not been directly raised. Nonetheless, sleep medicine practitioners may increasingly be requested to render their opinions on legal issues pertaining to violent or injurious behaviours allegedly arising during sleep. Although the understanding of NREM parasomnias has improved, there is still a dearth of evidence to support both medical and legal decisions in this area.@*CONCLUSION@#NREM parasomnias come with disquieting legal and forensic implications for adjudicating criminal responsibility. There is a need to critically examine legal perspectives on behaviours occurring during sleep. More reliable empirical studies investigating the pathophysiology of NREM parasomnias can offer clearer diagnostic guidelines and address complex behaviours of NREM that often come with medicolegal implications.

Advantages and disadvantages of transthoracic approach for adenocarcinoma of the esophagogastric junction / 中华胃肠外科杂志

Adenocarcinoma of the esophaogastric junction (AEG) has anatomical characteristics of spanning two organs and anatomical sites. Thoracic surgery and gastrointestinal surgery aim at the safe resection margin of esophagus, the scope of lower mediastinal lymph node dissection and whether transthoracic surgery will increase complications. However, there are great differences and controversies in the surgical approach, surgical method, lymph node dissection and extent of resection of AEG. For Siewert II AEG via abdominal mediastinal approach, due to the limitation of exposure and the difficulty of operation, it is difficult to acquire a satisfactory proximal resection margin, and very difficult to dissect the inferior mediastinal lymph nodes. The transthoracic approach can provide adequate exposure, reduce the difficulty of operation, obtain satisfactory resection margin of esophagus and allow lower mediastinal lymph node dissection, which may bring better prognosis. Although transthoracic approach may increase the incidence of pulmonary infection, the standard development of thoracoscopic technology will overcome the disadvantage of transthoracic approach for Siewert II AEG.

The effects of robotic-assisted versus laparoscopic-assisted radical right hemicolectomy on short-term outcome and long-term prognosis based on propensity score matching / 中华外科杂志

Objective: To compare the short-term and long-term outcomes between robotic-assisted and laparoscopic-assisted radical right hemicolectomy in patients with adenocarcinoma of the right colon. Methods: Retrospective review of a prospectively collected database identified 288 right colon cancer patients who underwent either robotic-assisted (n=57) or laparoscopic-assisted right hemicolectomy (n=231) between October 2014 and October 2020 at Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University. There were 161 males and 127 females, aging (60.3±12.8) years (range: 17 to 86 years). After propensity score matching as 1∶4 between robotic-assisted and laparoscopic-assisted right hemicolectomy, there were 56 cases in robotic group and 176 cases in laparoscipic group. Perioperative outcomes and overall survival were compared between the two groups using t test, Wilcoxon rank sum test, χ2 test, Fisher exact test, Kaplan-Meier method and Log-rank test, respectively. Results: The total operative time was similar between the robotic and laparoscopic group ((206.9±60.7) minutes vs. (219.9±56.3) minutes, t=-1.477, P=0.141). Intraoperative bleeding was less in the robotic group (50 (20) ml vs. 50 (50) ml, Z=-4.591, P<0.01), while the number of lymph nodes retrieved was significantly higher (36.0±10.0 vs. 29.0±10.1, t=4.491, P<0.01). Patients in robotic group experienced significantly shorter hospital stay, shorter time to first flatus, and defecation (t: -2.888, -2.946, -2.328, all P<0.05). Moreover, the overall peri-operative complication rate was similar between robotic and laparoscopic group (17.9% vs. 22.7%, χ²=0.596,P=0.465). The 3-year overall survival were 92.9% and 87.9% respectively and the 3-year disease-free survival rates were 83.1% and 82.6% with no statistical significance between the robotic and laparoscopic group (P>0.05). Conclusions: Compared to laparoscopic-assisted right hemicolectomy, robot-assisted right hemicolectomy could improve some short-term clinical outcomes. The two procedures are both achieving comparable survival.

Immunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine (KCONVAC) in Healthy Adults: Two Randomized, Double-blind, and Placebo-controlled Phase 1/2 Clinical Trials

BackgroundThe significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of a SARS-CoV-2 inactivated vaccine, KCONVAC, in healthy adults. MethodsTwo phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in Chinese healthy adults aged 18 through 59 years. The phase 1 trial was conducted in a manner of dosage escalation. The first 30 participants were randomized in a ratio of 4:1 to receive two doses of either KCONVAC at 5 g per dose or placebo on Day 0 and Day 14, and the second 30 participants were randomized to receive either KCONVAC at 10 g per dose or placebo following the same procedures. The participants in the phase 2 trial were randomized in a ratio of 2:2:1 to receive either KCONVAC at 5 g or 10 g per dose, or placebo on Day 0 and Day 14, or Day 0 and Day 28. In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following each vaccination. Antibody response and cellular response were assayed in the phase 1 trial. In the phase 2 trial, the primary immunogenicity endpoint was the seroconversion and titre of neutralization antibody, and the seroconversion of receptor binding domain (RBD)-IgG 28 days after the second dose. FindingsIn the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-g vaccine (N=24), 10-g vaccine (N=24), or placebo (N=12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-g vaccine (N=100 for 0/14 or 0/28 regimens), 10-g vaccine (N=100 for each regimen), or placebo (N=50 for each regimen). In the phase 1 trial, 13 (54%), 11(46%), and 7 (58%) participants reported at least one adverse event (AE), of whom 10 (42%), 6 (25%), and 6 (50%) participants reported at least one vaccination-related AE after receiving 5-g vaccine, 10-g vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and 9 (18%) participants reported at least one AE, of whom 13 (13%), 17 (17%), and 6 (12%) participants reported at least one vaccination-related AE after receiving 5-g vaccine, 10-g vaccine, or placebo at the regimen of Day 0/14, respectively. Similar results were observed in the three treatment groups of Day 0/28 regimen. All the AEs were grade 1 or 2 in intensity. No AE of grade 3 or more was reported. One SAE (foot fracture) was reported in the phase 1 trial. KCONVAC induced significant antibody response. 87{middle dot}5% (21/24) to 100% (24/24) of participants in the phase 1 trial and 83{middle dot}0% (83/100) to 100% (99/99) of participants in the phase 2 trial seroconverted for neutralising antibody to live virus, neutralising antibody to pseudovirus, and RBD-IgG after receiving two doses. Across the treatment groups in the two trials, the geometric mean titres (GMTs) of neutralising antibody to live virus ranged from 29{middle dot}3 to 49{middle dot}1 at Day 0/14 regimen and from 100{middle dot}2 to 131{middle dot}7 at Day 0/28 regimen, neutralising antibody to pseudovirus ranged from 69{middle dot}4 to 118{middle dot}7 at Day 0/14 regimen and from 153{middle dot}6 to 276{middle dot}6 at Day 0/28 regimen, and RBD-IgG ranged from 605{middle dot}3 to 1169{middle dot}8 at Day 0/14 regimen and from 1496{middle dot}8 to 2485{middle dot}5 at Day 0/28 regimen. RBD-IgG subtyping assay showed that a significant part of RBD-IgG was IgG1. The vaccine induced obvious T-cell response with 56{middle dot}5% (13/23) and 62{middle dot}5% (15/24) of participants in 5-g and 10-g vaccine groups showed positive interferon-{gamma} enzyme-linked immunospot responses 14 days after the second dose in the phase 1 trial, respectively. InterpretationKCONVAC is well tolerated and able to induce robust antibody response and cellular response in adults aged 18 to 59 years, which warrants further evaluation with this vaccine in the upcoming phase 3 efficacy trial. FundingGuandong Emergency Program for Prevention and Control of COVID-19 (2020A1111340002) and Shenzhen Key Research Project for Prevention and Control of COVID-19.

Predicting hosts based on early SARS-CoV-2 samples and analyzing later world-wide pandemic in 2020

The SARS-CoV-2 pandemic has raised the concern for identifying hosts of the virus since the early-stage outbreak. To address this problem, we proposed a deep learning method, DeepHoF, based on extracting the viral genomic features automatically, to predict host likelihood scores on five host types, including plant, germ, invertebrate, non-human vertebrate and human, for novel viruses. DeepHoF made up for the lack of an accurate tool applicable to any novel virus and overcame the limitation of the sequence similarity-based methods, reaching a satisfactory AUC of 0.987 on the five-classification. Additionally, to fill the gap in the efficient inference of host species for SARS-CoV-2 using existed tools, we conducted a deep analysis on the host likelihood profile calculated by DeepHoF. Using the isolates sequenced in the earliest stage of COVID-19, we inferred minks, bats, dogs and cats were potential hosts of SARS-CoV-2, while minks might be one of the most noteworthy hosts. Several genes of SARS-CoV-2 demonstrated their significance in determining the host range. Furthermore, the large-scale genome analysis, based on DeepHoFs computation for the later world-wide pandemic in 2020, disclosed the uniformity of host range among SARS-CoV-2 samples and the strong association of SARS-CoV-2 between humans and minks.

Mortality analysis and time trend of prostate cancer in China from 2004 to 2008 / 上海预防医学

Objective:To obtain the temporal and spatial trends on prostate cancer mortality in China from 2004 to 2018. Methods:The data of prostate cancer mortality was collected from 605 national disease surveillance sites and age-standardized according to the demographic structure of China in 2000. The crude mortality rate （CMR） and age-standardized mortality rate （ASMR）， and the ratio of ASMRs of rural to urban areas（RR）， were calculated to analyze the distributions of the mortality of prostate cancer stratified by age， sex， region （rural/urban areas， eastern/central/western areas） or time. Results:The temporal trend on the CMR of prostate cancer from 2004 to 2018 increased significantly （APC=5.23%，P<0.001）， whereas the trend on the ASMR did not change （APC=0.65%，P=0.336）. The ASMR of urban areas was higher than that of rural areas（P<0.05）. The temporal trend on the ASMR of urban or rural did not change（P>0.05）. The same trend was detected for the RR value （P>0.05）. The ASMR of eastern urban areas was higher than that of the central or the western urban areas. The ASMR of eastern rural areas was higher than that of central and western areas. In the eastern areas， both the temporal trends for the ASMRs of the urban and the rural increased （The urban： APC=1.6%， P=0.015； the rural： APC=1.02%， P=0.013）. However， the RR values for the East， the Center or the West did not change. The ASMR of the people over 60 years old was higher than that of the people under 60 years old. However， the temporal trends on the ASMRs of the group under 60 years old or the group over 60 years did not change （P>0.05）. The ASMR of the people under 60 years old in 2018 was significantly lower than that in 2004（P=0.004）. Conclusion:A significant correlation exists between the death of prostate cancer and age. The mortality of prostate cancer in urban is higher than that in rural. The current screening strategy for prostate cancer has a limited impact on the prognosis of prostate cancer patients in China. Stratified refinement of prostate cancer screening strategies for people aged over 60 years in urban areas and the causal prophylaxis of prostate cancer are priorities for future prostate cancer prevention and control.

Mortality and trend analysis of bladder cancer in China from 2004 to 2008 / 上海预防医学

Objective:To analyze bladder cancer mortality in China from 2004 to 2018. Methods:The dataset of bladder cancer mortality from 2004 to 2018， based on 605 national surveillance sites and regularly published by the Chinese Center for Disease Control and Prevention， was collected and age-standardized according to the demographic structure of China in 2000. The crude mortality rate （CMR）， the age-standard mortality rate （ASMR）， and the ratio of ASMRs of rural to urban areas（RR）were calculated to analyze the distributions of the mortality of bladder cancer stratified by age， sex， region （rural/urban areas， eastern/central/western areas） or time. Results:The CMR of bladder cancer in China from 2004 to 2018 was 1.69/105， and the ASMR was 1.09/105. The temporal trend on the CMR of bladder cancer from 2004 to 2018 increased significantly （APC=2.91%，P<0.001）， whereas the trend on the ASMR decreased a little （APC=-1.29，P=0.008）. The temporal trend on the CMR of bladder cancer in the males increased （APC=3.29%，P<0.001）， whereas the trend on the ASMR did not change. The temporal trend on the CMR of bladder cancer in the female increased （APC=2.12%，P<0.001）， whereas the trend on the ASMR decreased （APC=-1.94，P=0.008）. Both the CMR and ASMR of urban areas were higher than those of rural areas （P<0.05）. However， the temporal trend on the ASMR of bladder cancer in the urban decreased significantly （APC=-2.05%，P=0.002）， mainly exhibited in eastern and western urban. The ASMR of eastern urban areas was higher than that of western urban areas. The temporal trend on the ASMR of bladder cancer in the rural did not change （P>0.05）， and no differences in the ASMR were detected between eastern， central and western rural areas. The gaps between rural and urban areas in the eastern （P<0.001） or western （P=0.002） region reduced. Although the temporal trend on the ASMR in urban people over 40 years old decreased significantly， the ASMR of urban people over 60 years old was much higher than that of other age groups in the urban or any age groups in rural areas. Conclusion:The age group over 60 years old in the urban is the major target population for bladder cancer prevention and treatment. Screening， diagnosis and treatment for bladder cancer in rural should be strengthened.

The application of multi-teaching mode based on MOOC in the practice course of epidemiology / 上海预防医学

At present， there is little research on the new teaching mode for the practice course of epidemiology. Based on the situation， this paper mainly discussed how the MOOC （Massive Open Online Course）-based multi-teaching mode was applied to the practice course of Epidemiology. The structure of this multi- teaching mode consisted of case base construction， class preparation， class presentation and learning evaluation. Thus， MOOC， flipped Class Mode and other new teaching modes were integrated into traditional face-to-face teaching. In addition， this paper also demonstrated the implementation of the multi-teaching mode in the teaching of preventive medicine. It is worth exploring how to integrate MOOC into the teaching of the practice course of epidemiology in the future.

Immunogenicity and safety of a severe acute respiratory syndrome coronavirus 2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-controlled phase 1 and phase 2 clinical trials / 中华医学杂志(英文版)

BACKGROUND@#The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults.@*METHODS@#Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.@*RESULTS@#In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.@*CONCLUSIONS@#Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.@*TRIAL REGISTRATION@#http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).

Real-time reverse transcription-polymerase chain reaction assay panel for the detection of severe acute respiratory syndrome coronavirus 2 and its variants / 中华医学杂志(英文版)

BACKGROUND@#With the ongoing worldwide coronavirus disease 2019 (COVID-19) pandemic, an increasing number of viral variants are being identified, which poses a challenge for nucleic acid-based diagnostic tests. Rapid tests, such as real-time reverse transcription-polymerase chain reaction (rRT-PCR), play an important role in monitoring COVID-19 infection and controlling its spread. However, the changes in the genotypes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may result in decreased sensitivity of the rRT-PCR assay and it is necessary to monitor the mutations in primers and probes of SARS-CoV-2 detection over time.@*METHODS@#We developed two rRT-PCR assays to detect the RNA-dependent RNA polymerase (RdRp) and nucleocapsid (N) genes of SARS-CoV-2. We evaluated these assays together with our previously published assays targeting the ORF1ab and N genes for the detection and confirmation of SARS-CoV-2 and its variants of concern (VOCs). In addition, we also developed two rRT-PCR assays (S484K and S501Y) targeting the spike gene, which when combined with the open reading frames (ORF)1ab assay, respectively, to form duplex rRT-PCR assays, were able to detect SARS-CoV-2 VOCs (lineages B.1.351 and B.1.1.7).@*RESULTS@#Using a SARS-CoV-2 stock with predetermined genomic copies as a standard, the detection limit of both assays targeting RdRp and N was five copies/reaction. Furthermore, no cross-reactions with six others human CoVs (229E, OC43, NL63, HKU1, severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus) were observed using these assays. In addition, the S484K and S501Y assays were combined with the ORF1ab assay, respectively.@*CONCLUSIONS@#Four rRT-PCR assays (RdRp, N, S484K, and S501Y) were used to detect SARS-CoV-2 variants, and these assays were shown to be effective in screening for multiple virus strains.

Host and infectivity prediction of Wuhan 2019 novel coronavirus using deep learning algorithm

The recent outbreak of pneumonia in Wuhan, China caused by the 2019 Novel Coronavirus (2019-nCoV) emphasizes the importance of detecting novel viruses and predicting their risks of infecting people. In this report, we introduced the VHP (Virus Host Prediction) to predict the potential hosts of viruses using deep learning algorithm. Our prediction suggests that 2019-nCoV has close infectivity with other human coronaviruses, especially the severe acute respiratory syndrome coronavirus (SARS-CoV), Bat SARS-like Coronaviruses and the Middle East respiratory syndrome coronavirus (MERS-CoV). Based on our prediction, compared to the Coronaviruses infecting other vertebrates, bat coronaviruses are assigned with more similar infectivity patterns with 2019-nCoVs. Furthermore, by comparing the infectivity patterns of all viruses hosted on vertebrates, we found mink viruses show a closer infectivity pattern to 2019-nCov. These consequences of infectivity pattern analysis illustrate that bat and mink may be two candidate reservoirs of 2019-nCov.These results warn us to beware of 2019-nCoV and guide us to further explore the properties and reservoir of it. One Sentence SummaryIt is of great value to identify whether a newly discovered virus has the risk of infecting human. Guo et al. proposed a virus host prediction method based on deep learning to detect what kind of host a virus can infect with DNA sequence as input. Applied to the Wuhan 2019 Novel Coronavirus, our prediction demonstrated that several vertebrate-infectious coronaviruses have strong potential to infect human. This method will be helpful in future viral analysis and early prevention and control of viral pathogens.

Acupoint selection rules of neurogenic dysphagia treated with acupuncture and moxibustion in ancient times / 中国针灸

Acupoint selection rules of neurogenic dysphagia treated with acupuncture and moxibustion from pre-Qin to late Qing Dynasty in were analyzed based on data mining. The literature regarding acupuncture and moxibustion for neurogenic dysphagia was searched and screened according to the inclusion and exclusion criteria in (5th Edition), the prescriptions were extracted according to the principle of acupoint extraction.The SPSS 21.0 and Clementine 12.0 were used to perform the cluster analysis and association rule analysis.A total of 191 acupuncture and moxibustion prescriptions were screened and extracted，including 45 acupoints. The top 5 acupoints of acupuncture and moxibustion for neurogenic dysphagia in frequency were Jiache (ST 6), Dicang (ST 4), Lieque (LU 7), Lianquan (CV 23), Shuigou (GV 26). The most involved meridians were the stomach meridian, the governor vessel and the conception vessel. The main acupoints were distributed in the scalp face neck and upper limbs. The most frequently used specific acupoints was crossing points,next was eight confluence points. There were 11 acupoint combinations with strong association according to the association rule analysis, and the top one acupoint combination was Hegu (LI 4)-Jiache (ST 6). There were 9 acupoint cluster groups according to the cluster analysis. Hegu (LI 4), Jiache (ST 6), Dicang (ST 4), Shuigou (GV 26) and Chengjiang (CV 24) were core acupoints for neurogenic dysphagia treated with acupuncture and moxibustion in ancient times, besides，selecting proximal and distal acupoints and selecting acupoints according to symptoms were emphasized.

Cure and death situation in early outbreak of COVID-19 in China / 上海预防医学

Objective To investigate the cure and mortality trend in the early outbreak of COVID-19 in China, to increase its entire epidemiological understanding, providing evidence for assessing the prevention and control measures against it and input-output in this regard. Methods Data were collected concerning daily new confirmed cases, the cumulative cure and death cases in China and Hubei Province and outside Hubei Province, which were reported officially from January 20th, 2020 to February 20th, 2020.Calculation was done of the fatality rate, the ratio of the numbers of cumulative cure cases to cumulative death cases, etc, and then the epidemiological description was made. Results As of Feb 20, 2020, the fatality rate of COVID-19 in Hubei Province was 3.42%, which was a little higher than the national figure of 2.96%.The fatality rate of COVID-19 outside Hubei Province in China was 0.71%.The trends on the indexes, including the daily new cure cases, daily new death and the ratio of cumulative cure cases to cumulative death, in Hubei Province and the whole country were found to be highly consistent, while the significant difference existed between Hubei Province and outside Hubei Province in China.The daily ratio of cumulative cure cases to cumulative death in Hubei Province (the whole country) exhibited the U-curve trend, which reached the lowest point on Jan 27 and subsequently rose more rapidly after Feb 5. Conclusion The ratio of cumulative cure cases to cumulative death is easier and effective to reflect the outbreak situation than other absolute indexes like the daily new cure cases or death.Since Feb 5, 2020, the daily cure status of COVID-19 is significantly better than the daily death, which indicates the effectiveness of series of the joint defense and control measures.However, plenty of challenges exist in recovering normal production and life when the epidemic comes to be sustainably prevented and controlled.

Cure and mortality trend in the early outbreak of Coronavirus Disease 2019 (COVID-19) in China / 上海预防医学

[Objective] To investigate the cure and mortality trend in the early outbreak of Coronavirus Disease 2019 (COVID-19) in China, enhance the entire epidemiological knowledge about COVID-19, screen the more effective evaluation indicators, and supply the solid evidence for assessing the prevention and control measures and input-output. [Methods] The daily new confirmed cases, the cumulative cure and death cases in China and Hubei Province and outside Hubei Province, which were reported officially from January 20, 2020 to February 20, 2020, were collected to calculate the fatality rate, the ratio of the numbers of cumulative cure cases to cumulative death cases, et al, and to make the epidemiological description. [Results] Till Feb 20, 2020, the fatality rate of COVID-19 in Hubei Province was 3.42%, which was a little higher than that of the global country (2.96%). The fatality rate of COVID-19 outside Hubei Province in China was 0.71%. The trends on the indexes, including the daily new cure cases, daily new death and the ratio of cumulative cure cases to cumulative death, in Hubei Province and the whole country was highly consistent, while the significant difference existed between Hubei Province and outside Hubei Province in China. The daily ratio of cumulative cure cases to cumulative death in Hubei Province (the global country) exhibited the U trend, which reached to the lowest point on Jan 27 and subsequently grew more rapidly after Feb 5. [Conclusion] The ratio of cumulative cure cases to cumulative death was easier and effective to reflect the outbreak situation than other absolute indexes like the daily new cure cases or death. Since Feb 5, 2020, the daily cure status of COVID-19 was superior to the daily death, which indicated the effectiveness of series of the joint defense and control measures from our government and society. However, plenty of challenges exist when recovering the normal production and life if the epidemic reaches to be sustainably defensed and controlled.