Risk factors for developing severe COVID-19 in China: an analysis of disease surveillance data.

BACKGROUND: COVID-19 has posed an enormous threat to public health around the world. Some severe and critical cases have bad prognoses and high case fatality rates, unraveling risk factors for severe COVID-19 are of significance for predicting and preventing illness progression, and reducing case fatality rates. Our study focused on analyzing characteristics of COVID-19 cases and exploring risk factors for developing severe COVID-19. METHODS: The data for this study was disease surveillance data on symptomatic cases of COVID-19 reported from 30 provinces in China between January 19 and March 9, 2020, which included demographics, dates of symptom onset, clinical manifestations at the time of diagnosis, laboratory findings, radiographic findings, underlying disease history, and exposure history. We grouped mild and moderate cases together as non-severe cases and categorized severe and critical cases together as severe cases. We compared characteristics of severe cases and non-severe cases of COVID-19 and explored risk factors for severity. RESULTS: The total number of cases were 12 647 with age from less than 1 year old to 99 years old. The severe cases were 1662 (13.1%), the median age of severe cases was 57 years [Inter-quartile range(IQR): 46-68] and the median age of non-severe cases was 43 years (IQR: 32-54). The risk factors for severe COVID-19 were being male [adjusted odds ratio (aOR) = 1.3, 95% CI: 1.2-1.5]; fever (aOR = 2.3, 95% CI: 2.0-2.7), cough (aOR = 1.4, 95% CI: 1.2-1.6), fatigue (aOR = 1.3, 95% CI: 1.2-1.5), and chronic kidney disease (aOR = 2.5, 95% CI: 1.4-4.6), hypertension (aOR = 1.5, 95% CI: 1.2-1.8) and diabetes (aOR = 1.96, 95% CI: 1.6-2.4). With the increase of age, risk for the severity was gradually higher [20-39 years (aOR = 3.9, 95% CI: 1.8-8.4), 40-59 years (aOR = 7.6, 95% CI: 3.6-16.3), ≥ 60 years (aOR = 20.4, 95% CI: 9.5-43.7)], and longer time from symtem onset to diagnosis [3-5 days (aOR = 1.4, 95% CI: 1.2-1.7), 6-8 days (aOR = 1.8, 95% CI: 1.5-2.1), ≥ 9 days(aOR = 1.9, 95% CI: 1.6-2.3)]. CONCLUSIONS: Our study showed the risk factors for developing severe COVID-19 with large sample size, which included being male, older age, fever, cough, fatigue, delayed diagnosis, hypertension, diabetes, chronic kidney diasease, early case identification and prompt medical care. Based on these factors, the severity of COVID-19 cases can be predicted. So cases with these risk factors should be paid more attention to prevent severity.

Evaluation of scrub typhus diagnosis in China: analysis of nationwide surveillance data from 2006 to 2016.

BACKGROUND: Scrub typhus is a life-threatening disease caused by Orientia tsutsugamushi, and specific antimicrobial medicine is available. Early and accurate diagnosis is essential for reducing the risk of severe complications and death. In this study, we aimed to evaluate the case diagnosis situation among medical care institutions and geographical regions in China, and the results will benefit both clinical practice and the disease surveillance system. METHODS: We extracted individual scrub typhus case data 2006-2016 from a national disease surveillance system in China. The diagnosis category and interval time from illness onset to diagnosis were compared among three levels of medical care institutions and provinces. The descriptive analysis method was performed in our study. RESULTS: During the 11-year study period, 93 481 scrub typhus cases, including 57 deaths, were recorded in the nationwide surveillance system. The overall proportion of laboratory-confirmed cases was only 4.7%, and this proportion varied greatly among primary medical centres (2.8%), county level hospitals (4.2%), and city level hospitals (6.3%). Notably, the proportion of laboratory-confirmed cases has consistently decreased from 16.3% in 2006 to 2.6% in 2016, and the same decreasing trend was found among all three levels of medical care institutions. The interval from illness onset to case diagnosis (Tdiag) for all cases was 5 days (interquartile range [IQR]: 2-9 days) and decreased from 7 days (IQR: 3-11 days) in 2006 to 5 days (IQR: 2-8 days) in 2016. The risk of death for patients with a Tdiag of > 7 days was 2.2 times higher (OR = 2.21, 95% CI: 1.05-5.21) than that of patients with a Tdiag of < 2 days. CONCLUSIONS: The interval time from illness onset to diagnosis for scrub typhus cases decreased greatly in China; however, the diagnosis rate of cases with laboratory-confirmed results must be increased among all levels of medical care institutions to reduce both the risk of death and the misuse of antibiotics associated with scrub typhus.

Prevalence of Enteropathogens in Outpatients with Acute Diarrhea from Urban and Rural Areas, Southeast China, 2010-2014.

Acute diarrhea is an important public health issue. Here, we focused on the differences of enteropathogens in acute diarrhea between urban and rural areas in southeast China. Laboratory- and sentinel-based surveillance of acute diarrhea (≥ 3 loose or liquid stools/24 hours) was conducted at 16 hospitals. Fecal specimens were tested for bacterial (Aeromonas sp., Campylobacter sp., diarrheagenic Escherichia coli, Plesiomonas shigelloides, non-typhoidal Salmonella, Shigella sp., Vibrio sp., and Yersinia sp.) and viral (adenovirus, astrovirus, Norovirus, Rotavirus, and Sapovirus) pathogens. Descriptive statistics were used. Between January 1, 2010, and December 31, 2014, 4,548 outpatients with acute diarrhea were enrolled (urban, n = 3,220; rural, n = 1,328). Pathogens were identified in 2,074 (45.6%) patients. Norovirus (25.7%), Vibrio parahaemolyticus (10.2%), enteroaggregative Escherichia coli (EAEC) (8.8%), group A Rotavirus (7.0%), and enterotoxigenic Escherichia coli (ETEC) (5.6%) were the most common pathogens. Enteropathogens were less common in urban than in rural areas (42.0% versus 54.4%, P < 0.001). In urban areas, EAEC and ETEC were more common in high-income than in middle-income regions. Interventions targeting the most common enteropathogens can substantially reduce the burden of acute diarrhea in southeast China.

Directed differentiation of skin-derived precursors into fibroblast-like cells.

Skin-derived precursors (SKPs), which are located at skin's dermis, display multi-lineage potential and can produce both neural and mesodermal progeny in vitro. SKPs are considered to take part in dermal reconstruction and may be an important source of fibroblast during wound repairing. To explore the possibility of differentiation of SKPs into fibroblasts, the 3(rd) passage SKPs were treated with 0, 20, 40, 100, or 500 ng/ml human recombinant connective tissue growth factor (CTGF) for 48 h or treated with 100 ng/ml CTGF for 0, 24, 48, 72, or 96 h. Subsequently, a series of methods were to be used to observe cells immunocytochemistry changes under fluorescence microscope, to validate the mRNA expression change of collagen I, collagen III, fibroblast-specific protein 1 (FSP-1) and alpha smooth muscle actin (α-SMA) by quantitative real-time reverse transcriptase polymerase chain reaction (QRT-PCR), to analyze the expression of collagen I and collagen III protein by Enzyme-linked immunosorbent assay (ELISA), to semiquantitatively measure the expression of FSP-1 and α-SMA by western-blot. After differentiation, cells showed that positively staining for collagen I, collagen III, α-SMA, and FSP-1, which are markers for fibroblasts, but negative expression for neural precursors. The effects of CTGF on collagen I, collagen III, FSP-1 and α-SMA in SKPs were detected both on the transcriptional and posttranscriptional levels. These findings indicate that SKPs can be induced to differentiate into fibroblast-like cells with CTGF treatment that may be a key source of fibroblast in wound healing.

Superiority of metastatic lymph node ratio to the 7th edition UICC N staging in gastric cancer.

AIM: To compare and evaluate the appropriate prognostic indicators of lymph node basic staging in gastric cancer patients who underwent radical resection. METHODS: A total of 1042 gastric cancer patients who underwent radical resection and D2 lymphadenectomy were staged using the 6th and 7th edition International Union Against Cancer (UICC) N staging methods and the metastatic lymph node ratio (MLNR) staging. Homogeneity, discriminatory ability, and gradient monotonicity of the various staging methods were compared using linear trend χ(2), likelihood ratio χ(2) statistics, and Akaike information criterion (AIC) calculations. The area under the curve (AUC) was calculated to compare the predictive ability of the aforementioned three staging methods. RESULTS: Optimal cut-points of the MLNR were calculated as MLNR0 (0), MLNR1 (0.01-0.30), MLNR2 (0.31-0.50), and MLNR3 (0.51-1.00). In univariate, multivariate, and stratified analyses, MLNR staging was superior to the 6th and 7th edition UICC N staging methods. MLNR staging had a higher AUC, higher linear trend and likelihood ratio χ(2) scores and lower AIC values than the other two staging methods. CONCLUSION: MLNR staging predicts survival after gastric cancer more precisely than the 6th and 7th edition UICC N classifications and should be considered as an alternative to current pathological N staging.

Intensive statin therapy: a favorable adjunct to the improvement of small-diameter vascular grafts.

To assess the effect of intensive statins therapy on the outcome of small-diameter vascular prosthesis, we investigated whether atorvastatin treatment (30 mg/d) could accelerate the re-endothelialization process and improve the patency rate in a canine infrarenal abdominal aorta-expanded polytetrafluoroethylene (ePTFE) bypass model. Furthermore, we also evaluated the effect of atorvastatin on the migratory and adherent capacity of circulating endothelial progenitor cells (EPCs) in vitro. Improved patency was confirmed by Doppler sonography and arteriography. Histological and scanning electron microscopy illustrated enhanced re-endothelialization process. Treatment with atorvastatin enhanced the circulating pool of EPCs with fortified migratory and adherent capacity. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that atorvastatin treatment increased endothelial nitric oxide synthase (eNOS) and kinase insert domain receptor (KDR) messenger RNA (mRNA) expression in cultured EPCs and neointima. In conclusion, intensive statin therapy could be considered a favorable option to improve small-diameter vascular graft patency.

Combination of stromal-derived factor-1alpha and vascular endothelial growth factor gene-modified endothelial progenitor cells is more effective for ischemic neovascularization.

BACKGROUND: Recruitment and entrapment of bone marrow-derived endothelial progenitor cells (EPCs) is important in vascular endothelial growth factor (VEGF)-induced angiogenesis. EPC mobilization and differentiation are modulated by stromal-derived factor-1alpha (SDF-1alpha/CXCL12), another important chemokine. In this study, we investigated the hypothesis that SDF-1alpha and VEGF might act synergistically on EPC-mediated vasculogenesis. METHODS: EPCs were isolated and cultured from human peripheral blood, then transduced with retroviral vectors pBabe containing human VEGF(165) complimentary DNA (Td/V-EPCs) and pBabe wild-type (Td/p-EPCs). EPC migration activity was investigated with a modified Boyden chamber assay. EPC apoptosis induced by serum starvation was studied by annexin V assays. The combined effect of local administration of SDF-1alpha and Td/V-EPC transplantation on neovascularization was investigated in a murine model of hind limb ischemia. RESULTS: Over-expression of hVEGF(165) increased SDF-1alpha-mediated EPC migration. SDF-1alpha-mediated migration was significantly increased when EPCs were modified with VEGF (Td/V-EPCs) vs when VEGF was not present (Td/p-EPCs) or when VEGF alone was present (Td/V-EPCs; 196.8 +/- 15.2, 81.2 +/- 9.8, and 67.4 +/- 7.4/mm(2), respectively P < .001). SDF-1alpha combined with VEGF reduced serum starvation-induced apoptosis of EPCs more than SDF-1alpha or VEGF alone (P < .001). To determine the effect of this combination in vivo, SDF-1alpha was locally injected alone into the ischemic hind limb muscle of nude mice or combined with systemically injected Td/V-EPCs. The SDF-1alpha plus VEGF group showed significantly increased local accumulation of EPCs, blood-flow recovery, and capillary density compared with the other groups. The ratio of ischemic/normal blood flow in Td/V-EPCs plus SDF-1alpha group was significantly higher (P < .01), as was capillary density (capillaries/mm(2)), an index of neovascularization (Td/V-EPCs plus SDF-1alpha group, 863 +/- 31; no treatment, 395 +/-13; SDF-1alpha, 520 +/- 29; Td/p-EPCs, 448 +/- 28; Td/p-EPCs plus SDF-1alpha, 620 +/- 29; Td/V-EPCs, 570 +/- 30; P < .01). To investigate a possible mechanistic basis, we showed that VEGF up-regulated the receptor for SDF-1alpha, CXCR4, on EPCs in vitro. CONCLUSION: The combination of SDF-1alpha and VEGF greatly increases EPC-mediated angiogenesis. The use VEGF and SDF-1alpha together, rather than alone, will be a novel and efficient angiogenesis strategy to provide therapeutic neovascularization.