Cerebral endothelial cells mediated enhancement of brain pericyte number and migration in oxygen-glucose deprivation involves the HIF-1α/PDGF-ß signaling.

The present study focused on whether hypoxia-inducible factor-1alpha (HIF-1α) and platelet-derived factor-beta (PDGF-ß) are involved in the crosstalk between brain microvascular endothelial cells (BMECs) and brain vascular pericytes (BVPs) under ischaemic-hypoxic conditions. Mono-cultures or co-cultures of BVPs and BMECs were made for the construction of the blood-brain barrier (BBB) model in vitro and then exposed to control and oxygen-glucose deprivation (OGD) conditions. BBB injury was determined by assessing the ability, apoptosis, and migration of BVPs and the transendothelial electrical resistance and horseradish peroxidase permeation of BMECs. Relative mRNA and protein levels of HIF-1α and PDGF-ß, as well as tight junction proteins ZO-1 and claudin-5 were analyzed by western blotting, reverse transcription quantitative PCR, and/or immunofluorescence staining. Dual-luciferase reporter assays assessed the relationship between PDGF-ß and HIF-1α. Co-culturing with BMECs alleviated OGD-induced reduction in BVP viability, elevation in BVP apoptosis, and repression in BVP migration. Co-culturing with BVPs protected against OGD-induced impairment on BMEC permeability. OGD-induced HIF-1α upregulation enhanced PDGF-ß expression in mono-cultured BMECs and co-cultured BMECs with BVPs. Knockdown of HIF-1α impaired the effect of BMECs on BVPs under OGD conditions, and PDGFR-ß silencing in BVPs blocked the crosstalk between BMECs and BVPs under OGD conditions. The crosstalk between BMECs and BVPs was implicated in OGD-induced BBB injury through the HIF-1α/PDGF-ß signaling.

Mining channel-regulated peptides from animal venom by integrating sequence semantics and structural information.

Channel-regulated peptides (CRPs) derived from animal venom hold great promise as potential drug candidates for numerous diseases associated with channel proteins. However, discovering and identifying CRPs using traditional bio-experimental methods is a time-consuming and laborious process. While there were a few computational studies on CRPs, they were limited to specific channel proteins, relied heavily on complex feature engineering, and lacked the incorporation of multi-source information. To address these problems, we proposed a novel deep learning model, called DeepCRPs, based on graph neural networks for systematically mining CRPs from animal venom. By combining the sequence semantic and structural information, the classification performance of four CRPs was significantly enhanced, reaching an accuracy of 0.92. This performance surpassed baseline models with accuracies ranging from 0.77 to 0.89. Furthermore, we employed advanced interpretable techniques to explore sequence and structural determinants relevant to the classification of CRPs, yielding potentially valuable bio-function interpretations. Comprehensive experimental results demonstrated the precision and interpretive capability of DeepCRPs, making it an accurate and bio-explainable suit for the identification and categorization of CRPs. Our research will contribute to the discovery and development of toxin peptides targeting channel proteins. The source data and code are freely available at https://github.com/liyigerry/DeepCRPs.

Soft Economic Incentives and Soft Behavioral Interventions on the Public's Green Purchasing Behaviour - The Evidence from China.

Purpose: To explore the effects of "soft" behavioral intervention policies (eg, green emotions, social norms) and "soft" economic incentive policies (eg, high-intensity subsidies, low-intensity subsidies) and their combinations on the public's green product purchasing behavior. Participants and Methods: An online questionnaire experiment was conducted on Chinese users using Credamo online questionnaire platform to explore the effects of different "soft" intervention policies on consumers' green purchasing behavior, and the sample data were examined using multiple regression. In Study 1, a total of 460 valid samples were collected to explore the differences in the effects of single intervention policies; in Study 2, a total of 556 valid samples were collected to explore the effects of a combination of soft policies. Results: In the area of green product purchasing, both behavioral interventions and economic incentives alone can promote green consumption behavior; economic incentives have a more positive impact on guiding consumers to green consumption; the combination of "soft" behavioral interventions and "soft" economic incentives has a positive impact on green consumption. The combination of "soft" behavioral intervention policies and "soft" economic incentive policies is more effective than the individual policies. Conclusion: The experimental results of Study 1 show that the policy effects of both behavioral intervention policies and economic incentive intervention policies are evident for goods with different value attributes. Meanwhile, comparing the two types of soft intervention policies, we find that the effect of economic incentive intervention policies is stronger than that of soft behavioral intervention policies. In Study 2, the empirical analysis of the policy mix shows that the policy mix is more effective. The combination of "soft" economic incentive policies and "soft" behavioral intervention policies can effectively increase the salience of policy instruments, and the effect of policy combinations is greater than that of single policies.

Intermittent Hypoxia Inhibits Hepatic CYP1a2 Expression and Delays Aminophylline Metabolism.

Purpose: In this study, we aimed to determine the effects of intermittent hypoxia (IH) on hepatic cytochrome P450 1A2 (CYP1A2) expression and the pharmacokinetics of CYP1A2-mediated aminophylline and warfarin in vitro and in a rabbit model of obstructive sleep apnea. Materials: Human normal liver (LO-2) cells were exposed to 30 min each of 1%, 1-21%, 21%, and 21-1% O2, and then, CYP1A2 expression and drug concentrations were analyzed. We compared the pharmacokinetic parameters of drugs administered to normoxic rabbits and those exposed to 10 min of IH during which the oxygen level fluctuated from 21% to 8%-10% (n = 10 per group). Result: s. The expression of CYP1A2 protein in vitro was significantly reduced in the IH compared with the normoxic cells (0.56 ± 0.11 vs. 1.27 ± 0.17, p < 0.001). Aminophylline was more abundant in cell culture supernatants after 48 h of IH than in those under normoxia. The T 1/2, AUC0-24 h, and Ke values for aminophylline were significantly higher in the IH group. Conclusion: Intermittent hypoxia inhibits hepatic CYP1A2 expression and delays aminophylline metabolism, suggesting that the impact of IH on the expression of CYP enzymes should be closely monitored in clinical practice.

Factors associated with secondary immune thrombocytopenia in patients with primary Sjögren's syndrome: a retrospective study of 639 cases.

OBJECTIVES: To investigate the clinical characteristics and relevant factors of secondary immune thrombocytopenia (ITP) in patients with primary Sjögren's syndrome (pSS). METHODS: Patients with pSS being treated between 2013 and 2020 in China-Japan Friendship Hospital were retrospectively analysed. Clinical characteristics were compared between pSS patients with and without secondary ITP. Logistic regression analysis was performed to identify factors associated with secondary ITP in patients with pSS. RESULTS: 639 patients with pSS were included in this study, among which 566 (88.6%) were women. The prevalence of secondary ITP in patients with pSS were 12.4%. Among pSS patients with secondary ITP, 55.7% had mucocutaneous bleeding and 8.9% experienced visceral bleeding. Lymphopenia (OR=3.154, 95% CI 1.185-8.395, p=0.021), anaemia (OR=2.416, 95% CI 1.250-4.668, p=0.009), low C4 (OR=2.904, 95% CI 1.563-5.394, p=0.001), and positive anti-RNP (OR=2.777, 95% CI 1.070-7.202, p=0.036) were significantly related to secondary ITP, while interstitial lung disease (ILD, OR=0.429, 95% CI 0.203-0.907, p=0.027), ANA ≥1:320 (OR=0.469, 95% CI 0.221-0.996, p=0.049) and positive anti-SSB (OR=0.288, 95% CI 0.126-0.685, p=0.003) were negatively associated with secondary ITP in patients with pSS. CONCLUSIONS: Over 10% of patients with pSS had secondary ITP, among whom visceral bleeding was comparatively rare. Lymphopenia and anaemia were positively related to secondary ITP, while ILD was negatively associated with secondary ITP. Low C4 and positive anti-RNP seem to be two potential risk factors for secondary ITP in patients with pSS, while ANA ≥1:320 and positive anti-SSB may be two potential protective factors.

Chemotherapy or Allogeneic Stem Cell Transplantation as Salvage Therapy for Patients with Refractory Acute Myeloid Leukemia: A Multicenter Analysis.

INTRODUCTION: The overall outcome of patients with refractory AML (rAML) remains poor. Though allogeneic hematopoietic stem cell transplantation (allo-HSCT) is considered as the only curative therapy, it is routinely recommended only for patients after remission with salvage chemotherapy. OBJECTIVE: In this study, we evaluated the impact of salvage chemotherapy or allo-HSCT on the overall outcome in rAML. METHODS: We collected the clinical data of 220 patients from 4 medical centers and performed retrospective analysis of prognosis factors, including salvage chemotherapy, intensity of chemotherapy, and allo-HSCT. RESULTS: A total of 29 patients received allo-HSCT directly without salvage chemotherapy, 26 patients achieved complete remission (CR) or complete remission with incomplete hematological recovery (CRi) after transplantation and 4-year leukemia-free survival (LFS) and overall survival (OS) were 45.0 ± 10.7 and 51.0 ± 10.6%, respectively. Another 191 patients received salvage chemotherapy and 81 (42.2%) achieved CR or CRi. Thirty-four patients among them underwent subsequent allo-HSCT with 4-year LFS and OS of 46.0 ± 8.8 and 46.2 ± 9.0%. The 4-year LFS and OS in 26 patients who failed to obtain CR or CRi but received allo-HSCT with active disease were 32.9 ± 10.0 and 36.9 ± 10.8%, respectively. For patients who received salvage chemotherapy but not allo-HSCT, few of them became long-term survivors. In multivariate analysis, salvage chemotherapy and the intensity of chemotherapy failed to have significant impact on both OS and LFS. Allo-HSCT was the only prognostic factor for improved OS and LFS in multivariate analysis. CONCLUSIONS: These results indicate the benefit of allo-HSCT in patients with rAML and direct allo-HSCT without salvage chemotherapy could be treatment option.

Inhibitory effect on subretinal fibrosis by anti-placental growth factor treatment in a laser-induced choroidal neovascularization model in mice.

AIM: To investigate whether anti-placental growth factor (PGF) can inhibit subretinal fibrosis and whether this effect is mediated by the inhibitory effect of PGF on epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells. METHODS: Subretinal fibrosis model was established in laser induced choroidal neovascularization (CNV) mice on day 21 after laser photocoagulation. Immunofluorescence staining (IFS) of cryosections and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of PGF. IFS of whole choroidal flat-mounts was used to detect the degree of subretinal fibrosis. IFS of cryosections and ELISA were used to detect the expression of EMT related indicators in subretinal fibrosis lesions. RESULTS: The expression of PGF protein in subretinal fibrosis lesions was significantly up-regulated (P<0.05), and mainly co-stained with pan-cytokeratin labeled RPE cells. Intravitreal injection of anti-PGF neutralizing antibody reduced the area of subretinal fibrosis and the ratio of fibrotic/angiogenic area significantly at the concentrations of 0.25, 0.5, 1.0, and 2.0 µg/µL (all P<0.05). The expression of E-cadherin in the local RPE cells decreased, while α-SMA increased significantly in subretinal fibrosis lesions, and the application of anti-PGF neutralizing antibody could reverse these changes (P<0.05). CONCLUSION: The expression of PGF is up-regulated in the lesion site of subretinal fibrosis and mainly expressed in RPE cells. Intravitreal injection of anti-PGF neutralizing antibody can significantly inhibit the degree of subretinal fibrosis in CNV mice, and this effect may be mediated by the inhibition of PGF on EMT of RPE cells.

[Identification and expression analysis of NRT1 family genes in Rehmannia glutinosa].

NRT1 family proteins play an important roles for absorbing and transporting of nitrate in different plants. In order to identify the NRT1 family genes of Rehmannia glutinosa, this study used 11 NRT1 homologous proteins of Arabidopsis as probe sequences and aligned with the transcriptome data of R. glutinosa by using NCBI BLASTN software. Resulting there were 18 NRT1 proteins were identified in R. glutinosa. On basis of this, a series of the molecular characteristics of R. glutinosa NRT1 proteins including the conserved domains, the transmembrane structure, the subcellular location and phylogenetic features were in detail analyzed. At same time, it were systematically analyzed that the temporal and spatial expression patterns and characteristics of R. glutinosa NRT1 family genes in response to different stress factors. The results indicated that 18 R. glutinosa NRT1 family genes with the length of coding region from 1 260 bp to 1 806 bp, encoded proteins ranging from 419 to 601 amino acids, and all of they owned the domains of typical peptide transporter with 7 to 12 transmembrane domains. These R. glutinosa NRT1 family proteins mostly were found to locate on cellular plasma membrane, and belonged to the hydrophobic proteins. Furthermore, the evolutionary analysis found that the 18 R. glutinosa NRT1 protein family could be divided into two subfamilies, of which 14 NRT1 family genes might occur the positive selection, and 4 genes occur the passivation selection during the evolution process of R. glutinosa. In addition the expression analysis showed that 18 R. glutinosa NRT1 family genes have the distinct expression patterns in different tissues of R. glutinosa, and their expression levels were also obvious difference in response to various stress. These findings infield that 18 R. glutinosa NRT1 family proteins might have obviously different functional roles in nitrate transport of R. glutinosa. In conclusion, this study lays a solid theoretical foundation for clarifying the absorption and transport molecular mechanism of N element during R. glutinosa growth and development, and at same time for deeply studying the molecular function of R. glutinosa NRT1 proteins in absorption and transport of nitrate.

Evaluation of the association between mammographic density and the risk of breast cancer using Quantra software and the BI-RADS classification.

To determine the association between mammographic density (MD) and the risk of breast cancer (BC) in Chinese women and to investigate the role of fertility risk factors in regulating the relationship between MD and BC.We used Quantra software and the BI-RADS classification to assess MD in 466 patients and 932 controls. Conditional matched logistic multiple regression analysis was used to determine the relationship between MD and BC, and risk was evaluated with the odds ratio (OR) and 95% confidence interval (CI).The ORs for category 4 versus category 2 were 1.95 (95% confidence interval [95% CI] (1.42∼2.66)) and 1.76 (95% CI (1.28∼2.42)) for the BI-RADS and Quantra classifications, respectively. The ORs for category 5 volumetric breast density (VBD) versus category 2 VBD and 5 fibroglandular tissue volume (FGV) versus category 2 FGV were 1.63 (95% CI (1.20∼2.23)) and 1.92 (95% CI (1.40∼2.63)), respectively. Females with category 5 VBD whose age at menarche was ≤13 years had the highest risk of BC (OR = 2.16, 95% CI (1.24∼3.79)), and females with category 5 FGV whose age at menarche was = 15 years had the lowest risk of BC (OR = 1.65, 95% CI (1.05∼2.62)). Females with categories 3-5 VBD and categories 3-5 FGV had reduced risks of BC with increasing number of births. Females with category 5 VBD had an increased risk of BC with increasing age at first childbirth (the OR increased from 1.49 to 1.95). Those with category 5 VBD had a reduced risk of BC with increasing breastfeeding duration (the OR decreased from 2.08 to 1.55). Females with category 5 FGV had a reduced risk of BC with increasing breastfeeding duration (the OR decreased from 4.12 to 1.62).Both the BI-RADS density classification and Quantra measures indicated that MD is positively associated with the risk of BC in Chinese women and that associations between MD and BC risk differ by age at menarche, parity, age at first childbirth and breastfeeding duration.

Comparing the performance of time series models with or without meteorological factors in predicting incident pulmonary tuberculosis in eastern China.

BACKGROUND: Many studies have compared the performance of time series models in predicting pulmonary tuberculosis (PTB), but few have considered the role of meteorological factors in their prediction models. This study aims to explore whether incorporating meteorological factors can improve the performance of time series models in predicting PTB. METHODS: We collected the monthly reported number of PTB cases and records of six meteorological factors in three cities of China from 2005 to 2018. Based on this data, we constructed three time series models, including an autoregressive integrated moving average (ARIMA) model, the ARIMA with exogenous variables (ARIMAX) model, and a recurrent neural network (RNN) model. The ARIMAX and RNN models incorporated meteorological factors, while the ARIMA model did not. The mean absolute percentage error (MAPE) and root mean square error (RMSE) were used to evaluate the performance of the models in predicting PTB cases in 2018. RESULTS: Both the cross-correlation analysis and Spearman rank correlation test showed that PTB cases reported in the study areas were related to meteorological factors. The predictive performance of both the ARIMA and RNN models was improved after incorporating meteorological factors. The MAPEs of the ARIMA, ARIMAX, and RNN models were 12.54%, 11.96%, and 12.36% in Xuzhou, 15.57%, 11.16%, and 14.09% in Nantong, and 9.70%, 9.66%, and 12.50% in Wuxi, respectively. The RMSEs of the three models were 36.194, 33.956, and 34.785 in Xuzhou, 34.073, 25.884, and 31.828 in Nantong, and 19.545, 19.026, and 26.019 in Wuxi, respectively. CONCLUSIONS: Our study revealed a possible link between PTB and meteorological factors. Taking meteorological factors into consideration increased the accuracy of time series models in predicting PTB, and the ARIMAX model was superior to the ARIMA and RNN models in study settings.

Noninvasive model for predicting future ischemic strokes in patients with silent lacunar infarction using radiomics.

BACKGROUND: This study aimed to investigate integrating radiomics with clinical factors in cranial computed tomography (CT) to predict ischemic strokes in patients with silent lacunar infarction (SLI). METHODS: Radiomic features were extracted from baseline cranial CT images of patients with SLI. A least absolute shrinkage and selection operator (LASSO)-Cox regression analysis was used to select significant prognostic factors based on ModelC with clinical factors, ModelR with radiomic features, and ModelCR with both factors. The Kaplan-Meier method was used to compare stroke-free survival probabilities. A nomogram and a calibration curve were used for further evaluation. RESULTS: Radiomic signature (p < 0.01), age (p = 0.09), dyslipidemia (p = 0.03), and multiple infarctions (p = 0.02) were independently associated with future ischemic strokes. ModelCR had the best accuracy with 6-, 12-, and 18-month areas under the curve of 0.84, 0.81, and 0.79 for the training cohort and 0.79, 0.88, and 0.75 for the validation cohort, respectively. Patients with a ModelCR score < 0.17 had higher probabilities of stroke-free survival. The prognostic nomogram and calibration curves of the training and validation cohorts showed acceptable discrimination and calibration capabilities (concordance index [95% confidence interval]: 0.7864 [0.70-0.86]; 0.7140 [0.59-0.83], respectively). CONCLUSIONS: Radiomic analysis based on baseline CT images may provide a novel approach for predicting future ischemic strokes in patients with SLI. Older patients and those with dyslipidemia or multiple infarctions are at higher risk for ischemic stroke and require close monitoring and intensive intervention.

Adjuvant transarterial chemoembolization following radical resection for intrahepatic cholangiocarcinoma: A multi-center retrospective study.

Background and Aims: The prognosis of intrahepatic cholangiocarcinoma (ICC) after radical resection is far from satisfactory, but the effect of postoperative transarterial chemoembolization (p-TACE) remains controversial. This multi-center retrospective study was to evaluate the clinical value of p-TACE and identify the selected patients who would benefit from p-TACE. Methods: Data of ICC patients who underwent radical resection with/without p-TACE therapy was obtained from 12 hepatobiliary centers in China between Jan 2014 and Jan 2017. Overall survival (OS) was set as the primary endpoint, which was analyzed by the Kaplan-Meier method before and after propensity score matching (PSM). Subgroup analysis was conducted based on the established staging system and survival risk stratification. Results: A total of 335 patients were enrolled in this study, including 39 patients in the p-TACE group and 296 patients in the non-TACE group. Median OS in the p-TACE group was longer than that in the non-TACE group (63.0 months vs. 18.0 months, P=0.041), which was confirmed after 1:1 PSM (P=0.009). According to the 8th TNM staging system, patients with stage II and stage III stage would be benefited from p-TACE (P=0.021). Subgroup analysis stratified by risk factors showed that p-TACE could only benefit patients with risk factors <2 (P=0.027). Conclusion: Patients with ICC should be recommended to receive p-TACE following radical resection, especially for those with stage II, stage III or risk factors <2. However, the conclusion deserved further validation.

Efficacy and safety of 0.0015% tafluprost versus 0.005% latanoprost in primary open angle glaucoma, ocular hypertension: a Meta-analysis.

AIM: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of tafluprost 0.0015% eye drops [benzalkonium chloride (BAK) 0.1 mg/mL] compared with that of latanoprost 0.005% eye drops (BAK 0.2 mg/mL) for primary open angle glaucoma (POAG) and ocular hypertension (OHT). METHODS: All the randomized controlled trials (RCTs) about treating POAG and OHT comparing tafluprost and latanoprost were collected by searching PubMed, Embase, Cochrane Library, CNKI and VIP. The outcomes of interest to evaluate the clinical efficacy and adverse effects included IOP and patient-related drop discomfort. RESULTS: Five RCTs involving 888 glaucoma patients were included. The results showed that, 1) at the end of the study, no statistically significant differences were observed in IOP reduction [standard mean difference (SMD) =0.48, 95%CI 0.07 to 0.88, P=0.085] between tafluprost and latanoprost; 2) No statistically significant differences were observed in adverse events of foreign-body sensation [relative risk (RR) =0.62, 95%CI 0.26 to 1.46, P=0.269], eye irritation (RR=1.16, 95%CI 0.49 to 2.75, P=0.744), eye pain (RR=2.000, 95%CI 0.949 to 4.216, P=0.07), iris hyper-pigmentation (RR=0.741, 95%CI 0.235 to 2.334, P=0.61), dry eye (RR=1.154, 95%CI 0.409 to 3.256, P=0.79) and eye pruritus (RR=1.600, 95%CI 0.536 to 4.774, P=0.4) between tafluprost and latanoprost. However, tafluprost showed more reported incidence of conjunctival hyperaemia than latanoprost (RR=2.11, 95%CI 1.24 to 3.59, P=0.006). CONCLUSION: Tafluprost 0.0015% eye drops (BAK 0.1 mg/mL) and latanoprost 0.005% eye drops (BAK 0.2 mg/mL) are comparable in lowering IOP for open angle glaucoma (OAG) and OHT. It does not differ in the incidence of foreign-body sensation, eye irritation, eye pain, iris hyper-pigmentation, dry eye and eye pruritus, but tafluprost shows less ocular tolerability because of more incidence of conjunctival hyperaemia.

OCT proves that vitreomacular adhesion is significantly more likely to develop vision-threatening retinal complications than vitreomacular separation.

BACKGROUND: SD-OCT is becoming commonplace in everyday practice. Vitreomacular adhesions (VMAs) are being more routinely diagnosed. Predictive studies to the natural course of VMA are thus clinically significant. Spectral domain-optical coherence tomography (SD-OCT) was presently utilized to analyze the incidence of floaters, the complete vitreomacular separation or VMA, the VMA complication, the vitreomacular angle (VMAng), and the complication mechanism. METHODS: Monthly SD-OCT was performed on patients with/without symptomatic floaters. OCT allowed VMA and vitreomacular separation to be compared. The incidence was assessed applying one-tailed Fisher's exact tests. The VMAngs between the inner retina and posterior hyaloid were measured, and the complication mechanism was studied using OCT image. For macular hole (MH), pre- and/or post-operative best corrected visual acuities (BCVAs; LogMAR), refractions and photoreceptor conditions were also evaluated. RESULTS: Totally, 124 eyes were included; there were 116 eyes with VMA and 8 eyes with vitreomacular separation. Considering the percentages over 124 eyes, floaters were present in 14.5% of enrolled eyes (=18/124), consisting of 12.9% of eyes with VMA (16/124) and 1.6% of eyes with vitreomacular separation (2/124). Moreover, there were twelve eyes (9.7%) with VMA-associated vision-threatening complications, including MH (n = 8; 6.5%), retinal detachment (RD; n = 2; 1.6%), vitreomacular traction (VMT; n = 1; 0.8%) and macular pucker (MP; n = 1; 0.8%). Eyes with initial VMA had a significantly greater possibility of complications than eyes with initial vitreomacular separation (p = 0.03). Among these eyes with MH (n = 8), the pre-operative BCVA (LogMAR) was 1.1 ± 0.5, which was insignificantly (p = 0.35) improved to 0.8 ± 0.7 post-operatively. The VMAng of VMA eyes with MHs was 24.2 ± 24.9° (n = 8). The critical VMAng was 13.3°. CONCLUSIONS: A minority of eyes with VMA or vitreomacular separation had floaters. Moreover, the use of SD-OCT could identify vision-threatening sequelae, namely MH, RD, MP and VMT, and this was significantly more frequent in eyes with VMA than in eyes with complete vitreomacular separation. Therefore, SD-OCT might be a useful way of identifying either identity, and evaluating VMA-associated complications. Whether VMA eyes with MH (n = 8) that have a VMAng greater than critical VMAng have a greater likelihood of tangential traction and subsequent MH needs further investigation.

Clinical characteristics and outcomes of hospitalised patients with COVID-19 treated in Hubei (epicentre) and outside Hubei (non-epicentre): a nationwide analysis of China.

BACKGROUND: During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences. METHODS: Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined. RESULTS: At the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7 versus 44.9 years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5 days) compared with patients outside Hubei. Patients in Hubei (severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, HR (95% CI) for critical illness 1.59 (1.05-2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity. However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4 versus 4.7 days) and prognosis (HR (95%) 0.84 (0.40-1.80)) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01-1.08)). CONCLUSION: There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre. Future studies to determine the reason for delaying hospitalisation are warranted.

Reproductive Risk Factors Associated with Breast Cancer Molecular Subtypes among Young Women in Northern China.

PURPOSE: Accumulated evidence suggests that reproductive factors are related to different breast cancer subtypes, but most studies on these relationships are mainly focused on middle-aged and older patients, and it remains unclear how reproductive factors impact different subtypes of breast cancer in young women. METHODS: We assessed the relationships between fertility factors and luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple-negative breast cancer (TNBC) subtypes in 3792 patients and 4182 controls aged 20-70 years. Data on the reproductive history of the study participants were acquired through face-to-face interviews and questionnaires. We conducted case-control comparisons among tumor subtypes based on estrogen receptor (ER), progesterone receptor (PR), and HER2 statuses using unconditional polychotomous multivariate logistic regression models to compute odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Parity was inversely related to both luminal A and luminal B subtypes in young women and older women (all P trend < 0.05). Later age at first full-term birth was inversely related to the luminal A subtype (P trend < 0.05) in young women but correlated with an increased risk of the luminal A subtype (P trend < 0.05) in older women. Parous Chinese women 40 years old or younger who breastfed for 12 months or longer had a lower risk of luminal B and TNBC subtypes than women who never breastfed (OR = 0.55, 95% CI 0.36-0.84 and OR = 0.52, 95% CI 0.28-0.99, respectively). CONCLUSIONS: Our results implied that parity exerted a strong protective effect against luminal A and luminal B subtype breast cancer in young Chinese women, and long-term breastfeeding obviously decreased the risk of luminal B and TNBC subtypes in this population.

Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. OBJECTIVE: To evaluate the risk of serious adverse outcomes in patients with COVID-19 by stratifying the comorbidity status. METHODS: We analysed data from 1590 laboratory confirmed hospitalised patients from 575 hospitals in 31 provinces/autonomous regions/provincial municipalities across mainland China between 11 December 2019 and 31 January 2020. We analysed the composite end-points, which consisted of admission to an intensive care unit, invasive ventilation or death. The risk of reaching the composite end-points was compared according to the presence and number of comorbidities. RESULTS: The mean age was 48.9 years and 686 (42.7%) patients were female. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached the composite end-points. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD (HR (95% CI) 2.681 (1.424-5.048)), diabetes (1.59 (1.03-2.45)), hypertension (1.58 (1.07-2.32)) and malignancy (3.50 (1.60-7.64)) were risk factors of reaching the composite end-points. The hazard ratio (95% CI) was 1.79 (1.16-2.77) among patients with at least one comorbidity and 2.59 (1.61-4.17) among patients with two or more comorbidities. CONCLUSION: Among laboratory confirmed cases of COVID-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes.