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China banned the use of colistin as animal growth promoter in April 2017. Herein, we report the prevalence of mcr-1 in the intestine of healthy humans and risk factors associated with mcr-1 carriage after the implementation of the ban.We recruited 719 healthy volunteers from Shenzhen City from 1 March 2018 to 31 December 2019 to investigate the prevalence of mcr-1 in human intestine, and undertook a case-control study to ascertain the risk factors associated with the mcr-1-positive population. A further comparative study was conducted to identify differences between genetic characteristics of mcr-1-positive and mcr-1-negative Escherichia coli.Overall, 56 (7.8%, 95% CI 5.9%-10.0%, n = 719) individual faecal samples were positive for mcr-1, and prevalence of mcr-1 among individuals in 2019 (2.4%, 95% CI 8.7%-15.0%, 7/294) was significantly lower than that in 2018 (11.5%, 95% CI 1.0%-4.8%, 49/425) (p 0.0001). After the colistin ban, animal-derived food (pork and chicken meat) was no longer a risk factor for mcr-1 carriage in human intestine, whereas a higher intake of fish and seafood (75 g/day) and whole grains (150 g/day) was associated with higher and lower risk of mcr-1 carriage, respectively (OR 2.175, 95% CI 1.047-4.517; OR 0.045, 95% CI 0.004-0.567). Compared with mcr-1-negative E. coli, the mcr-1-positive E. coli had different patterns of resistance genes and genetic heterogeneity.Our study implicates aquatic food as beeing associated with mcr-1 carriage in the healthy population, even after the ban on colistin. Dietary modification (e.g. whole grains) may help to combat mcr-1-positive bacterial colonization of the gut.

Pansharpening aims at integrating a high-spatial-resolution panchromatic (PAN) image with a low-spatial-resolution multispectral (MS) image to generate a high-resolution MS (HRMS) image. It is a fundamental and significant task in the field of remotely sensed images. Classic and convolutional neural network (CNN)-based algorithms have been developed, over the last decades, for pansharpening based on the spatial detail injection model. However, these algorithms have difficulties in extracting sufficient details or lack interpretability. In this letter, we present an algorithm unfolding pansharpening (AUP) for this task. In the proposed AUP, a two-step optimization model is first designed based on the spatial detail decomposition model. Then, the iteration processes induced by an optimization model are mapped to several detailed convolution (dc) blocks to solve the detail injection by a trainable neural network. Finally, the desired MS details are obtained in end-to-end manners through a decoder. The superiority of the proposed AUP is demonstrated by extensive experiments on datasets acquired by two different kinds of satellites. Each module of the AUP is interpretable, and its fused results are with fewer spectral and spatial distortions.

Objective Reducing suicidal behavior among patients in the healthcare system requires accurate and explainable predictive models of suicide risk across diverse healthcare settings. Materials and Methods We proposed a general targeted fusion learning framework that can be used to build a tailored risk prediction model for any specific healthcare setting, drawing on information fusion from a separate more comprehensive dataset with indirect sample linkage through patient similarities. As a proof of concept, we predicted suicide-related hospitalizations for pediatric patients in a limited statewide Hospital Inpatient Discharge Dataset (HIDD) fused with a more comprehensive medical All-Payer Claims Database (APCD) from Connecticut. Results We built a suicide risk prediction model for the source data (APCD) and calculated patient risk scores. Patient similarity scores between patients in the source and target (HIDD) datasets using their demographic characteristics and diagnosis codes were assessed. A fused risk score was generated for each patient in the target dataset using our proposed targeted fusion framework. With this model, the averaged sensitivities at 90% and 95% specificity improved by 67% and 171%, and the positive predictive values for the combined fusion model improved 64% and 135% compared to the conventional model. Discussion and Conclusions We proposed a general targeted fusion learning framework that can be used to build a tailored predictive model for any specific healthcare setting. Results from this study suggest we can improve the performance of predictive models in specific target settings without complete integration of the raw records from external data sources.

ObjectiveTo characterise safety of the Janus kinase-1 preferential inhibitor filgotinib in patients with moderately to severely active rheumatoid arthritis.MethodsData were integrated from seven trials (NCT01668641, NCT01894516, NCT02889796, NCT02873936, NCT02886728, NCT02065700, NCT03025308). Results are from placebo (PBO)-controlled (through week (W)12) and long-term, as-treated (all available data for patients receiving ≥1 dose filgotinib 200 (FIL200) or 100 mg (FIL100) daily) datasets. We calculated exposure-adjusted incidence rates (EAIRs)/100 patient-years filgotinib exposure (100PYE) for treatment-emergent adverse events (TEAEs).Results3691 patients received filgotinib for 6080.7 PYE (median 1.6, maximum 5.6 years). During the PBO-controlled period, TEAEs, including those of grade ≥3, occurred at comparable rates with filgotinib or PBO; long-term EAIRs of TEAEs grade ≥3 were 6.4 and 7.6/100PYE for FIL200 and FIL100. EAIRs for deaths were 0.6/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 0.5 and 0.3/100PYE for FIL200 and FIL100. EAIRs for serious infection were 3.9, 3.3 and 2.4/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 1.6 and 3.1/100PYE for FIL200 and FIL100. EAIRs for herpes zoster were 0.6, 1.1, and 1.1/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 1.8 and 1.1/100PYE for FIL200 and FIL100. EAIRs for major adverse cardiovascular events were 0, 1.7 and 1.1/100PYE for FIL200, FIL100 and PBO; long-term EAIRs were 0.4 and 0.6/100PYE for FIL200 and FIL100. No venous thromboembolism occurred during the PBO-controlled period; long-term EAIRs were 0.2 and 0/100PYE for FIL200 and FIL100.ConclusionsOver a median of 1.6 and maximum of 5.6 years of exposure, safety/tolerability of FIL200 and FIL100 were similar, with a lower incidence of infections with FIL200 among the long-term, as-treated dataset.

Patients with conventional adenoma removal are recommended to undergo colonoscopy surveillance to prevent colorectal cancer (CRC). However, evidence supporting the guidelines of colonoscopy surveillance is limited, especially among the Chinese population. We investigated the association between colonoscopy adenoma findings and CRC risk among individuals aged 40-74 years who underwent baseline colonoscopy from 2007 to 2016 in Jiashan and Haining, Zhejiang, China. 34 382 participants were categorized into advanced adenoma, nonadvanced adenoma and no adenoma based on adenoma findings. Multivariable Cox regression model was used to estimate the hazard ratio (HR) of CRC incidence with adjustment for potential confounding factors. After a median follow-up time of 7.7 years, 113 incident cases of CRC were identified (18 occurred in 1632 participants with advanced adenoma, 16 in 3973 participants with nonadvanced adenoma and 79 in 28 777 participants with no adenoma). Compared with no adenoma group, the adjusted HR for CRC in advanced adenoma group was 4.01 (95% CI, 2.37, 6.77). For nonadvanced adenomas, individuals with ≥3 adenomas showed an increased risk of CRC (HR, 3.65; 95% CI, 1.43, 9.31), but no significantly increased risk of CRC was found for 1-2 nonadvanced adenomas, compared with those with no adenoma. Our study suggested that the risk of subsequent CRC increased in individuals with high-risk adenoma (at least one advanced adenoma or ≥3 nonadvanced adenomas), but not in those with 1-2 nonadvanced adenomas. These results provide the first evidence from the Chinese population for the current surveillance guidelines. This article is protected by copyright. All rights reserved.

Background and ObjectivesTo explore efficacy/safety of natalizumab, a humanized monoclonal anti–α4-integrin antibody, as adjunctive therapy in adults with drug-resistant focal epilepsy.MethodsParticipants with ≥6 seizures during the 6-week baseline period were randomized 1:1 to receive natalizumab 300 mg IV or placebo every 4 weeks for 24 weeks. Primary efficacy outcome was change from baseline in log-transformed seizure frequency, with a predefined threshold for therapeutic success of 31% relative reduction in seizure frequency over the placebo group. Countable seizure types were focal aware with motor signs, focal impaired awareness, and focal to bilateral tonic-clonic. Secondary efficacy endpoints/safety were also assessed.ResultsOf 32 and 34 participants dosed in the natalizumab 300 mg and placebo groups, 30 (94%) and 31 (91%) completed the placebo-controlled treatment period, respectively (one participant was randomized to receive natalizumab but not dosed due to IV complications). Estimated relative change in seizure frequency of natalizumab over placebo was −14.4% (95% confidence interval [CI] –46.1%–36.1%; p = 0.51). The proportion of participants with ≥50% reduction from baseline in seizure frequency was 31.3% for natalizumab and 17.6% for placebo (odds ratio 2.09, 95% CI 0.64–6.85; p = 0.22). Adverse events were reported in 24 (75%) and 22 (65%) participants receiving natalizumab vs placebo.DiscussionAlthough the threshold to demonstrate efficacy was not met, there were no unexpected safety findings and further exploration of possible anti-inflammatory therapies for drug-resistant epilepsy is warranted.Trial Registration InformationThe ClinicalTrials.gov registration number is NCT03283371.Classification of EvidenceThis study provides Class I evidence that IV natalizumab every 4 weeks, compared to placebo, did not significantly change seizure frequency in adults with drug-resistant epilepsy. The study lacked the precision to exclude an important effect of natalizumab.

Breakthrough infections of hepatitis B virus (HBV) after neonatal vaccination occurred in some adolescents and young adults who were born to mothers with hepatitis B surface antigen (HBsAg). We aimed to determine the impacts of prenatal HBsAg exposure on the generation of T follicular helper (Tfh) cells and antibodies (anti-HBs) specific to HBsAg. To mimic human prenatal HBsAg exposure, we mated female Alb1-HBV (HBV-M) mice with male C57BL/6J mice. Of their first filial generation (F1), HBV-M/F1+ expressed HBsAg in liver tissues and blood, and HBV-M/F1− mice exposed HBsAg in amniotic fluid. At their four weeks old, each HBV-M/F1 mouse was immunized with hepatitis B vaccine containing 5 μg HBsAg subcutaneously. Both HBV-M/F1− and HBV-M/F1+ mice had reduced generation of HBsAg-specific CD4+CXCR5+PD1+ Tfh cells and CD138+IgD− plasma cells in comparison with C57BL/6J mice. Results of coculturing the Tfh cells with B cells that were isolated from different strains of mice indicated that CD4+ T cell activation in response to HBsAg was critical for anti-HBs generation after prenatal HBsAg exposure. When interleukin (IL) 21 was supplemented, the generation of HBsAg-specific Tfh and plasma cells in HBV-M/F1− mice was improved, while supplementation showed little effect in HBV-M/F1+ mice. In HBV-M/F1− mice, HBV vaccine booster improved the generation of Tfh cells and plasma cells, and enhanced anti-HBs production. Conclusion Impaired generation of HBsAg-specific Tfh cells and plasma cells after prenatal HBsAg exposure can be improved by HBV vaccine booster, most likely increasing IL-21 production.

Identification of clinically applicable molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) is crucial to improving patient outcomes. However, the traditional tissue-dependent transcriptional subtyping strategies are invasive and not amenable to routine clinical evaluation. In this study, we developed a circulating extracellular vesicle (cEV) long RNA (exLR)-based PDAC subtyping method and provided exLR-derived signatures for predicting immunogenic features and clinical outcomes in PDAC. We enrolled 426 individuals, among which 227 PDACs served as an internal cohort, 118 PDACs from two other medical centers served as an independent validation cohort, and 81 healthy individuals served as the control. ExLR sequencing was performed on all plasma samples. We found that PDAC could be categorized into three subtypes based on plasma exLR profiles. Each subpopulation showed its own molecular features and was associated with patient clinical prognosis. The immunocyte-derived cEV fractions were altered among PDAC subtypes and interconnected with tumor-infiltrating lymphocytes in cancerous tissue. Additionally, we found a significant concordance of immunoregulators between tissue and blood EVs, and we harvested potential PDAC therapeutic targets. Most importantly, we constructed a nine exLR-derived, tissue-applicable signature for prognostic assessment of PDAC. The circulating exLR-based features may offer an attractive platform for personalized treatment and predicting patient outcomes in multiple types of cancer., Graphical abstract, This is the first study to use large-scale cEV transcriptome analysis for cancer risk stratification and uncover a complex interaction network of immunogenic components with clinical implications between circulatory particles and primary nidus from PDAC cases.

BACKGROUND Cervical cancer is 1 of the most common cancers in females worldwide. Understanding the most recent global patterns and temporal trends of cervical cancer burden might be helpful for its prevention and control. METHODS Data on cervical cancer (International Classification of Diseases, Tenth Revision, code C53) incidence and mortality in 2018 were extracted from the GLOBOCAN 2018 database and further analyzed for their correlations with the Human Development Index. Temporal trends were analyzed using the annual percent change with joinpoint analysis among 31 countries with highly qualified data from the Cancer Incidence in Five Continents Plus and World Health Organization mortality databases. Future trends for the next 15 years were predicted using an open-source age-period-cohort model. RESULTS Cervical cancer incidence and mortality rates were both negatively correlated with the Human Development Index (r = -0.56 for incidence, r = -0.69 for mortality; P < .001) in cross-sectional analysis, and both remained stable in 12 countries or even decreased in 14 and 18 countries for incidence and mortality, respectively, during the most recent 10 data years. Similar findings were observed for the next 15 years. CONCLUSIONS Cervical cancer burden was correlated with socioeconomic development. An overwhelming majority of countries had stable or decreasing trends in incidence and mortality rates, especially in those with effective cervical cancer screening programs and human papillomavirus vaccination. LAY SUMMARY The authors investigated the most up-to-date data from official databases released by the International Agency for Research on Cancer and found that cervical cancer incidence and mortality were negatively correlated with socioeconomic development. Among the 31 countries analyzed, most (26 countries were analyzed for incidence, and 30 were analyzed for mortality) had stable or even decreasing temporal trends over the most recent 10 years, especially in those with effective cervical cancer screening programs. In addition, the predicted trends for the next 15 years were basically consistent with the observed trends among most of the analyzed countries (19 countries for incidence and 26 countries for mortality).

BACKGROUND Intervertebral disc calcification (IDC) combined with ossification of the posterior longitudinal ligament (OPLL) in cervical discs is rarely reported. This case study presents a rare case of IDC combined with OPLL in the C2-C3 segment. CASE SUMMARY Here, we present a case of a 6-year-old Asian boy with severe neck pain and stiffness. Physical examination showed no neurological or other abnormalities. Digital radiography and computed tomography (CT) revealed a calcified intervertebral disc and OPLL at the C2-C3 vertebrae. The spinal canal compromise at C2-C3 was approximately 50% on magnetic resonance imaging. The final diagnosis was IDC combined with OPLL. We applied a neck brace for the patient to protect the neck. The patient's neck pain and stiffness recovered significantly within approximately 3 wk. At the 3 mo follow-up, the follow-up CT showed resolution of the ossified intervertebral disc herniation, and a small amount of calcification and slight OPLL remained at the involved segment. CONCLUSION IDC combined with OPLL is a relatively rare condition in children. However, the majority of patients could have a favorable outcome, and the ossified mass in the canal would be spontaneously resolved with conservative therapy.

High-density lipoprotein cholesterol (HDL-C) concentration and variability are both important factors of cardiovascular disease (CVD) and mortality. We aimed to explore the associations of HDL-C and longitudinal change in HDL-C with risk of mortality.We recruited a total of 69,163 participants aged ≥40 years and had medical examination records of HDL-C during 2010-2014 from the Yinzhou District, Ningbo, China. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. We observed a non-linear association of HDL-C with risks of non-accidental and CVD mortality. Compared with the moderate concentration group (1.4-1.6 mmol/L), HDL-C 1 mmol/L was associated with a higher risk of non-accidental mortality (HR: 1.13 (95% CI: 1.01-1.27)) and both HDL-C 1 mmol/L and ≥2 mmol/L were associated with a higher risk of CVD mortality (HRs: 1.23 (95% CI: 1.01-1.50) and 1.37 (95% CI: 1.03-1.82), respectively). Compared with the stable group ([-0.1, +0.1 mmol/L]), a large decrease ([-0.5, -0.3 mmol/L]) and very large decrease (-0.5 mmol/L) in HDL-C were associated with a higher risk of non-accidental mortality (HRs: 1.40 (95% CI: 1.21-1.63) and 1.78 (95% CI: 1.44-2.20), respectively). Similar results were observed for CVD mortality and cancer mortality.Extremely low or high HDL-C and a large decrease or very large decrease in HDL-C were associated with a higher risk of cause-specific mortality. Monitoring of HDL-C may have utility in identifying individuals at higher risk of mortality.

RAS mutations (HRAS, NRAS, and KRAS) are among the most common oncogenes, and around 19% of patients with cancer harbor RAS mutations. Cells harboring RAS mutations tend to undergo malignant transformation and exhibit malignant phenotypes. The mutational status of RAS correlates with the clinicopathological features of patients, such as mucinous type and poor differentiation, as well as response to anti-EGFR therapies in certain types of human cancers. Although RAS protein had been considered as a potential target for tumors with RAS mutations, it was once referred to as a undruggable target due to the consecutive failure in the discovery of RAS protein inhibitors. However, recent studies on the structure, signaling, and function of RAS have shed light on the development of RAS-targeting drugs, especially with the approval of Lumakras (sotorasib, AMG510) in treatment of KRASG12C-mutant NSCLC patients. Therefore, here we fully review RAS mutations in human cancer and especially focus on emerging strategies that have been recently developed for RAS-targeting therapy.

Objectives To assess the respective diagnostic value of Sonazoid™ and SonoVue® for characterizing FLLs as benign or malignant and the corresponding safety. Methods This prospective Phase 3 study was conducted at 17 centres in China and Korea (May 2014 to April 2015); 424 patients (20 to 80 years) with at least 1 untreated focal liver lesion (FLL) ( Results Sonazoid-enhanced and SonoVue-enhanced ultrasound provided a statistically significant improvement in specificity for all 3 readers comparing to unenhanced ultrasound (for Sonazoid: p = 0.0093, p = 0.002, 0.03, 0.12, respectively). Difference in accuracy improvement between the 2 groups was within the pre-specified non-inferiority margin of 20% for all 3 readers (6.1%, 95% CI: − 5.0 to 17.2; − 7.5%, 95% CI: − 18.4 to 3.5; − 0.3%, 95% CI: − 11.3 to 10.7). The diagnostic confidence level for all 3 readers increased with post-contrast images relative to pre-contrast images. Both contrast agents were well tolerated. Conclusion Results showed a similar efficacy for Sonazoid™ and SonoVue® in diagnosing FLLs as benign or malignant, and underlined the benefit of CEUS imaging over unenhanced ultrasound imaging in reaching a confident diagnosis without having to refer patients for additional imaging exams.

Knot detection is a challenging problem for the wood industry. Traditional methodologies depend heavily on the features selected manually and therefore were not always accurate due to the variety of knot appearances. This paper proposes an automated framework for addressing the aforementioned problem by using the state-of-the-art YOLO-v5 (the fifth version of You Only Look Once) detector. The features of surface knots were learned and extracted adaptively, and then the knot defects were identified accurately even though the knots vary in terms of color and texture. The proposed method was compared with YOLO-v3 SPP and Faster R-CNN on two datasets. Experimental results demonstrated that YOLO-v5 model achieved the best performance for detecting surface knot defects. F-Score on Dataset 1 was 91.7% and that of Dataset 2 was up to 97.7%. Moreover, YOLO-v5 has clear advantages in terms of training speed and the size of the weight file. These advantages made YOLO-v5 more suitable for the detection of surface knots on sawn timbers and potential for timber grading.

Background Numerous studies have suggested that fasting plasma glucose (FPG) was associated with the risk of mortality. However, relationship on longitudinal changes of FPG with the risk of mortality remained inconsistent. Methods We examined the association of FPG at baseline and its longitudinal changes with risk of mortality based on a cohort study in Yinzhou, China, during 2010–2018. Cox regression models and competing risk models were separately used to examine the association of FPG levels and long‐term fluctuation with risk of total and cause‐specific mortality. Results Subjects who had an impaired fasting glucose or diabetes suffered a higher risk of total mortality than subjects who had a normal fasting glucose (HRs and 95% CIs: 1.17 [1.01–1.35], 1.30 [1.10–1.53], respectively). The HR for total mortality was 1.54 (95% CI: 1.29–1.84) and for cancer mortality was 1.41 (95% CI: 1.04–1.92) in the highest quartile of coefficient of variation of FPG. Trajectory analysis indicated that subjects with a significantly changed FPG suffered a higher risk of total mortality. Conclusion According to this cohort study, we found that long‐term fluctuation of FPG was significantly associated with the risk of total and cancer mortality. Our findings suggest that long‐term fluctuation of FPG could be used as an efficient indicator for predicting the subsequent risk of mortality., Fasting plasma glucose variation could increase risk of cancer mortality. Controlling fasting plasma glucose fluctuations is of great health significance.

Objective To examine the association between siesta and hypertension by sex and nighttime sleep duration among Chinese adults aged ≥35 years in Yinzhou, Ningbo City. Methods All data were obtained from physical examinations and structured questionnaires. A total of 44, 652 participants were included. Logistic regression models were applied to calculate odds ratios and 95% confidence intervals for the association between siesta and hypertension. Results When compared with no siesta, siesta durations of 60∼89 min (OR = 1.10, 95% CI:1.04–1.17) and ≥90 min (OR = 1.21, 95% CI:1.08–1.36) were associated with higher risk of hypertension in women. But no significant association was observed in men. Siesta durations of 30∼59 min (OR = 1.09, 95% CI:1.00–1.19) and 60–89 min (OR = 1.10, 95% CI:1.05–1.16) were associated with hypertension in people with 6∼8 h sleep, and this association appeared seemingly stronger with ≥90 min siesta either in short ( 8 h) sleepers (OR = 1.29, 95% CI: 1.00–1.68). However, in short sleepers, 60∼89 min siesta seemed to be associated with decreased risk of hypertension (OR = 0.95, 95% CI: 0.85–1.06); while in long sleepers, the same range of siesta seemed to be associated with increased risk of hypertension (OR = 1.11, 95% CI: 0.93–1.34). Conclusion Long siesta was associated with increased risk of hypertension in women but not in men. Not too long siesta may be related to decreased risk of hypertension in short sleepers but not in people with adequate or even long sleep. These findings warrant further examination with prospective studies and laboratory investigations.

The near fault (NF) line waves send out signal envelopes that oscillate over lengthy periods of time with periodic impulses. Like train bridges, train tracks demonstrate comparable track-bridge (TB...

Although low-density lipoprotein cholesterol (LDL-C) has been considered as a risk factor of atherosclerotic cardiovascular disease, limited studies can be available to evaluate the association of LDL-C with risk of mortality in the general population. This study aimed to examine the association of LDL-C level with risk of mortality using a propensity-score weighting method in a Chinese population, based on the health examination data. We performed a retrospective cohort study with 65,517 participants aged 40 years or older in Ningbo city, Zhejiang. LDL-C levels were categorized as five groups according to the Chinese dyslipidemia guidelines in adults. To minimize potential biases resulting from a complex array of covariates, we implemented a generalized boosted model to generate propensity-score weights on covariates. Then, we used Cox proportional hazard regression models with all-cause and cause-specific mortality as the dependent variables to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs). During the 439,186.5 person years of follow-up, 2403 deaths occurred. Compared with the median LDL-C group (100–130 mg/dL), subjects with extremely low LDL-C levels (group 1) had a higher risk of deaths from all-cause (HR = 2.53, 95% CI:1.80–3.53), CVD (HR = 1.84, 95% CI: 1.28–2.61), ischemic stroke (HR = 2.29, 95% CI:1.32–3.94), hemorrhagic stroke (HR = 3.49, 95% CI: 1.57–7.85), and cancer (HR = 2.12, 95% CI: 1.04–4.31) while the corresponding HRs in LDL-C group 2 were relatively lower than that in group 1. Low LDL-C levels were associated with an increased risk of all-cause, CVD, ischemic stroke, hemorrhagic stroke, and cancer mortality in the Chinese population.

This study tested the hypothesis that combined therapy with human umbilical cord‐derived mesenchymal stem cells (HUCDMSCs) and hyperbaric oxygen (HBO) was superior to either one on preserving neurological function and reducing brain haemorrhagic volume (BHV) in rat after acute intracerebral haemorrhage (ICH) induced by intracranial injection of collagenase. Adult male SD rats (n = 30) were equally divided into group 1 (sham‐operated control), group 2 (ICH), group 3 (ICH +HUCDMSCs/1.2 × 106 cells/intravenous injection at 3h and days 1 and 2 after ICH), group 4 (ICH +HBO/at 3 hours and days 1 and 2 after ICH) and group 5 (ICH +HUCDMSCs‐HBO), and killed by day 28 after ICH. By day 1, the neurological function was significantly impaired in groups 2‐5 than in group 1 (P

Offshore drilling is a complex and hazardous operation. The safety of the drilling operation is a strong function of many time-dependent parameters. The traditional risk analysis model fails to capture the impact of spatial and temporal variations of these parameters. This paper presents a Bayesian Network (BN) model for the offshore drilling operation. The model uniquely considers the evolution of hazards as a function of time and space, and failure of the safety barriers. The model development is explained using the bowtie approach, which is routinely used in the industry for risk management. The bowtie model is subsequently transformed into a BN model and simulated for the well blowout scenarios. The blowout risk is updated based on operational field observations. An uncertainty analysis is also conducted to capture the spatial variability of the parameters. The results of the BN model provide a dynamic risk profile of the blowout accident during the drilling operation. Other possible accident scenarios, such as lost circulation, can also be analyzed using the proposed model. The proposed BN model serves as a robust tool for risk management of offshore drilling operations.

PURPOSE Serum/glucocorticoid-regulated kinase 1 (SGK1) has recently emerged as a critical regulator of inflammatory diseases. In this study, we examined SGK1 expression and its possible pathogenic roles in chronic rhinosinusitis (CRS). METHODS Immunohistochemistry, western blotting, Bio-Plex assay, enzyme-linked immunosorbent assays, and quantitative real-time polymerase chain reaction were performed to assess protein and gene expression levels. The mRNA expression levels of SGK1 and interleukin-6 (IL-6) were extracted from a CRS database to perform correlation analysis. Stable cell lines with SGK1 overexpression (16HBE) and knockdown (A549) were constructed to investigate the interaction between SGK1 and IL-6 in vitro. RESULTS SGK1 exhibited strong cytoplasmic and nuclear staining in the epithelial layers and the lamina propria of nasal polyps (NPs) and in the mucosal tissues of CRS without nasal polyps (CRSsNP). The mRNA and protein expression levels of SGK1 and IL-6 were significantly increased in NPs and CRSsNP tissues, compared to control tissues. SGK1 phosphorylation was significantly greater in NPs than in CRSsNP tissues (P < 0.01). The mRNA levels of SGK1 and IL-6 were significantly correlated (P < 0.001, r = 0.649). Exposure to IL-6 significantly increased SGK1 expression in cultured dispersed NP cells, 16HBE cells, and A549 cells. IL-6 expression was significantly down-regulated in SGK1-overexpressing 16HBE cells (P < 0.01) and significantly up-regulated in SGK1-knockdown A549 cells (P < 0.05). Administration of GSK650394, a SGK1 inhibitor, significantly increased IL-6 self-induced mRNA expression in cultured dispersed NP cells and 16HBE cells. CONCLUSIONS The interaction between SGK1 and IL-6 may play an anti-inflammatory role in IL-6-induced inflammation in the pathogenesis of CRS.

Background Budd-Chiari syndrome (BCS) is a rare heterogeneous liver disease characterized by obstruction of the hepatic venous outflow tract. The incidence of BCS is so low that it is difficult to detect in general practice and difficult to include within the scope of routine diagnosis. The clinical manifestations of BCS are not specific; hence, BCS tends to be misdiagnosed. Case summary We report the case of a 33-year-old Chinese woman who presented with progressive distension in the upper abdomen. She was initially misdiagnosed with liver cirrhosis (LC) due to abnormalities on an upper abdominal computed tomography scan. Although she was taking standard anti-cirrhosis therapy, her symptoms did not improve. Magnetic resonance imaging showed caudate lobe hypertrophy; and dilated lumbar and hemiazygos veins. Venography revealed membranous obstruction of the inferior vena cava owing to congenital vascular malformation. A definitive diagnosis of BCS was made. Balloon angioplasty was performed to recanalize the obstructed inferior vena cava and the patient's symptoms were completely resolved. Conclusion BCS lacks specific clinical features and can eventually lead to LC. Clinicians and radiologists must carefully differentiate BCS from LC. Correct diagnosis and timely treatment are vital to the patient's health.

Joint actions of social organizations have been frequently seen and continuously optimized since the outbreak of the COVID-19. This article is aimed to identify and explore the typical forms and development trends of collaborative networks of social organizations. Given the case studies on joint actions of social organizations, it builds an analysis framework based on actor-network theory (ANT). Research findings are as follows. First, there are, among social organizations in their joint actions against COVID-19, “loose”, “vertical”, “decentralized” and other typical forms of collaborative network, with “decentralized” collaboration showing quite a high degree of initiative. Second, “complex needs” and “political opportunities” that emerge in times of emergency response, “social entrepreneurship” and “bridging connective social capital” that accumulate in normal times, among other factors, have combined to drive vertical collaborative networks towards decentralization. The above three forms of collaboration, each with irreplaceable functions, together comprise an ecosystem of joint actions of social organizations. This article calls the landscape of dynamic practice of joint actions of social organizations a “ladder of collaboration”.

Researchers often have to deal with heterogeneous population with mixed regression relationships, increasingly so in the era of data explosion. In such problems, when there are many candidate predictors, it is not only of interest to identify the predictors that are associated with the outcome, but also to distinguish the true sources of heterogeneity, that is, to identify the predictors that have different effects among the clusters and thus are the true contributors to the formation of the clusters. We clarify the concepts of the source of heterogeneity that account for potential scale differences of the clusters and propose a regularized finite mixture effects regression to achieve heterogeneity pursuit and feature selection simultaneously. We develop an efficient algorithm and show that our approach can achieve both estimation and selection consistency. Simulation studies further demonstrate the effectiveness of our method under various practical scenarios. Three applications are presented, namely, an imaging genetics study for linking genetic factors and brain neuroimaging traits in Alzheimer's disease, a public health study for exploring the association between suicide risk among adolescents and their school district characteristics, and a sport analytics study for understanding how the salary levels of baseball players are associated with their performance and contractual status.

In order to improve the quality of the body-in-white (BIW), optical coordination measurement machines (OCMM) are used to measure the dimensional variation for BIW. The big OCMM online measurement d...

BACKGROUND Primary retroperitoneal tumor is a rare type of tumor with insidious onset, large tumor size at the time of diagnosis, and often extensive involvement of surrounding tissues and blood vessels in the retroperitoneum. Surgery for primary retroperitoneal tumors is technically challenging. Preoperative imaging evaluation is critical for the selection of the optimal surgical approach and can influence complete resection and recurrence rates. Three-dimensional model reconstruction combined with virtual reality is useful for preoperative assessment. CASE SUMMARY A 17-year-old female patient was admitted for abdominal pain lasting for half a year that had been worsening for half a month. Abdominopelvic enhanced helical computed tomography revealed a retroperitoneal space-occupying lesion about 11.3 cm × 9.1 cm in size, with well-defined borders in the upper left quadrant of the abdomen. The lesion compressed the left renal artery and vein resulting in vascular displacement and deformation. A multidisciplinary team decided on the optimal treatment approach. Preoperative three-dimensional visualization and virtual reality technology were used to assess and simulate the surgical procedure. Then, retroperitoneal tumor resection along with renal artery reconstruction was decided as the treatment. Complete resection of the retroperitoneal tumor was performed. Stable blood flow was established after renal artery reconstruction. The tumor was diagnosed as mature cystic teratoma (retroperitoneal tumor) by postoperative pathologic analysis. The patient, who recovered well, was discharged after 2 wk and maintains regular follow-ups. CONCLUSION A combination of three-dimensional reconstruction and virtual reality technology before surgery improves the rate of complete resection of retroperitoneal teratoma.

Near-fault (NF) earthquakes cause severe bridge damage, particularly urban bridges subjected to light rail transit (LRT), which could affect the safety of the light rail transit vehicle (“light rail vehicle” or “LRV” for short). Now when a variety of studies on the fault fracture effect on the working protection of LRVs are available for the study of cars subjected to far-reaching soil motion (FFGMs), further examination is appropriate. For the first time, this paper introduced the LRV derailment mechanism caused by pulse-type near-fault ground motions (NFGMs), suggesting the concept of pulse derailment. The effects of near-fault ground motions (NFGMs) are included in an available numerical process developed for the LRV analysis of the VBI system. A simplified iterative algorithm is proposed to assess the stability and nonlinear seismic response of an LRV-reinforced concrete (RC) viaduct (LRVBRCV) system to a long-period NFGMs using the dynamic substructure method (DSM). Furthermore, a computer simulation software was developed to compute the nonlinear seismic responses of the VBI system to pulse-type NFGMs, non-pulse-type NFGMs, and FFGMs named Dynamic Interaction Analysis for Light-Rail-Vehicle Bridge System (DIALRVBS). The nonlinear bridge seismic reaction determines the impact of pulses on lateral peak earth acceleration (Ap) and lateral peak land (Vp) ratios. The analysis results quantify the effects of pulse-type NFGMs seismic responses on the LRV operations' safety. In contrast with the pulse-type non-pulse NFGMs and FFGMs, this article's research shows that pulse-type NFGM derail trains primarily via the transverse velocity pulse effect. Hence, this study's results and the proposed method can improve the LRT bridges' seismic designs.

Patients with Bipolar Disorder (BD) are associated with aberrant uncinate fasciculus (UF) that connects amygdala-ventral prefrontal cortex (vPFC) system, but the casual relationship is still uncertain. The research aimed to investigate the integrity of UF among offspring of patients with BD and investigate its potential causal association with subsequent declaration of BD. The fractional anisotropy (FA) and mean diffusivity (MD) of UF were compared in asymptomatic offspring (AO, n = 46) and symptomatic offspring (SO, n = 45) with a parent with BD, and age-matched healthy controls (HCs, n = 35). Logistic regressions were performed to assess the predictive effect of UF integrity on the onset of BD. The three groups did not differ at baseline in terms of FA and MD of the UF. Nine out of 45 SO developed BD over a follow-up period of 6 years, and the right UF FA predicted the onset of BD (p = 0.038, OR = 0.212, 95% CI = 0.049–0.917). The ROC curve revealed that the right UF FA predicted BD onset (area-under-curve = 0.859) with sensitivity of 88.9% and specificity of 77.3%. The complementary whole-brain tract-based spatial statistics (TBSS) showed that widespread increases of FA were found in the SO group compared with HCs, but were not associated with the onset of BD. Our data provide evidence supporting the causal relationship between the white matter structural integrity of the amygdala-vPFC system and the onset of BD in genetically at-risk offspring of BD patients.

The multiplexing capability of fluorescence microscopy is severely limited by the broad fluorescence spectral width. Spectral imaging offers potential solutions, yet typical approaches to disperse the local emission spectra notably impede the attainable throughput. Here we show that using a single, fixed fluorescence emission detection band, through frame-synchronized fast scanning of the excitation wavelength from a white lamp via an acousto-optic tunable filter, up to six subcellular targets, labeled by common fluorophores of substantial spectral overlap, can be simultaneously imaged in live cells with low (~1%) crosstalks and high temporal resolutions (down to ~10 ms). The demonstrated capability to quantify the abundances of different fluorophores in the same sample through unmixing the excitation spectra next enables us to devise novel, quantitative imaging schemes for both bi-state and Förster resonance energy transfer fluorescent biosensors in live cells. We thus achieve high sensitivities and spatiotemporal resolutions in quantifying the mitochondrial matrix pH and intracellular macromolecular crowding, and further demonstrate, for the first time, the multiplexing of absolute pH imaging with three additional target organelles/proteins to elucidate the complex, Parkin-mediated mitophagy pathway. Together, excitation spectral microscopy provides exceptional opportunities for highly multiplexed fluorescence imaging. The prospect of acquiring fast spectral images without the need for fluorescence dispersion or care for the spectral response of the detector offers tremendous potential., Spectrally resolved fluorescence microscopy is achieved through frame-synchronized scanning of the excitation wavelength, thus enabling highly multiplexed fast imaging of live cells for both multitargets and quantitative biosensing.

Compared to extremely high efficiencies achieved by their normal mesoscopic counterparts, significant improvement in those of inverted mesoporous perovskite solar cells (PSCs) has yet to be made. The incorporation of plasmonic nanostructures into mesoporous films has been reported to improve their optoelectronic properties through plasmon resonance effects. Herein, gold nanoparticles coated with a thin layer of a semiconductor (NiOx) are introduced into a mesoporous NiOx layer. Using illumination-dependent characterization, we identify a plasmon-assisted metal-to-semiconductor charge transfer (PACT) mechanism. The hole injection from the Au core into the NiOx shell is not only achieved in the dark due to the ohmic contact nature at the Au@NiOx heterostructure, but also facilitated under illumination due to the plasmon-induced interfacial processes. The charge transfer is observed to substantially downshift the valence band edge and enhance the photoconductivity, as well as favor trap filling of the mesoporous NiOx film, which can lower the effective energy barrier and facilitate hole extraction in PSCs. Consequently, embedding Au@NiOx into the mesoporous layer elevates all of the device parameters simultaneously, with a power conversion efficiency of 20.6% in inverted mesostructured PSCs. These results advance our physical understanding of metal–semiconductor heterostructures and offer additional strategies for manipulating the carrier dynamics of PSCs.

Objective Hepatocellular carcinoma (HCC) development among hepatitis B surface antigen (HBsAg) carriers shows gender disparity, influenced by underlying liver diseases that display variations in laboratory tests. We aimed to construct a risk-stratified HCC prediction model for HBsAg-positive male adults. Methods HBsAg-positive males of 35-69 years old (N=6,153) were included from a multi-center population-based liver cancer screening study. Randomly, three centers were set as training, the other three centers as validation. Within 2 years since initiation, we administrated at least two rounds of HCC screening using B-ultrasonography and α-fetoprotein (AFP). We used logistic regression models to determine potential risk factors, built and examined the operating characteristics of a point-based algorithm for HCC risk prediction. Results With 2 years of follow-up, 302 HCC cases were diagnosed. A male-ABCD algorithm was constructed including participant's age, blood levels of GGT (γ-glutamyl-transpeptidase), counts of platelets, white cells, concentration of DCP (des-γ-carboxy-prothrombin) and AFP, with scores ranging from 0 to 18.3. The area under receiver operating characteristic was 0.91 (0.90-0.93), larger than existing models. At 1.5 points of risk score, 26.10% of the participants in training cohort and 14.94% in validation cohort were recognized at low risk, with sensitivity of identifying HCC remained 100%. At 2.5 points, 46.51% of the participants in training cohort and 33.68% in validation cohort were recognized at low risk with 99.06% and 97.78% of sensitivity, respectively. At 4.5 points, only 20.86% of participants in training cohort and 23.73% in validation cohort were recognized at high risk, with positive prediction value of 22.85% and 12.35%, respectively. Conclusions Male-ABCD algorithm identified individual's risk for HCC occurrence within short term for their HCC precision surveillance.

Digital data trails from disparate sources covering different aspects of student life are stored daily in most modern university campuses. However, it remains challenging to (i) combine these data to obtain a holistic view of a student, (ii) use these data to accurately predict academic performance, and (iii) use such predictions to promote positive student engagement with the university. To initially alleviate this problem, in this article, a model named Augmented Education (AugmentED) is proposed. In our study, (1) first, an experiment is conducted based on a real-world campus dataset of college students ( $N =156$ ) that aggregates multisource behavioral data covering not only online and offline learning but also behaviors inside and outside of the classroom. Specifically, to gain in-depth insight into the features leading to excellent or poor performance, metrics measuring the linear and nonlinear behavioral changes (e.g., regularity and stability) of campus lifestyles are estimated; furthermore, features representing dynamic changes in temporal lifestyle patterns are extracted by the means of long short-term memory (LSTM). (2) Second, machine learning-based classification algorithms are developed to predict academic performance. (3) Finally, visualized feedback enabling students (especially at-risk students) to potentially optimize their interactions with the university and achieve a study-life balance is designed. The experiments show that the AugmentED model can predict students’ academic performance with high accuracy.

Yi Zhao,1 Gang Wang,2 Wenqiong Ni,3 Zhiqiang Song,4 Kun Chen,5 Chunlei Zhang,6 Shoumin Zhang,7 Yangfeng Ding,8 Min Zheng,9 Yulin Shi,10 Zhimiao Lin,11 Xiaomin Liu,12 Xiaofei Zhang,13 Qintian Zhou,14 Kazi Deluwar Ahmed14 1Department of Dermatology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of China; 2Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China; 3Department of Dermatology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, People’s Republic of China; 4Department of Dermatology, Southwest Hospital, The Third Military Medical University, Chongqing, People’s Republic of China; 5Institute of Dermatology, Chinese Academy of Medical Science and Peking Union Medical College, Nanjing, People’s Republic of China; 6Department of Dermatology, Peking University Third Hospital, Beijing, People’s Republic of China; 7Department of Dermatology, Henan Provincial People’s Hospital, Zhengzhou 450003, People’s Republic of China; 8Department of Dermatology, Shanghai Skin Disease Hospital, Shanghai, People’s Republic of China; 9Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 10Department of Dermatology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine; Institute of Psoriasis, Tongji University School of Medicine, Shanghai, People’s Republic of China; 11Department of Dermatology and Venereology, Peking University First Hospital, Beijing, People’s Republic of China; 12Department of Dermatology, The University of Hong Kong–Shenzhen Hospital, Shenzhen, People’s Republic of China; 13Department of Clinical Epidemiology and Biostatistics, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of China; 14Scientific Affairs and MSL Department, LEOPharma China, Shanghai, People’s Republic of ChinaCorrespondence: Yi ZhaoDepartment of Dermatology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, No. 168 Litang Road, Beijing 102218, People’s Republic of ChinaEmail zhaoyimd@tsinghua.edu.cnGang WangDepartment of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, People’s Republic of ChinaEmail xjwgang@fmmu.edu.cnObjective: We aimed to prospectively evaluate the visit adherence in mild to moderate psoriasis patients.Methods: Plaque psoriasis patients aged 18 or above who were prescribed with a two-component formula ointment were eligible for the study. The patients were randomly assigned to group A or B, and received management with or without planned patient-doctor communication via a mobile platform. The outpatient visit was scheduled at week 2, 8, 16, 28, 48, and 52. Visit adherence was evaluated as the visit rate of the patients.Results: Two hundred twenty-one patients were included. Generally, the visit adherence dropped over time during follow-up. The visit rates in group A were 5.2– 15.7% through the 52 weeks, and similar rates were found in group B (7.5– 17.0%, vs group A, P > 0.05). A negative binomial regression model showed that older age and higher BSA were correlated with more frequent visits.Conclusion: The visit adherence of mild to moderate psoriasis patients was very low in China. Proactive inquiries of the doctors via the mobile platform failed to improve the visit adherence of the patients.Keywords: psoriasis, visit adherence, topical treatment

Objective Cataplexy is a pathognomonic symptom of narcolepsy type 1. This study was conducted to clarify the clinical characteristics of cataplexy by staging, and to further analyse the correlations of clinical features and cataplectic stages in patients with narcolepsy type 1 (NT1). Methods We experimentally triggered patients with NT1 into cataplexy while under video-polysomnography (v-PSG) monitoring in the sleep lab. The most serious cataplectic attack from each patient was analysed. Each cataplectic episode was segmented into four stages according to the v-PSG. Correlations were analysed between cataplectic stages in pairs, and between cataplectic stages and other clinical features. Results We observed 81 cataplectic episodes in 21 patients with diverse triggers, including humorous or exciting videos, tickling, recalling horrible memories and exercising. Nine patients (43%) went through complete cataplectic attacks while the others experienced partial attacks. Four cataplectic stages (ie, triggering, resisting, atonic, and recovering) were identified according to clinical and electromyograms characteristics. Resisting stage is predominant (56.4%) in cataplexy, while atonic stage is most related with the total duration of cataplexy. The Epworth Sleepiness Scale score (ESS) has a positive correlation with the total duration of cataplexy. Both duration of cataplexy and ESS score are negatively correlated with disease course. However, medication history seems have no influence on either cataplexy duration or ESS score. Conclusion Four-stage segmentation shows the dynamic process of the cataplectic attack, which is different from the traditional classification of complete or partial cataplexy. Resisting stage is necessary for every cataplexy and might reflect the compensation mechanism, while atonic stage may be omitted in some patients. The severity of narcolepsy reduces with the extension of natural course regardless of medication history.

Information security is of great importance for modern society with all things connected. Physical unclonable function (PUF) as a promising hardware primitive has been intensively studied for information security. However, the widely investigated silicon PUF with low entropy is vulnerable to various attacks. Herein, we introduce a concept of bionic optical PUFs inspired from unique biological architectures, and fabricate four types of bionic PUFs by molding the surface micro-nano structures of natural plant tissues with a simple, low-cost, green and environmentally friendly manufacturing process. The laser speckle responses of all bionic PUFs are statistically demonstrated to be random, unique, unpredictable and robust enough for cryptographic applications, indicating the broad applicability of bionic PUFs. On this ground, the feasibility of implementing bionic PUFs as cryptographic primitives in entity authentication and encrypted communication is experimentally validated, which shows its promising potential in the application of future information security.

Introduction:. Vitiligo and psoriasis are common skin diseases, while its co-occurrence in one patient is rare. Here, we reported a patient with co-occurrence of vitiligo and psoriasis. Case presentation:. An 11-year-old girl developed depigmented patches on her right chin for 6 months. The noticed areas of depigmented skin steadily increased in size with no clinical symptoms. Wood's lamp examination and laser scanning confocal revealed the clinical diagnosis of co-occurrence of vitiligo and psoriasis. Discussion:. Speculations related to co-pathogenesis of vitiligo and psoriasis are still elusive, some explanations of this phenomenon like of isomorphic reaction, shared genetic basis of autoimmunity and inflammation, shared cellular immune pathways including Th1, Th17 and related cellular molecules such as TNF-α, IFN-α, IL-17 have been reported. Conclusion:. The analysis and summary of the underlying association in co-occurrence of psoriasis and vitiligo may amplify future therapeutic options for both disease.Clinicians should pay attention to the methods that could simultaneously improve these two conditions.

Introduction Angiotensin-converting enzyme 2 (ACE2) provides an adhesion site for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients with COPD could have severe outcomes after SARS-CoV-2 infection. The objective of this study was to investigate ACE2 regulation by air pollution during the development of COPD. Methods Sprague Dawley rats were exposed to unconcentrated traffic-related air pollution for 3 and 6 months. We examined lung injury markers, oxidative stress, inflammation, emphysema, ACE2 and angiotensin II receptor type 1 (AT1) and 2 (AT2) in the lungs after exposure. Results Lung injury occurred due to an increase in permeability and lactate dehydrogenase cytotoxicity was observed after 6 months of exposure to fine particulate matter of, Short-term exposure to PM1 increases ACE2 overexpression in lungs. Long-term exposure to PM1 decreases the ACE2 overexpression in emphysema. Air pollution may be a risk for #SARSCoV2 adhesion during the development of COPD. https://bit.ly/2Vfykur

INTRODUCTION Although numerous studies have suggested that lifestyle-related factors are associated with chronic diseases and preventable deaths, limited evidence is available for the Chinese population. METHODS This study established a prospective cohort of >360,000 residents on the basis of the Yinzhou Health Information System in China during 2004-2017 and calculated the combined effects of lifestyle-related factors, including BMI, smoking, alcohol consumption, and physical activity, using a points system. A Cox regression model estimated the combined effects of lifestyle-related factors on total mortality, and a competing risk model estimated the combined effects on cancer and cardiovascular disease mortality. All data analyses were conducted in 2018‒2019. RESULTS During 3,755,879 person-years of follow-up, 11,791 deaths were identified, including 4,983 from cancer and 3,143 from cardiovascular disease. Having a standard BMI, never smoking, never drinking, and engaging in physical activity more than 4 times per week had protective effects on total mortality. Overall, the risk of total and cause-specific mortality increased with the increment of risk score. Compared with subjects in the lowest quartile, the risk of total and cause-specific mortality peaked among individuals in the fourth quartile (total mortality: hazard ratio=1.87, 95% CI=1.77, 1.98; cancer mortality: hazard ratio=2.05, 95% CI=1.87, 2.25; cardiovascular disease mortality: hazard ratio=1.51, 95% CI=1.35, 1.68). Sensitivity analyses excluding individuals with follow-up

We assumed that the effect of adjuvant trastuzumab on survival is mediated by the treatment time and we conducted this trial-level meta-regression to determine the appropriate length of treatment. Twelve adjuvant trastuzumab trials (from January 2000 to June 2019, consisting of 20,271 patients) were included. We considered 12-month trastuzumab treatment as the standard. The primary study endpoint was disease-free survival (DFS). By quantifying the relationship between shortened treatment time (month) and altered recurrence risk (expressed as hazard ratio), we found the regression coefficient β was 0.05 (95% confidence interval: 0.02–0.08, P = 0.002), indicating the recurrence risk would increase 5.1% for each month that treatment was shortened. Accordingly, 3, 6, and 9-month reductions in treatment time resulted in 16%, 35%, and 57% increases in recurrence risk, respectively. We revealed a significant linear association between shortened treatment time of trastuzumab and recurrence risk. The clinical duration of adjuvant trastuzumab should be tailored.

Acute myocardial infarction (AMI) induces blood leukocytosis, which correlates inversely with patient survival. The molecular mechanisms leading to leukocytosis in the infarcted heart, remain poorly understood. Using an AMI mouse model, we identified gasdermin D (GSDMD) in activated leukocytes early in AMI. We demonstrated that GSDMD is required for enhanced early mobilization of neutrophils to the infarcted heart. Loss of GSDMD resulted in attenuated IL-1β release from neutrophils and subsequent decreased neutrophils and monocytes in the infarcted heart. Knockout of GSDMD in mice significantly reduced infarct size, improved cardiac function, and increased survival post AMI. Through a series of bone marrow transplantation studies and leukocytes depletion experiments, we further clarified that excessive bone marrow derived and GSDMD-dependent early neutrophil production and mobilization (24 hours post AMI), contributed to the detrimental immunopathology after AMI. Pharmacological inhibition of GSDMD also conferred cardioprotection post AMI, through reduction of scar size and enhancement of heart function. Our study provides new mechanistic insights into molecular regulation of neutrophil generation and mobilization after AMI, and supports GSDMD as a new target for improved ventricular remodeling and reduced heart failure after AMI.

Previous systematic reviews elucidate the efficacy of Tai Chi on the rehabilitation and treatment for various chronic diseases. Yet, no consensus has been reached on its efficacy and safety from those with chronic kidney disease (CKD). Therefore, we conducted a systematic review to critically summarize what is already known about the prevailing benefits of Tai Chi for CKD patients. There was no evidence that Tai Chi had adverse effects on CKD patients. Long-term Tai Chi exercises could improve quality of life, cardiorespiratory fitness, and physical motor function for the end-stage renal disease (ERSD) patients undergoing dialysis. Regular Tai Chi exercises might exert modest influences in delaying CKD progression for mild–moderate CKD patients. However, there is insufficient evidence to demonstrate positive effects of Tai Chi exercises on bone health of the ESRD patients. Accordingly, rigorously designed, longer-term studies of Tai Chi are warranted to identify its efficacy on CKD patients across different stages, especially targeting potential mechanisms in terms of Tai Chi altering biological gene profile expressions.

Giant condyloma acuminatum (GCA) which is also called Buschke-Lowenstein tumor. It is a rare tumor of the anorectal area and external genitalia associated with low-risk HPV types 6 or 11. GCA has a high-rate of recurrence (66%) and malignant transformation (56%). The clinical features of GCA are progression of exophytic, ulcerative, and cauliflower-shaped tumors, it has significant dimensions and may undergo malignant transformation such as squamous cell carcinoma or cervical cancer. It is difficult to treat GCA, and it may be impossible for GCA to self-healing, but we herein report a rare case of a 19-year-old female with self-healing GCA.

Introduction: Caowu, the main root of the Aconitum plant, is widely used in China. Aconitine is the main toxic component of Aconitum, which can cause a variety of malignant arrhythmias and lead to death. Four patients who developed malignant arrhythmia after drinking medicinal wine containing Caowu were reported in this study. Cardiac arrest occurred soon after symptom onset. All patients received venoarterial extracorporeal membrane oxygenation (VA-ECMO) support after conservative medical treatment had failed. Patients who were directly transferred to our hospital received VA-ECMO support earlier than patients who were first treated at a local hospital. One patient received hemoperfusion in the emergency room before VA-ECMO support; the other three patients began hemoperfusion after VA-ECMO treatment. Surviving patients who received VA-ECMO earlier after symptom onset showed no obvious neurological complications. The patient who received a longer cardiopulmonary resuscitation time but received hemoperfusion before VA-ECMO had mild neurological complications. The mortality rate was 25% (1 of 4 patients). Two patients had thrombotic complications in venous vessels.Conclusions: Cardiogenic shock due to refractory ventricular tachycardia caused by aconitine is lethal. Conservative supportive treatment did not provide a short-term antiarrhythmic effect and the cardiogenic shock was not well controlled. VA-ECMO treatment combined with hemoperfusion is promising temporary support to successfully treat aconitine-induced cardiogenic shock caused by refractory ventricular tachycardia.

BackgroundMaffucci’s syndrome is characterized by the coexistence of multiple enchondromas and soft-tissue hemangiomas. It has been clear that somatic mosaic isocitrate dehydrogenase type 1 (IDH1) or isocitrate dehydrogenase type 2 (IDH2) mutations are associated with Maffucci’s syndrome and Ollier disease, but the mechanisms underlying hemangiomas of the Maffucci’s syndrome is still obscure. This study aimed to determine the mechanism of hemangiomas in Maffucci’s syndrome.MethodsWe received a 26-year-old female patient with typical Maffucci’s syndrome, and exome sequencing was conducted using DNA from her peripheral blood and enchondroma tissues. Somatic mutations were characterized by a comparative analysis of exome sequences and further confirmed by the sequencing of PCR products derived from original blood and tissue samples. The mutations of an additional 69 patients with Ollier disease were further tested. The functional impacts of these somatic mutations on Maffucci’s syndrome, especially the development of hemangiomas, were evaluated.ResultsWe reported a typical case of Maffucci’s syndrome, which was confirmed by both imaging findings and pathology. Through exome sequencing of this patient’s DNA samples, we identified an R132C mutation in the isocitrate dehydrogenase type 1 (IDH1) gene and an L309I mutation in the ELKS/RAB6-interacting/CAST family member 2 (ERC2) gene in this patient. Approximately 33.3% of the clones were positive for the IDH1 R132C mutation, and 19.0% of the clones were positive for the ECR2 L309I mutation. The IDH1 R132C mutation was detected in most of the patients with Ollier disease (51/69 patients), and the mean frequency of this mutation was 63.3% in total sequence readouts, but the ECR2 L309I mutation was absent in all of the patients with Ollier disease. In vitro experiments confirmed that the IDH1 R132C mutation promotes chondrocyte proliferation, and the ERC2 L309I mutation enhances angiogenesis.ConclusionsOur results suggest that while IDH1 is a known pathogenic gene in enchondromatosis, ERC2 is a novel gene identified in Maffucci’s syndrome. The somatic L309I mutation of ERC2 contributes to the pathogenesis of hypervascularization to facilitate the development of hemangiomas in Maffucci’s syndrome. The combination of the IDH1 R132C and ERC2 L309I mutations contributes to the development of Maffucci’s syndrome, and these results may enable further research on the pathogenesis of Maffucci’s syndrome.

This study tested the hypothesis that melatonin (Mel) therapy preserved the brain architectural and functional integrity against ischaemic stroke (IS) dependently through suppressing the inflammatory/oxidative stress downstream signalling pathways. Adult male B6 (n = 6 per each B6 group) and TLR4 knockout (ie TLR4-/- ) (n = 6 per each TLR4-/- group) mice were categorized into sham control (SCB6 ), SCTLR4-/- , ISB6 , ISTLR4-/- , ISB6 + Mel (i.p. daily administration) and ISTLR4-/- + Mel (i.p. daily administration). By day 28 after IS, the protein expressions of inflammatory (HMBG1/TLR2/TLR4/MAL/MyD88/RAM TRIF/TRAF6/IKK-α/p-NF-κB/nuclear-NF-κB/nuclear-IRF-3&7/IL-1β/IL-6/TNF-α/IFN-γ) and oxidative stress (NOX-1/NOX-2/ASK1/p-MKK4&7/p-JNK/p-c-JUN) downstream pathways as well as mitochondrial-damaged markers (cytosolic cytochrome C/cyclophilin D/SRP1/autophagy) were highest in group ISB6 , lowest in groups SCB6 and SCTLR4-/- , lower in group ISTLR4-/- + Mel than in groups ISTLR4-/- and ISB6 + Mel and lower in group ISB6 + Mel than in group ISTLR4-/- (all P

Background Localization of small pulmonary nodules is an inevitable challenge for the thoracic surgeon. This study aimed to investigate the accuracy of three‐dimensional (3D) printing technology for localizing small pulmonary nodules, especially ground‐glass nodules (GGNs). Methods This study enrolled patients with peripheral small pulmonary nodules (≤ 2 cm) who required preoperative localization. In the comparison period, patients underwent both computed tomography‐guided (CT‐G) and 3D‐printing template guided (3D‐G) localization to compare the accuracies of the two methods. In the testing period, the 3D‐printing technique was implemented alone. The 3D‐printing physical navigational template was designed based on data from perioperative CT images. Clinical data, imaging data, surgical data, and evaluation index were collected for further analysis. The learning curve of the 3D‐printing localization technique was assessed using cumulative sum (CUSUM) analysis and multiple linear regression analysis. Results In the comparison period (n = 14), the success rates of CT‐G and 3D‐G were 100% and 92.9% (P = 0.31), respectively; in the testing period (n = 23), the success rate of 3D‐G was 95.6%. The localization times of CT‐G, 3D‐G (comparison), and 3D‐G (testing) were 23.6 ± 5.3, 19.3 ± 6.8, and 9.8 ± 4.6 minutes, respectively. The CUSUM learning curve was modeled using the equation: Y = 0.48X2 − 0.013X − 0.454 (R2 = 0.89). The learning curve was composed of two phases, phase 1 (the initial 20 patients) and phase 2 (the remaining 17 patients). Conclusions 3D printing localization has adequate accuracy and is a feasible and accessible strategy for use in localizing small pulmonary nodules, especially in right upper lobe. The use of this technique could facilitate lung nodule localization prior to surgery., Localization of small pulmonary nodules is an inevitable challenge for the thoracic surgeon. This study demonstrated that the 3D printing localization technique is a feasible and accessible strategy to localize non‐palpable pulmonary nodules.