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Background: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation: In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. Funding: European Society of Intensive Care Medicine, European Respiratory Society.

The clinical success of the percutaneous coronary intervention (PCI) is highly dependent on endovascular manipulation skills and dexterous manipulation strategies of interventionalists. However, the analysis of endovascular manipulations and related discussion for technical skill assessment are limited. In this study, a multilayer and multimodal-fusion architecture is proposed to recognize six typical endovascular manipulations. The synchronously acquired multimodal motion signals from ten subjects are used as the inputs of the architecture independently. Six classification-based and two rule-based fusion algorithms are evaluated for performance comparisons. The recognition metrics under the determined architecture are further used to assess technical skills. The experimental results indicate that the proposed architecture can achieve the overall accuracy of 96.41%, much higher than that of a single-layer recognition architecture (92.85%). In addition, the multimodal fusion brings significant performance improvement in comparison with single-modal schemes. Furthermore, the K -means-based skill assessment can obtain an accuracy of 95% to cluster the attempts made by different skill-level groups. These hopeful results indicate the great possibility of the architecture to facilitate clinical skill assessment and skill learning.

INTRODUCTION We assessed the safety as well as the efficacy of self-expanding stent placement for the treatment of malignant superior vena cava syndrome (SVCS), besides identifying the predictable probable factors for the clinical improvement of endovascular stent treatment in SVCS. METHODS The study reviewed 112 patients (92 men) with malignant SVCS retrospectively from January 2015 to December 2020. RESULTS Out of total 112 patients, 106 stents were successfully placed in 102 patients, however 4 patient's occlusions could not be passed and 6 patient's procedure was abandoned due to intraluminal thrombus as detected in venography. In 92 patients, complete resolution of syndrome was observed within 72 hours but 10 patients did not to intervention. In 102 patients, procedure-related 8 complications were noted including stent migrations (n=4), pulmonary embolism (n=2), and pulmonary edemas (n=2). Besides after stenting, three hemorrhages with anticoagulation therapy were observed with 4 recurrences at 22, 36, 51 and day 58 in six months. The pressure gradient across the lesion (≥ 20mmHg) was used as a predictor for clinical efficacy of stent therapy for SVCS. CONCLUSION Endovascular stent insertion is a safe and effective intervention for malignant SVCS, especially for those with pressure gradient across the lesions ≥ 20mmHg.

The cT3 substage criteria based on extramural depth of tumor invasion in rectal cancer have several limitations.This study proposed that the distance between the deepest tumor invasion and mesorectal fascia on pretherapy MRI can distinguish the prognosis of patients with cT3 rectal cancer.This is a cohort study.This study included a prospective, single-center, observational cohort and a retrospective, multicenter, independent validation cohort.Patients who had cT3 rectal cancer with negative mesorectal fascia undergoing neoadjuvant chemoradiotherapy followed by radical surgery were included in 4 centers in China from January 2013 to September 2014.Baseline MRI with the distance between the deepest tumor invasion and mesorectal fascia, extramural depth of tumor invasion, and mesorectum thickness were measured.The cutoff of the distance between the deepest tumor invasion and mesorectal fascia was determined by time-dependent receiver operating characteristic curves, supported by a 5-year progression rate from the prospective cohort, and was then validated in a retrospective cohort.There were 124 and 274 patients included in the prospective and independent validation cohorts. The distance between the deepest tumor invasion and mesorectal fascia was the only predictor for cancer-specific death (HR, 0.1; 95% CI, 0.0-0.7) and was also a significant predictor for distant recurrence (HR, 0.4; 95% CI, 0.2-0.9). No statistically significant difference was observed in prognosis between patients classified as T3a/b and T3c/d.The sample size is relatively small, and the study focused on cT3 rectal cancers with a negative mesorectal fascia.A cutoff of 7 mm of the distance between the deepest tumor invasion and mesorectal fascia on baseline MRI can distinguish cT3 rectal cancer from a different prognosis. We recommend using the distance between the deepest tumor invasion and mesorectal fascia on baseline MRI for local and systemic risk assessment and providing a tailored schedule of neoadjuvant treatment. See Video Abstract at http://links.lww.com/DCR/B682.CORRELACIÓN ENTRE LA DISTANCIA DE LA FASCIA MESORRECTAL Y EL PRONÓSTICO DEL CÁNCER DE RECTO cT3: RESULTADOS DE UN ESTUDIO MULTICÉNTRICO DE CHINAANTECEDENTES:Los criterios de subestadificación cT3 basados en la profundidad extramural de invasión tumoral en el cáncer de recto tienen varias limitaciones.OBJETIVO:Este estudio propuso que la distancia entre la invasión tumoral más profunda y la fascia mesorrectal en la resonancia magnética preterapia puede distinguir el pronóstico de los pacientes con cT3.DISEÑO:Estudio de cohorte.ENTORNO CLINICO:El estudio incluyó una cohorte observacional, prospectiva, unicéntrica, y una cohorte de validación retrospectiva, multicéntrica e independiente.PACIENTE:Se incluyeron pacientes con cáncer de recto cT3 con fascia mesorrectal negativa sometidos a quimio-radioterapia neoadyuvante seguida de cirugía radical en cuatro centros de China desde enero de 2013 hasta septiembre de 2014.INTERVENCIÓN:Imágenes de resonancia magnética de referencia fueron medidas con la distancia entre la invasión tumoral más profunda y la fascia mesorrectal; la profundidad extramural de la invasión tumoral y el grosor del mesorrecto.PRINCIPALES MEDIDAS DE VALORACION:El límite de la distancia entre la invasión tumoral más profunda y la fascia mesorrectal se determinó mediante curvas características operativas del receptor dependientes del tiempo y se apoyó en la tasa de progresión a 5 años de la cohorte prospectiva, y luego se validó en una cohorte retrospectiva.RESULTADOS:Se incluyeron 124 y 274 pacientes en la cohorte de validación prospectiva e independiente, respectivamente. La distancia entre la invasión tumoral más profunda de la fascia mesorrectal fue el único predictor de muerte específica por cáncer (Hazard ratio: 0.1, 95% CI, 0,0-0,7); y también fue un predictor significativo de recurrencia distante Hazard ratio: 0,4, 95% CI, 0,2-0,9). No se observaron diferencias estadísticamente significativas en el pronóstico entre los pacientes clasificados como T3a/b y T3c/d.LIMITACIONES:El tamaño de la muestra es relativamente pequeño y el estudio se centró en los cánceres de recto cT3 con fascia mesorrectal negativa.CONCLUSIONES:Un límite de 7 mm de distancia entre la invasión tumoral más profunda y la fascia mesorrectal en la resonancia magnética de referencia puede distinguir el cáncer de recto cT3 de diferentes pronósticos. Recomendamos la distancia entre la invasión tumoral más profunda y la fascia mesorrectal en la resonancia magnética de referencia para la evaluación del riesgo local y sistémico, proporcionando un programa personalizado de tratamiento neoadyuvante. Consulte Video Resumen en http://links.lww.com/DCR/B682. (Traducción- Dr. Francisco M. Abarca-Rendon).

Background Interferon regulatory factor 2 (IRF-2) acts as an anti-oncogene in gastric cancer (GC); however, the underlying mechanism remains unknown. Methods This study determined the expression of IRF-2 in GC tissues and adjacent non-tumor tissues using immunohistochemistry (IHC) and explored the predictive value of IRF-2 for the prognoses of GC patients. Cell function and xenograft tumor growth experiments in nude mice were performed to test tumor proliferation ability, both in vitro and in vivo. Chromatin immunoprecipitation sequencing (ChIP-Seq) assay was used to verify the direct target of IRF-2. Results We found that IRF-2 expression was downregulated in GC tissues and was negatively correlated with the prognoses of GC patients. IRF-2 negatively affected GC cell proliferation both in vitro and in vivo. ChIP-Seq assay showed that IRF-2 could directly activate AMER-1 transcription and regulate the Wnt/β-catenin signaling pathway, which was validated using IHC, in both tissue microarray and xenografted tumor tissues, western blot analysis, and cell function experiments. Conclusions Increased expression of IRF-2 can inhibit tumor growth and affect the prognoses of patients by directly regulating AMER-1 transcription in GC and inhibiting the Wnt/β-catenin signaling pathway.

Background:. The scale assessment was helpful in predicting the presence of antibodies to autoimmune encephalitis. This study aimed to evaluate the application of antibody prevalence in Chinese patients with epilepsy and encephalopathy (APE2-CHN) and response to immunotherapy in Chinese patients with epilepsy and encephalopathy (RITE2-CHN) for patients with different neuronal surface antibodies. Methods:. A total of 1365 patients with epileptic seizures as the prominent feature in Xuanwu Hospital, Capital Medical University, from June 2016 to June 2020 were enrolled in our study. Of these, 915 patients with epilepsy of unknown etiology whose serum and/or cerebrospinal fluid samples were examined for autoimmune antibodies were selected. All patients were scored with antibody prevalence in patients with epilepsy and encephalopathy (APE2), response to immunotherapy with epilepsy and encephalopathy (RITE2), APE2-CHN, and RITE2-CHN scores. Results:. Of the 915 patients, 191 patients were positive for neural-surface specific antibodies (115 N-methyl-D-aspartate receptor (NMDAR) Ab, 47 leucine-rich glioma-inactivated protein 1 (LGI1) Ab, 8 contactin-associated protein 2 (CASPR2) Ab, 4 AMPA2R-Ab, and 11 GABAR-B-Ab; 3 CASPR2-Ab and LGI1-Ab, 2 NMDAR-Ab and CASPR2-Ab, and 1 NMDAR-Ab and myelin-oligodendrocyte glycoprotein [MOG] Ab). The sensitivity and specificity of APE2 ≥4 in predicting the presence of neural-surface specific antibodies in our study were 74.35% and 81.77%, respectively, and the sensitivity and specificity of APE2-CHN ≥4 were 75.92% and 84.53%, respectively. Eight cases had an APE2 score

Background:. Patients’ recovery after surgery is the major concern for all perioperative clinicians. This study aims to minimize the side effects of peri-operative surgical stress and accelerate patients’ recovery of gastrointestinal (GI) function and quality of life after colorectal surgeries, an enhanced recovery protocol based on pre-operative rehabilitation was implemented and its effect was explored. Methods:. A prospective randomized controlled clinical trial was conducted, patients were recruited from January 2018 to September 2019 in this study. Patients scheduled for elective colorectal surgeries were randomly allocated to receive either standardized enhanced recovery after surgery (S-ERAS) group or enhanced recovery after surgery based on pre-operative rehabilitation (group PR-ERAS). In the group PR-ERAS, on top of recommended peri-operative strategies for enhanced recovery, formatted rehabilitation exercises pre-operatively were carried out. The primary outcome was the quality of GI recovery measured with I-FEED scoring. Secondary outcomes were quality of life scores and strength of handgrip; the incidence of adverse events till 30 days post-operatively was also analyzed. Results:. A total of 240 patients were scrutinized and 213 eligible patients were enrolled, who were randomly allocated to the group S-ERAS (n = 104) and group PR-ERAS (n = 109). The percentage of normal recovery graded by I-FEED scoring was higher in group PR-ERAS (79.0% vs. 64.3%, P 0.050). Conclusions:. Peri-operative rehabilitation exercise might be another benevolent factor for early recovery of GI function and life of quality after colorectal surgery. Newer, more surgery-specific rehabilitation recovery protocol merits further exploration for these patients. Trial Registration:. ChiCTR.org.cn, ChiCTR-ONRC-14005096

The morbidity and mortality of cardiovascular diseases (CVDs) are increasing worldwide and seriously threaten human life and health. Fibroblast growth factor 21 (FGF21), a metabolic regulator, regulates glucose and lipid metabolism and may exert beneficial effects on the cardiovascular system. In recent years, FGF21 has been found to act directly on the cardiovascular system and may be used as an early biomarker of CVDs. The present review highlights the recent progress in understanding the relationship between FGF21 and CVDs including coronary heart disease, myocardial ischemia, cardiomyopathy, and heart failure and also explores the related mechanism of the cardioprotective effect of FGF21. FGF21 plays an important role in the prediction, treatment, and improvement of prognosis in CVDs. This cardioprotective effect of FGF21 may be achieved by preventing endothelial dysfunction and lipid accumulating, inhibiting cardiomyocyte apoptosis and regulating the associated oxidative stress, inflammation and autophagy. In conclusion, FGF21 is a promising target for the treatment of CVDs, however, its clinical application requires further clarification of the precise role of FGF21 in CVDs.

Background:. Breast cancer patients with ipsilateral supraclavicular lymph node metastasis (ISLNM) but without distant metastasis are considered to have a poor prognosis. This study aimed to develop a nomogram to predict the overall survival (OS) of breast cancer patients with ISLNM but without distant metastasis. Methods:. Medical records of breast cancer patients who received surgical treatment at the Affiliated Cancer Hospital of Zhengzhou University, Jiyuan People's Hospital and Huaxian People's Hospital between December 21, 2012 and June 30, 2020 were reviewed retrospectively. Overall, 345 patients with pathologically confirmed ISLNM and without evidence of distant metastasis were identified. They were further randomized 2:1 and divided into training (n = 231) and validation (n = 114) cohorts. A nomogram to predict the probability of OS was constructed based on clinicopathologic variables identified by the univariable and multivariable analyses. The predictive accuracy and discriminative ability were measured by calibration plots, concordance index (C-index), and risk group stratification. Results:. Univariable analysis showed that estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), human epidermal growth factor receptor 2-positive (HER2+) with Herceptin treatment, and a low axillary lymph node ratio (ALNR) were prognostic factors for better OS. PR+, HER2+ with Herceptin treatment, and a low ALNR remained independent prognostic factors for better OS on multivariable analysis. These variables were incorporated into a nomogram to predict the 1-, 3-, and 5-year OS of breast cancer patients with ISLNM. The C-indexes of the nomogram were 0.737 (95% confidence interval [CI]: 0.660–0.813) and 0.759 (95% CI: 0.636–0.881) for the training and the validation cohorts, respectively. The calibration plots presented excellent agreement between the nomogram prediction and actual observation for 3 and 5 years, but not 1 year, OS in both the cohorts. The nomogram was also able to stratify patients into different risk groups. Conclusions:. In this study, we established and validated a novel nomogram for predicting survival of patients with ISLNM. This nomogram may, to some extent, allow clinicians to more accurately estimate prognosis and to make personalized therapeutic decisions for individual patients with ISLNM.

Background:. Obesity and insulin resistance (IR) are common features of polycystic ovary syndrome (PCOS). Metformin (MET) increases insulin sensitivity, but it is associated with unsatisfactory weight loss. The glucagon-like peptide-1 receptor agonist exenatide has been shown to reduce weight and IR in patients with diabetes. This study aimed to explore the therapeutic effects of exenatide once-weekly (QW) combined with MET on body weight, as well as metabolic and endocrinological parameters in overweight/obese women with PCOS. Methods:. Fifty overweight/obese women with PCOS diagnosed via the Rotterdam criteria were randomized to one of two treatment groups: MET (500 mg three times a day [TID]) or combination treatment (COM) (MET 500 mg TID, exenatide 2 mg QW) for 12 weeks. The primary outcomes were anthropometric changes associated with obesity, and the secondary outcomes included changes in reproductive hormone levels, glucose and lipid metabolism, and C-reactive protein. Results:. Forty (80%) patients completed the study. COM therapy was superior to MET monotherapy in reducing weight (P = 0.045), body mass index (BMI) (P = 0.041), and waist circumference (P = 0.023). Patients in the COM group on an average lost 3.8 ± 2.4 kg compared with 2.1 ± 3.0 kg in the MET group. In the COM group, BMI and waist circumference decreased by 1.4 ± 0.87 kg/m2 and 4.63 ± 4.42 cm compared with 0.77 ± 1.17 kg/m2 and 1.72 ± 3.07 cm in the MET group, respectively. Moreover, levels of fasting glucose, oral glucose tolerance test (OGTT) 2-h glucose, and OGTT 2-h insulin were significantly lower with COM therapy than with MET (P

Background:. Computed tomography (CT) and magnetic resonance imaging (MRI) data can be fused to identify the tumor boundaries. This enables surgeons to set close but tumor-free surgical margins and excise the tumor more precisely. This study aimed to report our experience in performing computer navigation-aided joint-preserving resection and custom-made endoprosthesis reconstruction to treat bone sarcoma in the diaphysis and metaphysis of the femur and tibia. Methods:. Between September 2008 and December 2015, 24 patients with bone sarcomas underwent surgical resection and joint-sparing reconstruction under image-guided computer navigation. The cohort comprised 16 males and eight females with a median age of 19.5 years (range: 12–48 years). The tumor location was the femoral diaphysis in three patients, distal femur in 19, and proximal tibia in two. The tumors were osteosarcoma (n = 15), chondrosarcoma (n = 3), Ewing sarcoma (n = 3), and other sarcomas (n = 3). We created a pre-operative plan for each patient using navigation system software and performed navigation-aided resection before reconstructing the defect with a custom-made prosthesis with extracortical plate fixation. Results:. Pathological examination verified that all resected specimens had appropriate surgical margins. The median distance from the tumor resection margin to the joint was 30 mm (range: 13–80 mm). The median follow-up duration was 62.5 months (range: 24–134 months). Of the 24 patients, 21 remain disease free, one is alive with disease, and two died of the disease. One patient developed local recurrence. Complications requiring additional surgical procedures occurred in six patients, including one with wound hematoma, one with delayed wound healing, one with superficial infection, one with deep infection, and two with mechanical failure of the prosthesis. The mean Musculoskeletal Tumor Society score at the final follow-up was 91% (range: 80%–100%). The 5- and 10-year implant survival rates were 91.3% and 79.9%, respectively. Conclusions:. Computer navigation-aided joint-preserving resection and custom-made endoprosthesis reconstruction with extracortical plate fixation is a reliable surgical treatment option for bone sarcoma in the diaphysis and metaphysis of the femur and tibia.

Purpose To assess the MRI performance in differentiating pancreatic ductal adenocarcinomas (PDACs), from solid pseudopapillary neoplasms (SPNs) and pancreatic neuroendocrine tumors (PNETs) using non-gaussian diffusion-weighted imaging models. Methods This was a retrospective study of patients diagnosed with PDACs (01/2015–06/2019) or with PNETs or SPNs diagnosed (01/2011–12/2019) at our hospital. The lesions were randomized 1:1 to the primary and validation cohorts. The regions of interest (ROIs) were manually drawn on each slice at DWI (b = 1500 s/mm2) from 3 T MRI. D (diffusion coefficient), D* (pseudodiffusion coefficient), f (perfusion fraction), distributed diffusion coefficient (DDC), α (diffusion heterogeneity index), mean diffusivity (MD) and mean kurtosis (MK) were obtained. The parameters with largest performance for differentiation were used to establish a diagnostic model. Results There were 148, 56, and 60 patients with PDAC, PNET, and SPN, respectively. For differentiating PDACs from SPNs, f and MK values were used to establish a diagnostic model with areas under the receiver operating characteristic curves (AUCs) of 0.92 and 0.89 in the primary and validation groups, respectively. For distinguishing PDACs from PNETs, α and MK values were used to establish a diagnostic model with AUCs of 0.87 and 0.86 in the primary and validation groups, respectively. The accuracy rate of the subjective evaluation with the assistance of non-gaussian DWI models for differentiating PDAC from SPNs and PNETs were higher than that of subjective diagnosis alone (P Conclusions The non-gaussian DWI models could assist radiologists in accurately differentiating PDACs from PNETs and SPNs.

Background:. Investigations of the pathogenic mechanisms in motor neurons (MNs) derived from amyotrophic lateral sclerosis (ALS) disease-specific induced pluripotent stem (iPS) cell lines could improve understanding of the issues affecting MNs. Therefore, in this study we explored mutant superoxide dismutase 1 (SOD1) protein expression in MNs derived from the iPS cell lines of ALS patients carrying different SOD1 mutations. Methods:. We generated induced pluripotent stem cell (iPSC) lines from two familial ALS (FALS) patients with SOD1-V14M and SOD1-C111Y mutations, and then differentiated them into MNs. We investigated levels of the SOD1 protein in iPSCs and MNs, the intracellular Ca2+ levels in MNs, and the lactate dehydrogenase (LDH) activity in the process of differentiation into the MNs derived from the controls and ALS patients’ iPSCs. Results:. The iPSCs from the two FALS patients were capable of differentiation into MNs carrying different SOD1 mutations and differentially expressed MN markers. We detected high SOD1 protein expression and high intracellular calcium levels in both the MN and iPSCs that were derived from the two SOD1 mutant patients. However, at no time did we observe stronger LDH activity in the patient lines compared with the control lines. Conclusions:. MNs derived from patient-specific iPSC lines can recapitulate key aspects of ALS pathogenesis, providing a cell-based disease model to further elucidate disease pathogenesis and explore gene repair coupled with cell-replacement therapy. Incremental mutant expressions of SOD1 in MNs may have disrupted MN function, either causing or contributing to the intracellular calcium disturbances, which could lead to the occurrence and development of the disease.

Background:. Ubiquitin-conjugating enzyme E2C (UBE2C) has been shown to be associated with the occurrence of various cancers and involved in many tumorigenic processes. This study aimed to investigate the specific molecular mechanism through which UBE2C affects breast cancer (BC) proliferation. Methods:. BC-related datasets were screened according to filter criteria in the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. Then differentially expressed genes (DEGs) were identified using Venn diagram analysis. By using DEGs, we conducted the following analyses including Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI), and survival analysis, and then validated the function of the hub gene UBE2C using quantitative reverse transcription-polymerase chain reaction (RT-qPCR), cell counting kit-8 (CCK-8) assay, transwell assay, and Western blot assay. Results:. In total, 151 DEGs were identified from the GEO and TCGA databases. The results of GO analysis demonstrated that the DEGs were significantly enriched with mitotic nuclear division, lipid droplet, and organic acid-binding. KEGG analysis showed that the peroxisome proliferators-activated receptor (PPAR) signaling pathway, regulation of lipolysis in adipocytes, and proximal tubule bicarbonate reclamation were significantly enriched in the signal transduction pathway category. The top three hub genes that resulted from the PPI network were FOXM1, UBE2C, and CDKN3. The results of survival analysis showed a close relationship between UBE2C and BC. The results of CCK-8 and transwell assays suggested that the proliferation and invasion of UBE2C knockdown cells were significantly inhibited (P

Wei Bai,1– 3,* Yanjie Zhao,1– 3,* Fengrong An,4,* Qinge Zhang,4,* Sha Sha,4,* Teris Cheung,5 Calvin Pak-Wing Cheng,6 Chee H Ng,7 Yu-Tao Xiang1– 3 1Unit of Psychiatry, Department of Public Health and Medicinal Administration, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macao SAR, People’s Republic of China; 2Centre for Cognitive and Brain Sciences, University of Macau, Macao SAR, People’s Republic of China; 3Institute of Advanced Studies in Humanities and Social Sciences, University of Macau, Macao SAR, People’s Republic of China; 4The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders Beijing Anding Hospital & the Advanced Innovation Center for Human Brain Protection, Capital Medical University, School of Mental Health, Beijing, People’s Republic of China; 5School of Nursing, Hong Kong Polytechnic University, Hong Kong SAR, People’s Republic of China; 6Department of Psychiatry, University of Hong Kong, Hong Kong SAR, People’s Republic of China; 7Department of Psychiatry, The Melbourne Clinic and St Vincent’s Hospital, University of Melbourne, Richmond, VIC, Australia*These authors contributed equally to this workCorrespondence: Yu-Tao XiangFaculty of Health Sciences, University of Macau, 1/F, Building E12, Avenida da Universidade, Taipa, Macao SAR, People’s Republic of ChinaTel +853 8822-4223Fax +853 2288-2314Email xyutly@gmail.comChee H NgDepartment of Psychiatry, The Melbourne Clinic and St Vincent’s Hospital, University of Melbourne, Richmond, VIC, AustraliaEmail cng@unimelb.edu.auPurpose: The coronavirus disease 2019 (COVID-19) pandemic is associated with increased risk of insomnia symptoms (insomnia hereafter) in health-care professionals. Network analysis is a novel approach in linking mechanisms at the symptom level. The aim of this study was to characterize the insomnia network structure in mental health professionals during the COVID-19 pandemic.Patients and Methods: A total of 10,516 mental health professionals were recruited from psychiatric hospitals or psychiatric units of general hospitals nationwide between March 15 and March 20, 2020. Insomnia was assessed with the insomnia severity index (ISI). Centrality index (ie, strength) was used to identify symptoms central to the network. The stability of network was examined using a case-dropping bootstrap procedure. The network structures between different genders were also compared.Results: The overall network model showed that the item ISI7 (interference with daytime functioning) was the most central symptom in mental health professionals with the highest strength. The network was robust in stability and accuracy tests. The item ISI4 (sleep dissatisfaction) was connected to the two main clusters of insomnia symptoms (ie, the cluster of nocturnal and daytime symptoms). No significant gender network difference was found.Conclusion: Interference with daytime functioning was the most central symptom, suggesting that it may be an important treatment outcome measure for insomnia. Appropriate treatments, such as stimulus control techniques, cognitive behavioral therapy and relaxation training, could be developed. Moreover, addressing sleep satisfaction in treatment could simultaneously ameliorate daytime and nocturnal symptoms.Keywords: sleep, insomnia, SARS-CoV-2, COVID-19, physicians

Background:. Existing clinical prediction models for in vitro fertilization are based on the fresh oocyte cycle, and there is no prediction model to evaluate the probability of successful thawing of cryopreserved mature oocytes. This research aims to identify and study the characteristics of pre-oocyte-retrieval patients that can affect the pregnancy outcomes of emergency oocyte freeze-thaw cycles. Methods:. Data were collected from the Reproductive Center, Peking University Third Hospital of China. Multivariable logistic regression model was used to derive the nomogram. Nomogram model performance was assessed by examining the discrimination and calibration in the development and validation cohorts. Discriminatory ability was assessed using the area under the receiver operating characteristic curve (AUC), and calibration was assessed using the Hosmer–Lemeshow goodness-of-fit test and calibration plots. Results:. The predictors in the model of “no transferable embryo cycles” are female age (odds ratio [OR] = 1.099, 95% confidence interval [CI] = 1.003–1.205, P = 0.0440), duration of infertility (OR = 1.140, 95% CI = 1.018–1.276, P = 0.0240), basal follicle-stimulating hormone (FSH) level (OR = 1.205, 95% CI = 1.051–1.382, P = 0.0084), basal estradiol (E2) level (OR = 1.006, 95% CI = 1.001–1.010, P = 0.0120), and sperm from microdissection testicular sperm extraction (MESA) (OR = 7.741, 95% CI = 2.905–20.632, P 10 mm on the day of hCG administration.

Background Esophageal fistula is one of the most serious complications of chemotherapy or chemoradiotherapy (CRT) for advanced esophageal cancer. This study aimed to evaluate the performance of quantitative computed tomography (CT) analysis and to establish a practical imaging model for predicting esophageal fistula in esophageal cancer patients treated with chemotherapy or chemoradiotherapy. Methods This study retrospectively enrolled 204 esophageal cancer patients (54 patients with fistula, 150 patients without fistula) and all patients were allocated to the primary and validation cohorts according to the time of inclusion in a 1:1 ratio. Ulcer depth, tumor thickness and length, and minimum and maximum enhanced CT values of esophageal cancer were measured in pretreatment CT imaging. Logistic regression analysis was used to evaluate the associations of CT quantitative measurements with esophageal fistula. Receiver operating characteristic curve (ROC) analysis was also used. Results Logistic regression analysis showed that independent predictors of esophageal fistula included tumor thickness [odds ratio (OR) = 1.167; p = 0.037], the ratio of ulcer depth to adjacent tumor thickness (OR = 164.947; p p = 0.039) in the primary cohort at baseline CT imaging. These predictors were used to establish a predictive model for predicting esophageal fistula, with areas under the receiver operating characteristic curves (AUCs) of 0.946 and 0.841 in the primary and validation cohorts, respectively. The quantitative analysis combined with T stage for predicting esophageal fistula had AUCs of 0.953 and 0.917 in primary and validation cohorts, respectively. Conclusion Quantitative pretreatment CT analysis has excellent performance for predicting fistula formation in esophageal cancer patients who treated by chemotherapy or chemoradiotherapy.

Bitter melon (Momordica charantia) has traditionally been used in the management of diabetes in many countries and territories. However, standardized information on the use of this vegetable as an ...

Background:. Pregnancy-associated breast cancer (PABC) is a special type of breast cancer that occurs during pregnancy and within 1 year after childbirth. With the rapid social development and the adjustment of reproductive policies in China, the average age of females at first childbirth is increasing, which is expected to lead to an increase in the incidence of PABC. This study aimed to accumulate clinical experience and to investigate and summarize the prevalence, diagnosis, and treatment of PABC based on large multicenter samples in China. Methods:. According to the Chinese Society of Breast Surgery, a total of 164 patients with PABC in 27 hospitals from January 2016 to December 2018 were identified. The pregnancy status, clinicopathological features, comprehensive treatment methods, and outcomes were retrospectively analyzed. Survival curves were plotted using the Kaplan-Meier method. Results:. A total of 164 patients of PABC accounted for 0.30% of the total number of cases in the same period; of which, 83 patients were diagnosed during pregnancy and 81 patients during lactation. The median age of PABC was 33 years (24–47 years). Stage I patients accounted for 9.1% (15/164), stage II 54.9% (90/164), stage III 24.4% (40/164), and stage IV 2.4% (4/164). About 9.1% (15/164) of patients were luminal A. Luminal B patients accounted the most (43.3% [71/164]). About 15.2% (25/164) of patients were human epidermal growth factor receptor 2 (Her-2) overexpression and 18.9% (31/164) of patients were triple-negative breast cancer. For pregnancy breast cancer, 36.1% (30/83) of patients received direct surgery and 20.5% (17/83) received chemotherapy during pregnancy. About 31.3% (26/83) chose abortion or induction of labor. The median follow-up time was 36 months (3–59 months); 11.0% (18/164) patients had local recurrence or distant metastasis and 3.0% (5/164) died. Conclusions:. It is safe and feasible to standardize surgery and chemotherapy for PABC.

Background:. Multiple techniques are commonly used for posterior cruciate ligament (PCL) reconstruction. However, the optimum method regarding the fixation of PCL reconstruction after PCL tears remains debatable. The purpose of this study was to compare the biomechanical properties among three different tibial fixation procedures for transtibial single-bundle PCL reconstruction. Methods:. Thirty-six porcine tibias and porcine extensor tendons were randomized into three fixation study groups: the interference screw fixation (IS) group, the transtibial tubercle fixation (TTF) group, and TTF + IS group (n = 12 in each group). The structural properties of the three fixation groups were tested under cyclic loading and load-to-failure. The slippage after the cyclic loading test and the stiffness and ultimate failure load after load-to-failure testing were recorded. Results:. After 1000 cycles of cyclic testing, no significant difference was observed in graft slippage among the three groups. For load-to-failure testing, the TTF + IS group showed a higher ultimate failure load than the TTF group and the IS group (876.34 ± 58.78 N vs. 660.92 ± 77.74 N [P

Background:. Functional mitral regurgitation (FMR) is common in critically ill patients and may cause left atrial (LA) pressure elevation. This study aims to explore the prognostic impact of synergistic LA pressure elevation and FMR in patients with shock. Methods:. We retrospectively screened 130 consecutive patients of 175 patients with shock from April 2016 to June 2017. The incidence and impact of FMR and early diastolic transmitral velocity to early mitral annulus diastolic velocity ratio (E/e’) ≥ 4 within 6 h of shock on the prognosis of patients were evaluated. Finally, the synergistic effect of FMR and E/e’ were assessed by combination, grouping, and trend analyses. Results:. Forty-four patients (33.8%) had FMR, and 15 patients (11.5%) had E/e’ elevation. A multivariate analysis revealed FMR and E/e’ as independent correlated factors for 28-day mortality (P = 0.043 and 0.028, respectively). The Kaplan-Meier survival analysis revealed a significant difference in survival between patients with and without FMR (χ2 = 7.672, P = 0.006) and between the E/e’ ≥ 14 and E/e’ < 14 groups (χ2 = 19.351, P

Background:. Age-related macular degeneration (AMD) is the leading cause of vision loss worldwide. However, the mechanisms involved in the development and progression of AMD are poorly delineated. We aimed to explore the critical genes involved in the progression of AMD. Methods:. The differentially expressed genes (DEGs) in AMD retinal pigment epithelial (RPE)/choroid tissues were identified using the microarray datasets GSE99248 and GSE125564, which were downloaded from the gene expression omnibus database. The overlapping DEGs from the two datasets were screened to identify DEG-related biological pathways using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The hub genes were identified from these DEGs through protein-protein interaction network analyses. The expression levels of hub genes were evaluated by quantitative real-time polymerase chain reaction following the induction of senescence in ARPE-19 with FK866. Following the identification of AMD-related key genes, the potential small molecule compounds targeting the key genes were predicted by PharmacoDB. Finally, a microRNA-gene interaction network was constructed. Results:. Microarray analyses identified 174 DEGs in the AMD RPE compared to the healthy RPE samples. These DEGs were primarily enriched in the pathways involved in the regulation of DNA replication, cell cycle, and proteasome-mediated protein polyubiquitination. Among the top ten hub genes, HSP90AA1, CHEK1, PSMA4, PSMD4, and PSMD8 were upregulated in the senescent ARPE-19 cells. Additionally, the drugs targeting HSP90AA1, CHEK1, and PSMA4 were identified. We hypothesize that Hsa-miR-16-5p might target four out of the five key DEGs in the AMD RPE. Conclusions:. Based on our findings, HSP90AA1 is likely to be a central gene controlling the DNA replication and proteasome-mediated polyubiquitination during the RPE senescence observed in the progression of AMD. Targeting HSP90AA1, CHEK1, PSMA4, PSMD4, and/or PSMD8 genes through specific miRNAs or small molecules might potentially alleviate the progression of AMD through attenuating RPE senescence.

In endovascular and cardiovascular surgery, real-time guidewire morphological and positional analysis is an important prerequisite for robot-assisted intervention, which can aid in reducing the radiation dose, contrast agent, and procedure time. Nevertheless, this task often comes with the challenge of the deformable elongated structure with low contrast in noisy X-ray fluoroscopy. In this article, a real-time multifunctional framework is proposed for fully automatic guidewire morphological and positional analysis, namely, guidewire segmentation, endpoint localization, and angle measurement. In the first stage, the proposed fast attention recurrent network (FAR-Net) achieves real-time and accurate guidewire segmentation. In the second stage, the endpoint localization and angle measurement algorithm robustly obtain subpixel-level endpoint and angle of the guidewire tip. Quantitative and qualitative evaluations on the MSGSeg data set consisting of 180 X-ray sequences from 30 patients demonstrate that the proposed framework significantly outperforms simpler baselines as well as the best previously published result for this task. The proposed approach reached ${F_{1}}$ -Score of 0.938, mean distance error of 0.596 pixels, endpoint localization and angle measurement accuracy of 97.8% and 95.3%, and an inference rate of approximately 13 FPS. The proposed framework not only addresses the issues of extreme class imbalance and misclassified examples but also meets the real-time requirements, achieving state-of-the-art performance. The proposed approach is promising for integration into robotic navigation frameworks to various intravascular applications, enabling robotic-assisted intervention.

Background:. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder associated with loss of motor neurons. Our objective was to explore the epidemiology, clinical features, and survival factors of 1809 patients with ALS. Methods:. We analyzed 1809 ALS patients, who were recruited from the Peking University Third Hospital from January 2005 to December 2015. Demographic data and disease-related parameters were collected. Kaplan-Meier curves were used to compare survival time. Cox proportional hazards function and the hazard ratio were used to identify adjusted prognostic predictors. Results:. The results showed that the average annual incidence in Beijing alone was 0.38 cases/100,000 person-years and the mean age of onset was 48.88 ± 11.35 (95% confidence interval [CI]: 48.17–49.85) years. The median survival time from onset to death/tracheostomy was 58.89 ± 33.03 (95% CI: 51.46–63.84) months. In the adjusted Cox proportional hazard model, age of onset, diagnosis delay, rate of disease progression (Amyotrophic Lateral Sclerosis Functional Rating Scale Revised decline [points/month]), and body mass index all had an independent effect on survival in ALS. Conclusions:. Our study provides information on epidemiology, clinical features, and survival factors of patients with ALS in China. These results can be helpful in clinical practice, clinical trial design, and validation of new tools to predict disease progression.

Background:. Unawareness of stroke symptoms and low income are two barriers that affect the seeking of emergency medical service (EMS). This study aimed to assess the effect of unawareness and low income on seeking EMS and to investigate the regional distribution of the unawareness and low-income status and their associations with failing to call EMS in China. Methods:. A total of 187,723 samples from the China National Stroke Screening Survey was interviewed cross-sectionally. Four status of awareness and annual income were identified: unaware and low-income, unaware-only, low-income-only, and aware and regular income. The outcomes were whether they intended to call EMS or not. The regional distribution of each status and their associations with not calling EMS were presented. Results:. The status of unaware and low-income, unaware-only, and low-income-only accounted for 6.3% (11,806/187,673), 11.9% (22,241/187,673), and 21.5% (40,289/187,673) of the total sample, respectively. Not calling EMS was significantly associated with the status of unaware and low-income (odds ratio [OR]: 3.21, 95% confidence interval [CI]: 3.07–3.35), unaware-only (OR: 2.38, 95% CI: 2.31–2.46), and low-income-only (OR: 1.67, 95% CI: 1.63–1.71), compared with the aware and regular income status. The Midwest regions had higher percentages of people in the unaware and low-income status; the East, South, and Central had higher percentages of unaware-only status; the North and Northeast regions had a higher percentage of low-income-only status, compared with other regions. Conclusion:. The existence of the regional difference in unawareness and low income justifies the specific stroke education strategies for the targeted regions and population.

BACKGROUND Primary extra-pancreatic pancreatic-type acinar cell carcinoma (ACC) is a rare malignancy, and has only been reported in the gastrointestinal tract, liver, and lymph nodes until now. Extra-pancreatic pancreatic-type ACC in the perinephric space has not been reported. Herein, we report the first case of ACC in the perinephric space and describe its clinical and imaging features, which should be considered when differentiating perinephric space neoplasms. CASE SUMMARY A 48-year-old man with a 5-year history of hypertension was incidentally found to have an asymptomatic right retroperitoneal mass during a routine health check-up. Laboratory tests were normal. Abdominal computed tomography and magnetic resonance imaging showed an oval hypervascular mass with a central scar and enhanced capsule in the right perinephric space. After surgical resection of the neoplasm, the diagnosis was primary extra-pancreatic pancreatic-type ACC. The patient was alive without recurrence or metastasis during a 15-mo follow-up. CONCLUSION This is the first report of an extra-pancreatic ACC in right perinephric space, which should be considered as a possible diagnosis in perinephric tumors.

The influences of superheat and cooling intensity on macrostructure and macrosegregation of one new kind duplex stainless steel (DSS) were studied. Thermal simulation equipment was applied to prepare samples, which could reproduce the industrial processes of DSS manufactured by a vertical continuous slab caster. Macrostructure and macrosegregation were analyzed using the digital single lens reflex and laser-induced breakdown spectroscope (LIBSOPA-200), respectively. The percentage of both chill zone and center equiaxed zone increases with the superheat decreasing, while that of the columnar zone decreases. There is only equiaxed grain existing as the superheat is 10 and 20 °C. The lower the superheat is, the coarser the gain size is. High cooling intensity in mold could remarkably decrease the chill zone length and refine the grains in chill zone and center equiaxed zone. The influences of cooling intensity on macrosegregation are greater than those of superheat. The macrosegregation of Si, Mn and Cr is slightly dependent on superheat, while that of Cu, Mo and Ni changes greatly with superheat increasing.

Background: The 2019 coronavirus disease (COVID-19) pandemic has impacted the mental health and well-being of medical personnel, including nursing students. Network analysis provides a deeper characterization of symptom-symptom interactions in mental disorders. The aim of this study was to elucidate characteristics of anxiety and depressive symptom networks of Chinese nursing students during the COVID-19 pandemic. Method: A total of 932 nursing students were included. Anxiety and depressive symptom were measured using the seven-item Generalized Anxiety Disorder Scale (GAD-7) and two-item Patient Health Questionnaire (PHQ-2), respectively. Central symptoms and bridge symptoms were identified via centrality indices and bridge centrality indices, respectively. Network stability was examined using the case-dropping procedure. Results: Irritability, Uncontrollable worry, Trouble relaxing, and Depressed mood had the highest centrality values. Three bridge symptoms (Depressed mood, Nervousness, and Anhedonia) were also identified. Neither gender nor region of residence was associated with network global strength, distribution of edge weights or individual edge weights. Limitations: Data were collected in a cross-sectional study design, therefore, causal relations and dynamic changes between anxiety and depressive symptoms over time could not be inferred. Generalizability of findings may be limited to Chinese nursing students during a particular phase of the current pandemic. Conclusions: Irritability, Uncontrollable worry, Trouble relaxing, and Depressed mood constituted central symptoms maintaining the anxiety-depression network structure of Chinese nursing students during the pandemic. Timely, systemic multi-level interventions targeting central symptoms and bridge symptoms may be effective in alleviating co-occurring experiences of anxiety and depression in this population.

Background:. Deep brain stimulation (DBS) has seizure-suppressing effects but the molecular mechanisms underlying its therapeutic action remain unclear. This study aimed to systematically elucidate the mechanisms underlying DBS-induced seizure suppression at a molecular level. Methods:. We established a macaque model of mesial temporal lobe epilepsy (mTLE), and continuous high-frequency hippocampus DBS (hip-DBS) was applied for 3 months. The effects of hip-DBS on hippocampus gene expression were examined using high-throughput microarray analysis followed by bioinformatics analysis. Moreover, the microarray results were validated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses. Results:. The results showed that chronic hip-DBS modulated the hippocampal gene expression. We identified 4119 differentially expressed genes and assigned these genes to 16 model profiles. Series test of cluster analysis showed that profiles 5, 3, and 2 were the predominant expression profiles. Moreover, profile 5 was mainly involved in focal adhesion and extracellular matrix-receptor interaction pathway. Nine dysregulated genes (Arhgap5, Col1a2, Itgb1, Pik3r1, Lama4, Fn1, Col3a1, Itga9, and Shc4) and three genes (Col1a2, Itgb1, and Flna) in these two pathways were further validated by qRT-PCR and Western blot analyses, respectively, which showed a concordance. Conclusion:. Our findings suggest that hip-DBS could markedly reverse mTLE-induced abnormal gene expression. Findings from this study establish the basis for further investigation of the underlying regulatory mechanisms of DBS for mTLE.

Background:. Geriatric hip fracture patients receiving clopidogrel are a surgical challenge. In China, most of these patients undergo delayed surgical treatment after clopidogrel withdrawal for at least 5 to 7 days. However, delayed surgery is associated with increased complications and mortality in the older adults. This retrospective paralleled comparison study investigated the safety of early surgery for geriatric hip fracture patients within 5 days of clopidogrel withdrawal. Methods:. Acute hip fracture patients (≥65 years) who were hospitalized in the orthogeriatric co-management ward of Beijing Jishuitan Hospital between November 2016 and April 2018 were retrospectively reviewed. Sixty patients taking clopidogrel before injury and discontinued 0.050). The percentages of patients with coronary heart disease (61.7% vs. 18.3%; P 0.050). There was no significant difference in perioperative complications, and 30-day and 1-year mortality rates between the groups. Conclusions:. Early hip fracture surgery is safe for elderly patients within 5 days of clopidogrel withdrawal, without increased perioperative blood loss, transfusion requirement, complications, and mortality compared with patients not taking antiplatelet drugs.

Background::Glucose control is an important aspect in managing critically ill patients. The goal of this study was to compare the effects of sequential feeding (SF) and continuous feeding (CF) on the blood glucose of critically ill patients.Methods::A non-inferiority randomized controlled trial was adopted in this study. A total of 62 patients who were fed enteral nutritional suspension through gastric tubes were enrolled. After achieving 80% of the nutrition target calories (25 kcal·kg -1·day -1) through CF, the patients were then randomly assigned into SF and CF groups. In the SF group, the feeding/fasting time was reasonably determined according to the circadian rhythm of the human body as laid out in traditional Chinese medicine theory. The total daily dosage of the enteral nutritional suspension was equally distributed among three time periods of 7 to 9 o’clock, 11 to 13 o’clock, and 17 to 19 o’clock. The enteral nutritional suspension in each time period was pumped at a uniform rate within 2 h by an enteral feeding pump. In the CF group, patients received CF at a constant velocity by an enteral feeding pump throughout the study. Blood glucose values at five points (6:00/11:00/15:00/21:00/1:00) were monitored and recorded for seven consecutive days after randomization. Enteral feeding intolerance was also recorded. Non-inferiority testing was adopted in this study, the chi-square test or Fisher test was used for qualitative data, and the Mann-Whitney U test was used for quantitative data to determine differences between groups. In particular, a repeated measure one-way analysis of variance was used to identify whether changes in glucose value variables across the time points were different between the two groups. Results::There were no significant demographic or physiological differences between the SF and CF groups ( P > 0.050). The average glucose level in SF was not higher than that in CF (8.8 [7.3-10.3] vs. 10.7 [9.1-12.1] mmol/L, Z = -2.079, P for non-inferiority = 0.019). Hyperglycemia incidence of each patient was more common in the CF group than that in the SF group (38.4 [19.1-63.7]% vs. 11.8 [3.0-36.7]%, Z = -2.213, P = 0.027). Hypoglycemia was not found in either group. Moreover, there was no significant difference during the 7 days in the incidence of feeding intolerance ( P > 0.050). Conclusions::In this non-inferiority study, the average blood glucose in SF was not inferior to that in CF. The feeding intolerance in SF was similar to that in CF. SF may be as safe as CF for critically ill patients.Trial Registration:ClinicalTrials.gov, NCT03439618; https://clinicaltrials.gov/ct2/show/record/NCT03439618

Background:. According to the amyloid, tau, neurodegeneration research framework classification, amyloid and tau positive (A+T+) mild cognitive impairment (MCI) individuals are defined as prodromal Alzheimer disease. This study was designed to compare the clinical and biomarker features between A+T+MCI individuals who progressed to progressive MCI (pMCI) and those who remained stable MCI (sMCI), and to identify relevant baseline clinical biomarker and features that could be used to predict progression to dementia within 2 years. Methods:. We stratified 197 A+T+MCI individuals into pMCI (n = 64) and sMCI (n = 133) over 2 years. Demographics and cognitive assessment scores, cerebrospinal fluid (CSF), and neuroimaging biomarkers (18F-florbetapir positron emission tomography mean standardized uptake value ratios [SUVR] and structural magnetic resonance imaging [MRI]) were compared between pMCI and sMCI at baseline, 12- and 24-month follow-up. Logistic regression models then were used to evaluate clinical baseline and biomarker features that predicted dementia progression in A+T+MCI. Results:. pMCI individuals had higher mean 18F-florbetapir SUVR, CSF total-tau (t-tau), and p-tau181P than those in sMCI individuals. pMCI individuals performed poorer in cognitive assessments, both global and domain specific (memory, executive, language, attention, and visuospatial skills) than sMCI. At baseline, there were significant differences in regions of interest of structural MRI between the two groups, including bilateral amygdala, hippocampus and entorhinal, bilateral inferior lateral ventricle, left superior and middle temporal, left posterior and caudal anterior cingulate (P

Background:. Various prediction tools have been developed to predict biochemical recurrence (BCR) after radical prostatectomy (RP); however, few of the previous prediction tools used serum prostate-specific antigen (PSA) nadir after RP and maximum tumor diameter (MTD) at the same time. In this study, a nomogram incorporating MTD and PSA nadir was developed to predict BCR-free survival (BCRFS). Methods:. A total of 337 patients who underwent RP between January 2010 and March 2017 were retrospectively enrolled in this study. The maximum diameter of the index lesion was measured on magnetic resonance imaging (MRI). Cox regression analysis was performed to evaluate independent predictors of BCR. A nomogram was subsequently developed for the prediction of BCRFS at 3 and 5 years after RP. Time-dependent receiver operating characteristic (ROC) curve and decision curve analyses were performed to identify the advantage of the new nomogram in comparison with the cancer of the prostate risk assessment post-surgical (CAPRA-S) score. Results:. A novel nomogram was developed to predict BCR by including PSA nadir, MTD, Gleason score, surgical margin (SM), and seminal vesicle invasion (SVI), considering these variables were significantly associated with BCR in both univariate and multivariate analyses (P

Background:. It remains unclear whether the outcomes of ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI) during off-hours are as favorable as those treated during on-hours, especially those with a first medical contact-to-device (FMC-to-device) time within 90 min. We aimed to determine whether off-hours admission impacted late outcomes in patients undergoing PPCI and with an FMC-to-device time ≤90 min. Methods:. This multicenter retrospective study included 670 STEMI patients who underwent successful PPCI and had an FMC-to-device time ≤90 min from 19 chest pain centers in Beijing from January 2018 to December 2018. Patients were divided into on-hours group and off-hours group based on their arrival time. Baseline characteristics, clinical data, and key time intervals during treatment were collected from the Quality Control & Improvement Center of Cardiovascular Intervention of Beijing by the “Heart and Brain Green Channel” app. Results:. Overall, the median age of the patients was 58.8 years and 19.9% (133/670) were female. Of these, 296 (44.2%) patients underwent PPCI during on-hours and 374 (55.8%) patients underwent PPCI during off-hours. Compared with the on-hours group, the off-hours group had a longer FMC-to-device time and fewer patients with FMC-to-device time ≤60 min (P 0.05). According to the Cox regression analyses, off-hours admission was not a predictor of 2-year MACEs (P = 0.788). Similarly, the Kaplan-Meier curves showed that the risks of a MACE, all-cause death, reinfarction, and target vessel revascularization were not significantly different between the two groups (P > 0.05). Conclusions:. This real-world, multicenter retrospective study demonstrated that for STEMI patients who underwent PPCI within 90 min, off-hours admission was safe, with no difference in the risk of 2-year MACEs compared with those with on-hours admission.

Background Atrial fibrillation (AF) represents the most common clinical cardiac arrhythmia and substantially increases the risk of cerebral stroke, heart failure, and death. Although causative genes for AF have been identified, the genetic determinants for AF remain largely unclear. Objective This study aimed to investigate the molecular basis of AF in a Chinese kindred. Methods A 4-generation family with autosomal-dominant AF and other arrhythmias (atrioventricular block, sinus bradycardia, and premature ventricular contractions) was recruited. Genome-wide scan with microsatellite markers and linkage analysis as well as whole-exome sequencing analysis were performed. Electrophysiological characteristics and subcellular localization of the AF-linked mutant were analyzed using dual whole-cell patch clamps and confocal microscopy, respectively. Results A novel genetic locus for AF was mapped to chromosome 17q21.3, a 3.23-cM interval between markers D17S951 and D17S931, with a maximum 2-point logarithm of odds score of 4.2144 at marker D17S1868. Sequencing analysis revealed a heterozygous mutation in the mapping region, NM_005497.4:c.703A>T;p.(M235L), in the GJC1 gene encoding connexin45 (Cx45). The mutation cosegregated with AF in the family and was absent in 632 control individuals. The mutation decreased the coupling conductance in cell pairs (M235L/M235L, M235L/Cx45, M235L/Cx43, and M235L/Cx40), likely because of impaired subcellular localization. Conclusion This study defines a novel genetic locus for AF on chromosome 17q21.3 and reveals a loss-of-function mutation in GJC1 (Cx45) contributing to AF and other cardiac arrhythmias.

Background:. Reviving patients with prolonged disorders of consciousness (DOCs) has always been focused and challenging in medical research. Owing to the limited effectiveness of available medicine, recent research has increasingly turned towards neuromodulatory therapies, involving the stimulation of neural circuits. We summarised the progression of research regarding neuromodulatory therapies in the field of DOCs, compared the differences among different studies, in an attempt to explore optimal stimulation patterns and parameters, and analyzed the major limitations of the relevant studies to facilitate future research. Methods:. We performed a search in the PubMed database, using the concepts of DOCs and neuromodulation. Inclusion criteria were: articles in English, published after 2002, and reporting clinical trials of neuromodulatory therapies in human patients with DOCs. Results:. Overall, 187 published articles met the search criteria, and 60 articles met the inclusion criteria. There are differences among these studies regarding the clinical efficacies of neurostimulation techniques for patients with DOCs, and large-sample studies are still lacking. Conclusions:. Neuromodulatory techniques were used as trial therapies for DOCs wherein their curative effects were controversial. The difficulties in detecting residual consciousness, the confounding effect between the natural course of the disease and therapeutic effect, and the heterogeneity across patients are the major limitations. Large-sample, well-designed studies, and innovations for both treatment and assessment are anticipated in future research.

Background:. Vitamin D deficiency has been reported to be associated with diabetic microvascular complications, but previous studies have only focused on the relationship between vitamin D and specific complications. Therefore, we aimed to explore the relationship between vitamin D level and diabetic microvascular complications in general, including diabetic retinopathy (DR), diabetic nephropathy (DN), and diabetic peripheral neuropathy (DPN). Methods:. This was a cross-sectional study of 815 patients with type 2 diabetes mellitus (T2DM). Clinical information and laboratory results were collected from the medical records. The relationship between vitamin D and the three diabetic microvascular complications was investigated. Results:. The serum 25-hydroxyvitamin D (25 [OH] D) level of patients with DPN and/or DN was significantly lower than that of T2DM patients without any microvascular complications (P

Background:. It is currently unknown whether patients with a fever after controlled ovulation during egg retrieval could increase the risk of pelvic infection or not, and fever itself may affect endometrial receptivity or embryo quality with poor pregnancy outcomes. The aim of this study was to analyze the outcomes of patients with fever during oocyte retrieval after the first frozen-thawed embryo transfer (FET) cycle. Methods:. This was a 1:3 retrospective paired study matched for age. In this study, 58 infertility patients (Group 1) had a fever during the control ovulation, and the time of the oocyte retrieval was within 72 hours, they underwent ovum pick up and whole embryo freezing (“freeze-all” strategy). The control subjects (Group 2) are 174 patients matched for age who underwent whole embryo freezing for other reasons. The baseline characteristics, clinical data of ovarian stimulation, and outcomes, such as the clinical pregnancy rate, ongoing clinical pregnancy rate were compared between the two groups in the subsequent FET cycle. Results:. All patients had no pelvic inflammatory disease after oocyte retrieval. Anti-Mullerian hormone (AMH) levels (4.2 vs. 2.2, P