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Prescriptions for biologic therapy for treatment of Crohn's disease (CD) and ulcerative colitis (UC) have increased during the past two decades; however, trends are less clear regarding corticosteroid prescriptions in this context. We designed a cross-sectional study using the IQVIA Ambulatory Electronic Medical Records databases. Weighted linear regressions by age group were used to estimate annual percentage change from 2011 to 2020 in prescriptions for biologics and for corticosteroids among patients with or without biologic prescriptions within the same calendar year. Using 2019 data, we compared patient demographic and lifestyle risk factors using χ2 test for biologic prescriptions and corticosteroids with or without biologics prescriptions. There was an 11% (CD) and 16% (UC) annual increase in the percentage of patients prescribed biologics during the study period. The percentage of patients with biologics prescriptions prescribed corticosteroids decreased by 2% (CD) and 3% (UC) annually after 2015, while the percentage remained unchanged for corticosteroid prescriptions among patients without biologics. In 2019, differences in medication prescriptions existed by patient's demographic and lifestyle factors for patients with CD (n=52,892) and UC (n=52,280), including a higher percentage prescribed biologics among younger patients, men, those with fewer comorbidities, and current alcohol drinkers, and a higher percentage prescribed corticosteroids without biologics among women, those with more comorbidities, and a history of smoking. While medications continue to evolve during the biologic era, it is important to continue to monitor trends and differences in prescription patterns to assess progress toward optimizing treatment for patients with CD or UC.

Lung cancer is one of the most prevalent and malignant cancers, among which lung adenocarcinoma (LUAD) accounts for the majority and remains a major cause of cancer-related mortality worldwide (Cui et al., 2019). Despite the growing intensity of research on the pathobiology and progression of lung cancer and the fact that many genes have been identified as potential drivers and targets for therapy (Luo et al., 2019; Zhang et al., 2019), the treatment and prognosis of lung cancer patients have hardly improved. Therefore, this study aimed to investigate the precise mechanism of lung cancer development and explore efficient diagnostic and therapeutic methods for clinical treatment.

At-risk alcohol consumption is the established most important risk factor for cirrhosis in people without HBV/HCV infection. We aimed to develop and validate a simple and non-invasive tool for triaging cirrhosis risk in at-risk alcohol drinkers without HBV/HCV infection. A large-sample size, cross-sectional study within the framework of a population-based Cancer Screening Program in Urban China (CanSPUC) was conducted. Data on the liver cancer screening in Henan province, China were used. At-risk alcohol drinkers were those who currently drink one or more alcohol units per week for at least six months. A total of 6,581 eligible participants enrolled from October 1, 2013 to December 31, 2016 were included into the derivation dataset, and 2,096 eligible participants enrolled from January 1, 2017 to October 31, 2018 were included into the external validation dataset, respectively. Using the derivation dataset, a 20-point scale risk score model was developed, based on sex, education background, dietary intake of vegetables, dietary intake of roughage, smoking index, length of secondhand smoke exposure, history of fatty liver, history of diabetes, and first-degree family history of liver cancer. The model showed excellent discrimination (AUC = 0.787; 95% CI, 0.7603–0.812) and calibration (Hosmer–Lemeshow test: P = 0.123) in the derivation dataset and an optimal cut-off value of 12 yield sensitivity of 61.3%, specificity of 82.7%. The model also had achieved similar performance in the external validation dataset. In conclusion, this model can be a practical tool to identify and triage population at high risk of cirrhosis in at-risk alcohol drinkers without HBV/HCV infection. Prevention Relevance: The risk model we developed will not only be used as a practical tool to triage high risk groups for liver cirrhosis, but also have implications for public health measures, such as guidelines for the prevention of liver cancer, in at-risk alcohol drinkers without HBV/HCV infection.

Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) has recently been employed as a novel treatment for gastric outlet obstruction (GOO). The aim of this study was to evaluate the safety and efficacy of EUS-GE for GOO at different sites.Consecutive hospitalized patients who underwent EUS-GE for GOO at the Department of Gastroenterology, Nanjing Drum Tower Hospital from March 2017 to April 2020 were recruited in this retrospective study. Patients were divided into three groups depending on the obstruction site. The primary outcomes included technical success and clinical success. The secondary outcomes were operation time, post-procedure length of stay (LOS), hospitalization cost, and complications such as peritonitis, bleeding, pneumoperitoneum, abdominal pain, and infection.A total of 51 patients were included. Technical success achieved in 100% patients with proximal GOO and in 88.9% with distal GOO (P = 0.176). Clinical success declined from the oral side to the anal side (P = 0.510). Operation time, hospitalization costs, and post-procedural LOS were similar among groups (P = 0.532, 0.520, and 0.144, respectively). Complications were observed in 28 (54.9%) patients. In approaching the mature phase of the endosopist, clinical success improved, while the secondary outcomes showed no statistically significant difference compared with the initial phase.EUS-GE may be challenging for distal GOO; however, it is safe and effective when carried out by experienced endoscopists. A complete preoperative evaluation to assess the difficulty of the procedure is necessary. Prospective studies with large sample size are needed to further validate our findings.

We aimed to determine participation in low-dose computed tomography (LDCT) of individuals with a family history of common cancers in a population-based screening program to provide timely evidence in high-risk populations in China. The analysis was conducted using data from the Cancer Screening Program in Urban China (CanSPUC), which recruited 282 377 participants aged 40 to 74 years from eight cities in the Henan province. Using the CanSPUC risk score system, 55 428 participants were evaluated to have high risk for lung cancer and were recommended for LDCT. We calculated the overall and group-specific participation rates using family history of common cancers and compared differences in participation rates between different groups. Odds ratios (ORs) and 95% confidence intervals were derived by multivariable logistic regression. Of the 55 428 participants, 22 260 underwent LDCT (participation rate, 40.16%). Family history of lung, esophageal, stomach, liver and colorectal cancer was associated with increased participation in LDCT screening. The odds of participants with a family history of one, two, three and four or more cancer cases undergoing LDCT screening were 1.9, 2.7, 2.8 and 3.5 times, respectively, than those without a family history of cancer. Compared to those without a history of cancer, participation in LDCT gradually increased as the number of cancer cases in the family increased (P .001). Our findings suggest that there is room for improvement in lung cancer screening given the relatively low participation rate. Lung cancer screening in populations with a family history of cancer may improve efficiency and cost-effectiveness; however, this requires further verification.

Biofilm formation is easily found in patients suffered from ventilator-associated pneumonia (VAP) in neonatal intensive care unit (NICU) and makes the VAP infections not only harder to be treated but easier to relapse. In order to find some novel ways to inhibit biofilm formation, this study describe a previously unrecognized role for the human umbilical cord mesenchymal stem cells (hUCMSCs). In addition to multiple differentiation, hUCMSCs have the ability to prevent the biofilms formation in vitro by secreting antibacterial peptides (LL-37 and hBD-2). This occurred while P. aeruginosa PA27853 and hUCMSCs were cocultured, and the filtrated medium, which was the supernatant containing antibacterial peptides (5.9 ng/ml of LL-37, 1.77 ng/ml of hBD-2), and inhibited the growth of the bacterial biofilm on the surface of tracheal tube (2.5#, for preterm infant). Using microarrays, we were able to demonstrate that the antibacterial peptides from hUCMSC affected biofilm formation by downregulating the gene-encoded polysaccharide biosynthesis protein. In addition, in order to find out the most suitable concentration of hUCMSCs, P. aeruginosa was cocultured with eight-level concentrations of hUCMSCs, and we found that the concentration of LL-37 was positively correlated with the concentration of hUCMSCs. Meanwhile, the concentration of LL-37 became stable while the hUCMSC concentration reaches higher than 5 × 10 6 cells / ml . But the concentration of hBD-2 had no significant correlation with hUCMSCs. The collection of these stem cells is not only limited by ethics but also reduces host rejection. This makes it possible to use autologous hUCMSCs to treat neonatal VAP.

The arteriovenous fistulas (AVF) continue to be the most prevalent type of vascular access for hemodialysis (HD). However, the appropriate locations of AVF are controversial. We conducted the meta-analysis to investigate the differences in patency between upper-arm and forearm AVF.PubMed, EMBASE, CENTRAL, and ISI Web of Science were searched to identify studies with differences in AVF patency at different locations. Reviewers searched the database, screened studies according to inclusion criteria, and conducted Meta-analysis.A total of 12 studies involving 3437 patients were selected. Pooled data showed that primary patency (PP) of AVF were higher in upper-arm than forearm at 1 and 2 years (odds ratio [OR] = 1.54, p = 0.0005; OR = 2.45, p = 0.001), but the differences in cumulative patency (CP) were not statistically significant at 1 and 2 years (OR = 2.10, p = 0.08; OR = 2.16, p = 0.1). The differences in PP and CP between upper-arm and forearm AVF in patients older than 65 years were not statistically significant at 1 (OR = 1.61, p = 0.05; OR = 2.05, p = 0.17) and 2 years (OR = 3.40, p = 0.13; OR = 1.38, p = 0.16). In Asian patients, the differences in PP and CP between upper-arm and forearm AVF were not statistically significant at 1 (OR = 1.17, p = 0.41; OR = 1.02, p = 0.94) and 2 years (OR = 2.95, p = 0.08; OR = 1.23, p = 0.41).In this study, the CP of upper-arm and forearm AVF was similar in overall population. There was no difference in PP and CP of AVF between upper-arm and forearm in Asian population or the elderly. The forearm AVF could be consider to be the first choice. for Asian patients or the elderly.

Two large randomized controlled trials (RCTs) have demonstrated that low dose computed tomography (LDCT) screening reduces lung cancer mortality. Risk-prediction models have been proved to select individuals for lung cancer screening effectively. With the focus on established risk factors for lung cancer routinely available in general cancer screening settings, we aimed to develop and internally validated a risk prediction model for lung cancer.Using data from the Cancer Screening Program in Urban China (CanSPUC) in Henan province, China between 2013 and 2019, we conducted a prospective cohort study consisting of 282,254 participants including 126,445 males and 155,809 females. Detailed questionnaire, physical assessment and follow-up were completed for all participants. Using Cox proportional risk regression analysis, we developed the Henan Lung Cancer Risk Models based on simplified questionnaire. Model discrimination was evaluated by concordance statistics (C-statistics), and model calibration was evaluated by the bootstrap sampling, respectively.By 2020, a total of 589 lung cancer cases occurred in the follow-up yielding an incident density of 64.91/100,000 person-years (pyrs). Age, gender, smoking, history of tuberculosis and history of emphysema were included into the model. The C-index of the model for 1-year lung cancer risk was 0.766 and 0.741 in the training set and validation set, respectively. In stratified analysis, the model showed better predictive power in males, younger participants, and former or current smoking participants. The model calibrated well across the deciles of predicted risk in both the overall population and all subgroups.We developed and internally validated a simple risk prediction model for lung cancer, which may be useful to identify high-risk individuals for more intensive screening for cancer prevention.

Development of innovative nanomedicine formulations to traverse the blood-brain barrier (BBB) for effective theranostics of glioma remains a great challenge. Herein, we report the creation of macrophage membrane-camouflaged multifunctional polymer nanogels coloaded with manganese dioxide (MnO2) and cisplatin for magnetic resonance (MR) imaging-guided chemotherapy/chemodynamic therapy (CDT) of orthotopic glioma. Redox-responsive poly(N-vinylcaprolactam) (PVCL) nanogels (NGs) formed via precipitation polymerization were in situ loaded with MnO2 and physically encapsulated with cisplatin to have a mean size of 106.3 nm and coated with macrophage membranes to have a good colloidal stability. The generated hybrid NGs display dual pH- and redox-responsive cisplatin and Mn(II) release profiles and can deplete glutathione (GSH) rich in tumor microenvironment through reaction with disulfide-containing cross-linkers within the NGs and MnO2. The thus created Mn(II) enables enhanced CDT through a Fenton-like reaction and T1-weighted MR imaging, while the loaded cisplatin not only exerts its chemotherapy effect but also promotes the reactive oxygen species generation to enhance the CDT efficacy. Importantly, the macrophage membrane coating rendered the hybrid NGs with prolonged blood circulation time and ability to traverse BBB for specific targeted chemotherapy/CDT of orthotopic glioma. Our study demonstrates a promising self-adaptive and cooperative NG-based nanomedicine platform for highly efficient theranostics of glioma, which may be extended to tackle other difficult cancer types.

Messenger RNA (mRNA) vaccine technology has shown its power in preventing the ongoing COVID-19 pandemic. Two mRNA vaccines targeting the full-length S protein of SARS-CoV-2 have been authorized for emergency use. Recently, we have developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor-binding domain (RBD) of SARS-CoV-2 (termed ARCoV), which confers complete protection in mouse model. Herein, we further characterized the protection efficacy of ARCoV in nonhuman primates and the long-term stability under normal refrigerator temperature. Intramuscular immunization of two doses of ARCoV elicited robust neutralizing antibodies as well as cellular response against SARS-CoV-2 in cynomolgus macaques. More importantly, ARCoV vaccination in macaques significantly protected animals from acute lung lesions caused by SARS-CoV-2, and viral replication in lungs and secretion in nasal swabs were completely cleared in all animals immunized with low or high doses of ARCoV. No evidence of antibody-dependent enhancement of infection was observed throughout the study. Finally, extensive stability assays showed that ARCoV can be stored at 2–8 °C for at least 6 months without decrease of immunogenicity. All these promising results strongly support the ongoing clinical trial.

To explore the common questions of acupuncture translational medicine study and the development strategy of its translational application. It is believed that the research on the individual and common mechanisms of acupuncture effects, and the common molecule of acupoint and parameter research for the effect onset of acupuncture may promote clinical translation and instrument research and development. The study of meridian theory should be fully applied to clinical practice to build a meridian diagnostic system with clinical significance. Using evidence-based medicine, the clinical research of acupuncture can be transformed into clinical guidelines to provide the effective regimens for clinical practice. The communication and cooperation should be enhanced between the basic research and clinical application in the field of acupuncture. It is suggested that the promotion of acupuncture translational medicine research is contribute to the overall development of acupuncture discipline, and to better service for the human health engineering.探讨针灸转化医学研究共性问题及其转化应用的发展策略。认为针灸起效的个性机制和共性机制研究、针灸起效的腧穴共性分子和参数研究，可促进临床转化及仪器研发；经络理论研究应最大限度应用于临床实践，构建具有临床意义的经络诊断体系；利用循证医学将针灸临床研究转化为临床指南，为临床提供行之有效的治疗方案；加强针灸基础研究与临床应用的沟通和合作。推动针灸转化医学研究有利于促进针灸学科全面发展，进而更好地服务于人类健康工程。.

BACKGROUND It is necessary to assess the association between the preoperative indicators and the maturation and survival of arteriovenous fistula (AVF). METHODS We retrospectively identified 236 patients with a new AVF created between 2016 and 2018 in our Dialysis Center. RESULTS Multivariate Logistic regression showed that preoperative arterial diameter (odds ratio [OR] = 1.452, 95% confidence interval [CI] [1.233, 1.710], p

Identification of high-risk population among hepatitis B virus (HBV)/hepatitis C virus (HCV)-infected individuals with first-degree relatives (FDR) who have liver cancer is important to implement precise intervention. A cross-sectional study was conducted under the framework of a population-based Cancer Screening Program in Urban China (CanSPUC), aimed to develop and validate a simple noninvasive model that could assess and stratify cirrhosis risk, in HBV/HCV-infected individuals with FDRs who have liver cancer. People who participated in liver cancer screening in Henan province were enrolled. Using the data set consisting of participants admitted from October 1, 2013, to December 31, 2016, a 24-point scale risk score model was developed through logistic regression, based on educational background, dietary habit, smoking index, cooking oil fume exposure, history of severe trauma, HBV/HCV infection status, history of diabetes, history of hyperlipidemia, and parent history of liver cancer. The model showed excellent discrimination with area under the receiver operator characteristic curve (AUROC) of 0.875 [95% confidence interval (CI), 0.853–0.896] and fair calibration with a Hosmer–Lemeshow test P = 0.106. The prevalence rates in the medium- and high-risk groups were 2.87 (95% CI, 1.94–4.25) and 47.57 (95% CI, 31.59–71.63) times of low-risk group, respectively. After internal validation, bias-corrected AUROC was 0.874 (95% CI, 0.873–0.875). In the external validation data set consisting of participants admitted from January 1, 2017, to October 31, 2018, the model had achieved similar discrimination, calibration, and risk stratification ability. In conclusion, the risk score model we developed can be a practical tool for the screening and prevention of liver cirrhosis among HBV/HCV-infected individuals with FDRs who have liver cancer. Prevention Relevance: We created a simple and noninvasive cirrhosis risk model for individuals infected by HBV/HCV who have FDRs with liver cancer. This model is useful not only for the prognosis of HBV/HCV infection, but also for the prevention of hepatocellular carcinoma.

Many studies have shown that chitinase-3-like protein 1 (CHI3L1), also known as YKL-40, is associated with asthma. The purpose of this meta-analysis was to evaluate the role of serum YKL-40 in the diagnosis and differential diagnosis of asthma, severity grading, and determination of disease state. The PubMed, Ovid, and Cochrane databases were searched. A total of 17 articles involving 5696 subjects were included in this meta-analysis. The results showed that the level of YKL-40 was significantly higher in asthmatic patients than in the normal group regardless of age and residential location, and increased with severity and acute exacerbation (p

BACKGROUND Irisin is not only a myokine but also an adipokine that is critical in many diseases including in the development of such diseases as obesity, diabetes mellitus, metabolic syndrome, coronary artery disease, and chronic inflammation. However, the association between irisin and chronic kidney disease (CKD) is unclear. This systematic review aimed to assess circulating irisin levels in patients with CKD and compare them with those in non-CKD patients. METHODS PubMed, EMBASE, CENTRAL, ISI Web of Science, and CNKI were searched to identify observational studies of circulating irisin levels in patients with CKD. Two reviewers independently searched the databases and screened studies according to the inclusion criteria. Data were extracted using a standardized collection form. Meta-analysis was performed to compare the differences in circulating irisin levels between CKD and non-CKD patients. RESULTS A total of 9 studies (6 cross-sectional and 3 case controls) involving 859 CKD patients and 393 non-CKD individuals were selected. The pooled data indicated that circulating irisin concentrations were significantly lower in CKD nondialysis patients (WMD = - 84.79, 95% CI - 170.23, 0.50; p

Skeletal muscle tissue engineering (SMTE) is of great significance in the study of skeletal muscle physiology and pathology, which could be used in skeletal muscle graft. The scientometric analysis of SMTE can help researchers to quickly understand the evolutive history, status, novelties, and trend of this field. In this study, we performed a scientometric study that can be used to construct and visualize networks of SMTE using VOSviewer. A total of 1384 documents published between 1994 and 2020 were retrieved and analyzed. Our results showed that number of publications in SMTE has increased slowly from 1994 to 2014 and has increased rapidly from 2015 to 2020. The geographical distribution of publications in terms of total publications about SMTE is concentrated in Europe and the United States. The most productive institution was University of Michigan, while Harvard University and the University of Pittsburgh were ranked the second and third places. SMTE influenced a wide spectrum of disciplines, including Biology and Medicine and Physical Sciences. In addition, the research hotspot of SMTE was expanding from seed cells to the combination with advanced strategies (electrostatic spinning, bioprinting, and materials) for emulating the highly bionic engineered skeletal muscle tissues. This study provided a unique perspective for understanding the history and trends of SMTE, which could help to promote the rapid development of the field. Impact statement Skeletal muscle tissue engineering (SMTE), which acts as an important branch of tissue engineering, hold a great promise in the study of skeletal muscle physiology and pathology. The field of SMTE has developed rapidly in recent decades while still lacking studies based on scientometric methods. This article provided the first scientometric study of SMTE from development trends and evolution of the field. The results indicated that the field of SMTE was experiencing rapid growth and had a significant impact on multiple fields, particularly in Biology and Medicine and Physical Sciences.

Background Current methods for cervical cancer screening result in an increased number of referrals and unnecessary diagnostic procedures. This study aimed to develop and evaluate a more accurate model for cervical cancer screening. Methods Multiple predictors including age, cytology, high-risk human papillomavirus (hrHPV) DNA/mRNA, E6 oncoprotein, HPV genotyping, and p16/Ki-67 were used for model construction in a cross-sectional population including women with normal cervix (N = 1085), cervical intraepithelial neoplasia (CIN, N = 279), and cervical cancer (N = 551) to predict CIN2+ or CIN3+. A base model using age, cytology, and hrHPV was calculated, and extended versions with additional biomarkers were considered. External validations in two screening cohorts with 3-year follow-up were further conducted (NCohort-I = 3179, NCohort-II = 3082). Results The base model increased the area under the curve (AUC, 0.91, 95% confidence interval [CI] = 0.88–0.93) and reduced colposcopy referral rates (42.76%, 95% CI = 38.67–46.92) compared to hrHPV and cytology co-testing in the cross-sectional population (AUC 0.80, 95% CI = 0.79–0.82, referrals rates 61.62, 95% CI = 59.4–63.8) to predict CIN2+. The AUC further improved when HPV genotyping and/or E6 oncoprotein were included in the base model. External validation in two screening cohorts further demonstrated that our models had better clinical performances than routine screening methods, yielded AUCs of 0.92 (95% CI = 0.91–0.93) and 0.94 (95% CI = 0.91–0.97) to predict CIN2+ and referrals rates of 17.55% (95% CI = 16.24–18.92) and 7.40% (95% CI = 6.50–8.38) in screening cohort I and II, respectively. Similar results were observed for CIN3+ prediction. Conclusions Compared to routine screening methods, our model using current cervical screening indicators can improve the clinical performance and reduce referral rates.

EGFR inhibitor therapies have brought significant benefit to NSCLC patients. However, all patients gradually progress to acquired resistance

Cartilage damage is the key pathological mechanism in the progressive development of osteoarthritis(OA). Slowing down cartilage damage and accelerating cartilage repair are strategies for effective treatment of OA. Acupuncture and moxibustion therapies are widely used in relieving symptoms of OA and have a protective effect on cartilage. In this paper, we reviewed the mechanisms of acupuncture and moxibustion underlying relieving cartilage damage from three aspects: 1) promoting chondrocyte homeostasis by inhibiting apoptosis and improving cellular autophagy, 2) regulating extracellular matrix (ECM) metabolism (inhibiting decomposition and promoting synthesis) by suppressing the release of inflammatory factors and the activity of proteolytic enzymes, and 3) improving OA microenvironment by reducing the number of macrophagocyte 1 (M1) and increasing the ratio of M2/M1 in the local inflammatory locus. In addition, most studies on the mechanisms of acupuncture and moxibustion underlying remission of OA focus on the improvement of pathological changes, such as joint histopathology, cartilage morphology, synovial inflammatory reaction and infiltration, subchondral bone remodeling, etc., thus, the exact functions of acupuncture and moxibustion in ameliorating cartilage injury remain unknown. In view of the important role of mitochondrial dysfunction in promoting OA development and cartilage damage and the current use of tissue engineering methods of chondrocytes and mesenchymal stem cells to repair articular cartilage injury, it is highly recommended that future studies should pay more attention to these aspects.软骨损伤是骨关节炎(OA)进行性发展的关键病理机制。减缓软骨损伤, 加速软骨修复是治疗OA的有效策略。针灸广泛用于OA的治疗, 具有软骨保护作用。本文从软骨细胞稳态、细胞外基质代谢以及OA微环境3个方面, 就针灸抑制软骨损伤的机制进行综述, 并提出线粒体内源性途径及外泌体工程作为针灸治疗OA的研究方向, 可为后续研究提供参考。.

Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors.From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13 hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collectedThirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9%) were men. Among them, nearly two-thirds (62.5%) of the survivors were moderate, three (9.4%) were severe, and more than half (59.4%) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6% at 3 months to 15.8% at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1%) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period.The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

ObjectiveSystemic inflammation is associated with a poor prognosis in acute heart failure (AHF). This study was to assess the long-term prognostic value of combining the accessible inflammatory markers in relation to all-cause mortality in patients with AHF.MethodsConsecutive patients with AHF who were hospitalized between March 2012 and April 2016 at the Department of Cardiology of the First Affiliated Hospital of Nanjing Medical University were enrolled in this prospective study. The LASSO regression model was used to select the most valuable inflammatory biomarkers to develop an inflammatory prognostic scoring (IPS) system. Kaplan-Meier method, multivariate COX regression and time-dependent ROC analysis were used to assess the relationship between inflammatory markers and AHF prognosis. A randomized survival forest model was used to estimate the relative importance of each inflammatory marker in the prognostic risks of AHF.ResultsA total of 538 patients with AHF were included in the analysis (mean age, 61.1 ± 16.0 years; 357 [66.4%] men). During a median follow-up of 34 months, there were 227 all-cause deaths (42.2%). C-reactive protein (CRP), red blood cell distribution width (RDW) and neutrophil-to-lymphocyte ratio (NLR) were incorporated into the IPS system (IPS = 0.301×CRP + 0.263×RDW + 0.091×NLR). A higher IPS meant a significantly worse long-term prognosis in Kaplan-Meier analysis, with 0.301 points as the optimal cut-off value (P log-rank ConclusionsInflammatory biomarkers were associated with the risk of all-cause mortality in patients with AHF, while IPS significantly improved the predictive power of the model and could be used as a practical tool for individualized risk stratification of patients with AHF.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematopoietic malignancy characterized by poor prognosis even following an allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed 15 patients diagnosed with BPDCN who underwent an allo-HSCT with myeloablative conditioning (MAC) at our center. The male to female ratio was 11:4. The median age of 36 (range: 6-70) years, all patients initially presented with extramedullary lesions (13 with cutaneous lesions, 1 in the breast and 1 in the lymph nodes) and involved the bone marrow, two cases were diagnosed as central nervous system leukemia (CNSL). Nine patients were in CR1 and six patients were in CR2 status prior to HSCT. All patients received the MAC regimen and an unmanipulated graft. All patients successfully engraftment and achieved full donor chimerism. One patient developed poor graft function, three patients developed aGVHD (Grade I, II, and IV), and seven patients developed cGVHD (mild in 6; moderate in 1). The median follow-up time for survival was 34 (range: 6-64) months. The primary endpoint, overall leukemia-free survival (LFS) rate and overall survival rate was 73.3 ± 10.5%. Allo-HSCT with MAC is a valid option for BPDCN patients in complete remission.

Graphic abstract Paeonol, derived from natural plants (Moutan Cortex), has a wide range of biological effects, including anti-inflammatory and antitumor effects as well as favorable effects against cardiovascular and neurodegenerative diseases. The anti-inflammatory action is the main pharmacological activity of paeonol and has the greatest clinical relevance. However, the anti-inflammatory mechanism of paeonol has not been reported in sufficient detail. We systematically analyzed the anti-inflammatory mechanism of paeonol using network pharmacological databases and platforms, including TCMSP, Swiss TargetPrediction, OMIM, DrugBank, TTD, Jevnn, STRING11.0, and Metascape. Furthermore, we used high-throughput molecular docking method to prove the results of the above analyses, providing a reference for exploring the mechanism of paeonol and developing targeted drugs.

Objectives: The study aimed at analyzing the prevalence of five psychological outcomes (depression, anxiety, stress, post-traumatic stress disorder (PTSD), and suicidal ideation) among Chinese healthcare workers (HCWs), and measured the total possible negative psychological impact 1 year after the COVID-19 initial outbreak.Methods: A cross-sectional nationwide multi-center study was performed between November 2020 and March 2021 in China. A self-report questionnaire was applied, and three psychological scales were used. Binary logistic regression was performed to analyze the risk factors associated with each psychological outcome.Results: The findings demonstrated that the COVID-19 pandemic had a negative psychological impact on HCWs, which was still evident 1 year after the initial outbreak. Nurses showed higher depression and anxiety than other HCWs. Female gender, passive coping, long working hours, having a chronic disease, and experiencing violence, among other factors, were all risk factors for psychological impairment.Conclusion: Developing and promoting programs to improve mental health among HCWs, and identifying those who might need psychological support is still relevant 1 year after the initial outbreak.

Targeting metabolic reprogramming to treat cancer could increase overall survival and reduce side effects. Here, we put forward a strategy using arene-ruthenium(II)/osmium(II) complexes to potentiate the anticancer effect of metformin (Met.) via glucose metabolism reprogramming. Complexes 1-6 with oxoglaucine derivatives as ligands were synthesized and their anti-tumor activities were tested under hypoglycemia. Results indicated that 2 and 5 potentiated the anticancer effects of Met. under hypoglycemia, exhibiting lower toxicity, slower blood glucose decline and inhibition of early tumor liver metastasis. Combination of 5 with Met. could be used as a new strategy to treat cancer under hypoglycemia through glucose metabolism reprogramming.

Objective: The dorsolateral prefrontal cortex (dlPFC) is strongly associated with mood symptoms. This study used functional near-infrared spectroscopy (fNIRS) technology to explore the features of brain neural activity in the dlPFC of anxious and depressed college students, during an emotional autobiographical memory task, and to understand the differences in brain cognitive mechanisms caused by anxiety and depression. Methods: A simple random sampling method was used to test 440 college students at a university with a healthy control group (HC, 220 participants), a pure depression group (PD, 92 participants), and a pure anxiety group (PA, 128 participants). The average oxyhemoglobin in the dlPFC of the subjects during the emotional autobiographical memory task was collected by a 53-channel functional near-infrared spectroscopy imaging device. Results: The activation of the left dlPFC (ch13) in the pure depression group was significantly higher than in the pure anxiety group. The activation of the right dlPFC (ch48) was significantly higher under positive emotions than under negative emotions. The interaction between emotion valence and group was marginally significant, and the activation of the right dlPFC (ch41) in the pure depression group was significantly higher under positive emotion than in negative emotion. The activation of the pure depression group under positive emotions was significantly higher than that of the pure anxiety group. In comparison, the activation of the pure depression group under negative emotions was significantly lower than that of the healthy control group. The results of correlation analysis showed that the activation of the left dlPFC (ch13) was significantly negatively correlated with anxiety in positive emotions, but the activation of the right dlPFC (ch34, ch42) was significantly positively correlated with anxiety in positive and negative emotions. Conclusions: The right dlPFC was insensitive to positive emotions in college students with high-anxiety symptoms, whereas this region was insensitive to negative emotions in college students with high depressive symptoms, which might be one of the critical differences in the cognitive mechanisms of anxiety and depression. Furthermore, left and right dlPFC activation correlated differently with anxiety. The higher the anxiety level, the lower the activation on the left side, and the higher the activation on the right side. The results suggested that anxiety might reduce the function of the left dlPFC.

Objective To investigate the effect of diabetes mellitus and hypoglycemic treatment on the diameter and biochemical parameters of abdominal aortic aneurysm (AAA).Methods A case-control study was conducted to retrospectively analyze the clinical data of AAA patients in Peking Union Medical College Hospital from 2015 to 2021.The AAA patients were classified into a group with diabetes mellitus (

The present study investigated the correlation of plasma A-FABP with glucose dysregulation under different body mass index (BMI) and metabolic states in a Han Chinese population from Yunnan plateau. We cross-sectionally analyzed data from the China Multi Ethnic Cohort, Yunnan province. Participants were divided into two groups. Group A contained 297 obese individuals with metabolic syndrome (MetS). Group B contained 326 age-, sex-, and region-matched normal BMI subjects without MetS. Glucose dysregulation was defined as elevated fasting plasma glucose (FPG) (FPG ≥ 5.6 mmol/L or current use of oral hypoglycemic agents or insulin). Circulating A-FABP were assayed by ELISA method. Binary and multiple regression analyses were preformed to evaluate the correlation between A-FABP and glucose dysregulation. Plasma A-FABP level was significantly higher in group A compared with group B (p 0.001). Plasma A-FABP level correlated positively with elevated FPG in group A (r = 0.120, p = 0.039), but negatively with elevated FPG in group B (r = -0.115, p = 0.039). Multiple logistic regression analysis revealed that A-FABP was an independent predictor for elevated FPG in group A (β, 0.028; 95% CI, 1.001-1.056; p 0.05), but not in group B (β, -0.008; 95% CI, 0.882-1.117; p 0.05). In this study, A-FABP was an independent risk factor for glucose dysregulation in obese individuals with MetS living in the Yunnan plateau, but not for those without obesity and MetS.

This study aimed to explore the risk factors of peripherally inserted central catheter (PICC)-related venous thromboembolism (CRT) in patients with hematological malignancies and the predictive ability of the thrombotic risk assessment models (RAMs). The clinical data of the 117 eligible patients with hematological neoplasms at Mianyang Central Hospital with PICC from May 2018 to May 2020 were analyzed in this retrospective study. Thrombosis risk scores were calculated in patients with image-confirmed PICC-related thromboembolism. CRT occurred in 19 cases. Compared to the CRT-free group, the CRT group was older and showed higher body mass index (BMI), leukocyte count level, and the prevalence of diabetes mellitus. Multivariable logistic regression analysis showed that BMI (P = 0.03) was a significant risk factor for CRT. The area under the receiver operating characteristic curve for the Caprini scale (P = 0.01) was higher than that of the modified Wells scale (P = 0.94), the revised Geneva scale (P = 0.83), Padua scale (P = 0.59), and Michigan scale (P = 0.80). The sensitivity and specificity for the Caprini scale, Padua scale, modified Wells scale, the revised Geneva scale, and Michigan risk score were 63.3%/73.7%, 100%/0.00%, 95.9%/5.3%, 31.6%/73.7%, and 1.0%/99.0%, respectively. Caprini RAM had a better predictive ability for CRT in patients with hematological malignancies. Michigan risk score may not be better than Caprini RAM in this population.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is characterized by chronic inflammation of the gastrointestinal tract. The number of affected persons worldwide has increased from 3.7 million in 1990 to 6.8 million in 2017 (1). The disease is more prevalent among non-Hispanic White persons than it is among persons in other racial/ethnic groups (2). As the prevalence increases with age group (2), it is important to understand the disease epidemiology among the older population. CDC analyzed 2018 Medicare data among beneficiaries aged ≥67 years to examine differences by demographic characteristics for both diseases and to assess trends of prevalence from 2001 through 2018 both overall and by race and ethnicity. In 2018, 0.40% and 0.64% of 25.1 million Medicare fee-for-service beneficiaries aged ≥67 years had received a diagnosis of either Crohn's disease or ulcerative colitis. Prevalence varied by age, sex, race and ethnicity, urban-rural residency, and state. During 2001-2018, the age-adjusted prevalence of both diseases increased (Crohn's disease annual percentage change [APC] = 3.4%, ulcerative colitis APC = 2.8%). The increase was higher among non-Hispanic Black persons (Crohn's disease APC = 5.0%, ulcerative colitis APC = 3.5%) than it was among non-Hispanic White, Hispanic, and Asian/Pacific Islander (A/PI) persons. Prevalence was consistently highest among non-Hispanic White persons for both diseases and lowest among A/PI persons for Crohn's disease. The study findings of increasing prevalence in all racial/ethnic groups among older adults, especially the higher rate of increase among certain racial/ethnic minority groups, underscore the importance for promoting health equity, guiding efforts to tailor disease management strategies for different populations, and continuing to monitor the temporal trends of the disease.

LianhuaQingwen capsule, prepared from an herbal combination, is officially recommended as treatment for COVID-19 in China. Of the serial pharmacokinetic investigations we designed to facilitate identifying LianhuaQingwen compounds that are likely to be therapeutically important, the current investigation focused on the component Glycyrrhiza uralensis roots (Gancao). Besides its function in COVID-19 treatment, Gancao is able to induce pseudoaldosteronism by inhibiting renal 11β-HSD2. Systemic and colon-luminal exposure to Gancao compounds were characterized in volunteers receiving LianhuaQingwen and by in vitro metabolism studies. Access of Gancao compounds to 11β-HSD2 was characterized using human/rat, in vitro transport, and plasma protein binding studies, while 11β-HSD2 inhibition was assessed using human kidney microsomes. LianhuaQingwen contained a total of 41 Gancao constituents (0.01–8.56 μmol/day). Although glycyrrhizin ( 1 ), licorice saponin G2 ( 2 ), and liquiritin/liquiritin apioside ( 21 / 22 ) were the major Gancao constituents in LianhuaQingwen, their poor intestinal absorption and access to colonic microbiota resulted in significant levels of their respective deglycosylated metabolites glycyrrhetic acid ( 8 ), 24-hydroxyglycyrrhetic acid ( M2 D ; a new Gancao metabolite), and liquiritigenin ( 27 ) in human plasma and feces after dosing. These circulating metabolites were glucuronized/sulfated in the liver and then excreted into bile. Hepatic oxidation of 8 also yielded M2 D . Circulating 8 and M2 D , having good membrane permeability, could access (via passive tubular reabsorption) and inhibit renal 11β-HSD2. Collectively, 1 and 2 were metabolically activated to the pseudoaldosterogenic compounds 8 and M2 D . This investigation, together with such investigations of other components, has implications for precisely defining therapeutic benefit of LianhuaQingwen and conditions for its safe use.

OBJECTIVE: To assess the prevalence of migraine or severe headache among US adults by inflammatory bowel disease (IBD) status. BACKGROUND: Emerging evidence in clinical settings suggests a higher prevalence of migraine among patients with IBD than those without IBD. METHODS: Data from 60,436 US adults aged ≥18 years participating in the 2015 and 2016 National Health Interview Survey (NHIS) were analyzed. The relationship between IBD status and migraine or severe headache was assessed overall and stratified by levels of selected characteristics including sex, age, race/ethnicity, education, poverty status, marital status, smoking status, obesity status, serious psychological distress, and major chronic condition status. RESULTS: Overall, the age-adjusted prevalence of migraine or severe headache was 15.4% (n = 9062) and of IBD was 1.2% (n = 862). A higher age-adjusted migraine or severe headache prevalence was reported among participants with IBD than those without IBD (28.1% vs. 15.2%, p

A case who revealed the longest duration of viral shedding (67 days) in current reports, presented complicated characteristic on the relapse of COVID-19 due to the inconsistent performance of chest radiography and SARS-CoV-2-RNA detection after discharge. Lopinavir-interferon α2b boosted ribavirin following with lopinavir boosted budesonide might be a potent treatment for viral clearance.

Regulatory T lymphocytes are important targets for the treatment of acute respiratory distress syndrome (ARDS). IL-35 is a newly identified IL-12 cytokine family member that plays an important protective role in a variety of immune system diseases by regulating Treg cell differentiation; however, the role of IL-35 in the pathogenesis of ARDS is still unclear. Here, we found that IL-35 was significantly elevated in adult patients with ARDS compared to controls. Additionally, IL-35 was positively and significantly correlated with IL-6, IL-10 and the oxygenation index (PaO2/FiO2 ratio) but negatively correlated with TNF-α, IL-1β and APACHE II score during ARDS. Moreover, the proportion of Treg/CD4+ cells in the peripheral blood of ARDS patients and the expression of NF-κB in PMBCs were significantly higher than in healthy individuals. Recombinant IL-35 improved survival in a murine model of CLP-induced ARDS. Additionally, IL-35 administration decreased the inflammatory response, as reflected by lower levels of cytokines (including IL-2, TNF-α, IL-1β and IL-6) and less lung damage in CLP-induced ARDS. Furthermore, recombinant IL-35 reduced the apoptosis of lung tissue and the expression of NF-κB signalling in a CLP-induced ARDS model and increased the proportion of Treg cells in spleen and peripheral blood. In vitro experiments revealed that IL-35 can affect the phosphorylation of STAT5 during differentiation of naive CD4+ T lymphocytes into Foxp3+Helios+ Tregs. Our findings suggest that IL-35 attenuates ARDS by promoting the differentiation of naive CD4+ T cells into Foxp3+Helios+ Tregs, thereby providing a novel tool for anti-ARDS therapy.

Objective Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients’ medical records. Multivariable logistic regression models were used to estimate the odds ratio (OR) and 95% confidence interval (95% CI) of the associations between comorbidities (cardiometabolic or non-cardiometabolic diseases), clinical severity, and treatment outcomes of COVID-19. Results Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30–6.32), type 2 diabetes (T2DM) (3.57, 2.32–5.49), cardiovascular disease (CVD) (3.78, 1.81–7.89), fatty liver disease (7.53, 1.96–28.96), hyperlipidemia (2.15, 1.26–3.67), other lung diseases (6.00, 3.01–11.96), and electrolyte imbalance (10.40, 3.00–26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89–12.75), CVD (8.47, 6.03–11.89), and electrolyte imbalance (19.44, 11.47–32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25–9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46–29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.

Although peripheral venous blood biomarkers are related to respiratory function in Amyotrophic lateral sclerosis (ALS) patients, there are still few prediction models that predict pulmonary function. This study aimed to investigate the venous blood biomarkers associated with respiratory function in patients with ALS from southwest China and to create prediction models based on those clinical biomarkers using logistic regression. A total of 319 patients with ALS from the retrospective cohort and 97 patients with ALS from the prospective cohort were enrolled in this study. A multivariable prediction model for the correlation between peak expiratory flow (PEF) and hematologic, biochemical laboratory parameters, and clinical factors in patients with ALS was created. Along with female patients, bulbar-onset, lower body mass index (BMI), later age of onset, lower level of creatinine, uric acid, triglyceride, and a higher level of high-density lipoprotein cholesterol (HDL_C) were related to reduced PEF. The area under the receiver operating characteristics (ROC) curve is.802 for the test set and.775 for the validation set. The study constructed a multivariable prediction model for PEF in patients with ALS. The results can be helpful for clinical practice to predict respiratory impairment.

BackgroundOwing to the coronavirus disease 2019 (COVID-19) pandemic and the emergency use of different types of COVID-19 vaccines, there is an urgent need to consider the effectiveness and persistence of different COVID-19 vaccines.MethodsWe investigated the immunogenicity of CoronaVac and Covilo, two inactivated vaccines against COVID-19 that each contain inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The levels of neutralizing antibodies to live SARS-CoV-2 and the inhibition rates of neutralizing antibodies to pseudovirus, as well as the immunoglobulin (Ig)G and IgM responses towards the spike (S) and nucleocapsid (N) protein of SARS-CoV-2 at 180 days after two-dose vaccination were detected.ResultsThe CoronaVac and Covilo vaccines induced similar antibody responses. Regarding neutralizing antibodies to live SARS-CoV-2, 77.9% of the CoronaVac vaccine recipients and 78.3% of the Covilo vaccine recipients (aged 18–59 years) seroconverted by 28 days after the second vaccine dose. Regarding SARS-CoV-2-specific antibodies, 97.1% of the CoronaVac vaccine recipients and 95.7% of the Covilo vaccine recipients seroconverted by 28 days after the second vaccine dose. The inhibition rates of neutralizing antibody against a pseudovirus of the SARS-CoV-2 Delta variant were significantly lower compared with those against a pseudovirus of wildtype SARS-CoV-2. Associated with participant characteristics and antibody levels, persons in the older age group and with basic disease, especially a chronic respiratory disease, tended to have lower anti-SARS-CoV-2 antibody seroconversion rates.ConclusionAntibodies that were elicited by these two inactivated COVID-19 vaccines appeared to wane following their peak after the second vaccine dose, but they persisted at detectable levels through 6 months after the second vaccine dose, and the effectiveness of these antibodies against the Delta variant of SARS-CoV-2 was lower than their effectiveness against wildtype SARS-CoV-2, which suggests that attention must be paid to the protective effectiveness, and its persistence, of COVID-19 vaccines on SARS-CoV-2 variants.

Sepsis is a common complication of combat injuries and trauma, and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is also one of the significant causes of death and increased health care costs in modern intensive care units. The use of antibiotics, fluid resuscitation, and organ support therapy have limited prognostic impact in patients with sepsis. Although its pathophysiology remains elusive, immunosuppression is now recognized as one of the major causes of septic death. Sepsis-induced immunosuppression is resulted from disruption of immune homeostasis. It is characterized by the release of anti-inflammatory cytokines, abnormal death of immune effector cells, hyperproliferation of immune suppressor cells, and expression of immune checkpoints. By targeting immunosuppression, especially with immune checkpoint inhibitors, preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host resistance. Here, we comprehensively discuss recent findings on the mechanisms, regulation and biomarkers of sepsis-induced immunosuppression and highlight their implications for developing effective strategies to treat patients with septic shock.

Novel coronavirus pneumonia is a novel kind of highly contagious disease without any specific drugs. Considering the successful experience of antiviral therapy combined with glucocorticoids (GCs) in severe acute respiratory syndrome, this study was designed to evaluate the clinical efficacy of GCs in treating patients with coronavirus disease 2019 (COVID-19).A cohort of 42 patients with COVID-19 admitted to The First Hospital of Jiaxing from January 4, 2020, to February 16, 2020, were included and grouped into a test group (n=20) and control group (n=22) based on their therapeutic regimens. There were no significant differences in baseline characteristics between patients in the two groups. Conventional treatment (antiviral therapy) was given to patients in both groups, while an additional hormone drug (GCs) was used in patients in the test group. Indices including body temperature, blood routine indices [white blood cell (WBC), lymphocyte, monocyte, and C-reactive protein (CRP)], blood biochemical indices [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)], and complications were recorded during the treatment. Time to achieve negative virus nucleic acid (nCoV-RNA) testing, and hospital stays were also observed and compared between the two groups.All included patients completed the trial. After treatment, superior therapeutic efficacy was achieved in patients in the test group, with body temperature dropping more significantly with a much shorter recovery time compared to the control group (P=0.0412). Simultaneously, the percentage of patients with abnormal blood routine indices (WBC), monocyte, and (CRP) in the test group was reduced more sharply, while no noticeable difference was observed in the number of patients who developed abnormal blood biochemical indices during treatment between the two groups. Additionally, a shorter duration of hospital stays was found in the test group relative to the control group (14.84±8.76 vs. 18.25±7.42 days, P0.05). Patients who received GCs had a shorter recovery time for body temperature and inflammation.Hormonotherapy with GCs can accelerate the recovery time for body temperature as well as inflammation in patients with COVID-19. It deserves promotion and application in the clinical treatment of coronavirus disease as a form of adjuvant medicine. The ongoing focus of research is on long-term adverse events in GCs.

Background Early prediction of patients’ deterioration is helpful in early intervention for patients at greater risk of deterioration in Intensive Care Unit (ICU). This study aims to apply machine learning approaches to heterogeneous clinical data for predicting life-threatening events of patients in ICU. Methods We collected clinical data from a total of 3151 patients admitted to the Medical Intensive Care Unit of Peking Union Medical College Hospital in China from January 1st, 2014, to October 1st, 2019. After excluding the patients who were under 18 years old or stayed less than 24 h at the ICU, a total of 2170 patients were enrolled in this study. Multiple machine learning approaches were utilized to predict life-threatening events (i.e., death) in seven 24-h windows (day 1 to day 7) and their performance was compared. Results Light Gradient Boosting Machine showed the best performance. We found that life-threatening events during the short-term windows can be better predicted than those in the medium-term windows. For example, death in 24 h can be predicted with an Area Under Curve of 0.905. Features like infusion pump related fluid input were highly related to life-threatening events. Furthermore, the prediction power of static features such as age and cardio-pulmonary function increased with the extended prediction window. Conclusion This study demonstrates that the integration of machine learning approaches and large-scale high-quality clinical data in ICU could accurately predict life-threatening events for ICU patients for early intervention.

To investigate the prevalence of, and clinicodemographic factors associated with, frailty and sarcopenia in patients with multiple system atrophy or progressive supranuclear palsy.A total of 264 participants were recruited in this study. Demographic and clinical data were collected through structured interviews. Frailty was assessed with the clinical frailty scale (CFS), and sarcopenia was assessed with the simple five-item scoring questionnaire (SARC-F).The prevalence of frailty and sarcopenia was 48.57% and 35.71% in multiple system atrophy, and 51.09% and 39.13% in progressive supranuclear palsy. Multiple system atrophy patients with frailty or sarcopenia were more likely to be female and have longer disease duration, greater motor impairment, greater non-motor burden, and lower life quality. In multiple system atrophy, frailty was associated with reduced motor function and sarcopenia was associated with female sex, reduced motor function, and orthostatic hypotension. Progressive supranuclear palsy patients with frailty or sarcopenia had more severe motor impairment and non-motor burden, longer disease duration, and lower life quality. In progressive supranuclear palsy, frailty was associated with mentation and gait/midline symptoms, while sarcopenia was associated with reduced daily activity and severe gait/midline symptoms.Frailty and sarcopenia may be more common among patients with multiple system atrophy or progressive supranuclear palsy than among the general population, and they are associated with more severe forms of the two diseases. Prospective studies are necessary to clarify causal relationships between frailty/sarcopenia and clinical manifestations of multiple system atrophy and progressive supranuclear palsy.

Since the first report of SARS-CoV-2 virus in Wuhan, China in December 2019, a global outbreak of Corona Virus Disease 2019 (COVID-19) pandemic has been aroused. In the prevention of this disease, accurate diagnosis of COVID-19 is the center of the problem. However, due to the limitation of detection technology, the test results are impossible to be totally free from pseudo-positive or -negative. Improving the precision of the test results asks for the identification of more biomarkers for COVID-19. On the basis of the expression data of COVID-19 positive and negative samples, we first screened the feature genes through ReliefF, minimal-redundancy-maximum-relevancy, and Boruta_MCFS methods. Thereafter, 36 optimal feature genes were selected through incremental feature selection method based on the random forest classifier, and the enriched biological functions and signaling pathways were revealed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Also, protein-protein interaction network analysis was performed on these feature genes, and the enriched biological functions and signaling pathways of main submodules were analyzed. In addition, whether these 36 feature genes could effectively distinguish positive samples from the negative ones was verified by dimensionality reduction analysis. According to the results, we inferred that the 36 feature genes selected via Boruta_MCFS could be deemed as biomarkers in COVID-19.

Objective. To explore the effect of family participatory nursing model based on WeChat platform on psychological elasticity and life quality of patients with lung cancer. Methods. One hundred patients with lung cancer treated in our hospital from February 2019 to April 2021 were enrolled. The patients were randomly assigned into control group and study group. The control group received routine nursing and the study group received family participatory nursing model based on WeChat platform. The scores of nursing satisfaction, self-feeling burden, symptom group assessment scale, family care index, and compliance and life quality were compared. Results. First of all, we compared the nursing satisfaction: the study group was very satisfied in 25 cases, satisfactory in 20 cases, general in 5 cases, the satisfaction rate was 100.00%; the control group was very satisfied in 14 cases, satisfactory in 17 cases, general in 13 cases, dissatisfied in 6 cases, and the satisfaction rate was 88.00%. Compared between the two groups, the nursing satisfaction in the study group was higher compared to the control group ( P < 0.05 ). Secondly, we compared the self-perceived burden, the emotional burden, physical burden, and economic burden and total scores of the study group were lower compared to the control group ( P < 0.05 ). Comparing the scores of symptom group evaluation scale, the scores of respiratory symptoms, fatigue symptoms, psychological and emotional symptoms, digestive tract symptoms, and nervous system symptoms in the study group were lower compared to the control group ( P < 0.05 ). In terms of the family care index of the two groups, the scores of fitness, cooperation, length, emotion, and intimacy in the study group were higher compared to the control group ( P < 0.05 ). Comparison of compliance, the study group was very compliant in 42 cases, compliant in 7 cases, noncompliant in 1 case, the compliance rate was 98.00%; the control group was very compliant in 24 cases, compliant in 20 cases, noncompliant in 6 cases, the compliance rate was 88.00%. The compliance rate in the study group was higher compared to the control group ( P < 0.05 ). Finally, we compared the scores of qualities of life. Before nursing, there exhibited no significant difference ( P > 0.05 ). The scores of physiological function, psychological function, social function, and health self-cognition in the study group were lower compared to the control group ( P < 0.05 ). Conclusion. The family participatory nursing model based on WeChat platform helps to facilitate the psychological elasticity and quality of life of patients with lung cancer and further promote patients’ self-care ability and compliance with lung cancer. It can also effectively enhance family care and nursing satisfaction; the nursing model is worth popularizing and applying in clinic.

Evidence from a recent trial has shown that the antiinflammatory effects of colchicine reduce the risk of cardiovascular events in patients with recent myocardial infarction, but evidence of such a risk reduction in patients with chronic coronary disease is limited.In a randomized, controlled, double-blind trial, we assigned patients with chronic coronary disease to receive 0.5 mg of colchicine once daily or matching placebo. The primary end point was a composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. The key secondary end point was a composite of cardiovascular death, spontaneous myocardial infarction, or ischemic stroke.A total of 5522 patients underwent randomization; 2762 were assigned to the colchicine group and 2760 to the placebo group. The median duration of follow-up was 28.6 months. A primary end-point event occurred in 187 patients (6.8%) in the colchicine group and in 264 patients (9.6%) in the placebo group (incidence, 2.5 vs. 3.6 events per 100 person-years; hazard ratio, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P0.001). A key secondary end-point event occurred in 115 patients (4.2%) in the colchicine group and in 157 patients (5.7%) in the placebo group (incidence, 1.5 vs. 2.1 events per 100 person-years; hazard ratio, 0.72; 95% CI, 0.57 to 0.92; P = 0.007). The incidence rates of spontaneous myocardial infarction or ischemia-driven coronary revascularization (composite end point), cardiovascular death or spontaneous myocardial infarction (composite end point), ischemia-driven coronary revascularization, and spontaneous myocardial infarction were also significantly lower with colchicine than with placebo. The incidence of death from noncardiovascular causes was higher in the colchicine group than in the placebo group (incidence, 0.7 vs. 0.5 events per 100 person-years; hazard ratio, 1.51; 95% CI, 0.99 to 2.31).In a randomized trial involving patients with chronic coronary disease, the risk of cardiovascular events was significantly lower among those who received 0.5 mg of colchicine once daily than among those who received placebo. (Funded by the National Health Medical Research Council of Australia and others; LoDoCo2 Australian New Zealand Clinical Trials Registry number, ACTRN12614000093684.).

The R-spondin family plays important roles in embryonic development, including in humans. However, information on the relationship between R-spondin2 and hepatocellular carcinoma (HCC) is lacking. This study aimed was to explore the mechanisms of R-spondin2 action in the progression of HCC. By analyzing R-spondin2 expression levels in HCC tissues by IHC and database, we identified that HCC tissues had lower expression levels of R-spondin2, correlated with a poor prognosis. We also established R-spondin2–overexpressing and knockdown cell lines and measured their viabilities and invasion abilities in vitro and their oncogenic capacity in vivo. Human mRNA microarray analysis was performed to screen for mRNAs that were differentially expressed between R-spondin2–overexpressing and control HCC cells. Microarray and Western blot analyses showed significant changes in the MAPK signaling pathway after transfection. Furthermore, in vivo experiments indicated that R-spondin2 knockdown increased the tumorigenicity of HCC cells after subcutaneous implantation in mice. Altogether, our results indicate that the R-spondin2, which might be a novel tumor suppressor gene, were responsible for inhibiting the proliferation and invasion of HCC via the MAPK signaling pathway. Implications: R-spondin2 gene might be a novel tumor suppressor gene providing new clues to clarify the biological behavior of HCC and thus reduce patient mortality and prolong survival.

Pulmonary hypertension due to left heart disease (PH-LHD) is the most prevalent type of pulmonary hypertension (PH). The hemodynamic diagnostic standard of pulmonary arterial wedge pressure (PAWP)15 mm Hg that is traditionally recommended by guidelines is being challenged.To address this problem, we analyzed the data of 154 patients with PH-LHD admitted to our center from April 2013 to March 2018. Pharmacological or nonpharmacological treatment of underlying left heart disease was offered to all 154 patients.In total, there were 24 patients (15.6%) with PAWP ≤15 mm Hg. Comparison of echocardiography and right heart catheterization parameters between the two groups (PAWP15 mm Hg and PAWP ≤15 mm Hg) showed that the group with PAWP ≤15 mm Hg had smaller left ventricular diameter, higher cardiac output, lower pressure and higher oxygen saturation in the pulmonary artery, right atrium, right ventricle, and superior vena cava. No significant difference was found regarding dilated cardiomyopathy, diabetes mellitus, hypertension, atrial fibrillation, and left heart valvular disease, but a significant difference was found for coronary heart disease (higher morbidity in group with PAWP ≤15 mm Hg) between the two groups.We found that 15.6% of the patients with PH-LHD under pharmacological or nonpharmacological treatment had PAWP ≤15 mm Hg. These results suggest that the diagnostic criterion of PAWP and the characteristics for this group of patients should be further investigated.HINTERGRUND: Eine pulmonale Hypertonie aufgrund einer Linksherzerkrankung (PH-LHD) stellt den Typ der pulmonalen Hypertonie (PH) mit der höchsten Prävalenz dar. Der bisher in Leitlinien empfohlene Standard der hämodynamischen Diagnostik mit einem pulmonalarteriellen Wedge-Druck (PAWP)15 mm Hg wird nun infrage gestellt.Zur Klärung dieser Frage wurden die Daten von 154 Patienten mit PH-LHD untersucht, die zwischen April 2013 und März 2018 in die Klinik der Autoren aufgenommen wurden. Allen 154 Patienten wurde eine pharmakologische oder nichtpharmakologische Therapie der zugrunde liegenden Herzerkrankung angeboten.Bei 24 Patienten (15,6%) lag ein PAWP ≤15 mm Hg vor. Im Vergleich von Parametern der Echokardiographie und der Rechtsherzkatheteruntersuchung zwischen den beiden Gruppen (PAWP15 mm Hg und PAWP ≤15 mm Hg) zeigte sich, dass die Gruppe mit PAWP ≤15 mm Hg einen kleineren linksventrikulären Durchmesser, höheren kardialen Output, niedrigeren Druck und höhere Sauerstoffsättigung in der Pulmonalarterie, im rechten Vorhof, rechten Ventrikel und der V. cava superior aufwies. Es bestand kein signifikanter Unterschied in Bezug auf dilatative Kardiomyopathie, Diabetes mellitus, Hypertonie, Vorhofflimmern und Linksherzklappenerkrankungen, aber es gab einen signifikanten Unterschied bei der koronaren Herzkrankheit (höhere Morbidität in der Gruppe mit PAWP ≤15 mm Hg) zwischen den beiden Gruppen.Es stellte sich heraus, dass 15,6% der Patienten mit PH-LHD unter pharmakologischer oder nichtpharmakologischer Therapie einen PAWP ≤15 mm Hg aufwiesen. Diese Ergebnisse sind ein Hinweis darauf, dass das diagnostische Kriterium des PAWP und die Eigenschaften dieser Patientengruppe weiter untersucht werden sollten.

To investigate histopathological placental lesions and adverse neonatal outcomes by Pre-eclampsia (PE) with Gestational Diabetes Mellitus (GDM).This was a retrospective cohort study of pregnancies with PE delivered between 1 January 2012 to 1 January 2014. Pregnant women with PE were recruited, and divided into PE with GDM (PE + GDM) group (The (PE + GDM) group was significantly associated with high placenta weight (534.8 ± 124.1 vs 519.3 ± 132.3 g,GDM increased the offspring's complication in pregnancy with PE, the potential mechanism might be that GDM increased the placenta inflammation.

To explore the diagnostic value of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for small, solid or semi-solid pancreatic lesions (≤20 mm) and the factors affecting its accuracy. Methods Altogether 92 patients with small, solid or semi-solid pancreatic lesions who underwent EUS-FNA at the Nanjing Drum Tower Hospital from November 2009 to January 2019 were retrospectively analyzed. Univariate and multivariate analyses were used to determine the factors affecting the accuracy of EUS-FNA for detecting these lesions. Results Among the 92 cases, 56 (60.9%) were diagnosed as having malignant lesions and 36 (39.1%) as benign lesions, respectively. The overall sensitivity, specificity and accuracy of EUS-FNA for the diagnosis of small, solid or semi-solid pancreatic lesions were 71.4%, 100% and 82.6%, respectively. When considering the impact of the presence of a tissue core on the diagnosis, the sensitivity, specificity, and accuracy of EUS-FNA with tissue core compared with those based on cytology alone were 77.3% vs 50.0%; 100% vs 100%; and 86.8% vs 62.5%, respectively. The multivariate analysis showed that larger tumor size (>15-20 mm) (odds ratio [OR] 4.200, 95% confidence interval [CI] 1.21-14.53, P = 0.023) and histologic diagnosis based on tissue core (OR 4.593, 95% CI 1.03-20.47, P = 0.046) were related to a higher accuracy of EUS-FNA. Adverse events were observed in three patients, all were treated conservatively and recovered within 3 days. Conclusions EUS-FNA is effective and safe for diagnosing small pancreatic lesions. Tumor size and presence of tissue core are related to higher accuracy of the EUS-FNA.