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Dementia is one of the greatest global challenges for public health; however, the relationship between anticholinergic drugs and dementia remains unclear. The aim of the present study was to perform a systematic review and meta-analysis of the predictive roles of anticholinergic drugs in dementia risk. After pooling fourteen longitudinal and case-control studies with a total of 1,564,181 subjects, anticholinergic drug use was associated with an increased risk of all-cause dementia and Alzheimer's disease. Both low and high anticholinergic drug burdens were associated with dementia. Moreover, there was a dose-dependent relationship between anticholinergic drugs and risk of dementia. With respect to the categories of anticholinergic drugs, antiparkinson, urological drugs, and antidepressants increased the risk for dementia; however, cardiovascular and gastrointestinal drugs played potentially protective roles. These findings underscore the importance of anticholinergic drugs as a potential modifiable risk factor for dementia and provide treatment priorities to optimize dementia prevention.

Background Lung adenocarcinoma (LUAD) is the most common malignant tumor that seriously affects human health. Previous studies have indicated that abnormal levels of glycosylation promote progression and poor prognosis of lung cancer. Thus, the present study aimed to explore the prognostic signature related to glycosyltransferases (GTs) for LUAD. Methods The gene expression profiles were obtained from The Cancer Genome Atlas (TCGA) database, and GTs were obtained from the GlycomeDB database. Differentially expressed GTs-related genes (DGTs) were identified using edge package and Venn diagram. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and ingenuity pathway analysis (IPA) methods were used to investigate the biological processes of DGTs. Subsequently, Cox and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were performed to construct a prognostic model for LUAD. Kaplan–Meier (K–M) analysis was adopted to explore the overall survival (OS) of LUAD patients. The accuracy and specificity of the prognostic model were evaluated by receiver operating characteristic analysis (ROC). In addition, single-sample gene set enrichment analysis (ssGSEA) algorithm was used to analyze the infiltrating immune cells in the tumor environment. Results A total of 48 DGTs were mainly enriched in the processes of glycosylation, glycoprotein biosynthetic process, glycosphingolipid biosynthesis-lacto and neolacto series, and cell-mediated immune response. Furthermore, B3GNT3, MFNG, GYLTL1B, ALG3, and GALNT13 were screened as prognostic genes to construct a risk model for LUAD, and the LUAD patients were divided into high- and low-risk groups. K–M curve suggested that patients with a high-risk score had shorter OS than those with a low-risk score. The ROC analysis demonstrated that the risk model efficiently diagnoses LUAD. Additionally, the proportion of infiltrating aDCs (p MFNG and ALG3) were significantly correlated with infiltrating immune cells. Conclusion In summary, this study established a novel GTs-related risk model for the prognosis of LUAD patients, providing new therapeutic targets for LUAD. However, the biological role of glycosylation-related genes in LUAD needs to be explored further.

To evaluate if mixed micelles of Dox@FA-BSP-SA/TPGS can allow for the superior antitumor efficiency than Dox@FA-BSP-SA micelles. The complex of doxorubicin (Dox) and sodium cholate was encapsulated into the mixed micelles composed of folate-mediated stearic acid-modified Bletilla striata polysaccharide (FA-BSP-SA) and D-α-tocopheryl polyethylene glycol succinate (TPGS). Its average particle size increased whereas load capacity (LC) and encapsulation efficiency (EE) decreased with the increase of TPGS mass ratio in the mixed micelles. The changes of morphology, particle size and doxorubicin release in vitro demonstrated the pH sensitivity of micelles. FA-BSP-SA/TPGS mixed micelle exhibited average particle size of 147.3 nm, LC of 14.4% and EE of 91.9% for doxorubicin at the weight ratio of 3: 1. The doxorubicin release rate of micelles was faster in pH 5.0 media compared with that in pH 6.0 and 7.4 media. The cytotoxicity in vitro and antitumor efficacy in vivo results of Dox@FA-BSP-SA/TPGS micelle were more superior to that of free doxorubicin and Dox@FA-BSP-SA single micelle. For Dox@FA-BSP-SA/TPGS micelle, the clathrin-mediated endocytosis was the dominant mechanism of intracellular uptake. The FA-BSP-SA/TPGS mixed micelle may be a promising drug delivery system for cancer chemotherapy.

Background This study was conducted to evaluate and update the current prevalence of and risk factors for chronic kidney disease (CKD) and diabetic kidney disease (DKD) in a central Chinese urban population. Methods From December 2017 to June 2018, a total of 5231 subjects were randomly enrolled from 3 communities in 3 districts of Zhengzhou. CKD was defined as estimated glomerular filtration rate (eGFR) 2 or urinary albumin to creatinine ratio ≥ 30 mg/g (albuminuria). Diabetic subjects with systolic blood pressure > 140 mmHg, albuminuria or an eGFR less than 60 mL/min/1.73 m2 were classified as having DKD. Participants completed a questionnaire assessing lifestyle and relevant medical history, and blood and urine specimens were taken. Serum creatinine, uric acid, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein and urinary albumin were assessed. The age- and sex-adjusted prevalences of CKD and DKD were calculated, and risk factors associated with the presence of reduced eGFR, albuminuria, DKD, severity of albuminuria and progression of reduced renal function were analyzed by binary and ordinal logistic regression. Results The overall adjusted prevalence of CKD was 16.8% (15.8–17.8%) and that of DKD was 3.5% (3.0–4.0%). Decreased renal function was detected in 132 participants (2.9, 95% confidence interval [CI]: 2.5–3.2%), whereas albuminuria was found in 858 participants (14.9, 95% CI: 13.9–15.9%). In all participants with diabetes, the prevalence of reduced eGFR was 6.3% (95% CI = 3.9–8.6%) and that of albuminuria was 45.3% (95% CI = 40.4–50.1%). The overall prevalence of CKD in participants with diabetes was 48.0% (95% CI = 43.1–52.9%). The results of the binary and ordinal logistic regression indicated that the factors independently associated with a higher risk of reduced eGFR and albuminuria were older age, sex, smoking, alcohol consumption, overweight, obesity, diabetes, hypertension, dyslipidemia and hyperuricemia. Conclusions Our study shows the current prevalence of CKD and DKD in residents of Central China. The high prevalence suggests an urgent need to implement interventions to relieve the high burden of CKD and DKD in China.

The aim of this study was to design a pH- and redox-dual responsive Bletilla striata polysaccharide (BSP)-based copolymer to enhance anti-tumor drugs release at tumor sites and improve the therapeutic effect. The copolymer was synthesized using stearic acid (SA) and cystamine via a disulfide linkage and characterized using 1H-Nuclear Magnetic Resonance spectroscopy and Fourier Transform Infrared spectroscopy. The BSP-ss-SA copolymer could self-assemble into micelle in an aqueous environment and could encapsulate docetaxel therein. Its inhibitory effects on HepG2 cells and 4 T1 cells were determined. Besides, the anti-cancer effects in vivo and histopathological study of 4 T1-bearing tumor mice were also evaluated. Docetaxel-loaded BSP-ss-SA micelles showed significant pH-sensitive release behavior, supplying a greater drug release percentage in pH 5.0 media compared to pH 7.4 media. BSP-ss-SA micelles exhibited a clear redox-responsive release property in pH 7.4 media whereas the similar cumulative release percentage of docetaxel from BSP-ss-SA micelles in pH 5.0 media in the presence and absence of DL-dithiothreitol. The Docetaxel-loaded BSP-ss-SA micelles clearly inhibited the proliferation of HepG2 and 4 T1 cells compared with docetaxel solution. The results of MTT and histopathological study indicated that BSP-ss-SA copolymer exhibited good blood compatibility. The BSP-ss-SA copolymer may be used as carriers to deliver anti-tumor drugs to special tumor tissues.

Brain-computer interfaces (BCIs) are currently integrated into traditional rehabilitation interventions after stroke. Although BCIs bring many benefits to the rehabilitation process, their effects are limited since many patients cannot concentrate during training. Despite this outcome post-stroke motor-attention dual-task training using BCIs has remained mostly unexplored. This study was a randomized placebo-controlled blinded-endpoint clinical trial to investigate the effects of a BCI-controlled pedaling training system (BCI-PT) on the motor and cognitive function of stroke patients during rehabilitation. A total of 30 early subacute ischemic stroke patients with hemiplegia and cognitive impairment were randomly assigned to the BCI-PT or traditional pedaling training. We used single-channel Fp1 to collect electroencephalography data and analyze the attention index. The BCI-PT system timely provided visual, auditory, and somatosensory feedback to enhance the patient's participation to pedaling based on the real-time attention index. After 24 training sessions, the attention index of the experimental group was significantly higher than that of the control group. The lower limbs motor function (FMA-L) increased by an average of 4.5 points in the BCI-PT group and 2.1 points in the control group (P = 0.022) after treatments. The difference was still significant after adjusting for the baseline indicators ( β = 2.41 , 95%CI: 0.48-4.34, P = 0.024). We found that BCI-PT significantly improved the patient's lower limb motor function by increasing the patient's participation. (clinicaltrials.gov: NCT04612426).

Background Multiple myeloma is a disease of the older people, whose prognoses are highly heterogeneous. The International Myeloma Working Group (IMWG) proposed a geriatric assessment (GA) based on age, functional status and comorbidities to discriminate between fit and frail patients. Given the multidimensional nature of frailty and the relatively recent exploration of frailty in the field of MM, reaching a consensus on the measurement of frailty in MM patients remains challenging. Objective We sought to assess the feasibility of performing a comprehensive GA (CGA) in older MM patients in a real-world and multicentre setting and to evaluate their baseline CGA profiles. Results We studied 349 older patients with newly diagnosed MM (age range, 65–86 years). Our results showed that a CGA is feasible for older MM patients. Using the IMWG-GA criteria, we identified significantly more frail patients in our cohort comparing to in the IMWG cohort (43% vs 30%, P = 0.002). In the IMWG-GA ‘fit’ group, risk of malnutrition, depression and cognitive impairment remains. The median follow-up time was 26 months (range 1–38). The median overall survival (OS) was 34.7 months, and the estimated 3-year OS rate was 50%. A high MNA-SF score (MNA-SF ≥ 12), low GDS score (GDS ≤ 5) and high CCI score (CCI ≥ 2) can be used to predict the OS of older patients with newly diagnosed MM. This study is registered at www.clinicaltrials.gov (NCT03122327). Conclusions Our study justifies the need for a CGA in older patients with newly diagnosed MM.

The prediction of clinical outcome for patients with infiltrative gliomas is challenging. Although preoperative hematological markers have been proposed as predictors of survival in glioma and other cancers, systematic investigations that combine these data with other relevant clinical variables are needed to improve prognostic accuracy and patient outcomes. We investigated the prognostic value of preoperative hematological markers, alone and in combination with molecular pathology, for the survival of 592 patients with Grade II-IV diffuse gliomas. On univariate analysis, increased neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), and decreased albumin-to-globulin ratio (AGR), all predicted poor prognosis in Grade II/III gliomas. Multivariate analysis incorporating tumor status based on the presence of IDH mutations, TERT promoter mutations, and 1p/19q codeletion showed that in lower-grade gliomas, high NLR predicted poorer survival for the triple-negative, IDH mutation only, TERT mutation only, and IDH and TERT mutation groups. NLR was an independent prognostic factor in Grade IV glioma. We therefore propose a prognostic model for diffuse gliomas based on the presence of IDH and TERT promoter mutations, 1p/19q codeletion, and NLR. This model classifies lower-grade gliomas into nine subgroups that can be combined into four main risk groups based on survival projections.

Introduction: This study aimed to identify factors associated with individual emergency preparedness behaviors which play an important role in effective emergency response.Methods: Data were drawn from a cross-sectional survey conducted in China's Heilongjiang, Guangdong and Sichuan provinces in 2017. Questionnaires were administered through face-to-face interviews, and 2,506 were valid for data analyses. A structural equation model was established to test the direct and indirect effects of the relevant factors on individual emergency preparedness behaviors.Results: Low levels of emergency preparedness were found: 28% of respondents reported being fully/partly prepared. The attitudes of the respondents toward emergency preparedness had the strongest association with emergency preparedness behaviors, with a total effect of 0.483. This was followed by self-efficacy (0.305) and training/exercise (0.295). Risk perception had the weakest effect (0.045) on emergency preparedness behaviors.Discussion: Improving attitudes of the public as well as their ability to prepare for emergency events is important for effective emergency management.

Background Nonalcoholic fatty liver disease (NAFLD) is one of the main liver diseases, and its pathologic profile includes nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). However, there is no reliable non-invasive parameter in distinguishing NASH from NAFL in clinical practice. The present study was to find a non-invasive way to differentiate these two categories of NAFLD via lipidomic analysis. Methods Lipidomic analysis was used to determine the changes of lipid moieties in blood from 20 NAFL and 10 NASH patients with liver biopsy. Liver histology was evaluated after hematoxylin and eosin staining and Masson's trichrome staining. The profile of lipid metabolites in correlation with steatosis, inflammation, hepatocellular necroptosis, fibrosis, and NAFLD activity score (NAS) was analyzed. Results Compared with NAFL patients, NASH patients had higher degree of steatosis, ballooning degeneration, lobular inflammation. A total of 434 different lipid molecules were identified, which were mainly composed of various phospholipids and triacylglycerols. Many lipids, such as phosphatidylcholine (PC) (P-22:0/18:1), sphingomyelin (SM) (d14:0/18:0), SM (d14:0/24:0), SM (d14:0/22:0), phosphatidylethanolamine (PE) (18:0/22:5), PC (O-22:2/12:0), and PC (26:1/11:0) were elevated in the NASH group compared to those in the NAFL group. Specific analysis revealed an overall lipidomic profile shift from NAFL to NASH, and identified valuable lipid moieties, such as PCs [PC (14:0/18:2), PE (18:0/22:5) and PC (26:1/11:0)] or plasmalogens [PC (O-22:0/0:0), PC (O-18:0/0:0), PC (O-16:0/0:0)], which were significantly altered in NASH patients. In addition, PC (14:0/18:2), phosphatidic acid (18:2/24:4) were positively correlated with NAS; whereas PC (18:0/0:0) was correlated positively with fibrosis score. Conclusions The present study revealed overall lipidomic profile shift from NAFL to NASH, identified valuable lipid moieties which may be non-invasive biomarkers in the categorization of NAFLD. The correlations between lipid moieties and NAS and fibrosis scores indicate that these lipid biomarkers may be used to predict the severity of the disease.

Background: Sleep disturbances are highly prevalent in pregnancy and are frequently overlooked as a potential cause of significant morbidity. The association between sleep disturbances and pregnancy outcomes remains largely controversial and needs to be clarified to guide management. We conducted a systematic review and meta-analyses to investigate the association between sleep disturbances and maternal and fetal adverse outcomes. Methods: We searched PubMed, Embase and Web of Science from inception to May 31, 2019, for observational English studies of pregnant women with and without sleep disturbances assessing the risk of obstetric complications in the antenatal, intrapartum or postnatal period, and neonatal complications. We used Newcastle-Ottawa Scales to assess the methodological quality of included studies. We quantified the risks of maternal and fetal complications by comparing pregnant women with and without sleep disturbances and undertook subgroup analyses and meta-regression stratified by several clinical and demographic characteristics. We pooled the associations as odds ratios (OR) and 95% confidence intervals (CI) using fixed-effect or random-effect models as appropriate based on the heterogeneity test. Findings: We included 114 studies with a total of 58,100,274 pregnant women in this meta-analysis. Sleep disturbances were assessed, including poor sleep quality, extreme sleep duration, insomnia, restless legs syndrome, subjective sleep-disordered breathing and diagnosed obstructive sleep apnea. Women with overall sleep disturbances versus those without had a significantly higher risk of pre-eclampsia (OR=2·81, 95% CI:2·38-3·32), gestational hypertension (1·74, 1·54-1·98), gestational diabetes mellitus (1·60, 1·45-1·77), cesarean section (1·50, 1·33-1·69), preterm birth (1·41, 1·27-1·56), large for gestational age (1·40, 1·11-1·77), and stillbirth (1·25, 1·08-1·45), but not low birth weight (1·27, 0·98-1·64), or small for gestational age (1·06, 0·92-1·21). Sleep disturbances were related to higher risks of morbidities in pregnant women who are 30 years or older and overweight before pregnancy. Interpretation: Significant associations exist between sleep disturbances in pregnancy and a variety of adverse maternal and fetal outcomes. Sleep disturbances are treatable and deserve more attention from health-care providers during counseling and should be a part of prenatal health care. Funding Statement: The National Key Research and Development Program of China (no. 2019YFA0706200), and the NSFC-CIHR Joint Health Research Program (no. 81761128036). Declaration of Interests: The authors declare they have no conflicts of interest. Ethics Approval Statement: The study protocol was registered with PROSPERO, number CRD42020148586.

The causes of chronic antibiotic refractory pouchitis (CARP) and pouch failure in inflammatory bowel disease (IBD) patients remain unknown. Our previous small study showed peripouch fat area measured by MRI was associated with pouchitis.To explore the relationship between peripouch fat area on CT imaging and pouch outcomes.This is a historical cohort study. Demographic, clinical, and radiographic data of IBD patients with abdominal CT scans after pouch surgery between 2002 and 2017 were collected. Peripouch fat areas and mesenteric peripouch fat areas were measured on CT images at the middle pouch level.A total of 435 IBD patients were included. Patients with higher peripouch fat areas had a higher prevalence of CARP. Univariate analyses demonstrated that long duration of the pouch, high weight or body mass index, the presence of primary sclerosing cholangitis or other autoimmune disorders, and greater peripouch fat area or mesenteric peripouch fat area were risk factors for CARP. Multivariable analyses demonstrated that the presence of primary sclerosing cholangitis or autoimmuned disorders, and greater peripouch fat area (odds ratio [OR] 1.031; 95% confidence interval [CI] 1.016-1.047, P 0.001) or mesenteric peripouch fat area were independent risk factors for CARP. Of the 435 patients, 139 (32.0%) had two or more CT scans. Multivariable Cox proportional hazard analyses showed that "peripouch fat area increase ≥ 15%" (OR 3.808, 95%CI 1.703-8.517, P = 0.001) was an independent predictor of pouch failure.A great peripouch fat area measured on CT image is associated with a higher prevalence of CARP, and the accumulation of peripouch fat is a risk factor for pouch failure. The assessment of peripouch fat may be used to monitor the disease course of the ileal pouch.

The aim of the study was to investigate whether microvessel density (MVD) could be associated with skeletal extramedullary disease relapse (skeletal-EMDR) in patients with multiple myeloma (MM) who have skeletal-EMD at diagnosis. Seventy-nine newly diagnosed MM patients who have skeletal-EMD were retrospectively enrolled in this study. The 4-year cumulative incidence of skeletal-EMDR was 35.0%±8.3%. The 4-year probability of overall survival (OS) was 54.0%±7.6%. Multivariate analysis showed that skeletal-EMDR (HR = 4.144; 95% CI: 1.608–10.685; P = 0.003) was independently associated with inferior OS for the MM patients who have skeletal-EMD at diagnosis. The factors associated with skeletal-EMDR were MVD (HR = 3.990, 95%CI:1.136-14.018; P = 0.031), white blood cell (WBC) (HR = 0.262, 95% CI:0.090-0.769; P = 0.015), and the EMD sites involved at onset (HR = 0.263, 95% CI: 0.074-0.937; P = 0.039). The MVD in patients with thoracic and lumbar vertebrae as the involved sites at diagnosis was significantly lower than those with other sites involved (41.59 ± 14.39 vs. 60.82 ± 35.14, P=0.001). Our data suggest that increased MVD could be used to predict skeletal-EMDR, which is associated with inferior survival in patients with MM who have skeletal-EMD at diagnosis.

Background: Outflow tract (OFT) septation defects are a common cause of congenital heart disease. Numerous studies have focused on the septation mechanism of the OFT, but have reported inconsistent conclusions. This study, therefore, aimed to investigate the septation of the aortic sac and the OFT in the early embryonic human heart. Methods: Serial sections of 27 human embryonic hearts from Carnegie stage (CS) 10 to CS19 were immunohistochemically stained with antibodies against c-smooth muscle actin (α-SMA) and myosin heavy chain. Results: At CS10–CS11, the OFT wall was an exclusively myocardial structure that was continuous with the aortic sac at the margin of the pericardial cavity. From CS13 onward, the OFT was divided into nonmyocardial and myocardial portions. The cushion formed gradually, and its distal border with the OFT myocardium was consistently maintained. The aortic sac between the fourth and sixth aortic arch arteries was degenerated. At CS16, the α-SMA-positive aortopulmonary septum formed and fused with the two OFT cushions, thus septating the nonmyocardial portion of the OFT into two arteries. At this stage, the cushions were not fused. At CS19, the bilateral cushions were fused to septate the myocardial portion of the OFT. Conclusions: Data suggest that the OFT cushion is formed before the aortopulmonary septum is formed. Thus, the OFT cushion is not derived from the aortopulmonary septum. In addition, the nonmyocardial part of the OFT is septated into the aorta and pulmonary trunk by the aortopulmonary septum, while the main part of the cushion fuses and septates the myocardial portion of the OFT. Key words: Aortopulmonary Septum; Human Embryonic Heart; Immunohistochemistry; Outflow Tract; Outflow Tract Cushion

Background/Aims: CDH18 (cadherin 18) is specifically expressed in the central nervous system and associated with various neuropsychiatric disorders. In this study, the role of CDH18 in glioma carcinogenesis and progression was investigated. Methods: The expression of CDH18 and its prognostic value in patients with gliomas were analyzed in public database and validated by real-time PCR/immunohistochemical staining (IHC) in our cohort. CCK-8 assay, transwell migration assay, wound healing assay, clonogenic assay and tumorigenicity assay were used to compare the proliferation, invasion and migration ability of glioma cells with different expressions of CDH18. iTRAQ-based quantitative proteomic analysis were used to reveal the downstream target of CDH18. Rescue experiments were conducted to further validate the relationship between UQCRC2 and CDH18. Results: The expression of CDH18 was depressed in a ladder-like pattern from normal tissues to WHO IV gliomas, and was an independent prognostic factor in TCGA (The Cancer Genome Atlas), CGGA (the Chinese glioma genome-atlas) and our glioma cohorts (n=453). Functional experiments in vitro and in vivo demonstrated that CDH18 inhibited invasion/migration, enhanced chemoresistance and suppressed tumorigenicity of glioma cells. UQCRC2 was identified as the downstream target of CDH18 by proteomic analysis. The expression of UQCRC2 was gradually absent as the WHO grades of gliomas escalated and was positively correlated with the expression of CDH18. Furthermore, in vitro assays demonstrated that down-regulation of UQCRC2 partly reversed the inhibition of invasion/migration ability and chemoresistance in CDH18 overexpressed glioma cell lines. Survival analysis demonstrated that combined CDH18/UQCRC2 biomarkers significantly influenced the prognosis of glioma patients. Conclusions: The present research demonstrated that CDH18 exerted its tumor-suppressor role via UQCRC2 in glioma cells and CDH18 might serve as a therapeutic target for treating gliomas.

Pouch prolapse is a rare pouch complication which often leads to pouch failure in inflammatory bowel disease (IBD) patients. Its exact cause remains unknown. Floppy pouch complex (FPC) was defined as the presence of any one of the following pouch disorders: pouch prolapse, afferent limb syndrome (ALS), redundant loop, and pouch folding. We aimed to explore the role of peripouch fat area in the occurrence of pouch prolapse and FPC.Pouch patients with available pouchoscopy and abdominal CT scans who were followed up between 2011 and 2017 in Cleveland Clinic were reviewed. Peripouch fat was measured on CT images.Of the 93 included patients, 31 were females; 87 had J pouches and 6 had S pouches. The median duration of pouch was 8.0 (interquartile range [IQR] 5.0-16.5) years. A total of 18 cases (19.4%, 18/93) were identified as FPC, including 12 pouch prolapse, 5 ALS, 1 redundant loop, and 3 pouch folding. Patients with pouch prolapse had lower peripouch fat area (13.6 (9.3-18.5) vs. 27.6 (11.0-46.2)cmA lower peripouch fat area was observed in inflammatory bowel disease patients with pouch prolapse and FPC. Longitudinal studies are needed to further elucidate the role of peripouch fat in the pathogenesis of pouch prolapse and FPC.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curable strategy for the treatment of hematological malignancies and nonmalignant diseases. However, graft-versus-host disease (GVHD) and relapse are still two major causes of morbidity and mortality after allo-HSCT, and both restrict the improvement of transplant outcomes. Regulatory T cells (Tregs) has been successfully used in allo-SCT settings. In this review, we summarize recent advances in experimental studies that have evaluated the roles played by Tregs in the establishment of novel transplant modalities, the prevention of GVHD and the enhancement of immune reconstitution. We also discuss the application of Tregs in clinical to prevent acute GVHD, treat chronic GVHD, as well as enhance immune reconstitution and decrease leukemia relapse, all of which lead to improving transplant outcomes.

The link between depression and anxiety status and cancer outcomes has been well-documented but remains unclear. We comprehensively quantified the association between depression and anxiety defined by symptom scales or clinical diagnosis and the risk of cancer incidence, cancer-specific mortality, and all-cause mortality in cancer patients. Pooled estimates of the relative risks (RRs) for cancer incidence and mortality were performed in a meta-analysis by random effects or fixed effects models as appropriate. Associations were tested in subgroups stratified by different study and participant characteristics. Fifty-one eligible cohort studies involving 2,611,907 participants with a mean follow-up period of 10.3 years were identified. Overall, depression and anxiety were associated with a significantly increased risk of cancer incidence (adjusted RR: 1.13, 95% CI: 1.06-1.19), cancer-specific mortality (1.21, 1.16-1.26), and all-cause mortality in cancer patients (1.24, 1.13-1.35). The estimated absolute risk increases (ARIs) associated with depression and anxiety were 34.3 events/100,000 person years (15.8-50.2) for cancer incidence and 28.2 events/100,000 person years (21.5-34.9) for cancer-specific mortality. Subgroup analyses demonstrated that clinically diagnosed depression and anxiety were related to higher cancer incidence, poorer cancer survival, and higher cancer-specific mortality. Psychological distress (symptoms of depression and anxiety) was related to higher cancer-specific mortality and poorer cancer survival but not to increased cancer incidence. Site-specific analyses indicated that overall, depression and anxiety were associated with an increased incidence risks for cancers of the lung, oral cavity, prostate and skin, a higher cancer-specific mortality risk for cancers of the lung, bladder, breast, colorectum, hematopoietic system, kidney and prostate, and an increased all-cause mortality risk in lung cancer patients. These analyses suggest that depression and anxiety may have an etiologic role and prognostic impact on cancer, although there is potential reverse causality; Furthermore, there was substantial heterogeneity among the included studies, and the results should be interpreted with caution. Early detection and effective intervention of depression and anxiety in cancer patients and the general population have public health and clinical importance.

During neurological surgery, neurosurgeons have to transform the two-dimensional (2D) sectional images into three-dimensional (3D) structures at the cognitive level. The complexity of the intracranial structures increases the difficulty and risk of neurosurgery. Mixed reality (MR) applications reduce the obstacles in the transformation from 2D images to 3D visualization of anatomical structures of central nervous system. In this study, the holographic image was established by MR using computed tomography (CT), computed tomography angiography (CTA) and magnetic resonance imaging (MRI) data of patients. The surgeon's field of vision was superimposed with the 3D model of the patient's intracranial structure displayed on the mixed reality head-mounted display (MR-HMD). The neurosurgeons practiced and evaluated the feasibility of this technique in neurosurgical cases. We developed the segmentation image masks and texture mapping including brain tissue, intracranial vessels, nerves, tumors, and their relative positions by MR technologies. The results showed that the three-dimensional imaging is in a stable state in the operating room with no significant flutter and blur. And the neurosurgeon's feedback on the comfort of the equipment and the practicality of the technology was satisfactory. In conclusion, MR technology can holographically construct a 3D digital model of patient's lesions and improve the anatomical perception of neurosurgeons during craniotomy. The feasibility of the MR-HMD application in neurosurgery is confirmed.

Supplemental Digital Content is available in the text, Glioma is the most common malignant tumor in the central nervous system (CNS). Lower-grade gliomas (LGG) refer to Grade II and III gliomas. In LGG patients, seizure often appears as an initial symptom and play an important role in clinical performance and quality of life of the patients. To date, the relationship between the onset of seizures and the molecular pathology in gliomas is still poorly investigated. In this study, we investigate the potential relationship between isocitrate dehydrogenase (IDH)/telomerase reverse transcriptase promoter (TERTp) mutations and preoperative seizures in patients with LGG. 289 adult LGG patients were enrolled in this study. Data of clinical characteristics and molecular pathology were acquired. Sanger sequencing was used to detect IDH/TERTp mutations. Chi-square test was performed to determine if the IDH/TERTp mutations were associated with seizures and seizure types. In 289 LGG patients, preoperative seizures accounted for 25.3% (73/289), IDH mutations accounted for 34.3%(99/289), and TERTp mutations accounted for 44.3% (128/289). The correlation analysis demonstrated that IDH mutation is a significant factor influencing the occurrence of tumor-related epilepsy (P

Prospective study. The purpose of this study was to characterise risk factors for poor surgical outcome in patients with cervical spondylotic myelopathy (CSM). The prospective study included 110 consecutive patients who underwent surgical treatment for CSM. Surgical outcomes were evaluated according to the Japanese Orthopaedic Association (JOA) score. JOA recovery rate

Granulocyte colony-stimulating factor (G-CSF) has been widely accepted as a mediator of T cell tolerance. The immune modulatory effect of G-CSF on T cells is believed to be mediated exclusively through other effector cells, such as monocytes, tolerogenic dendritic cells (DC), and myeloid-derived suppressor cells. Recent advances confirmed the direct effects of G-CSF in inducing immune tolerance of T cells through the G-CSF-G-CSF receptor pathway and related molecular mechanisms. This review aims to summarize the findings associated with the direct and indirect mechanisms for T cell tolerance induced with G-CSF. The role of G-CSF in preventing graft-versus-host disease (GVHD) and in treating autoimmune diseases (ADs) is also discussed. It is conceivable that G-CSF and immune cell compositions, such as tolerogenic DC and CD4(+)CD25(+)Foxp3(+) T cells, modulated by G-CSF could become an integral part of the immunomodulatory therapies against GVHD and ADs in the future.

This cohort study assesses whether longitudinal patterns of habitual sleep duration are associated with subsequent risk of cardiovascular events and all-cause mortality in adults enrolled in a population-based study in China., Key Points Question Are longitudinal patterns of habitual sleep duration associated with subsequent risk of cardiovascular events and all-cause mortality? Findings In this cohort study that included 52 599 participants, 4 distinct sleep duration trajectories reported during a 4-year interval were identified. Compared with a stable sleep duration of 7.0 to 8.0 hours per night, normal-decreasing and low-increasing patterns were associated with increased risk of first cardiovascular events and all-cause mortality, respectively; individuals reporting consistently sleeping less than 5.0 hours per night had the highest risk. Meaning This study suggests that sleep duration trajectories with lower or unstable patterns may be associated with increased risk of subsequent first cardiovascular events and all-cause mortality., Importance Single self-reported measures of sleep duration are associated with adverse health outcomes; however, long-term patterns of self-reported sleep duration and their association with cardiovascular events (CVEs) and all-cause mortality remain unknown. Objective To determine whether trajectories of long-term vs single-measure sleep duration are associated with subsequent risk of CVEs and all-cause mortality. Design, Setting, and Participants The Kailuan study is a prospective, population-based cohort study that began in 2006. The present cohort included 52 599 Chinese adults without atrial fibrillation, myocardial infarction, stroke, or cancer to 2010. Trajectories in sleep duration from January 1, 2006, to December 31, 2010, were identified to investigate the association with risk of CVEs and all-cause mortality from January 1, 2010, to December 31, 2017. Data analysis was conducted from July 1 to October 31, 2019. Exposures Habitual self-reported nocturnal sleep durations were collected in 2006, 2008, and 2010. Trajectories in sleep duration for 4 years were identified by latent mixture modeling. Main Outcomes and Measures All-cause mortality and first incident CVEs (atrial fibrillation, myocardial infarction, and stroke) from 2010 to 2017 were confirmed by medical records. Based on the baseline sleep duration and patterns over time, 4 trajectories were categorized (normal stable, normal decreasing, low increasing, and low stable). Results Of the 52 599 adults included in the study (mean [SD] age at baseline, 52.5 [11.8] years), 40 087 (76.2%) were male and 12 512 (23.8%) were female. Four distinct 4-year sleep duration trajectory patterns were identified: normal stable (range, 7.4 to 7.5 hours [n = 40 262]), normal decreasing (mean decrease from 7.0 to 5.5 hours [n = 8074]), low increasing (mean increase from 4.9 to 6.9 hours [n = 3384]), and low stable (range, 4.2 to 4.9 hours [n = 879]). During a mean (SD) follow-up of 6.7 (1.1) years, 2361 individuals died and 2406 had a CVE. Compared with the normal-stable pattern and adjusting for potential confounders, a low-increasing pattern was associated with increased risk of first CVEs (hazard ratio [HR], 1.22; 95% CI, 1.04-1.43), a normal-decreasing pattern was associated with increased risk of all-cause mortality (HR, 1.34; 95% CI, 1.15-1.57), and the low-stable pattern was associated with the highest risk of CVEs (HR, 1.47; 95% CI, 1.05-2.05) and death (HR, 1.50; 95% CI, 1.07-2.10). Conclusions and Relevance In this study, sleep duration trajectories with lower or unstable patterns were significantly associated with increased risk of subsequent first CVEs and all-cause mortality. Longitudinal sleep duration patterns may assist in more precise identification of different at-risk groups for possible intervention. People reporting consistently sleeping less than 5 hours per night should be regarded as a population at higher risk for CVE and mortality.

Inflammation and immunoreaction markers were correlated with the survival of patients in many tumors. However, there were no reports investigating the relationships between preoperative hematological markers and the prognosis of medulloblastoma (MB) patients based on the molecular subgroups (WNT, SHH, Group 3, and Group 4). A total 144 MB patients were enrolled in the study. The differences of preoperative hematological markers among molecular subgroups of MB were compared by One-way ANOVA method. Kaplan-Meier method was used to calculate the curves of progression free survival (PFS) and overall survival (OS). The comparison of survival rates in different groups were conducted by the Log-rank test. Multivariate analysis was used to evaluate independent prognostic factors. Increased preoperative NLR (neutrophil-to-lymphocyte ratio, PFS, P = 0.004, OS, P P = 0.028, OS, P = 0.003) predicted poor prognosis in patients with MB, while preoperative MLR (monocyte-to-lymphocyte ratio), MPV (mean platelet volume), PDW (platelet distribution width), and AGR (albumin-to-globulin ratio) were revealed no predictive value on the prognosis of patients with MB. Furthermore, high preoperative NLR and PLR predicted unfavorable prognosis in childhood MB patients. However, preoperative NLR and PLR were not associated with the prognosis in adult MB patients. Multivariate analysis demonstrated preoperative NLR (PFS, P = 0.029, OS, P = 0.005) and PLR (PFS, P = 0.023, OS, P = 0.005) were the independent prognostic factors in MB patients. Emphatically, the levels of preoperative NLR and PLR in Group 3 MB were significantly higher than those in WNT MB. High preoperative NLR was associated with unfavorable OS in Group 3 (P = 0.032) and Group 4 (P = 0.027) tumors. Similarly, increased preoperative PLR predicted poor PFS (P = 0.012) and OS (P = 0.009) in Group 4 tumors. Preoperative NLR and PLR were the potential prognostic markers for MB patients. Preoperative NLR and PLR were significantly associated with the survival of Group 3 and Group 4 tumors.

A previous study revealed that ubiquitin-like with PHD and RING finger domains 1 (UHRF1) promoted cell proliferation and was a potential biomarker in medulloblastoma (MB). In the present study, we reported that miR-378 inhibited the expression of UHRF1 to affect the proliferation of MB through competitive binding to the same region of its 3'-UTR. We found that the expression of miR-378 was significantly downregulated in MB tissues and inversely correlated with the expression of UHRF1. Western blot analysis revealed that overexpression of miR-378 led to the suppression of UHRF1. Moreover, a dual-luciferase assay demonstrated that miR-378 negatively regulated the activity of target gene UHRF1 by binding to its 3'-UTR. An in vitro assay revealed that overexpression of miR-378 suppressed MB cell proliferation and promoted cell apoptosis. Ectopic expression of UHRF1 rescued miR-378-suppressed cell proliferation and miR-378-promoted cell apoptosis. Collectively, the present study demonstrated that miR-378 could inhibit the proliferation of MB by downregulation of UHRF1 and act as a potential therapeutic target against MB.

Purpose: To explore the correlation of vascular risk factors for Alzheimer’s disease (AD) in Chinese population. Methods: A total of 123 outpatients with probable AD followed up for 3 years were investigated. Severity of cognitive impairment and functional ability was assessed using Mini-Mental State Examination (MMSE) and modified activities of daily living (ADLs), respectively. The incidence of vascular risk factors was studied in patients with AD. Results: Univariate analysis showed significance difference in MMSE and ADL scores between patients with and without vascular risk factors ( P < .05). Multiple regression analysis showed age, education, hyperhomocysteinemia, and hypertension were significant variables associated with annual MMSE, while there were no significant correlations between annual MMSE and sex, initial MMSE, diabetes, and so on. Conclusions: Vascular risk factors are common comorbidities in patients with AD in China, with younger, better educated ones showing faster cognitive decline. Hypertension and hyperhomocysteinemia may also aggravate the progression, and it is important to prevent and treat patients with AD.

The second heart field (SHF) is indicated to contribute to the embryonic heart development. However, less knowledge is available about SHF development of human embryo due to the difficulty of collecting embryos. In this study, serial sections of human embryos from Carnegie stage 10 (CS10) to CS16 were stained with antibodies against Islet-1 (Isl-1), Nkx2.5, GATA4, myosin heavy chain (MHC) and α-smooth muscle actin (α-SMA) to observe spatiotemporal distribution of SHF and its contribution to the development of the arterial pole of cardiac tube. Our findings suggest that during CS10 to CS12, SHF of the human embryo is composed of the bilateral pharyngeal mesenchyme, the central mesenchyme of the branchial arch and splanchnic mesoderm of the pericardial cavity dorsal wall. With development, SHF translocates and consists of ventral pharyngeal mesenchyme and dorsal wall of the pericardial cavity. Hence, the SHF of human embryo shows a dynamic spatiotemporal distribution pattern. The formation of the Isl-1 positive condense cell prongs provides an explanation for the saddle structure formation at the distal pole of the outflow tract. In human embryo, the Isl-1 positive cells of SHF may contribute to the formation of myocardial outflow tract (OFT) and the septum during different development stages.

Many schizophrenia susceptibility loci have been identified through genome-wide association studies (GWASs) in European populations. However, until recently, schizophrenia GWASs in non-European populations were limited to small sample sizes and have yielded few loci associated with schizophrenia. To identify genetic risk variations for schizophrenia in the Han Chinese population, we performed a two-stage GWAS of schizophrenia comprising 4384 cases and 5770 controls, followed by independent replications of 13 single-nucleotide polymorphisms in an additional 4339 schizophrenia cases and 7043 controls of Han Chinese ancestry. Furthermore, we conducted additional analyses based on the results in the discovery stage. The combined analysis confirmed evidence of genome-wide significant associations in the Han Chinese population for three loci, at 2p16.1 (rs1051061, in an exon of VRK2, P=1.14 × 10-12, odds ratio (OR)=1.17), 6p22.1 (rs115070292 in an intron of GABBR1, P=4.96 × 10-10, OR=0.77) and 10q24.32 (rs10883795 in an intron of AS3MT, P=7.94 × 10-10, OR=0.87; rs10883765 at an intron of ARL3, P=3.06 × 10-9, OR=0.87). The polygenic risk score based on Psychiatric Genomics Consortium schizophrenia GWAS data modestly predicted case-control status in the Chinese population (Nagelkerke R2: 1.7% ~5.7%). Our pathway analysis suggested that neurological biological pathways such as GABAergic signaling, dopaminergic signaling, cell adhesion molecules and myelination pathways are involved in schizophrenia. These findings provide new insights into the pathogenesis of schizophrenia in the Han Chinese population. Further studies are needed to establish the biological context and potential clinical utility of these findings.

To observe the effect of electroacupuncture (EA) therapy on levels of oxygen free radicals (OFR) and hippocampal apoptosis-related protein expression in ischemic learning-memory disorder rats so as to investigate its mechanisms underlying improvement of ischemic learning-memory impairment.A total of 60 SD rats were randomly divided into sham operation (sham), model, medication, and EA groups, with 15 rats in each group. The learning-memory disorder model was made by occlusion of bilateral carotid arteries. EA (2- 3 Hz, 2 mA) was applied to "Zhi San Zhen" ["Shenting" (GV 24) and bilateral "Benshen" (GB 13)] for 30 min, once a day for 3 weeks. The rats of the medication group were treated by lavage of Aricept (0.03 mg . kg(-1) . d(-1)), once daily for 3 weeks. The rats' learning-memory ability was detected by Morris water maze tests and the state of hippocampal apoptosis cells was observed by light microscope after TUNEL staining and the expression of hippocampal Bcl-2, Bax and Caspase-3 proteins was detected by immunohistochemistry. Serum and hippocampal superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) contents were detected by chemical colorimetric analysis.Compared with the sham group, the escape latencies (place-navigation) after modeling were evidently prolonged, and the times of target-platform crossing in 90 sec (spatial probe test) considerably reduced in the model group (P0.01), suggesting an impairment of learning-memory ability. After the treatment for 21 d, the increased escape latency and the reduced target-platform crossing time in both EA and medication groups were reversed in comparison with the model group (P0.01), suggesting an improvement of memory ability, and the effect of the EA group was significantly superior to that of the medication group (P0.05). Compared with the sham group, the number of apoptotic cells in hippocampal CA 1- CA 3 regions, and the expression levels of hippocampal Bcl-2, Bax and Caspase-3 proteins, and serum and hippocampal MDA contents were significantly increased in the model group (P0.01), while serum and hippocampal SOD and GSH-Px levels obviously decreased in the model group (P0.01). After the treatment for 21 days, compared to the model group, the number of the apoptotic cells, the expression levels of hippocampal Bax and Caspase--3 proteins, and the contents of serum and hippocampal MDA were notably decreased in the EA and medication groups (P0.01), whereas, Bcl-2 protein expression levels, and serum and hippocampal SOD and GSH-Px activity were notably up-regulated in the EA and medication groups (P0.01). The effects of EA group were obviously superior to those of medication group in increasing hippocampal Bcl-2 immunoactivity, serum SOD and GSH-Px and hippocampal GSH-Px activity and in down-regulating serum MDA level (P0.01, P0.05).Electroacupuncture intervention can improve learning-memory ability in ischemic learning-memory disorder rats which may be associated with its effects in reducing blood and hippocampal OFR contents and hippocampal cellular apoptosis.

To compare the accuracy of different neuropsychological tests and their combinations for deriving reliable cognitive indices for dementia diagnosis in Parkinson’s disease (PD). One hundred forty consecutive patients with PD were recruited and administrated an extensive battery of neuropsychological tests. Discriminant analysis and receiver–operator characteristic curve were used to evaluate their correct classifications and validity. Patients with PD having dementia (PDD; 23.5%) performed significantly worse in all tests than patients without dementia. Age of onset, disease duration, Hoehn-Yahr grade, Unified Parkinson’s Disease Rating Scale part III scores, and education were associated with dementia in patients with PD. Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment, and Block Design (BD) showed better specificity and sensitivity when used alone, and combined use of MMSE and BD further increased the validity. Our results indicated that the accuracy of MMSE was better in dementia diagnosis of Chinese patients with PD, and combined use of MMSE and BD could further increase the validity of dementia diagnosis.

Background An increasing number of epidemiological studies have identified a close relationship between dyslipidemia and atherosclerotic stroke. Indeed, lipid metabolism is significantly different among the different ischemic stroke subtypes. There are few studies available regarding risk factors for specific subtypes of ischemic stroke, and in particular, there is little evidence about the role of dyslipidemia. The aim of this study is to determine the relationship between acute ischemic stroke subtype and serum lipid level. Methods The levels of serum lipid including TC, TG, LDL-C, HDL-C, apoA, apoB, apoE, and LP (a) were tested in 362 ischemic stroke patients and 181 healthy controls. Lipid levels were analyzed in stroke subtypes according to the TOAST classification. Results Levels of TC, TG, LDL-C, apoA, apoB, apoE, and LP (a) were significantly higher and HDL-C levels were significantly lower in the patient group relative to control. The TC/HDL-C ratio, TG/HDL-C ratio, and LDL-C/HDL-C ratio were remarkably higher in the patient group. The levels of TC, TG, LDL-C, apoA, apoB, apoE, and LP(a) were markedly higher and HDL-C was markedly lower in the large-artery atherosclerosis stroke subtype relative to the cardioembolism subtype. Compared with the small-vessel occlusion group, the level of LP(a), TC, and TC/HDL-C were strikingly higher in the cardioembolism group. The TC/HDL-C ratio was different among subgroups, with the large-artery atherosclerosis group exhibiting the highest value. For TC, TG, LDL-C, apoA, apoB, apoE, LP(a), TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C levels a statistically significant difference was found between the large-artery atherosclerosis group and the small-vessel occlusion group. Conclusions We found that LDL-C and TC levels may be independent predictors for the occurrence of large-artery atherosclerotic stroke.

The goal of the study was to investigate the expression of interleukin-17 (IL-17) and IL-17 receptor (IL-17R) in patients with myeloma bone diseases (MBD) and skeletal extramedullary disease (skeletal EMD). The levels of IL-17 were determined using ELISA. The expression of IL-17R on vascular endothelial cells of bone marrow (BM) and masses of skeletal EMD was detected using immunohistochemistry. The results showed an elevated IL-17 level in BM of BMD and skeletal EMD patients. The microvessel density (MVD) was significantly increased in the masses of skeletal EMD. IL-17R was almost exclusively expressed by endothelial cells, not by myeloma cells in the masses of skeletal EMD patients. We concluded that EMD masses showed increased angiogenesis mediated by IL-17 pathway and in part this may help in myeloma cell-growth under these conditions.

We evaluated the optimal flow velocity of transcranial doppler (TCD) in detecting unilateral middle cerebral artery (MCA) stenosis and stenosis grading by magnetic resonance angiography (MRA) as the reference standard. 302 nonconsecutive patients with unilateral MCA stenosis detected by TCD underwent MRA of the intracranial arteries. The peak systolic velocity (PSV), mean flow velocity (MFV), and end-diastolic velocity (EDV) of each MCA were recorded. 604 MCA were categorized into four groups depending on the stenosis severity: normal MCA (n = 319, 52.8 %), mild stenosis (n = 94, 15.6 %), moderate stenosis (n = 66, 10.9 %), and severe stenosis (n = 125, 20.7 %). Significant differences in PSV, MFV, and EDV between these four groups were observed (P

The goal of the study was to investigate the levels of interleukin-27 (IL-27) and IL-17 in bone marrow (BM) and peripheral blood (PB) of multiple myeloma (MM). The levels of IL-27 and IL-17 were determined in MM patients and controls using ELISA. The results showed a decreased IL-27 and elevated IL-17 level in MM patients and a negative association of IL-27 with IL-17. The ratio of IL-27:IL-17 in BM of newly diagnosed MM was significantly decreased and correlated with the progression of disease. Multivariate analysis showed that a higher ratio of IL-27:IL-17 in BM was associated with a superior progression-free survival (HR=0.160; 95% CI: 0.058-0.443; p

To investigate the clinical features and molecular diagnostic methods of three patients with DiGeorge anomaly.The clinical manifestations and immunological features of the three cases with DiGeorge anomaly were analyzed. We detected the chromosome 22q11.2 gene deletion by fluorescence in situ hybridization (FISH).(1) CLINICAL MANIFESTATIONS: All three cases had varying degrees of infection, congenital heart disease and small thymus by imaging; two cases had significant hypocalcemia (1.11 mmol/L and 1.22 mmol/L, respectively), accompanied by convulsions; only 1 case had cleft palate and all had no significant facial deformity. (2) Immunological characteristics: All three cases had varying degrees of T-cell immune function defects (percentage of T lymphocytes was 24% - 43%, absolute count was 309 - 803/µl), and levels of immunoglobulin G, A, M, and percent of B lymphocytes and absolute count were normal. (3) Detection of the chromosome 22q11.2 gene deletion: 400 cells of each case were detected. All cells showed two green and one red hybridization signal, indicating the presence of gene deletions in chromosome 22q11.2. (4) OUTCOME: All three cases were treated with thymosin, and appropriate clinical intervention for cardiac malformations, hypocalcemia, and were followed-up for 4 - 18 months, the prognosis was good.DiGeorge anomaly showed diverse clinical manifestations. We should consider the disease if patients had congenital heart disease, thymic hypoplasia, hypocalcemia and/or impaired immune function. FISH for detecting chromosome 22q11.2 gene deletion can be used as accurate and rapid diagnostic method. Thymosin treatment and other clinical intervention may help to improve the prognosis of patients with partial DiGeorge anomaly.

Improvements in health status in the People's Republic of China have led to a shift in the burden of illness from acute, communicable disease to long-term illness, particularly in urban areas. The Chinese family's response to chronic illness is influenced by many factors, including the traditional cultural value of family responsibility as well as economic determinants. Through direct interviews with 75 women, we sought to understand the financial, social, emotional, and physical effects of caring for a chronically ill child on a Chinese mother's life and caregiving ability and to identify the sources of support available to her.

Norcantharidin (NCTD), the demethylated analog of the Chinese medicine cantharidin, exhibits anti-myeloma activity by inactivating nuclear factor-κB (NF-κB), which is implicated in multiple myeloma (MM) cell survival and resistance to bortezomib (BTZ). We investigated whether NCTD could potentiate the anti-tumor activity of BTZ in MM. NCTD inhibited the proliferation of MM cells and potentiated the anti-myeloma effects of BTZ by down-regulating IKKα and p-IκBα, which induced the accumulation of IκBα and inhibited the constitutive activation of NF-κB. This effect was correlated with the suppression of NF-κB-regulated gene products. Furthermore, a chemotherapy-potentiating effect of NCTD on BTZ was also observed in vivo. Our study demonstrated that NCTD and BTZ exhibit significant therapeutic effects on MM through the NF-κB signal pathway in vitro and in vivo. Future studies will investigate the combined effects of NCTD and BTZ in patients with MM.

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency of phagocytic oxidative bursts leading to recurrent severe bacterial and fungal infections as well as granuloma formation. There were few reports on the clinical characteristics of this disease in China. The purpose of this study was to evaluate the clinical features of 48 Chinese cases with CGD which were confirmed by clinical features, dihydrorhodamine (DHR) assay and gene mutation analysis.The study cohort was the population of CGD patients diagnosed in Children's Hospital of Fudan University from January, 2004, to June, 2011. Cases included in our analysis were restricted to those who had complete data of the clinical symptoms and laboratory tests. The patients were followed up by outpatient visiting and telephone call regularly for 0.5 to 6 years. The history and data of physical examination and treatment of 48 cases were collected and reviewed.All the patients were diagnosed by DHR analysis. The age of onset of all the 48 patients were less than 6 months, including 43 male and 5 female. The mean age at diagnosis was 2.42 years; 12 patients were infants under six months, 10 were between 6 and 12 months, 9 were between 1 and 2 years, 5 patients were between 2 and 3 years, 4 were between 4 and 5 years, and 8 were between 6 and 10 years. Recurrent respiratory infection (44/48) and chronic diarrhea (31/48) were the common symptoms in all the patients, and then skin lesion (22/48), including marked reaction at BCG infected site, pustular eruption and infected skin ulcer and urinary tract infection (3/48) were also general symptoms in our study. In addition, lymphadenectasis occurred in 31 cases and 23 of them were considered to be associated with BCG vaccination. The pathogens caused the infection were mycobacteria (52.08%), fungi (43.75%) and pyogenic bacteria. Thirty-seven patients had mutations in CYBB/CYBA/NCF1/NCF2 genes. Recombinant human interferon-gamma (rhIFN-γ) plus sulfamethoxazole were used for the prevention and treatment of infection, the frequency and severity of the disease could be reduced.The age at onset and diagnosis of the present group of CGD was younger. Clinical symptoms were associated with recurrent mycobacterial, fungal and pyogenic bacterial infection, which involved respiratory tract, alimentary tract, skin and lymph node. rhIFN-γ partially improved the prognosis of CGD.

To explore the synergetic effect of norcantharidin (NCTD) and adriamycin (ADR) on the proliferation and apoptosis of multiple myeloma (MM) cells.Human MM cell line U266 cells were treated with NCTD alone (10 µmol/L) or in combination with ADR (0.25 µmol/L). MTT and Annexin V/PI staining were used to determine cell viability and apoptosis. The protein expression of nuclear factor-κB P65 (NF-κB P65), phosphorylated NF-κB p65 (p-NF-κB p65), NF-κB P65 inhibitor IκBα, phosphorylated IκBα (p-IκBα), survivin, Bcl-2 and Bax were determined by Western blot. Immunohistochemistry was used to determine the expression of vascular endothelial growth factor (VEGF).(1) NCTD potentiated the cytotoxicity and pro-apoptotic effects induced by ADR. The combination of NCTD and ADR had synergistic anti-proliferation effect. (2) Combination of ADR and NCTD downregulated the expression of nuclear NF-κB P65 and cytoplasm p-IκBα induced by ADR. The expression of nuclear NF-κB P65 and cytoplasm p-IκBα decreased from 2.08 ± 0.29 and 0.39 ± 0.07 to 0.48 ± 0.08 and 0.02 ± 0.01 respectively, while the expression of the cytoplasm NF-κB P65 and IκBα were unchanged in the ADR alone group and the combined group. (3) The expression of survivin and bcl-2 decreased from 0.31 ± 0.05 and 0.23 ± 0.05 to 0.03 ± 0.02 and 0.05 ± 0.02, while the expression of Bax increased from 0.46 ± 0.06 to 0.62 ± 0.08 respectively in ADR alone group and combined group. (4) The positive rate of VEGF in ADR group and combination group were (44.6 ± 4.4)% and (27.0 ± 2.1)% respectively, indicating that NCTD could potentiate the inhibition effect on VEGF induced by ADR.The results suggest that NCTD can potentialize the chemosensitivity of multiple myeloma cells to ADR through regulating NF-κB/IκBα signaling pathway and NF-κB-regulated gene products including survivin, Bcl-2, Bax and VEGF.

To investigate the evolution of cognitive function and its influence factors, so as to provide evidence for guiding treatment of cognitive impairment after stroke.A total of 98 cases of patients with stroke admitted in the First and Second Affiliated Hospital of Medical College of Xi'an Jiaotong University and Shaanxi Provincial People's Hospital between April and September 2009 were enrolled and recruited. Mini-mental state examination (MMSE) and Montreal cognitive function rating scale (MoCA) were adopted to assess the evolution of cognition at acute phase (within 2 weeks), 6 weeks, and 12 weeks after stroke among patients within 2 weeks after onset, questionnaire score ≤ 56, without aphasia and consciousness disturbance and at least one side of upper extremities muscle force ≥ grade 3.When using MMSE scale as criteria, the incidence of cognitive impairment was 24.5% at acute phase, 12.1% at 6 weeks and 9.9% at 12 weeks after stroke, while the incidence was 86.8%, 68.2%, and 38.0% respectively when using MoCA scale as criteria. The scales of MMSE and MoCA were increased and the incidence of cognitive impairment was decreased within 12 weeks after stroke. Logistic regression analysis indicated that, advanced age (β = -0.124), hypertension (β = -3.705), low education level(β = 0.560) and depression after stroke (β = 4.613) were related with cognitive impairment after stroke (all P values0.05); low education level(β = 0.710), coronary heart disease (β = -3.649), elevated total cholesterol (TC) (β = -3.361) and low density lipid cholesterol (LDL-C) (β = -5.833), and depression (β = -3.612) delayed recovery of cognition after stroke.The cognitive function improves and the incidence of cognitive impairment lowers as the time goes on within 12 weeks after stroke. The factors that may affect the improvement of cognitive function include low educational level, coronary heart disease, elevated TC and LDL-C, and post-stroke depression.

Huntington disease (HD) is an autosomal inherited disorder that causes the deterioration of brain cells. The polyglutamine (polyQ) expansion of huntingtin (Htt) is implicated in the pathogenesis of HD via interaction with an RNA splicing factor, Htt yeast two-hybrid protein A/forming-binding protein 11 (HYPA/FBP11). Besides the pathogenic polyQ expansion, Htt also contains a proline-rich region (PRR) located exactly in the C terminus to the polyQ tract. However, how the polyQ expansion influences the PRR-mediated protein interaction and how this abnormal interaction leads to the biological consequence remain elusive. Our NMR structural analysis indicates that the PRR motif of Htt cooperatively interacts with the tandem WW domains of HYPA through domain chaperoning effect of WW1 on WW2. The polyQ-expanded Htt sequesters HYPA to the cytosolic location and then significantly reduces the efficiency of pre-mRNA splicing. We propose that the toxic gain-of-function of the polyQ-expanded Htt that causes dysfunction of cellular RNA processing contributes to the pathogenesis of HD.

To study the characteristics and influencing factors of cognition on patients with Parkinson's disease (PD) in Xi'an in order to provide evidence for early recognition and treatment of cognitive impairment on PD patients.Clinically defined PD patients from 7 hospitals in Xi'an from Jan. to Apr. 2007 were assessed with mini-mental state examination (MMSE) and Montreal cognitive assessment (MOCA) for whole cognitive function. Furthermore, Fuld object memory test (FOM) was used to assess delayed memory while rapid verbal retrieve (RVR) was used to assess language fluency. Digit span subtest was used to assess attention and building blocks was used to assess visual space function respectively.100 PD patients were recruited, including 52 men and 48 women, from 43 to 86 years old (65.6 +/- 17.1). MMSE scores was used as the standard for Recognition, PD with cognitive impairment accounted for 16%. According to MOCA scores, with PD cognitive disturbances accounted for 83%. Ability for calculation, short-term memory, visual space function, abstract capability, attention and language fluency dysfunction were main cognitive disturbances of PD. Analysis from single factor logistic regression showed that education, age of onset and gender were closely related to the occurrence of cognitive impairment on PD patients.Cognitive impairment was common in PD. Ability of calculation, short-term memory, visual space function, abstract capability, attention and language fluency dysfunction were main cognitive disturbances of PD. Cognitive impairment of PD was more likely to occur with low degree of education, late onset of PD, and being female.

To investigate the treatment status of antiparkinsonism in Xi'an.Six general hospitals were randomly chosen in Xi'an and all Parkinson's disease (PD) patients were interviewed by questionnaire from Jan. 2007 to Apr. 2007.92 PD outpatients were enrolled in, including 48 males and 44 females, from 43 to 86 years old (mean 65.6 +/- 17.1) with duration of the disease from 0.2 to 27.8 years (mean 4.4 +/- 9.4). The preference of the drug use from the patients were: 40 (43.5%) preferred taking levodopa, 25 (27.2%) with amantadine and/or trihexyphenidyl, 14 (15.2%) with levodopa and others, 4 (4.4%) with dopamine agonist and others, 2 (2.2%) with other drugs, 7 (7.6%) with no treatment. There were 69 (75.0%) patients onset with resting tremor, 15 (16.3%) with bradykinesia, 6 (6.5%) with rigidity, and 2 (2.2%) with unknown symptoms. There was no startically significant difference in anti-PD drugs among the patients onset with different symptoms (P0.05). 45 patients appeared the onset of disease before 65 years old and with no dementia, 47 onset after 65 with or without dementia. There was no significant difference of anti-PD drugs between the two groups (P0.05). Most patients initiated anti-PD treatment with levodopa but few of them chose dopamine agonist. According to the classification of HoehnYahr, 25(27.2%)belonged to Grade I, 53 (57.6%) to Grade II, 8 (8.7%) to Grade III, 3 (3.3%) to Grade IV and 3 (3.3%) to Grade V. There was no significant differences of anti-PD drugs between different grades of the disease (P0.05). 55.3% of the patients changed their anti-PD drugs randomly during the therapy, but with no relation to their gender, age, educational level, dementia, the number of family members, course of diseases, or the degree of HoehnYahr, frequency and categories of medicine.Anti-PD treatment in Xi'an did not strictly follow the standardized protocol, with few patients using dopamine agonist and over 50% of the patients changed their drugs randomly.

To understand the relationship of the grading of periventricular echodensities (PVE) with the morbidity and the occurrence time of periventricular white matter cystic lesions in preterm infants.A retrospective, single-centre cohort study of 120 preterm infants with PVE diagnosed by ultrasonography between February 2005 and May 2008 was performed. The infants had a median gestational age of 32 weeks and a median birth weight of 2 230 g.Fifty-two infants (43%) were diagnosed as having PVE I, 42 infants (35%) having PVE II, and 26 infants (22%) having PVE III. The grading of PVE was closely related to birth weight, but not with gestational age. The total morbidity of periventricular white matter cystic lesions was 24% (29/120). The morbidity of the cystic lesions in PVE III patients (65%) was significantly higher than that in PVE II patients (21%) (0.01). The PVE III patients developed the cystic lesions earlier than the PVE II patients.The grading of PVE is closely related to the morbidity and the occurrence time of periventricular white matter cystic lesions in preterm infants.

The information on the ultrasonographic features of pediatric intussusception complicated by intestinal necrosis is limited at present. This study aimed to investigate the ultrasonographic findings of this disorder in children in order to provide references for selecting a right means of reduction in clinical practice.The ultrasonographic findings of 48 children with intussusception complicated by intestinal necrosis and who underwent operative reduction between 2004 and 2006 were reviewed retrospectively.The type of intussusception was closely correlated to the development of intestinal necrosis and the ileo-ileo-colonic intussusception was the most common one resulting in intestinal necrosis. The bowel wall of the invaginated segment was obviously thickened and the center of the invaginated segment was often accompanied with swollen lymph node and appendix caecalis. The intussusceptional fluidify, the expanding of distal segment accompanied with the thickened bowels wall, and weakening or disappearance of enterokinesia were the appearances of necrosis of most of bowel walls. The secondary intussusception was an important factor resulting in intestinal necrosis, and sound image of primary lesion was found in some patients. Seroperitoneum was a common manifestation in all of infants with intussusception complicated by intestinal necrosis.There are some obvious sonographic characteristics of intussusception complicated by intestinal necrosis in children. The means of intussusception reduction may be selected according to ultrasonographic characteristics.

Attention deficit hyperactivity disorder (ADHD) is a common childhood-onset behavioral disorder with a definite genetic component. The search for genes predisposing to ADHD has focused on genes involved in the regulation of monoamine systems. In this study, we emphasized genes that underlie various aspects of dopamine, norepinephrine and serotonin neurotransmissions and performed a comprehensive association analysis by screening with 245 single-nucleotide polymorphisms (SNPs) of 23 candidate genes in a sample of Chinese Han descent. A total of 182 DSM-IV ADHD children and 184 healthy controls were genotyped and analyzed with an average density of one SNP every 6.1 kb. Both single-SNP and multi-marker haplotype analyses were implemented to exploit association signal for ADHD and its diagnostic subtypes. Empirical P-values were derived on the basis of 5000 permutations to evaluate gene-wide statistical significance. MAOA yielded highly suggestive evidence of association (empirical P

To explore the incidence of dementia among elderly people in Xi'an and its related risk factors.Subjects that had been studied on the prevalence of dementia were follow-up, and the incidence of dementia, Alzheimer disease (AD) , and vascular dementia (VD) were counted by person-years. The clinical diagnosis on dementia,AD and VD were based upon the 3rd Edition of Diagnostic and Statistical of Manual of Mental Disorder, Revised version (DSM-III-R) and NINCDS-ADRDA criteria.2197 subjects of non-dementia being identified in 1998, were re-surveyed in 2001. Out of them, 47 new cases of dementia including 37 cases of AD and 8 cases of VD were identified, with an annual incidence rates of dementia, AD and VD as 0.68%, 0.54% and 0.12% among those of 55 years and over and 0.89%, 0.69% and 0.17% in 65 years and over, respectively. Analysis from single factor logistic regression showed that age and education but not gender were closely related to the occurrence of AD. On the contrary, age, hypertension and stroke were closely related to the occurrence of VD.The incidence of dementia in the "Xi' an cohort" was similar to that being reported from other countries. AD and VD were an age-related diseases but education seemed to have had great protective effect while lack of formal education served as risk factor to AD.

To explore the expression of oncogene C-erbB2 in breast cancer, its relationship to estrogen receptor (ER), progesterone receptor (PR) and PS2 and the prognostic significance.The expression of oncogene C-erbB2 in 245 cases with breast cancer was detected with immunohistochemical technique (LsAB).Expression of oncogene C-erbB2 was found in 60% cases of breast cancer. Tumors positive for C-erbB2 were 45.19% and 71.55% in ER positive group and ER negative group respectively, while tumors positive for C-erbB2 were 48.08% and 70.43% in PR positive group and PR negative group respectively. The expression of the C-erbB2 was 23.26% in group of PS2 positive and 50.75% in group of PS2 negative (P0.05). No significant association of C-erbB2 expression with age and tumor size was noted(P0.05), but its expression in breast cancer was correlated with advanced clinical stage, high histological grade, axillary lymph node involvement (P0.05).C-erbB2 would be helpful to the evaluation of prognosis and treatment in breast cancer.

To explore the role of angiogenesis in bone marrow in acute myeloid leukemia (AML).Bone marrow culture supernatant was assayed for vascular endothelial growth factor (VEGF) by ELISA, bone marrow biopsies from 28 newly diagnosed AML patients were assayed for microvessel density (MVD), VEGF and its receptors KDR, Flt-1 by immunohistochemical staining before and after induction chemotherapy.Culture supernatant of AML bone marrow mononuclear cells showed higher amount of VEGF (425.31 ng/L) than that of control (140.12 ng/L). The VEGF and KDR expressions and MVD were significantly higher in newly diagnosed AML patients (78.6%, 78.6% and 7.1%, respectively) than that of control group (P0.05). There was a positive correlation between VEGF, KDR and MVD. The positive rate of VEGF, KDR and MVD reduced to normal after the patients achieved complete remission, while in non-remission patients did not. Kaplan-Meier analysis showed that the survival time was longer in VEGF negative group than in VEGF positive group. The pre-treatment MVD and VEGF had no correlation with survival time.There is remarkable angiogenesis in AML and VEGF/KDR signaling pathway takes an important role in the pathological angiogenesis. VEGF could be used as a prognostic factor in AML.

To evaluate the diagnostic potential of previously published enterovirus (EV) reverse transcription polymerase chain reaction (RT-PCR) assay in detection of EV in CSF samples from children with a diagnosis of aseptic meningitis and to investigate the clinical characteristics of the patients seen in Shandong.EV RNA was detected in 187 CSF samples and serum and/or urine samples of a part of patients by RT-PCR and viral culture technique.RT-PCR was positive in all 62 CSF specimens which were positive by cell culture (100%). In addition, 93 of 125 (74.4%) CSF samples negative by cell culture were RT-PCR positive. In 4 of these 93 (4.3%) patients, viral culture of specimens from other sites (serum or urine) was also positive. The sensitivity of CSF RT-PCR based on clinical diagnosis in patients with meningitis of negative bacterial culture results was 82.9% (155/187), which was considerably higher than the sensitivity of CSF virus culture 33.2% (62/187). The results of RT-PCR can be reported within 4 hours, whereas the viral culture of CSF requires 4.6 days for a cytopathic effect to develop. EV meningitis occurred in a sporadic form and in some areas there were outbreaks. The clinical characteristics of 155 patients with EV meningitis were different in different age groups.EV was one of the most common causes of aseptic meningitis in Shandong area. The RT-PCR assay was rapid, sensitive and specific for the diagnosis of EV meningitis and may be a potential tests to shorten hospital stay and reduce the use of antibiotics.