Search

Background Impaired respiratory function caused by respiratory muscle dysfunction is one of the common consequences of chronic obstructive pulmonary disease (COPD). In this study, two-dimensional shear wave elastography (2D-SWE) was used to measure diaphragm stiffness (DS) and intercostal muscle stiffness (IMS) in patients with COPD; in addition, the value of 2D-SWE in evaluating respiratory function was determined. Methods In total, 219 consecutive patients with COPD and 20 healthy adults were included. 2D-SWE was used to measure the DS and IMS, and lung function was also measured. The correlation between respiratory muscle stiffness and lung function and the differences in respiratory muscle stiffness in COPD patients with different severities were analysed. Results 2D-SWE measurements of the DS and IMS presented with high repeatability and consistency, with ICCs of 0.756 and 0.876, respectively, and average differences between physicians of 0.10 ± 1.61 and 0.07 ± 1.65, respectively. In patients with COPD, the DS and IMS increased with disease severity (F1 = 224.50, F2 = 84.63, P 1)/forced vital capacity (FVC), predicted FEV1% value, residual volume (RV), total lung capacity (TLC), RV/TLC, functional residual capacity (FRC) and inspiratory capacity (IC) of DS (r1=-0.81, r2=-0.63, r3 = 0.65, r4 = 0.54, r5 = 0.60, r6 = 0.72 and r7=-0.41, respectively; P 1=-0.76, r2=-0.57, r3 = 0.57, r4 = 0.47, r5 = 0.48, r6 = 0.60 and r7=-0.33, respectively; P Conclusion 2D-SWE has potential for use in evaluating DS and IMS. A specific correlation was observed between respiratory muscle stiffness and lung function. With the worsening of the severity of COPD and the progression of lung function impairment, the DS and IMS gradually increased.

The purpose of the present study aims to develop a satisfactory model for predicting pro-social and pro-cognitive effects on azinesulfonamides of cyclic amine derivatives as potential antipsychotics. The three dimensional-quantitative structure affinity relationship (3D-QSAR) study was performed on a series of azinesulfonamides of cyclic amine derivative using comparative molecular similarity indices analysis (CoMSIA). The best statistical model of CoMSIA q2, r2, SEE and F values are 0.664, 0.973, 0.087, and 82.344, respectively. Based on the model contour maps and the highest activity structure of the 43rd compound, serial new structures were designed and the 43k1 compound was selected as the best structure. The dock results showed a good binding of 43k1 with the protein (PDB ID: 6A93). The QSAR model analysis of the contour maps can help us to provide guidelines for finding novel potential antipsychotics.

Ubiquitin-specific peptidases7 (USP7) participates in the regulation of various metabolic and immune disorders. However, the role of USP7 in lupus nephritis (LN) remains unknown. The current study set out to elucidate the regulatory role of USP7 in LN together with JMJD3 and NF-κB. SLE MRL/LPR mice and mouse glomerular mesangial cells SV40 MES 13 cells were employed for in vivo or vitro experiments. USP7, JMJD3 and NF-κB expression in MRL/LPR mice were detected, followed by investigation of their functions in the proliferation of mesangial cells and mesangial matrix. Subsequently, the interaction among USP7, JMJD3 and NF-κB was determined by means of ChIP and co-immunoprecipitation assay. The results indicated that USP7, JMJD3, p-NF-κB p65 were all highly-expressed in MRL/LPR mice. USP7 promoted the proliferation of mesangial cells and mesangial matrix, and stabilized the JMJD3 protein via deubiquitination in SV40 MES 13 cells. Meanwhile, silencing of JMJD3 inhibited the promotive effect of USP7 on the proliferation of mesangial cells and mesangial matrix. Furthermore, JMJD3 increased the expression of NF-κB p65 through demethylation, whereas silencing JMJD3 alleviated the proliferation of mesangial cells and mesangial matrix. Lastly, NF-κB p65 was proved to aggravate LN pathogenesis. Altogether, our findings highlighted that USP7 promoted the occurrence of LN by regulating the NF-κB p65 signaling pathway via stabilization of JMJD3.

Background: In recent years, the prevalence and mortality of autism spectrum disorder (ASD) have been increasing. The clinical features are different with different cases, so the treatment ways are different for each one. Objective: Baohewan Heshiwei Wen Dan Tang (BHWDT) has been recommended for treating autistic spectrum disorder. To investigate the mechanism of action and how the compounds interact with ASD targets, network pharmacology and molecular docking methods were used in this study. Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP) was used to screen the active components according to index of oral bio-activity and drug-likeness. Then, TCMSP and Swiss Target Prediction databases were used to screen potential target genes of active components. The related target genes of ASD were obtained from the Gene Cards database. Matescape database was utilized to get gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes pathway annotation of gene targets. Composition- target-pathway (C-T-P) and a protein-protein interaction (PPI) networks were built with Cytoscape 3.8.2 software. Results: The interaction of the main active components of BHWDT was verified by molecular docking. The key targets of MAPK1, IL6, CXCL8 and TP53 of BHWDT were obtained. The key active components Quercetin, Kaempferol and Iuteolin of BHWDT could bind with MAPK1, IL6, CXCL8 and TP53 of BHWDT, respectively. Conclusion: BHWDT can be highly effective for treating ASD and this study can help us to understand multiple targets and multiple pathways mechanism.

In this era of immune checkpoint inhibitors, inflammatory adverse events of anti-cancer therapies continue to pose a major challenge. Glucocorticoids, as the mainstay, were limited by serious side effects. Glucocorticoids induce myeloid-derived suppressor cells (MDSCs), and lactoferrin-induced polymorphonuclear MDSCs (PMN-MDSCs) were shown to relieve inflammatory conditions. Combined treatment with dexamethasone (DXM) and lactoferrin increased the generation of PMN-MDSCs in vitro (DXM/lactoferrin PMN-MDSCs) compared to DXM or lactoferrin treatment alone. DXM/lactoferrin PMN-MDSCs were distinct from tumor PMN-MDSCs in vivo with regard to gene expression profiles. DXM upregulated the myeloid cell response to lactoferrin by inducing the lactoferrin receptor Lrp1. DXM/lactoferrin PMN-MDSCs presented anti-bacterial capability, increased PGE2 production, increased survival capability, and decreased tumor tissue homing. Transfer of DXM/lactoferrin PMN-MDSCs relieved cisplatin-induced acute kidney failure, bleomycin-induced interstitial pneumonia, and allergic pneumonitis effectively without promoting tumor development. Our study shows that DXM/lactoferrin PMN-MDSCs are a promising cell therapy for inflammatory adverse events of anti-cancer therapies., Li et al. show that dexamethasone and lactoferrin induced polymorphonuclear myeloid-derived suppressor cells relieve inflammatory conditions in mouse models with minimal effect on tumour growth. This work demonstrates promise for combating inflammatory adverse events during anti-cancer treatments.

The aim of this study was to test the effectiveness, safety and stability of the 5G communication technology in clinical laparoscopic telesurgery.An ultra-remote radical cystectomy (network communication distance of nearly 3000 km) was performed on patient diagnosed with T2N0M0 stage bladder cancer using a domestically produced "MicroHand" surgical robot.The network delay, operative time, blood loss, intraoperative complications, postoperative recovery, and hospitalisation time were recorded. The 5G network was used throughout the operation, with an average total delay of 254 ms. The operation went well and the patient recovered smoothly.Ultra-remote clinical laparoscopic surgery can be performed safely and smoothly. More importantly, our model can provide insights for promoting the future development of telesurgery in China.

Background The measurement of liver stiffness (LS) and spleen stiffness (SS) based on ultrasound elastography can be used for non-invasive assessment of portal hypertension (PH). However, there are few studies on the corresponding mechanism of increased spleen stiffness. Our aim was to use two-dimensional shear wave elastrography (2D-SWE) to evaluate the relationship between LS and SS and the severity of PH in rats. And explore the mechanism of the increase of LS and SS in PH. Methods Sixty male Sprague–Dawley rats were randomly divided into portal hypertension (PH group, n = 45) and normal control (NC group, n = 15). At 12 weeks, LS and SS was detected by 2D-SWE in vivo. Related hemodynamic parameters and portal vein pressure (PVP) was measured. Spleen and liver 2D-SWE detection was performed again after sacrifice. Pathological changes were observed. Results The SS and LS were increased in PH group (P P r = 0.624, P r = 0.633, P r = 0.905, P Conclusions Spleen and liver measurement by 2D-SWE may be helpful in evaluating PVP. The correlation between SS and PVP is stronger than LS in rats measured by 2D-SWE. Hemodynamic circulation are important in the elevation of SS with portal hypertension. Pathological changes also have a degree of influence, but have more significance for the elevation of LS. SS may be a more effective noninvasive predictor of PH than LS.

Objectives:In December 2019, a new type of coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), appeared in Wuhan, China. Serious outbreaks of coronavirus disease 2019 (COVID-19), related to the SARS-CoV-2 virus, have occurred throughout China and the world. Therefore, we intend to shed light on its potential clinical and epidemiological characteristics.Methods:In this retrospective study, we included 50 confirmed fatal cases of SARS-CoV-2 reported on Chinese official media networks from January 16, 2020, to February 5, 2020. All the cases were confirmed by local qualified medical and health institutions. Specific information has been released through official channels. According to the contents of the reports, we recorded in detail the gender, age, first symptom date, death date, primary symptoms, chronic fundamental diseases, and other data of the patients, and carried out analyses and discussion.Results:In total, 50 fatal cases were reported: median age was 70 y old, and males were 2.33 times more likely to die than females. The median number of days from the first symptom to death was 13, and that length of time tended to be shorter among people aged 65 and older compared with those younger than 65 (12 days vs 17 days;P= 0.046). Therefore, the older patients had fewer number of days from the first symptom to death (r = -0.40;P= 0.012).Conclusions:In our study, we found that most of the deaths were elderly men with chronic fundamental diseases, and their COVID-19 progression to death time was shorter. At the same time, we demonstrated that older men are more likely to become infected with COVID-19, and the risk of death is positively correlated with age.

Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterized by abnormal T and B cells. B-cell activating factor (BAFF) has been suggested to play a crucial role in lupus by promoting the proliferation, differentiation, and survival of B cells. Increased serum levels of BAFF have been found in patients with lupus. However, the expression of BAFF and its receptors on immune cells and in skin has not been systematically reported before. Here, we report that SLE patients showed increased levels of BAFF on circulating CD3+ T cells and B-cell maturation antigen (BCMA) on CD14+ monocytes and dramatically increased expression of BAFF in lupus skin lesions compared with those of healthy controls. TACI was undetectable on circulating immune cells. An increased serum level of BAFF was also confirmed in lupus patients in this study. Our findings may provide a better understanding of the pathogenesis and predictors of BAFF antibody treatment response, as well as potential targets for skin therapies.

IgE multiple myeloma (MM) is a rare subtype of MM that is easily misdiagnosed. We report a rare case of IgE-MM and investigate the application of the SLiM-CRAB criteria to screen for high-risk smoldering MM (SMM) patients, so as to summarize the causes and methods used to prevent missed diagnosis or misdiagnosis in IgE-MM.The serum monoclonal protein (M-protein) classification and IgE quantification was performed and sent to several individual institutions. The results were collected and the causes of IgE detection defects were analyzed.Upon admission to our hospital, the patient's serum free kappa light chain was 1069.9 mg/L, free lambda light chain was 9.2 mg/L, and free kappa/lambda ratio was 115.9, which met the SLiM criteria, but without CRAB features. Immunofixation electrophoresis (IF) showed "M-like protein aggregation bands" in all lanes. After pretreatment with 1% β-mercaptoethanol to depolymerize the aggregation of monoclonal protein, the "M-like protein aggregation bands disappeared. The other five institutions did not provide the correct typing results. The quantification of serum IgE was as high as 2.06 × 10High-risk biomarkers in SLiM criteria can achieve good therapeutic effects in rare IgE-MM patients. Serum immunofixation performed without antisera against IgE, insufficient identification of the lytic bands produced by high macromolecule aggregation in IF, and the absence of a prozone effect avoidance procedure during IgE quantitative detection are the primary causes of missed diagnosis or misdiagnosis in patients with IgE-MM.

To optimize a screening method for macroprolactinemia and improve the accuracy of free prolactin (freePRL) detection.Overall efficiency, calculated as the product of the immunoglobulin G (IgG) precipitation rate and the freePRL recovery rate were employed to determine the concentration of the precipitant polyethylene glycol (PEG). Then, an optimized screening method for macroprolactinemia was established. The concentrations of freePRL, obtained by gel filtration chromatography (GFC), from 66 cases were used as the gold standard, and the sensitivity, specificity, accuracy and precision of the optimized and traditional methods for detecting macroprolactinemia were compared.(1) The IgG precipitation rate increased with increasing PEG6000 concentration, and the freePRL recovery rate decreased with increasing PEG6000 concentration; the overall efficiency first increased and then decreased. When the IgG concentrations in the mixture were 10 g/L, 25 g/L and 40 g/L, the concentrations of PEG6000 with the highest overall efficiency were 24%, 20% and 18%, respectively. (2) The effect of high and low IgG on the overall efficiency was 4.7% when using 20% PEG6000, which was lower than the effects when using 18% or 24% PEG6000 (9.2% and 13.2%). (3) In the optimized method established using 20% PEG6000, the macroprolactin (macroPRL) chromatographic peak disappeared, but the freePRL chromatographic peak was retained. The sensitivity of this macroprolactinemia screening method was 96.7%, and the specificity was 100%. (4) The freePRL concentrations obtained by the optimized method for samples from 30 macroprolactinemia cases and 36 true hyperprolactinemia cases were 15.8 (10.2-21.4) ng/mL and 60.2 (51.8-79.9) ng/mL; the concentrations were similar to those obtained using the GFC method (16.3 (11.9-27.2) ng/mL and 68.1 (49.5-92.9) ng/mL, respectively (p0.05)) and higher than those obtained using the traditional method (9.1 (6.1-17.6) ng/mL and 51.4 (43.7-71.9) ng/mL), respectively, p0.05)). (5) The relative deviation between the optimized and GFC methods was -7.0%, which was significantly lower than the relative deviation between the traditional and GFC methods (-21.4%, p0.01). (6) The in-batch coefficients of variation (CVs) for the dual-level quality control materials measured by the optimized method were 1.88% and 1.87%, and the within-laboratory CVs were 2.55% and 2.29%, which were slightly lower than the in-batch CVs (1.93% and 2.81%) and within-laboratory CVs (2.75% and 2.81%) measured by the traditional method.The established optimized method for screening macroprolactinemia using 20% PEG6000 as a precipitant can completely precipitate macroPRL components and effectively retain freePRL components. Compared with traditional methods, the optimized method is simpler, more accurate and more stable for the quantitative detection of freePRL.

Aims Here, we explored the potential application and selection of neuroendocrine biomarkers in the diagnosis and treatment of small cell lung cancer. Methods We retrospectively analyzed 118 patients with small cell lung cancer (SCLC), 166 patients with non-small cell lung cancer (NSCLC), 33 patients with benign lung disease (BLD), and 200 healthy individuals admitted to Zhejiang Provincial People’s Hospital between January 1, 2015 and May 31, 2019. All the patients were newly diagnosed with either SCLC, NSCLC, or BLD and previously untreated. Peripheral blood levels of ProGRP, NSE, CEA, and CYFRA21-1 were analyzed during the follow-up treatment, and 2-fold upper limit of reference intervals were defined as effective elevation. We used paired results to analyze the diagnostic efficiency of proGRP and NSE on SCLC. Results In the 118 SCLC patients, proGRP levels were significantly higher compared with NSE levels. The diagnostic efficiencies of NSE and ProGRP for SCLC were 0.8554 and 0.9053, respectively. The combined diagnostic efficiency (0.9426) was higher relative to NSE, but there was no significant difference compared with proGRP. The effective elevation rate of proGRP was 45.3% higher than that of NSE in the limited stage of SCLC. In the extensive disease of SCLC patients, 70.7% cases had more than 10-fold increase in proGRP value, whereas 56.9% cases had less than 5-fold increase in NSE value. Compared with pre-treatment, the median concentrations of proGRP increased by 204.0% higher than that of NSE (71.3%) in the progressive group. Besides, the dynamic change in imaging characteristics and tumor size had a strong correlation with the levels of proGRP. Significance ProGRP is a reliable neuroendocrine biomarker in SCLC. The effective elevation of proGRP has a potential diagnostic and efficacy value in the evaluation of SCLC. However, the combined detection of proGRP and NSE does not significantly improve the diagnosis of lung cancer.

Purpose The purpose of this study was to investigate the predictive capability of neutrophil-to-apolipoprotein A1 ratio (NAR) for predicting overall survival (OS) among patients with hepatocellular carcinoma (HCC) receiving transarterial chemoembolization (TACE). Patients and Methods We investigated the clinical features of 554 patients with HCC receiving TACE and assessed NAR's predictive value for OS with 222 patients (the discovery cohort) and 332 patients (the validation cohort). The association of NAR with circulation lectin-type oxidized low-density lipoprotein receptor-1–positive (LOX-1+) polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) was illustrated. Results Multivariate Cox regression revealed that lymphocyte count; Tumor, Node, Metastasis (TNM) stage; and NAR were independent prognostic factors in the discovery cohort. The validation cohort confirmed the independent prognostic value of TNM stage and NAR. Patients with low NAR ( Conclusion This study identified NAR as an independent predictor for OS among patients with HCC receiving TACE. NAR reflected circulation LOX-1+ PMN-MDSC level. Implications for Practice The present study identified neutrophil-to-apolipoprotein A1 ratio (NAR) as an independent predictor for overall survival among patients with hepatocellular carcinoma receiving transarterial chemoembolization. NAR reflected circulation level of lectin-type oxidized low-density lipoprotein receptor-1–positive polymorphonuclear myeloid-derived suppressor cells.

Background: in current clinical practice, the standard evaluation for axillary lymph node (ALN) status in breast cancer has a low efficiency and is based on an invasive procedure that causes operative-associated complications in many patients. Therefore, we aimed to use machine learning techniques to develop an efficient preoperative magnetic resonance imaging (MRI) radiomics evaluation approach of ALN status and explore the association between radiomics and the tumor microenvironment in patients with early-stage invasive breast cancer. Methods: in this retrospective multicenter study, three independent cohorts of patients with breast cancer (n = 1,088) were used to develop and validate signatures predictive of ALN status. After applying the machine learning random forest algorithm to select the key preoperative MRI radiomic features, we used ALN and tumor radiomic features to develop the ALN-tumor radiomic signature for ALN status prediction by the support vector machine algorithm in 803 patients with breast cancer from Sun Yat-sen Memorial Hospital and Sun Yat-sen University Cancer Center (training cohort). By combining ALN and tumor radiomic features with corresponding clinicopathologic information, the multiomic signature was constructed in the training cohort. Next, the external validation cohort (n = 179) of patients from Shunde Hospital of Southern Medical University and Tungwah Hospital of Sun Yat-Sen University, and the prospective-retrospective validation cohort (n = 106) of patients treated with neoadjuvant chemotherapy in prospective phase 3 trials [{"type":"clinical-trial","attrs":{"text":"NCT01503905","term_id":"NCT01503905"}}NCT01503905], were included to evaluate the predictive value of the two signatures, and their predictive performance was assessed by the area under operating characteristic curve (AUC). This study was registered with ClinicalTrials.gov, number {"type":"clinical-trial","attrs":{"text":"NCT04003558","term_id":"NCT04003558"}}NCT04003558. Findings: the ALN-tumor radiomic signature for ALN status prediction comprising ALN and tumor radiomic features showed a high prediction quality with AUC of 0·88 in the training cohort, 0·87 in the external validation cohort, and 0·87 in the prospective-retrospective validation cohort. The multiomic signature incorporating tumor and lymph node MRI radiomics, clinical and pathologic characteristics, and molecular subtypes achieved better performance for ALN status prediction with AUCs of 0·90, 0·91, and 0·93 in the training cohort, the external validation cohort, and the prospective-retrospective validation cohort, respectively. Among patients who underwent neoadjuvant chemotherapy in the prospective-retrospective validation cohort, there were significant differences in the key radiomic features before and after neoadjuvant chemotherapy, especially in the gray-level dependence matrix features. Furthermore, there was an association between MRI radiomics and tumor microenvironment features including immune cells, long non-coding RNAs, and types of methylated sites. Interpretation this study presented a multiomic signature that could be preoperatively and conveniently used for identifying patients with ALN metastasis in early-stage invasive breast cancer. The multiomic signature exhibited powerful predictive ability and showed the prospect of extended application to tailor surgical management. Besides, significant changes in key radiomic features after neoadjuvant chemotherapy may be explained by changes in the tumor microenvironment, and the association between MRI radiomic features and tumor microenvironment features may reveal the potential biological underpinning of MRI radiomics.

Autoimmune diseases can be chronic with relapse of inflammatory symptoms, but it can be also acute and life-threatening if immune cells destroy life-supporting organs, such as lupus nephritis. The etiopathogenesis of autoimmune diseases has been revealed as that genetics and environmental factors-mediated dysregulated immune responses contribute to the initiation and development of autoimmune disorders. However, the current understanding of pathogenesis is limited and the underlying mechanism has not been well defined, which lows the development of novel biomarkers and new therapeutic strategies for autoimmune diseases. To improve this, broadening and deepening our understanding of pathogenesis is an unmet need. As genetic susceptibility cannot explain the low accordance rate of incidence in homozygous twins, epigenetic regulations might be an additional explanation. Therefore, this review will summarize current progress of studies on epigenetic dysregulations contributing to autoimmune diseases, including SLE, rheumatoid arthritis (RA), psoriasis, type 1 diabetes (T1D), and systemic sclerosis (SSc), hopefully providing opinions on orientation of future research, as well as discussing the clinical utilization of potential biomarkers and therapeutic strategies for these diseases.

Antimyeloperoxidase (anti-MPO) is regarded as one of the most important circulating autoantibodies for anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAVs). Hence, it is crucial for highly sensitive detection of anti-MPO to monitor efficacy of AAVs in clinical diagnosis. Herein, a highly sensitive electrochemiluminescence (ECL) immunosensor for anti-MPO detection was constructed by combining reduced graphene oxide-supported PtCo nanocubes hybrids (PtCo@rGO) with hybridization chain reaction (HCR) as signal amplification. Multiple ECL luminophores (Dox-ABEI) prepared by cross-linking of N-(aminobutyl)-N-(ethylisoluminol) (ABEI) and doxorubicin (Dox) were intercalated into dsDNA products of HCR, achieving the effective immobilization of ECL luminophores to obtain strong ECL emission. Benefiting from the efficient catalytic activity of PtCo@rGO toward H2O2, the massive the superoxide radical (O2●-) were generated to further react with ABEI for ECL emission. Thus, the designed ECL immunoassay for anti-MPO detection exhibited excellent sensitivity of a concentration variation from 50 fg/mL to 1 ng/mL and a detection limit of 15.68 fg/mL. Importantly, this work proposed an enzyme-free ECL immunoassay with high sensitivity, excellent specificity for protein detection in clinical diagnosis.

Interleukin-21 (IL-21), an autocrine cytokine predominantly produced by follicular helper T (Tfh) and T helper 17 (Th17) cells, has been proven to play an important role in the immune system, for example, by promoting proliferation and the development of Tfh and Th17 cells, balancing helper T cell subsets, inducing B cell generation and differentiation into plasma cells, and enhancing the production of immunoglobulin. These effects are mainly mediated by activation of the JAK/STAT, MAPK and PI3K pathways. Some IL-21 target genes, such as B lymphocyte induced maturation protein-1 (Blimp-1), suppressor of cytokine signaling (SOCS), CXCR5 and Bcl-6, play important roles in the immune response. Therefore, IL-21 has been linked to autoimmune diseases. Indeed, IL-21 levels are increased in the peripheral blood and tissues of patients with systematic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1D), immune thrombocytopenia (ITP), primary Sjogren's syndrome (pSS), autoimmune thyroid disease (AITD) and psoriasis. This increased IL-21 even positively associates with Tfh cells, plasma cells, autoantibodies and disease activity in SLE and RA. Additionally, IL-21 has been utilized as a therapeutic target in SLE, RA, T1D and psoriatic mouse models. Profoundly, clinical trials have shown safety and improvement in RA patients. However, tolerance and long-term pharmacodynamics effects with low bioavailability have been found in SLE patients. Therefore, this review aims to summarize the latest progress on IL-21 function and its signaling pathway and discuss the role of IL-21 in the pathogenesis of and therapy for autoimmune diseases, with the hope of providing potential therapeutic and diagnostic strategies for clinical use.

We performed a meta-analysis to assess whether corticosteroids (C) plus (+) doublet immunosuppressive therapy (IT) is superior to the classical combination of C with single-agent IT in active proliferative lupus nephritis (LN).Randomized trials evaluating the benefits and risks of C+doublet versus single-agent IT in active proliferative LN were obtained by searching PubMed, EMBASE, and Cochrane Central Register. The primary outcome was overall response rate (ORR). The secondary outcomes were the change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SLE-DAI) score, negative conversion ratio of anti-double-stranded DNA (anti-dsDNA), and adverse events. The PROSPERO registry number is CRD42017068491.Eleven trials with 1855 patients were included. Compared with C+single-agent IT, C+doublet IT had a significantly higher ORR (relative risk [RR], 1.22; 95% confidence interval [CI], 1.09 to 1.35; P 0.01). In a subgroup analysis, C+doublet IT without biologics had a significantly higher ORR than C+single-agent IT (RR, 1.30; 95% CI, 1.13 to 1.50; P 0.01), while C+doublet IT including biologics improved ORR only for refractory severe LN (RR, 1.46; 95% CI, 1.09 to 1.96; P = 0.012). A larger change from baseline in SLE-DAI scores (standardized mean difference, - 0.49; 95% CI, - 0.68 to - 0.30; P 0.01) and a higher negative conversion ratio of anti-dsDNA (RR, 1.34; 95% CI, 1.06 to 1.69; P = 0.014) were observed with C+doublet IT than with C+single-agent IT. The rates of adverse events were similar between the two regimens.Compared with single-agent IT, the combination of C and doublet IT without biologics improved clinical outcomes in active proliferative LN. Key Points • Compared with corticosteroids + single-agent immunosuppressive therapy, corticosteroids + doublet immunosuppressive therapy without biologics had a significantly higher overall response rate in active proliferative lupus nephritis. • Compared with corticosteroids + single-agent immunosuppressive therapy, corticosteroids + doublet immunosuppressive therapy including biologics improved overall response rate only for refractory severe lupus nephritis. • A larger change from baseline in SLE-DAI scores and a higher negative conversion ratio of anti-dsDNA were observed with corticosteroids + doublet immunosuppressive therapy than with corticosteroids + single-agent immunosuppressive therapy.

Key Points Question Can multiparametric magnetic resonance imaging (MRI) radiomic profiles be used to predict axillary lymph node metastasis (ALNM) and disease-free survival (DFS) in patients with early-stage breast cancer? Findings In this prognostic study that included 1214 patients, 2 clinical-radiomic nomograms were developed that accurately predicted ALNM and stratified patients into low-risk and high-risk groups for DFS. Meaning In this study, clinical-radiomic nomograms were useful in clinical decision-making associated with personalized selection of surgical interventions and therapeutic regimens for patients with early-stage breast cancer., This prognostic study develops and validates dynamic contrast–enhanced magnetic resonance imaging (DCE-MRI) radiomic signatures for preoperative identification of axillary lymph node metastasis and to assess individual disease-free survival in patients with early-stage breast cancer., Importance Axillary lymph node metastasis (ALNM) status, typically estimated using an invasive procedure with a high false-negative rate, strongly affects the prognosis of recurrence in breast cancer. However, preoperative noninvasive tools to accurately predict ALNM status and disease-free survival (DFS) are lacking. Objective To develop and validate dynamic contrast–enhanced magnetic resonance imaging (DCE-MRI) radiomic signatures for preoperative identification of ALNM and to assess individual DFS in patients with early-stage breast cancer. Design, Setting, and Participants This retrospective prognostic study included patients with histologically confirmed early-stage breast cancer diagnosed at 4 hospitals in China from July 3, 2007, to September 21, 2019, randomly divided (7:3) into development and vaidation cohorts. All patients underwent preoperative MRI scans, were treated with surgery and sentinel lymph node biopsy or ALN dissection, and were pathologically examined to determine the ALNM status. Data analysis was conducted from February 15, 2019, to March 20, 2020. Exposure Clinical and DCE-MRI radiomic signatures. Main Outcomes and Measures The primary end points were ALNM and DFS. Results This study included 1214 women (median [IQR] age, 47 [42-55] years), split into development (849 [69.9%]) and validation (365 [30.1%]) cohorts. The radiomic signature identified ALNM in the development and validation cohorts with areas under the curve (AUCs) of 0.88 and 0.85, respectively, and the clinical-radiomic nomogram accurately predicted ALNM in the development and validation cohorts (AUC, 0.92 and 0.90, respectively) based on a least absolute shrinkage and selection operator (LASSO)–logistic regression model. The radiomic signature predicted 3-year DFS in the development and validation cohorts (AUC, 0.81 and 0.73, respectively), and the clinical-radiomic nomogram could discriminate high-risk from low-risk patients in the development cohort (hazard ratio [HR], 0.04; 95% CI, 0.01-0.11; P

Three-dimensional (3D) imaging instead of two-dimensional (2D) computed tomography (CT) for diagnosis and preoperative planning in infants and young children with complex liver tumors is a promising technique for precision hepatectomy. This study was a retrospective analysis of 26 infants and young children with giant liver tumors involving the hepatic hilum who underwent precise hepatectomy at the Affiliated Hospital of Qingdao University between February 2012 and January 2015. All patients received upper abdominal contrast-enhanced CT scanning before surgery. 16 patients used Hisense CAS system for 3D reconstruction as the reconstruction group. While ten patients underwent 3D CT reconstruction by the CT Workstation as the control group. The clinical outcomes were analyzed and compared between the two groups. The 3D reconstruction of abdominal organs and blood vessels was generated using the Hisense CAS system. Diagnosis and preoperative planning assisted by the system was used for preoperative and intraoperative decision-making for precise hepatectomy. All patients underwent successful surgery. The 3D models clearly demonstrated the association of liver tumors with the intrahepatic vascular system and provided a preoperative assessment of resectability, assisting surgeons in preoperative procedural planning. Anatomic hepatectomy was successfully completed in the reconstruction group. The mean operation time was shorter in the reconstruction group (137.81 ± 17.51 min) than in the control group (192 ± 34.66 min) (P

There is insufficient evidence on the efficacy of masks in the general population for the prevention of coronavirus disease 2019 (COVID-19) in public areas. Therefore, it is imperative to investigate the association of mandatory mask-wearing policies with behaviors associated with the transmission of COVID-19.To assess the association of mask wearing with face-touching behavior among the general population in public areas.This cross-sectional study used videos recorded in public transportation stations, streets, and parks among the general population in China, Japan, South Korea, Western Europe (ie, England, France, Germany, Spain, and Italy), and the US to analyze mask-wearing and face-touching behavior in public areas. Videos before the COVID-19 pandemic were defined as those recorded from January 2018 to October 2019, and those during the COVID-19 pandemic were defined as those recorded during February 2020 to March 2020 in China, Japan, and South Korea and during March 2020 in Western Europe and the US. Individuals who clearly displayed their face and face-touching behavior were included, and those whose behaviors were influenced by filming or public events were excluded.Mandatory mask-wearing policies enacted at various time points in China, Japan, South Korea, Western Europe, and the US.Proportion of individuals wearing masks and incidence of face touching.This study included 4699 individuals before the COVID-19 pandemic and 2887 individuals during the pandemic. During the periods studied, mask wearing increased in all regions except the US, from 20 of 1745 individuals (1.1%) to 1090 of 1097 individuals (99.4%) in mainland China (P .001), 44 of 1422 individuals (3.1%) to 346 of 893 individuals (38.7%) in Japan (P .001), 6 of 717 individuals (0.8%) to 277 of 324 individuals (85.5% ) in South Korea (P .001), 1 of 546 individuals (0.2%) to 6 of 379 individuals (1.6%) in Western Europe (P = .02), and 1 of 269 individuals (0.4%) to 4 of 194 individuals (2.1%) in the US (P = .17). Surgical masks were predominant in China (989 masks [89.1%]), and fabric masks were predominant in the other regions (Japan: 371 masks [95.1%]; South Korea: 240 masks [84.8%]; Western Europe: 6 masks [85.7%]; US: 5 masks [100%]). Face-touching behaviors decreased from before COVID-19 to during COVID-19 among individuals in China (72 incidences of 1745 observations [4.1%] to 12 incidences of 1097 observations [1.1%]; P .001), South Korea (80 incidences of 717 observations [11.2%] to 7 incidences of 324 observations [2.2%]; P .001), and Europe (62 incidences of 546 observations [11.4%] to 23 incidences of 379 observations [6.1%]; P = .01). Logistic regression found that mask wearing was associated with a reduction in face touching in China (odds ratio [OR], 3.91; 95% CI, 2.11-7.24) and South Korea (OR, 6.69; 95% CI, 2.69-16.69) and of touching the nose, mouth, and eyes (China: OR, 8.60; 95% CI, 2.65-27.86; South Korea: OR, 29.27; 95% CI, 1.79-478.22).The findings of this cross-sectional study suggest that mandatory mask-wearing policies were associated with increased mask wearing during the COVID-19 pandemic. Mask wearing was associated with reduced face-touching behavior, especially touching of the eyes, nose, and mouth, which may prevent contact transmission of COVID-19 among the general population in public areas.

This cohort study investigates whether MUC16 variation could be a useful biomarker for immune checkpoint inhibitor (ICI) therapy.

This cohort study explores long noncoding RNA–based immune subtypes associated with survival and response to cancer immunotherapy and presents a novel long noncoding RNA score for immunotherapy prediction using computational algorithms., Key Points Question Are long noncoding RNAs (lncRNAs) associated with immune molecular classification and clinical outcomes of cancer immunotherapy? Findings This cohort study of 348 patients with bladder cancer from the IMvigor210 trial and 71 patients with melanoma from The Cancer Genome Analysis identified 4 distinct classes with different immunotherapeutic overall survival and response. An lncRNA score was developed that also was associated with survival and immunotherapy response. Meaning This study identifies novel lncRNA-based immune classes in cancer immunotherapy and provides an lncRNA score for integration into multiomic panels for precision immunotherapy., Importance Long noncoding RNAs (lncRNAs) are involved in innate and adaptive immunity in cancer by mediating the functional state of immunologic cells, pathways, and genes. However, whether lncRNAs are associated with immune molecular classification and clinical outcomes of cancer immunotherapy is largely unknown. Objectives To explore lncRNA-based immune subtypes associated with survival and response to cancer immunotherapy and to present a novel lncRNA score for immunotherapy prediction using computational algorithms. Design, Setting, and Participants In this cohort study, an individual patient analysis based on a phase 2, single-arm clinical trial and multicohort was performed from June 25 through September 30, 2019. Data are from the phase 2 IMvigor210 trial and from The Cancer Genome Atlas (TCGA). The study analyzed lncRNA and genomic data of 348 patients with bladder cancer from the IMvigor210 trial and 71 patients with melanoma from TCGA who were treated with immunotherapy. In addition, a pancancer multicohort that included 2951 patients was obtained from TCGA. Main Outcomes and Measures The primary end point was overall survival (OS). Results Among 348 patients from the IMvigor210 trial (272 [78.2%] male) and 71 patients with melanoma from TCGA (mean [SD] age, 58.3 [13.4] years; 37 [52.1%] female), 4 distinct classes with statistically significant differences in OS (median months, not reached vs 9.6 vs 8.1 vs 6.7 months; P = .002) were identified. The greatest OS benefit was obtained in the immune-active class, as characterized by the immune-functional lncRNA signature and high CTL infiltration. Patients with low vs high lncRNA scores had statistically significantly longer OS (hazard ratio, 0.32; 95% CI, 0.24-0.42; P

Background In this study, images of 2450 benign thyroid nodules and 2557 malignant thyroid nodules were collected and labeled, and an automatic image recognition and diagnosis system was established by deep learning using the YOLOv2 neural network. The performance of the system in the diagnosis of thyroid nodules was evaluated, and the application value of artificial intelligence in clinical practice was investigated. Methods The ultrasound images of 276 patients were retrospectively selected. The diagnoses of the radiologists were determined according to the Thyroid Imaging Reporting and Data System; the images were automatically recognized and diagnosed by the established artificial intelligence system. Pathological diagnosis was the gold standard for the final diagnosis. The performances of the established system and the radiologists in diagnosing the benign and malignant thyroid nodules were compared. Results The artificial intelligence diagnosis system correctly identified the lesion area, with an area under the receiver operating characteristic (ROC) curve of 0.902, which is higher than that of the radiologists (0.859). This finding indicates a higher diagnostic accuracy (p = 0.0434). The sensitivity, positive predictive value, negative predictive value, and accuracy of the artificial intelligence diagnosis system for the diagnosis of malignant thyroid nodules were 90.5%, 95.22%, 80.99%, and 90.31%, respectively, and the performance did not significantly differ from that of the radiologists (p > 0.05). The artificial intelligence diagnosis system had a higher specificity (89.91% vs 77.98%, p = 0.026). Conclusions Compared with the performance of experienced radiologists, the artificial intelligence system has comparable sensitivity and accuracy for the diagnosis of malignant thyroid nodules and better diagnostic ability for benign thyroid nodules. As an auxiliary tool, this artificial intelligence diagnosis system can provide radiologists with sufficient assistance in the diagnosis of benign and malignant thyroid nodules.

In recent years, the research on the pathogenesis of systemic lupus erythematosus (SLE) has been deepened, from the level of histopathology to the cellular and molecular biology, thus promoting the progress of SLE drug therapeutics. In March 2011, the United States Food and Drug Administration (FDA) approved the humanized monoclonal antibody, Belimumab for the treatment of SLE and put an end to the dilemma of no new drug available to SLE for more than half a century. On the other hand, the continuous evidence-based medical information has enabled rheumatologists to have a more comprehensive and depth understanding of the application of SLE traditional therapies, further improve the treatment strategy of SLE and put forward higher requirements for treatment goals. At the same time, advances in therapies have significantly improved survival rate of the patients, and the importance of long-term complications such as early-onset atherosclerosis and cardiovascular events has become increasingly apparent as a new challenge. In view of the hot issues of SLE clinical treatment, this paper introduces the research progress in recent years.

Autophagy is a complicated cellular mechanism that maintains cellular and tissue homeostasis and integrity via degradation of senescent, defective subcellular organelles, infectious agents, and misfolded proteins. Accumulating evidence has shown that autophagy is involved in numerous immune processes, such as removal of intracellular bacteria, cytokine production, autoantigen presentation, and survival of lymphocytes, indicating an apparent and important role in innate and adaptive immune responses. Indeed, in genome-wide association studies, autophagy-related gene polymorphisms have been suggested to be associated with the pathogenesis of several autoimmune and inflammatory disorders, such as systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. In addition, conditional knockdown of autophagy-related genes in mice displayed therapeutic effects on several autoimmune disease models by reducing levels of inflammatory cytokines and autoreactive immune cells. However, the inhibition of autophagy accelerates the progress of some inflammatory and autoimmune diseases via promotion of inflammatory cytokine production. Therefore, this review will summarize the current knowledge of autophagy in immune regulation and discuss the therapeutic and pathogenic role of autophagy in autoimmune diseases to broaden our understanding of the etiopathogenesis of autoimmune diseases and shed light on autophagy-mediated therapies.

MicroRNAs (miRNAs) are small, single-stranded, endogenous non-coding RNAs that repress the expression of target genes via post-transcriptional mechanisms. Due to their broad regulatory effects, the precisely regulated, spatial-specific and temporal-specific expression of miRNAs is fundamentally important to various biological processes including the immune homeostasis and normal function of both innate and adaptive immune response. Aberrance of miRNAs is implicated in the development of various human diseases, especially cancers. Increasing evidence has revealed a dysregulated expression pattern of miRNAs in autoimmune diseases, among which many play key roles in the pathogenesis. In this review we summarize these findings on miRNA dysregulation implicated in autoimmune diseases, focusing on four representative systemic autoimmune diseases, i.e. systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis and dermatomyositis. The causes of the dysregulation of miRNA expression in autoimmune diseases may include genetic and epigenetic variants, and various environmental factors. Further understanding of miRNA dysregulation and its mechanisms during the development of different autoimmune diseases holds enormous potential to bring about novel therapeutic targets or strategies for these complex human disorders, as well as novel circulating or exosomal miRNA biomarkers.

This meta-analysis examines whether differences in biomarkers, such as programmed cell death ligand 1 (PD-L1) expression and tumor mutation burden, are associated with improved response to immunotherapy and survival in patients with advanced non–small cell lung cancer (NSCLC)., Key Points Question Is immunotherapy associated with beneficial outcomes for advanced non–small cell lung cancer and how can combination strategies and biomarkers be deployed to produce the best benefit? Findings In this meta-analysis including 14 395 patients and individual patient–level analysis including 1833 patients, immunotherapy was associated with improved survival, and pembrolizumab with platinum-based chemotherapy was identified as the best first-line checkpoint blockade strategy. Programmed cell death ligand 1 expression and tumor mutation burden jointly exhibited promising predictive and prognostic associations, and CD8+ T-cell tumor-infiltrating lymphocytes score further synergized with these 2 biomarkers. Meaning Integrated tumor microenvironment-based biomarkers may be an effective means to predict responsiveness to immunotherapy for patients with advanced non–small cell lung cancer., Importance The beneficial role of immunotherapy and the clinical relevance of current biomarkers in non–small cell lung cancer (NSCLC) remain inconclusive; thus, appropriate strategies and reliable predictors need further definition. Objectives To evaluate the association of clinical outcomes with immune checkpoint inhibitors, tumor vaccines, and cellular immunotherapy in patients with advanced NSCLC and to explore appropriate strategies, candidates, and predictors. Data Sources The PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched from inception to June 2018, using relevant search keywords and Medical Subject Headings (MeSH) terms, including tumor vaccine, cellular immunotherapy, immune checkpoint inhibitor, cytotoxic T-lymphocyte-associated protein 4, programmed death-ligand 1, programmed death receptor 1, and non-small cell lung carcinoma. Systematic reviews, meta-analyses, references, and conference proceedings were manually searched. Study Selection English-language randomized clinical trials with available data that measured overall survival (OS), progression-free survival (PFS), or objective response rate comparing immune checkpoint inhibitors, tumor vaccines, or cellular immunotherapy with conventional therapy for patients with advanced or metastatic NSCLC were included. Thirty-one immunotherapy randomized clinical trials were included, and multicohort data included next-generation sequencing data from patients with advanced NCSLC. Data Extraction and Synthesis Hazard ratios and 95% CIs were pooled to estimate the survival increases in OS and PFS. Dichotomous data, such as object response rate data, were analyzed using the risk ratio. Mantel-Haenszel random-effects model was used. I2 was used to assess the heterogeneity between trials; an I2 value exceeding 50% indicated the existence of substantial heterogeneity. Analyses took place from February 1, 2018, to August 31, 2018. Main Outcomes and Measures Primary outcomes were OS and PFS. Results In total, 14 395 patients (9500 [66.0%] men) were included in the meta-analysis, and 1833 patients (mean [SD], 65.2 [9.9] years; 1063 [58.0%] men) were included in the individual patient–level study. Compared with conventional therapy, immunotherapy was associated with significantly longer OS (hazard ratio, 0.76; 95% CI, 0.71-0.82; P

In this paper, it is presented that electromyography (EMG) is a shot noise based on the generation of EMG. A novel filter is proposed by applying a neural network (NN) ensemble where the noisy input signal and the desired one are the same in a learning process. Both incremental and batch mode are applied in the learning process of NNs that is better than generalized NN filters. This NN ensemble filter not only reduces additive and multiplicative white noise inside signals, but also preserves the signals' characteristics. In clinical EEG and EMG signals processing, the filter is capable of reducing EMG in the clinical EEG, and it is proved that there is randomness in EMG.

To provide more genetic information about meiotic segregation behavior and the possibility of interchromosomal effects (ICE) in spermatozoa from carriers of Robertsonian (Rob) translocations.Meiotic segregation behavior in spermatozoa from six carriers of Rob translocations, four t(13;14), one t(14;22) and one t(13;21), was investigated by dual fluorescence in-situ hybridization (FISH). Aneuploidy for chromosomes 18, X and Y was studied by triple FISH.The rate of normal/balanced spermatozoa resulting from alternate segregation ranged from 78.14 to 86.88%. The frequency of unbalanced spermatozoa resulting from adjacent segregation varied between 11.70 and 19.53%. The higher frequencies of aneuploidy for sex chromosome were observed in three Rob translocation carriers. In addition, the increased rates of diploid were found in two t(13;14) carriers.Alternate segregation is dominant in the different types of Rob translocations. Some carriers may be at an increased risk for ICE.

Although sperm dysfunction is the single most common cause of infertility, we have poor methods of diagnosis and surprisingly no effective treatment (excluding assisted reproductive technology). In this review, we challenge the usefulness of a basic semen analysis and argue that a new paradigm is required immediately. We discuss the use of at-home screening to potentially improve the diagnosis of the male and to streamline the management of the sub-fertile couple. Additionally, we outline the recent progress in the field, for example, in proteomics, which will allow the development of new biomarkers of sperm function. This new knowledge will transform our understanding of the spermatozoon as a machine and is likely to lead to non-ART treatments for men with sperm dysfunction.

Obstructive sleep apnea (OSA) is a serious disorder characterized by intermittent events of upper airway collapse during sleep. Snoring is the most common nocturnal symptom of OSA. Almost all OSA patients snore, but not all snorers have the disease. Recently, researchers have attempted to develop automated snore analysis technology for the purpose of OSA diagnosis. These technologies commonly require, as the first step, the automated identification of snore/breathing episodes (SBE) in sleep sound recordings. Snore intensity may occupy a wide dynamic range (>95 dB) spanning from the barely audible to loud sounds. Low-intensity SBE sounds are sometimes seen buried within the background noise floor, even in high-fidelity sound recordings made within a sleep laboratory. The complexity of SBE sounds makes it a challenging task to develop automated snore segmentation algorithms, especially in the presence of background noise. In this paper, we propose a fundamentally novel approach based on artificial neural network (ANN) technology to detect SBEs. Working on clinical data, we show that the proposed method can detect SBE at a sensitivity and specificity exceeding 0.892 and 0.874 respectively, even when the signal is completely buried in background noise (SNR

In this paper we describe an Independent Component Analysis (ICA) method for computing the brain signals of unknown source parameters for the inverse problem. First, a method is applied to estimate the number of dipoles beforehand and reduce dimensionality which can reduce the ICA complexity and improve the unmixing accuracy. We apply Blind Source Separation (BSS) for separating multichannel EEG evoked by multiple dipoles into temporally independent stationary sources. For every independent source, we are able to determine the electrode potentials evoked by every dipole separately by the projection of independent activation maps back onto the electrode arrays. Then for every set of electrode potentials, a source localization procedure is performed which only involves searching for one dipole, thus dramatically reducing the search complexity. In the paper, it is explored that the possibility of applying ICA for EEG multiple dipoles localization when the data are corrupted by additive noise. Furthermore, we also give the relationship of unmixing accuracy, distance between dipoles and dipoles moment movements.

Objective To evaluate the effect of growth differentiation factor-9 (GDF-9) and bone morphogenetic protein-15 (BMP-15) on the development of follicles among patients with polycystic ovary syndrome (PCOS). Design Case-control study. Setting University Hospital. Patient(s) Twenty-two oocytes were obtained from 15 patients with PCOS and 67 oocytes from 58 controls. Cumulus granulosa cells (GC) were obtained from 16 patients with PCOS and controls treated with intracytoplasmic sperm injection. Intervention(s) Immunofluorescence combined with laser scanning confocal microscopy and immunocytochemistry were used to analyze the expression of GDF-9 and BMP-15 in oocytes and cumulus GCs. Main Outcome Measure(s) To detect the protein expression levels. Result(s) No significant difference was found in the expression of GDF-9 and BMP-15 in the oocytes and BMP-15 in the cumulus GCs of patients with PCOS and controls. However, the expression of GDF-9 in cumulus GCs of patients with PCOS was decreased significantly compared with controls (8.88 ± 1.52 vs. 5.01 ± 0.83). Conclusion(s) The expression of GDF-9 and BMP-15 in the oocytes of patients with PCOS who received ovulation induction treatment was in the normal range, but the GDF-9 expression in cumulus GCs from patients with PCOS was significantly lower than the normal. Reduced GDF-9 expression in cumulus GCs of patients with PCOS appears to be associated with decreased long-term developmental potential of the oocytes of patients with PCOS.

A novel filter is proposed by applying back propagation neural network (BPNN) ensemble where the noisy signal and the reference one are the same. The neural network(NN) ensemble filter not only well reduces additive and multiplicative white noise inside signals, but also preserves signals' characteristics. It is proved that while power of noise is larger, the reduction of noise using NN ensemble filter is better than the improved epsiv nonlinear filter and single NN filter, and compared with the improved epsiv nonlinear filter, degradation of the capability for reduction of noise by NN ensemble due to the increase of noise power is much suppressed. Furthermore, it is presented of the relationship between noise reduction and bandwidth of noises. The performance of the NN ensemble filter is demonstrated in computer simulations and actual electroencephalogram (EEG) signals processing.

To investigate the clinical application of fluorescence in situ hybridization (FISH) for assessing chromosome disorders of embryos in preimplantation diagnosis of carriers with der(15)t(Y;15)(q12;p11) translocations.Multicolor FISH was performed using directly-labelled DNA probes, chromosome X with one (DXZ1, Xp11.1-q11.1), but Y with two (DYZ3, Yp11.1-q11.1 and DYZ1, Yq12). Normal embryos were transferred on day 6 at blastocyst stage.Couple A: Three of 6 biopsied embryos were normal. Two normal blastocysts were transferred, but no pregnancy was achieved. Couple B: Three of 6 biopsied embryos were normal. Two normal blastocysts were transferred. A normal male infant weighing 3,230 g was born by cesarean section on the 39th week of gestation. All of the remaining nonreplaced embryos showed mosaic or der(15).Embryos from carries of der(15)t(Y;15)(q12;p11) translocation showed a high frequency of chromosome abnormalities. PGD is a valuable screen tool for those couples to treat their infertility and break the transmission of der(15) chromosome for their offspring.

Bone morphogenetic protein-15 is expressed in ooctytes and cumulus granulosa cells. It may play an important role in the hCG-induced oocyte final maturation and corpus luteum (CL) formation.