A generalized l 2,p-norm regression based feature selection algorithm.

Feature selection is an important data dimension reduction method, and it has been used widely in applications involving high-dimensional data such as genetic data analysis and image processing. In order to achieve robust feature selection, the latest works apply the l 2 , 1 or l 2 , p -norm of matrix to the loss function and regularization terms in regression, and have achieved encouraging results. However, these existing works rigidly set the matrix norms used in the loss function and the regularization terms to the same l 2 , 1 or l 2 , p -norm, which limit their applications. In addition, the algorithms for solutions they present either have high computational complexity and are not suitable for large data sets, or cannot provide satisfying performance due to the approximate calculation. To address these problems, we present a generalized l 2 , p -norm regression based feature selection ( l 2 , p -RFS) method based on a new optimization criterion. The criterion extends the optimization criterion of ( l 2 , p -RFS) when the loss function and the regularization terms in regression use different matrix norms. We cast the new optimization criterion in a regression framework without regularization. In this framework, the new optimization criterion can be solved using an iterative re-weighted least squares (IRLS) procedure in which the least squares problem can be solved efficiently by using the least square QR decomposition (LSQR) algorithm. We have conducted extensive experiments to evaluate the proposed algorithm on various well-known data sets of both gene expression and image data sets, and compare it with other related feature selection methods.

[Correlation analysis of vitamin D level and anti-Müllerian hormone in infertile female and the role in predicting pregnancy outcome].

OBJECTIVE: To investigate the relationship between serum 25(OH)D and anti-Müllerian hormone (AMH) among infertile females and their predictive impacts on in vitro fertilization and embryo transfer pregnancy outcome. METHODS: Totally 756 infertile females treated with assisted reproductive technology were enrolled and divided into three groups according to their vitamin D levels (group A with serum 25(OH)D≤10 µg/L, group B with serum (10-20) µg/L, and group C with serum ≥20 µg/L). The serum AMH levels were detected. The differences among the groups were analyzed, as well as the correlation between vitamin D levels and serum AMH levels in various infertility types (fallopian tube/male factor, polycystic ovary syndrome (PCOS), ovulation disorders excluded PCOS, endometriosis, unexplained infertility, and others). Also, the predictive roles of vitamin D and AMH in pregnancy outcome in all the infertile females were discussed. RESULTS: (1) 87.7% of the enrolled females were insufficient or deficient in vitamin D. (2) The serum AMH levels in the three groups with different vitamin D levels were 1.960 (1.155, 3.655) µg/L, 2.455 (1.370, 4.403) µg/L, 2.360 (1.430, 4.780) µg/L and there was no significant difference in serum AMH levels among the three groups (P>0.05). (3) Serum 25(OH)D and AMH levels presented seasonal variations (P < 0.05). (4) There was no prominent correlation between the serum AMH level and serum 25(OH)D level in females of various infertility types after adjusting potential confounding factors [age, body mass index (BMI), antral follicle count (AFC), vitamin D blood collection season, etc.] by multiple linear regression analysis (P>0.05). (5) After adjusting for confounding factors, such as age, BMI, number of transplanted embryos and AFC, the results of binary Logistics regression model showed that in all the infertile females, the serum AMH level was an independent predictor of biochemical pregnancy outcome (P < 0.05) while the serum 25(OH)D level might not act as a prediction factor alone (P>0.05). In the meanwhile, the serum 25(OH)D level and serum AMH level were synergistic predictors of biochemical or clinical pregnancy outcome (P < 0.05). CONCLUSION: Based on the current diagnostic criteria, most infertile females had vitamin D insufficiency or deficiency, but there was not significant correlation between serum 25(OH)D and ovarian reserve. While vitamin D could not be used as an independent predictor of pregnancy outcome in infertile females, the serum AMH level could predict biochemical pregnancy outcome independently or jointly with vitamin D.

[Role of interaction between reactive oxygen species and ferroptosis pathway in methylglyoxal-induced injury in mouse embryonic osteoblasts].

OBJECTIVE: To explore the interaction between reactive oxygen species (ROS) and ferroptosis in methylglyoxalinduced injury of mouse embryonic osteoblasts (MC3T3-E1 cells). METHODS: MC3T3-E1 cells were treated with methylglyoxal to establish a cell model of diabetic osteoporosis. CCK-8 assay was used to detect the viability of MC3T3-E1 cells. Rhodamine 123 staining followed by photofluorography was used to examine mitochondrial membrane potential (MMP). The intracellular ROS level was detected by 2', 7'-dichlorodihydrofluorescein diacetate staining with photofluorograph. Alkaline phosphatase (ALP) activity in the cells was detected using an ALP kit, the number of mineralized nodules was determined with alizarin red S staining, and the level of iron ions was detected using a detection kit. The expression level of glutathione peroxidase 4 (GPX4, a marker protein that inhibits ferroptosis) in the osteoblasts was determined using Western blotting. RESULTS: Treatment of MC3T3-E1 cells with 0.6 mmol/L methylglyoxal for 24 h significantly inhibited the expression level of GPX4 (P < 0.001), increased intracellular iron ion concentration, decreased the cell viability, increased the loss of MMP and intracellular ROS level, decreased both ALP activity and the number of mineralized nodules in the cells (P < 0.001). Co-treatment of MC3T3-E1 cells with 2 mmol/L N-acetylcysteine (NAC, a ROS scavenger) and methylglyoxal significantly increased the expression level of GPX4 (P < 0.01); co-treatment with 4 mmo/L FER-1 (a ferroptosis inhibitor) and methylglyoxal obviously decreased the intracellular ROS level (P < 0.001). Co-treatment of the cells either with NAC and methylglyoxal or with FER-1 and methylglyoxal attenuated methylglyoxal-induced injuries in the osteoblasts (P < 0.001). CONCLUSION: The interaction between ROS and ferroptosis pathway plays an important role in methylglyoxal-induced injury of mouse embryonic osteoblasts.

[Heritability of body mass index based on twin studies: a Meta-analysis].

Objective: To use Meta analysis to understand the prevalence of the heritability of body mass index (BMI) in twins. Methods: All studies on the heritability of the twins' BMI published before December 31, 2020 were retrieved through the China National Knowledge Network, Wanfang, VIP, PubMed and Web of Science databases. The literature quality was evaluated by using Joanna Briggs Institute Critical Appraisal tools. Stata 16.0 was used to perform subgroup analysis on the outcome indicators (heritability, 95%CI) to explore the source of heterogeneity. The local weighted regression method was used to fit the trend of heritability with age. The publication bias test and the sensitivity analysis of included literatures were also performed by using Stata 16.0. Results: A total of 10 articles meeting the inclusion and exclusion criteria were included with 79 twins' independent estimates of heritability for BMI. Meta-analysis showed that the combined value of BMI heritability was 0.69 (95%CI: 0.65-0.71), the combined value of BMI (0.68, 95%CI: 0.65-0.70) in males was lower than that (0.70, 95%CI: 0.68-0.72) in females. The heritability of BMI (0.72, 95%CI: 0.68-0.76) in childhood and adolescence was higher than that (0.68, 95%CI: 0.66-0.70) in adulthood. The gender specific difference in BMI heritability in twins ≤18 years old was even greater, which was lower in males (0.68, 95%CI: 0.61-0.76) than in females (0.75, 95%CI: 0.69-0.81). The heritability increased with age in childhood, reached peak at about 18 years old, and then slowly decreased with age. Conclusions: The heritability of BMI varied with population characteristics, especially age and gender. In view of the high estimated value of BMI heritability in female children and adolescents, more attention should be paid to the start time of health intervention.

[Trends of a burden on atherosclerotic cardiovascular disease and its related risk factors in China, 1990 to 2019].

Objective: To quantitatively analyze the effects of population aging and other risk factors on the burden of atherosclerosis cardiovascular disease (ASCVD) in China from 1990 to 2019. Methods: Disability adjusted life years (DALY) and age-standardized rates obtained from the Global Burden of Disease Study 2019 (GBD2019) were used to describe the temporal trend of a burden on ASCVD. And a decomposition method established by Gupta was applied to quantify the burden related to population growth, aging, age-specific prevalence, and the severity of the disease. Results: In 2019, 61.00% of the burden of cardiovascular disease in China was caused by ASCVD. The DALY of ischemic heart disease increased by 133.66% compared with that in 1990, with 29.57% of the increase attributed to population growth, 108.74% due to population aging, and 8.87% due to the rise of age-specific prevalence and -13.53% benefited from changes in disease severity. The DALY of ischemic stroke increased by 138.64% compared with 1990, and the proportions attributable to the above four parts were 30.95%, 123.38%, 55.80%, and -71.49%, respectively. Hypertension remained the leading risk factor for ASCVD in 2019, followed by high LDL cholesterol. The age-standardized DALY rate attributable to drinking had the most significant increase (486.01%) from 1990, with an average annual growth of 10.93%. Conclusions: Aging population seems responsible for the main reason for the considerable increase in the burden of ASCVD in China. Still, the adverse trends of other avoidable risk factors, especially metabolic risk factors, can not be ignored.

Effect and mechanism of omega-3 polyunsaturated fatty acids on intestinal injury in rats with obstructive jaundice.

OBJECTIVE: Obstructive jaundice (OJ) is a common clinical pathological syndrome in hepatobiliary surgery. High incidence of multiple organ injuries during perioperative period and its associated mortality remains challenging in clinical practice. Omega-3 polyunsaturated fatty acids (ω-3 PUFA) is an important enteral immune nutrition. This study investigated the protective role of ω-3 PUFA in the regulation of inflammatory response in OJ. MATERIALS AND METHODS: Seventy-two rats were randomly divided into obstructive jaundice (OJ) group, obstructive jaundice + ω-3 PUFA group (OJPUFA) group, and sham group. OJ model was created by ligation of the bile duct. Abdominal thoracic catheter was placed to collect lymph. Body weight, liver function, serum and lymphatic levels of TNF-α, IL-1ß, IL-10, HMGB1, and nitric oxide (NO) were measured on day 3, day 7, and day 14 after operation. Hematoxylin staining and Alcian blue-periodic acid-Shiff (AB-PAS) staining were performed on the ileum tissue. Protein and mRNA expression of HMGB1, TLR4, and NF-κB p65 were measured at the aforementioned time points. RESULTS: The general condition, including body weight and liver function, were worse in the OJ and the OJPUFA group compared to that in the sham group. On day 14, the body weight recovery and liver function were significantly better in the OJPUFA group than those in the OJ group were (p<0.05 for all). No marked change in the serum and lymphatic levels of TNF-α, IL-1ß, IL-10, HMGB1 and NO was observed in the sham group after operation, while corresponding levels in the OJ and the OJPUFA groups were significantly higher. Compared with the OJPUFA group, serum and lymphatic levels of the above factors were consistently higher in the OJ group and were significantly higher on day 14 (p<0.05 for all). At the same time, ω-3 PUFA lowered the damage of intestinal villi and intestinal mucosal epithelium. It also improved the number and function of goblet cells in intestinal mucosal epithelium. The protein and mRNA expression of HMGB1, TLR4, and NF-κB p65 were significantly higher in the OJ group than those in the OJPUFA group (p<0.05 for all). CONCLUSIONS: ω-3 PUFA has protective effect in the management of obstructive jaundice. It can regulate the inflammatory response and reduce its damage to intestinal structure. Reducing the activation of HMGB1/TLR4/ NF-κB pathway might be a mechanism for its protective effect. We suggested that ω-3 PUFA and drugs targeted HMGB1/TLR4/NF-κB pathway might be potential treatment strategies in obstructive jaundice.

[Significance of circulating tumor cell monitoring in targeted therapy for gastrointestinal stromal tumors].

Objective: To explore the significance of circulating tumor cell (CTC) monitoring in evaluating the efficacy of targeted therapy for gastrointestinal stromal tumor (GIST). Methods: A prospective cohort study was performed. The data of patients with locally advanced GIST or liver metastasis who were admitted to The Affiliated Hospital of Nantong University from August 2013 to December 2018 were collected. Inclusion criteria: (1) patients aged older than 18 years; (2) patients who were diagnosed with GIST based on pathology; (3) patients without surgery, whose preoperative imaging evaluation of GIST found the violations of the surrounding organs or partial transfer of an estimated difficulty to achieve R0 resection, or the maximum diameter of the tumor > 10 cm, or the liver metastasis, or the expectation of higher risk of surgical complications; (4) patients who were treated with the imatinib 400 mg/d for the first time; (5) Eastern Cooperative Oncology Group (ECOG) score of 0-2. Exclusion criteria: (1) genetic testing revealed a D842V mutation in exon 18 of the PDGFRA gene; (2) alanine aminotransferase and/or aspartate aminotransferase > 2.5 times the normal upper limit; (3) serum total bilirubin >1.5 times of normal upper limit; (4) neutrophil count < 1.5×10(9)/L, or platelet count < 75×10(9)/L, or hemoglobin < 60 g/L; (5) creatinine > normal upper limit; (6) patients had serious cardiovascular and cerebrovascular diseases within 12 months before enrollment; (7) female patients were pregnant or lactating; (8) patients suffered from other serious acute and chronic physical or mental problems, and were not suitable for participating in this study judged by researchers. The patients who could not tolerate treatment regimen, or developed serious adverse reactions and did not follow the medication scheme after enrollment were excluded. Before imatinib treatment and 1-month and 2-month after treatment, quantitative PCR was used to detect the DOG-1 expression of monocytes in peripheral blood, and the ratio of DOG-1/ß-actin > 3×10(-5) was used as the CTC positive threshold of GIST. The positive rate of CTC, the efficacy of imatinib treatment (complete response, partial response, stable disease, progressive disease, and occurrence of adverse reactions), and the relationship between CTC positive rate and clinicopathological characteristics of patients were analyzed. Furthermore, the ratio of DOG-1 decrease/baseline DOG-1 after 1-month of treatment was used as an indicator to evaluate whether targeted therapy was effective. The receiver operating characteristic (ROC) curve was rendered, and the area under the curve (AUC) was calculated. Results: A total of 68 GIST patients were enrolled in this study, including 39 cases of locally advanced GIST and 29 cases with liver metastases, 32 males and 36 females with the mean age of (51.2±11.8) (range 31 to 74) years. After 2-month of imatinib treatment, 43 cases were evaluated as partial response, 11 cases as stable disease, and 14 cases as progressive disease, with an effective rate of 79.4% (54/68). During the treatment of imatinib, the incidence of grade 3 or higher adverse reactions was 22.1% (15/68), including 12 cases of grade 3 neutropenia and 3 of grade 4 drug eruption, which were all relieved after conservative treatment. The positive rates of CTC in 68 patients before treatment, 1-month and 2-month after treatment were 66.2% (45/68), 41.2% (28/68) and 23.5% (16/68), respectively. The positive rate of CTC was associated with tumor size, liver metastasis, mitotic count and risk level (all P<0.05). By analyzing the effective group and the ineffective group of targeted therapy, it was found that the positive rate of CTC in the effective group showed a decreasing trend, while the positive rate of CTC in the ineffective group showed an increasing trend. The AUC of predicting the efficacy of targeted therapy for GIST was 0.823 by detecting the change trend of CTC 1-month after treatment (P<0.001). When the DOG-1 content decreased by more than 57.5% 1-month after treatment, it can be used as an indicator to judge the effectiveness of the treatment, whose sensitivity was 72.2% and specificity was 100%. Conclusion: The detection of peripheral blood CTC can evaluate the efficacy of targeted therapy in GIST patients and can provide decision-making basis for further clinical treatment.

[SHOX2 promotes migration, invasion and stemness of bladder cancer cells in vitro].

OBJECTIVE: To explore the role of human short stature homeobox 2 (SHOX2) in regulating the migration, invasion and stemness of human bladder cancer cells. METHODS: We analyzed SHOX2 gene expression in bladder cancer and adjacent tissues based on TCGA database. Univariate survival analysis of SHOX2 gene expression in TCGA-BLCA data was performed using GEPIA. The probable function of SHOX2 was predicted using GSEA. Human bladder cancer T24 cell models of SHOX2 knockdown or overexpression were assessed for changes in migration and invasion abilities using wound healing assay and Transwell assay, and their cancer stem cell-like characteristics were evaluated using tumorsphere formation assay and colony formation assay. Western blotting was used to detect the expressions of epithelial mesenchymal transition (EMT) markers Ecadherin and vimentin and the TGF-ß signaling network component TßR-I in the cells. RESULTS: SHOX2 expression was significantly higher in bladder cancer tissues than in the adjacent tissues (P < 0.05), especially in paired tissue specimens (P < 0.01), and was negatively correlated with the overall survival of the patients (P < 0.05). SHOX2 gene expression was correlated positively with EMT-related (P < 0.05) and stemness-related gene signatures (P < 0.01). In T24 cells, SHOX2 knockdown significantly suppressed cell migration and invasion, which was significantly enhanced by SHOX2 overexpression (P < 0.01). The cancer stem cell-like characteristics of T24 cells was repressed by SHOX2 knockdown but significantly enhanced by SHOX2 overexpression (P < 0.01). SHOX2 knockdown induced morphological changes of the cells into epithelioid cells, whereas SHOX2 overexpression induced a mesenchymal morphology of the cells. SHOX2 knockdown increased E-cadherin expression and decreased vimentin and TßR-I expression, while SHOX2 overexpression increased the expressions of vimentin and TßR-I in the cells. CONCLUSION: SHOX2 promotes the migration, invasion and stemness of human bladder cancer cells possibly by regulating EMT via the TGF-ß signaling pathway.

[The association between myopic refraction and near work among children and adolescents based on genetic risk score].

Objective: To explore the relationship between myopic refraction and near work in children and adolescents with different genetic risks. Methods: From September to December 2016, Nankai District and Hongqiao District of Tianjin were taken as the study sites. Using the method of stratified cluster random sampling, 533 children and adolescents aged 6-14 years from one primary school and one junior middle school in each of the two districts were included as the study subjects. Refraction measurements by an auto-kerato-refractor and questionnaire survey about near work were conducted. 11 single nucleotide polymorphisms in the selected myopia susceptibility genes were detected, and the genetic risk of each individual was scored. After grouping by genetic risk score, the relationship between myopia and near work was analyzed by the multivariate logistic regression, and the relationship between near work and refraction was analyzed by the multivariate linear regression. Results: The age of 553 subjects was (9.8±2.5) years, including 295 boys (53.3%). The overall detection rate of myopia was 62.0%. The spherical equivalent refraction (SER) was (-1.30±1.85) D. The results of the multivariate logistic regression showed that in the low risk group of GRS, compared with those with continuous near work time less than half an hour, those with continuous near work time no less than half an hour had a higher risk of myopia [OR (95%CI) = 2.64 (1.07, 6.52)]. In the moderate risk group of GRS, the risk of myopia increased with the increase of daily computer use [OR (95%CI) = 2.14 (1.03, 4.77)]. In the high risk group of GRS, the risk of myopia increased with the increase of the total daily reading and writing time [OR (95%CI) = 1.27 (1.01, 1.59)]. The results of the multivariate linear regression showed that in the low risk group of GRS, with increase of 1 hour in the total daily reading and writing time and mobile phone time, the SER decreased by 0.18 D (95%CI:-0.30, -0.07) and 0.95 D (95%CI:-1.51, -0.39), respectively. In the moderate risk group of GRS, with increase of 1 hour in the total daily reading and writing time and computer use time, the SER decreased by 0.25 D (95%CI:-0.31, -0.18) and 0.57 D (95%CI:-0.97, -0.18), respectively. In the high risk group of GRS, with increase of 1 hour in the daily total reading and writing time, the SER decreased by 0.33 D (95%CI:-0.43, -0.22). Conclusion: Continuous near work time no less than half an hour, daily computer use time, the total daily reading and writing time, and daily mobile phone use time were associated with myopic refraction in children and adolescents.

[Interventional treatment of hemorrhage after percutaneous nephrolithotomy].

OBJECTIVE: To evaluate the effectiveness of super-selective renal artery embolization in treatment of post-percutaneous nephrolithotomy bleeding, and to analyse the causes of failure embolization. METHODS: In the study, 65 post-percutaneous nephrolithotomy patients with severe renal bleeding and hemodynamic instability were treated by super-selective renal artery embolization. First of all, we performed selective renal arteriography. After clarifying the location of the bleeding, superselective intubation of the injured vessel with a microcatheter was carried out. Then the injured vessel was embolized with Tornado micro-coil. When complete embolization was not achieved with micro-coil, a small amount of gelatin sponge particles were added. If there was no positive finding of the beginning selective renal arteriography, the following measures could be taken to prevent missing lesions: (1) Abdominal aorta angiography was performed to determine whether there were anatomical variations, such as accessory renal arteries or multiple renal arteries; (2) Ultra-selective intubation angiography next to the nephrostomy tube path was performed; (3) Renal arteriography was repeated; (4) Renal arteriography after removing the nephrostomy tube while retaining the puncture channel. We evaluated the different angiographic findings and analysed the causes of embolization failure. RESULTS: Bleeding was successfully controled in 60 patients (62 kidneys) whose renal arteriography was postive. Positive findings included: pseudoaneurysm formation, patchy contrast extravasation, pseudoaneurysm combined with arteriovenous fistula, contrast agent entering the collection system, extravascular perinephric leakage of contrast. After first embolization, bleeding was controled in 53 patients (55 kidneys). The success rate after the first and second embolization was 88.7% and 96.7% respectively. The second session was required because of failure to demonstrate bleeding arteries during the first session (4 patients, 57.1%) and recurrent hemorrhage of the embolized injured arteries (2 patients, 28.6%). In 5 patients with no positive findings, after conservative treatment, hematuria disappeared. All the patients were followed up for 3, 6, and 12 months after embolization, and no hematuria occurred again, and no sustained and serious renal insufficiency. CONCLUSION: Super-selective renal artery embolization is an effective treatment for post percutaneous nephrolithotomy bleeding. The main cause of failure is omitting of injured arteries during renal arteriography. Renal artery branch injury has various manifestations. Attention should paid to the anatomical variation of the renal artery, and patient and meticulous superselective intubation angiography is the key to avoiding missing the lesion and improving the success rate of embolization.

OIP5-AS1 promotes the progression of gastric cancer cells via the miR-153-3p/ZBTB2 axis.

OBJECTIVE: Gastric cancer (GC) remains a serious disease to human health with high mortality worldwide. Evolving evidence implied that long non-coding RNA Opa interacting protein 5-antisense RNA1 (OIP5-AS1) went in for the pathological progress of GC. Nevertheless, the potential molecular mechanism of OIP5-AS1 needed to be further investigated. MATERIALS AND METHODS: Levels of OIP5-AS1, microRNA (miR)-153-3p, and zinc finger and BTB domain containing 2 (ZBTB2) were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot assays. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) was implemented to detect cell proliferation in vitro. Cell apoptosis was evaluated by flow cytometry. Besides, transwell assay was conducted to examine cell migration and invasion in AGS and MKN45 cells. The interaction between miR-153-3p and OIP5-AS1 or ZBTB2 was validated utilizing dual-luciferase reporter assay. Lastly, the role of OIP5-AS1 in tumor growth was researched through adopting xenograft tumor model. RESULTS: OIP5-AS1 and ZBTB2 were strongly higher in GC tissues than noncancerous samples. OIP5-AS1 silencing remarkably curbed cell proliferation, migration and invasion, and elevated cell apoptosis in both AGS and MKN45 cells. Functional analysis indicated that OIP5-AS1 regulated ZBTB2 expression via binding to miR-153-3p. Moreover, the role of miR-153-3p in cell growth and metastasis was abrogated by ZBTB2 overexpression. Above all, OIP5-AS1 could reduce the growth of xenograft tumor in vivo. CONCLUSIONS: OIP5-AS1 exerted its role via miR-153-3p/ZBTB2 axis in the progression of GC cells. These findings might supply a biomarker for the diagnosis and therapy of GC clinically.

Long non-coding RNA TOB1-AS1 modulates cell proliferation, apoptosis, migration and invasion through miR-23a/NEU1 axis via Wnt/b-catenin pathway in gastric cancer.

OBJECTIVE: Gastric cancer (GC) is the fourth common cancer worldwide. Long non-coding RNA TOB1 antisense RNA 1 (TOB1-AS1) has been found to participate in the process of GC, while the precise role of TOB1-AS1 is still not understood in GC progression. MATERIALS AND METHODS: We collected 21-paired GC and para-carcinoma tissue specimens, and the levels of TOB1-AS1 and lysosomal sialidase (NEU1) were detected by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). The protein expression levels of NEU1, b-catenin, c-Myc, Cyclin D1, N-cadherin were determined via Western blot. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flow cytometry was performed to evaluate cell proliferation. Besides, GC cell migration and invasion capacities were identified by transwell assay. Dual-Luciferase reporter assay was employed to examine the interrelation between miR-23a and TOB1-AS1 or NEU1. Finally, the role of TOB1-AS1 was verified in vivo. RESULTS: The levels of TOB1-AS1 were decreased in GC tissues and cell lines. Either TOB1-AS1 or NEU1 upregulation accelerated GC cell apoptosis, hampered proliferation, migration, and invasion. Further, the role of TOB1-AS1 silencing on cell behaviors was abrogated by NEU1 upregulation. TOB1-AS1 and NEU1 exerted their roles via Wnt/b-catenin signaling pathway. Overexpression of TOB1-AS1 blocked GC development in vivo. Mechanically, miR-23a was targeted by TOB1-AS1, but directly targeted NEU1. CONCLUSIONS: TOB1-AS1/miR-23a/NEU1 axis regulated proliferation, apoptosis, migration, and invasion of GC cells via Wnt/b-catenin pathway, providing the evidence for serving TOB1-AS1 as an underlying therapeutic target in human GC treatment.

Synergistic recruitment of multi-scale myoelectric oscillations of upper limb during infant crawling.

It has been widely accepted that the central nervous system (CNS) modulates muscle synergies to simplify motion control. However, it is still unclear that if there is a synergistic recruitment strategy to organize oscillation components of surface electromyography (sEMG) signals for limb movement. The sEMG signals were recorded from bilateral biceps brachii (BB) and triceps brachii (TB) muscles during infant crawling. The multivariate empirical mode decomposition (MEMD) was applied to decompose multi-channel sEMG signals into multi-scale oscillations. Then, non-negative matrix factorization (NMF) method was employed to extract oscillation synergy patterns. The results indicated that there were three stable oscillation synergies in sEMG signals for crawling movement, and the recruitment coefficient curves reflected the role of muscle during crawling movement. Our preliminary work suggested that synergistic recruitment of multi-scale oscillation components maybe a new way to understand the organization of MU recruitment strategy by the CNS.

Decreased Expression of TIM-3 on Th17 Cells Associated with Ophthalmopathy in Patients with Graves' Disease.

PURPOSE: Thyroid-associated Ophthalmopathy (TAO) is one of the most common orbital immunological diseases in adults. CD4+ helper T (Th) cells play important roles in the pathogenesis of TAO. But the mechanisms regulating CD4+ T cell activity is unclear. This study examines T cell immunoglobulin domain and mucin domain 3 (TIM-3) expression in helper T cell type 1 (Th1), Th17, and regulatory T cells in sufferers of TAO. METHODS: Participants were divided into 3 groups: patients with TAO, patients with Graves' disease but without orbitopathy (GD), and healthy control patients (HC). Peripheral blood samples were collected for each patient in the designated group. Flow cytometry methods assessed the frequency of Th1 (CD4+IFN-γ+), Th17 (CD4+IL-17+), regulatory T cells (CD4+CD25hiCD127lo), and TIM-3 protein expression. Mean fluorescence intensity (MFI) measured the magnitude of TIM-3 expression and the percentage of TIM-3+ cells for each patient. RESULTS: Compared to the GD group, TAO patients possessed higher frequencies of Th1 and Th17 cells in peripheral blood samples. The percentage of TIM-3+ Th1 and Th17 cells was significantly lower in the TAO patients than the GD group. Across all patients sampled, TIM-3+ cell percentage negatively correlated with Th1 cell frequency. Th1 and Th17 cells exhibited significantly decreased expression of TIM-3 in TAO patients compared to healthy controls. Regulatory T cells showed little TIM-3 expression and we observed no significant differences in frequency between groups. CONCLUSION: These results suggest a role for TIM-3 in the regulation of Th1 and Th17 cells and the pathogenesis of Graves' ophthalmopathy.

Modelling invasive group A streptococcal disease using bioluminescence.

BACKGROUND: The development of vaccines and evaluation of novel treatment strategies for invasive group A streptococcal (iGAS) disease requires suitable models of human infection that can be monitored longitudinally and are preferably non-invasive. Bio-photonic imaging provides an opportunity to reduce use of animals in infection modelling and refine the information that can be obtained, however the range of bioluminescent GAS strains available is limited. In this study we set out to develop bioluminescent iGAS strains for use in in vivo pneumonia and soft tissue disease models. RESULTS: Using clinical emm1, emm3, and emm89 GAS strains that were transformed with constructs carrying the luxABCDE operon, growth and bioluminescence of transformed strains were characterised in vitro and in vivo. Emm3 and emm89 strains expressed detectable bioluminescence when transformed with a replicating plasmid and light production correlated with viable bacterial counts in vitro, however plasmid instability precluded use in the absence of antimicrobial pressure. Emm89 GAS transformed with an integrating construct demonstrated stable bioluminescence that was maintained in the absence of antibiotics. Bioluminescence of the emm89 strain correlated with viable bacterial counts both in vitro and immediately following infection in vivo. Although bioluminescence conferred a detectable fitness burden to the emm89 strain during soft tissue infection in vivo, it did not prevent dissemination to distant tissues. CONCLUSION: Development of stably bioluminescent GAS for use in vitro and in vivo models of infection should facilitate development of novel therapeutics and vaccines while also increasing our understanding of infection progression and transmission routes.

[Sub-health status of middle school teachers and its correlation analysis with occupational stress].

Objective: To study the distribution of sub-health and occupational stress as well as their correlation among middle school teachers in Tianjin, then provide evidences for prevention and control of the status of sub-health. Methods: A total of 3 522 middle school teachers from six districts of Tianjin were recruited with stratified cluster sampling strategy for the investigation of Sub-Health Measurement Scale version 1.0 (SHMS V1.0) and Occupational Stress Inventory-Revised Edition (OSI-R) . Results: Detection rate of sub-health status among Tianjin middle school teachers was 58.55%. Men had significantly lower sub-health detection rate (55.19%) than women (59.71%) . Sub-health detection rate increased with age (P<0.05) , the sub-health detection rate among middle school teachers more than 50 years old was the highest (66.84%) . The mean score of OSI-R was 403.18±41.80 with the scores of 176.00±21.05, 103.17±17.53, and 124.02±20.28 for ORQ, PSQ, PRQ, respectively, which showed significantly difference compared with the occupational stress norm of China (P<0.001) . The mean scores of OSI-R, ORQ, PSQ, PRQ in different health status were significantly different (P<0.001) . The partial correlation analysis between the scores of sub-health and occupational stress of middle school teachers showed that the scores of occupational role and personal strain were negatively correlated with the scores of sub-health state (P< 0.001) , while, there was significantly positive correlation between the scores of personal resource and the scores of sub-health state (P<0.001) . Conclusion: Sub-health detection rate of middle school teachers in Tianjin is higher. Effective measures should be taken to appropriately mitigate the occupational stress level of middle school teachers, increase personal resources, and scientific and effective health guidance and education should be strengthened.

Quality of meta-analyses in major leading orthopedics journals: A systematic review.

BACKGROUND: Meta-Analyses are the basis of professional and healthcare agencies recommendations and have a growing importance. Quality of meta-analyses has been investigated in some medical fields but to our best knowledge this issue remains under investigated in orthopedics. Therefore, we performed a systematic analysis to: 1) after the introduction of PRISMA statement as a comprehensive guideline and the use of the AMSTAR tool as the standard for sufficient review methodology, has the quality of MAs improved because of that? 2) have some general characteristics influenced the quality of MAs (country, funding source, number of authors)? MATERIAL AND METHODS: We systematically searched the meta-analyses in the top four journals with the impact factor (2015) as following: JBJS, Osteoarthritis Cartilage Arthroscopy and Clin Orthop Relat Res from 2005 to 2008 and from 2012 to 2015. Likewise from 2012-2015, we also analyzed the meta-analyses from OTSR. Characteristics were extracted based on the PRISMA statement and the AMSTAR tool. Country, number of authors, funding source were also extracted. RESULTS: A total of 154 meta-analyses were included in the present study. Score with PRISMA statement and the AMSTAR checklist were 20.86±3.04 out of a maximum of 27 and 7.86±1.55 out of a maximum of 11. The best journal was OTSR according to the PRISMA (23.06±1.92) and AMSTAR (9.13±0.87) scores. And the worst journal was Clin Orthop Relat Res according to the PRISMA score (19.4±2.70) and JBJS according to the AMSTAR score (6.78±1.65). Twelve items showed significant difference in the PRISMA statement, and five items in the AMSTAR checklist. Integral score of PRISMA statement and AMSTAR checklist has a significant difference between 2005-2008 and 2012-2015. The MAs reported from U.S. (56, 36.4%) were more than any other region in the world. And the MAs published by Asia/Oceania increased remarkably between these two period times [from (4, 10.8%) to (45, 38.5%)]. CONCLUSION: This study showed that methodological reporting quality of meta-analyses in the major orthopedics journals has improved after the publication of the PRISMA statement. LEVEL OF EVIDENCE: Level III.

The serum protein levels of the tPA-BDNF pathway are implicated in depression and antidepressant treatment.

Evidence demonstrates that brain-derived neurotrophic factor (BDNF) has a pivotal role in the pathogenesis of major depressive disorder (MDD). Precursor-BDNF (proBDNF) and mature BDNF (mBDNF) have opposing biological effects in neuroplasticity, and the tissue-type plasminogen activator (tPA)/plasmin system is crucial in the cleavage processing of proBDNF to mBDNF. However, very little is known about the role of the tPA-BDNF pathway in MDD. We examined serum protein concentrations in the tPA-BDNF pathway, including tPA, BDNF, tropomyosin receptor kinase B (TrkB), proBDNF and p75NTR, obtained from 35 drug-free depressed patients before and after 8 weeks of escitalopram (mean 12.5 mg per day) or duloxetine (mean 64 mg per day) treatment and 35 healthy controls using sandwich ELISA (enzyme-linked immunosorbent assay) methods. Serum tPA and BDNF and the ratio of BDNF/proBDNF were significantly lower in the MDD patients than in controls, whereas TrkB, proBDNF and its receptor p75NTR were higher. After 8 weeks of treatment, tPA, BDNF and proBDNF and the BDNF/proBDNF ratio were reversed, but p75NTR was higher than baseline, and TrkB was not significantly changed. tPA, BDNF, TrkB, proBDNF and p75NTR all yielded fairly good or excellent diagnostic performance (area under the receiver operating characteristic curve (AUC) >0.8 or 0.9). Combination of these five proteins demonstrated much better diagnostic effectiveness (AUC: 0.977) and adequate sensitivity and specificity of 88.1% and 92.7%, respectively. Our results suggest that the tPA-BDNF lysis pathway may be implicated in the pathogenesis of MDD and the mechanisms underlying antidepressant therapeutic action. The combination of tPA, BDNF, TrkB, proBDNF and p75NTR may provide a diagnostic biomarker panel for MDD.

Continuous treatment with lenalidomide and low-dose dexamethasone in transplant-ineligible patients with newly diagnosed multiple myeloma in Asia: subanalysis of the FIRST trial.

The phase 3 FIRST (Frontline Investigation of REVLIMID + Dexamethasone Versus Standard Thalidomide) trial demonstrated that lenalidomide plus low-dose dexamethasone (Rd) until disease progression (Rd continuous) is an effective treatment option for transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). Given genetic differences between Asian and Western populations, this subanalysis of the FIRST trial examined the safety and efficacy of Rd (given continuously or for 18 cycles [Rd18]) and MPT (melphalan, prednisone, thalidomide) in 114 Asian patients from Mainland China, South Korea and Taiwan. Efficacy and safety with Rd continuous in Asian patients were consistent with those in the overall study population. The overall response rates were 77·8% for Rd continuous, 57·5% for MPT and 65·8% for Rd18. The risk of progression or death was reduced by 39% with Rd continuous versus MPT and by 35% with Rd continuous versus Rd18. Rd continuous improved the 3-year survival rate compared with MPT (70·2% vs. 56·4%) and Rd18 (58·1%). Common grade 3/4 adverse events in the Rd continuous and MPT arms were neutropenia (25·0% vs. 43·6%), infection (19·4% vs. 28·2%) and anaemia (19·4% vs. 15·4%), respectively. Thromboembolic event rates were low, and no second primary malignancies were observed. Rd continuous is safe and effective in transplant-ineligible Asian patients with NDMM.