Obesity is an independent risk factor for osteoarthritis and has been associated with increased rate of complications following lower-extremity total joint arthroplasty (TJA). Bariatric surgery (BS) is a surgical option for weight loss and for reducing obesity-related comorbidities in morbidly obese patients.

Inflammation and oxidative stress are common factors involved in the pathogenesis of retinal diseases, such as aged-related macular degeneration (AMD) and diabetic retinopathy (DR). Autophagy is a catabolic process essential to cell survival in response to stress. This process is highly active in retinal pigment epithelium (RPE) cells. Our previous findings demonstrated that lipopolysaccharide (LPS) induces an inflammatory response of RPE cells that implies classical phospholipases D (PLD1 and 2) activation, cyclooxygenase-2 (COX-2) expression, prostaglandin E2 (PGE2) production and reduced cell viability. In this work, we studied the autophagic process and its modulation by the PLD pathway in D407 and ARPE-19 RPE cells exposed to LPS. LPS (10 μg/ml or 25 μg/ml) exposure for 24 h increased light chain 3B-II (LC3B-II) content (an autophagy marker) and LC3B-positive punctate structures in both RPE cell lines studied. Next, the drug bafilomycin A1 (BAF, 50 nM) was used to block the autophagic flux. In cells pre-incubated with BAF, LC3B-II and sequestosome 1 (SQSTM1/p62) levels and autophagosome-like structures were increased by LPS, demonstrating that the inflammatory injury increases the autophagic process in RPE cells. To study the role of the PLD pathway, cells were pre-incubated for 1 h with selective PLD1 (VU0359595) or PLD2 (VU0285655-1) inhibitors prior to LPS addition. Under control condition, LC3B-positive punctate structures were increased in cells pre-incubated with PLD2 inhibitor while with PLD1 inhibitor were increased in cells exposed to LPS. MTT reduction assays showed that early autophagy inhibitors, 3-methyladenin (3-MA) or LY294002, enhanced the loss in cell viability induced by LPS exposure for 48 h. On the contrary, the inhibition of PLD1 and PLD2 prevented the loss in cell viability induced by LPS. In conclusion, our results show that even though LPS treatment promotes an inflammatory response in RPE cells, it also triggers the activation of the autophagic process which in turn may serve as a protective mechanism for the cells. In addition, we demonstrate that the PLD pathway modulates the autophagic process in RPE cells. Our findings contribute to the knowledge of the molecular basis of retinal inflammatory and degenerative diseases and open new avenues for potential therapeutic exploration.

Rett syndrome is an X linked dominant neurodevelopmental disorder which almost exclusively affects females. The syndrome is usually caused by mutations in MECP2 gene, which is a nuclear protein that selectively binds CpG dinucleotides in the genome.

The characteristics of paediatric neuromyelitis optica spectrum disorder (NMOSD) may indicate the degree of disability and identify factors that predict the response to treatment.

Cap Analysis of Gene Expression (CAGE) is one of the most popular 5'-end sequencing methods. In a single experiment, CAGE can be used to locate and quantify the expression of both Transcription Start Sites (TSSs) and enhancers. This is workflow is a case study on how to use the CAGEfightR package to orchestrate analysis of CAGE data within the Bioconductor project. This workflow starts from BigWig-files and covers both basic CAGE analyses such as identifying, quantifying and annotating TSSs and enhancers, advanced analysis such as finding interacting TSS-enhancer pairs and enhancer clusters, to differential expression analysis and alternative TSS usage. R-code, discussion and references are intertwined to help provide guidelines for future CAGE studies of the same kind.

To evaluate the long-term safety and efficacy of ab-interno trabeculectomy with trabectome for the treatment of glaucoma.

To analyze the incidence and mortality rates of esophagus cancer in China from 2008 to 2012.

Tumor microenvironment, especially the host immune system, plays a pivotal role in tumor initiation and progression. Profiling of immune signature within tumor might uncover biomarkers for targeted therapies and clinical outcomes. However, systematic analysis of immune-related genes in gastric cancer (GC) has not been reported.

Purpose: Total glucosides of paeony (TGP) have been confirmed to reduce hepatotoxicity caused by methotrexate (MTX) and leflunomide (LEF) in rheumatoid arthritis (RA). Nevertheless, high-quality evidence-based meta-analysis data on the issue are unavailable. This study aimed to evaluate the efficacy and safety of this combination treatment for RA. Materials and methods: PubMed, EMBASE, Web of Science, Cochrane Library, ClinicalTrials, Chinese Biomedical Literature database, China National Knowledge Internet, Wan Fang, and VIP were searched up to February 2019. Randomized controlled trials (RCTs) on the efficacy and safety of TGP combined MTX and LEF for RA were included. Results: Eight RCTs were included in the final meta-analysis. Pooled results showed better therapeutic effects against RA in the TGP-treated group (RR =1.10, 95% CI: 1.04 -1.16). The TGP+MTX+LEF group showed a reduced erythrocyte sedimentation rate (MD = -2.80 mm/h, 95% CI: -5.08 - -0.52), C-reactive protein level (MD = -4.17 mg/L, 95% CI: -7.84 - -0.51), and rheumatoid factor (MD = -12.09 IU/mL, 95% CI: -14.05 - -10.14). Besides, the combination treatment tended to benefit lipid profiles (total cholesterol: 95% CI: -1.27-0.06; triglycerides: 95% CI: -0.49 - -0.08; high-density lipoprotein cholesterol: 95% CI: 0.15-0.83; and low-density lipoprotein cholesterol: 95% CI: -0.54 - -0.02). Adverse events, hepatotoxicity in particular, significantly decreased (RR =0.55, 95% CI: 0.38-0.80) in the TGP group. Conclusion: Compared to MTX and LEF therapy, TGP combination treatment may be a more effective and safer strategy. It is advisable to apply TGP as an adjuvant given its hepatoprotective and possible lipid-regulating effect. However, further large-scale and high-quality clinical trials are warranted, and the efficacy of TGP in terms of its effect on lipid profiles should be further confirmed.

Background: miR-29a, a downstream factor of Wnt/β-catenin signaling, promotes the activity of the Wnt/β-catenin signaling in a positive feedback loop. Our previous work showed that 5,7,3',4'-tetramethoxyflavone (TMF), a major constituent from Murraya exotica L., exhibited chondroprotective activity by inhibiting the activity of Wnt/β-catenin signaling. Purpose: To investigate whether TMF showed the inhibitory effects on miR-29a/β-catenin signaling by up regulation of Foxo3a expression. Methods: Rat knee OA models were duplicated by using Hulth's method. TMF (5 μg/mL and 20 μg/mL) was used for administration to cultured cells, which were isolated from the rat cartilages. Analysis of chondrocytes apoptosis, gene expression, and protein expression were conducted. In addition, miR-29a mimics and pcDNA3.1(+)-Foxo3a vector were used for transfection, luciferase reporter assay for detecting the activity of Wnt/β-catenin signaling, and co-immunoprecipitation for determining proteins interaction. Results: TMF down regulated miR-29a/β-catenin signaling activity and cleaved caspase-3 expression and up regulated Foxo3a expression in OA rat cartilages. In vitro, miR-29a mimics down regulated the expression of Foxo3a and up regulated the activity of Wnt/β-catenin signaling and cleaved caspase-3 expression. TMF ameliorated miR-29a/β-catenin-induced chondrocytes apoptosis by up regulation of Foxo3a expression. Conclusion: TMF exhibited chondroprotective activity by up regulating Foxo3a expression and subsequently inhibiting miR-29a/Wnt/β-catenin signaling activity.

Objectives: Hospital-based health technology assessment (HB-HTA) needs to consider all relevant data to help decision making, including patients' preferences. In this study, we comprehensively describe the process of identification, refinement and selection of attributes and levels for a discrete choice experiment (DCE). Methods: A mixed-methods design was used to identify attributes and levels explaining low back pain (LBP) patients' choice for a non-surgical treatment. This design combined a systematic literature review with a patients' focus group, one-on-one interactions with experts and patients, and discussions with stakeholder committee members. Following the patient's focus group, preference exercises were conducted. A consensus about the attributes and levels was researched during discussions with committee members. Results: The literature review yielded 40 attributes to consider in patients' treatment choice. During the focus group, one additional attribute emerged. The preference exercises allowed selecting eight attributes for the DCE. These eight attributes and their levels were discussed and validated by the committee members who helped reframe two levels in one of the attributes and delete one attribute. The final seven attributes were: treatment modality, pain reduction, onset of treatment efficacy, duration of efficacy, difficulty in daily living activities, sleep problem, and knowledge about their body and pain. Conclusion: This study is one of the few to comprehensively describe the selection process of attributes and levels for a DCE. This may help ensure transparency and judge the quality of the decision-making process. In the context of a HB-HTA unit, this strengthens the legitimacy to perform a DCE to better inform decision makers in a patient-centered care approach.

Background/Objectives: Major depressive disorder (MDD) is a highly prevalent disorder, frequently diagnosed and treated in a primary care setting; however, little information is available about the treatment decision-making process between MDD patients and their providers. A shared decision-making and goal attainment approach to establishing and tracking progress toward treatment goals that are meaningful to individual patients is explored in this survey study. In addition, information about patient perspectives on setting treatment goals, medication selection/switching, and engaging patients with their health care professionals was also collected and evaluated. Methods: A 50-question online survey was administered to members of the PatientsLikeMe community who indicated an MDD diagnosis and a switch in antidepressant medications within the past 2 years. Follow-up interviews were also conducted with a small subset of these participants. Results: Of the 200 participants who completed the survey, 42% reported currently having goals for MDD treatment. These goals were typically in the areas of physical health (62.7%), cognitive functioning (60.2%), and social aspects of life (57.8%). A majority of survey participants (61%) believed the goal attainment approach would be helpful to set and evaluate treatment goals. Conclusions: The data provide important insights into patient perspectives on the development of formal treatment plans and goals for MDD. In addition, the data also support the use of a patient-centric approach to shared decision-making by using a goal attainment scale to establish and track progress toward treatment goals that are meaningful to MDD patients in real-world clinical practice. The results of this study can be used to inform best practices in patient-clinician communication when developing an MDD treatment plan and goals.

Effects of different nanoparticles (NPs) exposure at acutely non-cytotoxic concentrations are particularly worthy to figure out, compare, and elucidate.

Purpose: Post-stroke depression (PSD) is a psychiatric complication after stroke that leads to poorer stroke outcomes. Recent observational studies have indicated that lipid profiles were associated with a higher risk of stroke and depression. This study aims to further explore the possible relationship between serum lipid profiles and the development of PSD. Methods: A total of 373 acute ischemic stroke patients were examined. Serum lipid profiles including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), total cholesterol (TC), apolipoprotein A1 (Apo A1) and apolipoprotein B (Apo B) were measured within 24 hrs of admission. Depression symptoms were assessed by the 17-item Hamilton Depression Scale (HAMD-17) at the one-month follow-up, and HAMD scores ≥7 indicated a diagnosis of PSD. Results: A total of 114 patients were diagnosed with PSD at the one-month follow-up, for a percentage of 30.6%. There were significant differences in HDL-C levels (P<0.001), LDL-C levels (P=0.002) and the LDL/HDL ratio (P<0.001) between the PSD and non-PSD groups, but no differences were observed in TGs, TC, Apo A1 or Apo B. Low serum HDL-C levels (r = -0.157, P<0.001) and elevated LDL-C levels (r =0.139, P=0.002) and the LDL/HDL ratio (r =0.227, P<0.001) were associated with HAMD scores. After adjusting for the NIHSS score, BI score, mRS score and alcohol consumption in the logistic analysis, low HDL-C levels and the highest quartile (≥3.07) of the LDL/HDL ratio were independently associated with the development of PSD (OR =0.250, 95% CI, 0.077-0.813, P=0.021 and OR =1.874, 95% CI, 1.050-3.347, P=0.034, respectively). Conclusion: Decreased levels of HDL-C and elevated levels of LDL/HDL ratio are associated with PSD. HDL-C and the LDL/HDL ratio are independent predictors of PSD.

Purpose: The purpose of the current study was to evaluate the effectiveness of ultrasound-guided percutaneous carpal tunnel release in hemodialysis patients with carpal tunnel syndrome. Methods: From February 2009 to April 2013, a prospective review of 113 consecutive cases of ultrasound-guided percutaneous carpal tunnel release was carried out in 84 hemodialysis patients. Results were analyzed by clinical subjective scale, two self-administered questionnaires, and functional evaluations at seven time points (1 week and 1, 3, 6, 12, 18, and 24 months). Results: Satisfactory symptom improvement in patients was 82%, 80%, 86%, 89%, 90%, 91%, and 90% at 1 week and 1, 3, 6, 12, 18, and 24 months postoperatively, respectively. Moderate pain was suffered in 11.5% of patients within 1 week, 8.8% within 1 month, 2.7% within 3 months, and none after 12 months postoperatively. Static two-point discrimination and Semmes-Weinstein monofilament examinations presented significant improvements after 1 week and 1 month postoperatively and with time. Postoperative grip power demonstrated recovery and a significant increase after 3 and 6 months postoperatively. Three-jaw chuck-pinch strength showed significant increase after 1 month postoperatively. There were no operative complications. Conclusion: Ultrasound-guided percutaneous carpal tunnel release is an effective and safe procedure in hemodialysis patients with carpal tunnel syndrome. The advantages include a less invasive procedure, no tourniquet needed, only limited infiltration anesthesia, minimal soft-tissue exploration, and relatively short operation time. Our data suggest this technique can reliably relieve clinical symptoms, with early restoration of grip and pinch strength.

Objective: The soluble cluster of differentiation 14 subtype (sCD14-ST) or presepsin has recently been identified as a promising biomarker in sepsis. The present meta-analysis is performed to assess the prognostic value of presepsin in septic patients. Further, we compare the prognostic performance between presepsin and procalcitonin (PCT) in predicting all-cause mortality in these patients. Methods: A systemic and comprehensive search was conducted in PubMed, Embase and Cochrane databases by using Exploded Medical Subject Headings and appropriate corresponding keywords. Studies were eligible if they assessed the prognostic value of presepsin in sepsis and provided sufficient information to construct a 2×2 contingency table. A bivariate meta-analysis model was used to calculate the pooled sensitivity, specificity, positive/negative likelihood ratios and diagnostic odds ratio. The Chi-square and I 2 index were used to assess the heterogeneity and inconsistency. The Deek's funnel plot asymmetry test was used to assess the likelihood of publication bias. Results: Nine publications, comprising 1,561 patients, were included in this study. The overall area under the receiver operating characteristic curve (AUROC) of presepsin was 0.77 (95% CI, 0.73-0.81) with a pooled prognostic sensitivity (SEN) and specificity (SPE) of 0.83 (95% CI, 0.72-0.90) and 0.69 (95% CI, 0.63-0.74), respectively. Additionally, the PLR, NLR and DOR of presepsin were 2.6 (95% CI, 2.1-3.3), 0.25 (95% CI, 0.15-0.44) and 10 (95% CI, 5-22), respectively. The AUROC of PCT was 0.81 (95% CI, 0.78-0.84) with a pooled SEN of 0.76 (95% CI, 0.55-0.89) and SPE of 0.74 (95% CI, 0.33-0.94). There is no statistically significant difference in the performance of pooled SEN and SPE between presepsin and PCT, with a p value of 0.39 and 0.71, respectively. Conclusions: Based on the results of this meta-analysis, both presepsin and PCT are promising biomarkers for the prognosis of mortality in sepsis.

Purpose: It has been reported that miRNA-124 inhibits hepatocellular carcinoma (HCC) progression, while lncRNA-UCA1 promotes HCC. The aim of this study is to find whether miRNA-124, as a tumor suppressor in HCC can inhibit lncRNA-UCA1 in HCC cell. Methods: Tumor tissues and adjacent healthy tissues were obtained from 66 patients diagnosed with HCC in Binzhou Medical University Hospital from January 2011 to January 2013. Cell proliferation assay, in vitro cell migration and invasion assay were applied for the research. Results: In the present study we found that miRNA-124 was downregulated, while lncRNA-UCA1 was upregulated in tumor tissues comparing to adjacent healthy tissues of HCC patients. Expression of miRNA-124 and lncRNA-UCA1 in tumor tissues were not affected by HBV or HCV infection. Analysis of followed-up data revealed that low miRNA-124 level and high lncRNA-UCA1 level were closely correlated with poor survival. Overexpression of miRNA-124 led to inhibited lncRNA-UCA1 expression in cells of HCC cell lines, while overexpression of lncRNA-UCA1 failed to significantly affect miRNA-124 expression. Expression levels of miRNA-124 and lncRNA-UCA1 were inversely and significantly correlated in tumor tissues but not in adjacent healthy tissues. Overexpression of miRNA-124 led to inhibited, while overexpression of lncRNA-UCA1 led to increased proliferation, migration and invasion rates of HCC cell lines. In addition, lncRNA-UCA1 overexpression attenuated the inhibitory effects of miRNA-124 overexpression on cancer cell proliferation, migration and invasion. Conclusion: Therefore, miRNA-124 may inhibit the proliferation, migration and invasion of cancer cell in hepatocellular carcinoma by downregulating lncRNA-UCA1.

Objective: Ciprofloxacin resistance (CIPR) for Shigella isolates is becoming more prevalent. This study systematically investigated the antibacterial activity of ciprofloxacin (CIP)/fosfomycin (FOS) combination in vitro and in vivo against CIPR S. flexneri isolates. Method: Eighty CIPR S. flexneri isolates were selected for synergy studies by the microtiter plate checkerboard assay. Two S. flexneri isolates (GN120471, CIPRFOSR; GN120454, CIPRFOSS) were used to investigate the efficacy of the CIP/FOS combination by the time-kill methodology. Clinically relevant concentrations (CIP, 0.5, 1, or 2.5 μg/mL; FOS, 30, 150, or 300 μg/mL) were combined, and the colony counts were conducted at 3, 5, 8, and 24 hours. The in vivo activity of the CIP/FOS combination was assessed using a Galleria mellonella larvae model. Results: In checkerboard assays, 31 strains (38.75%) showed synergy for the CIP/FOS combination. For the isolate GN120471, monotherapy with CIP or FOS at all concentrations produced little or no bacterial killing, while the CIP/FOS combination produced enhanced bacterial killing with FOS concentrations of 150 and 300 μg/mL, especially when combined with CIP at 2.5 μg/mL. For the isolate GN120454, the CIP/FOS combination at all concentrations produced more rapid and extensive killing (up to 5log10 colony forming units (CFU)/mL with many combinations) than with either antibiotic alone. Mortality at 96 hours was around 80% at approximately 104 CFU/larva for GN120471 and GN120454. When CIP at 2.5 μg/mL was combined with FOS at 150 μg/mL for the bactericidal activity in vivo, the survival rates for CIP/FOS combination against GN120471-infected and GN120454-infected larvae were significantly higher than that of CIP (68.75% vs 25%, P=0.013; 81.25% vs 37.5%, P=0.012, respectively). Conclusion: Against CIPR S. flexneri isolates, the CIP/FOS combination induced synergy, and increased bacterial killing in vitro and in a simple invertebrate model of infection.

Purpose: To date, increasing evidences have demonstrated that the aberrant expression of miR-371-3 cluster has been verified in various cancers and could be potentially used as a biomarker for tumor diagnosis and prognosis. To explore the role of miR-371-3 cluster in tumor diagnosis and prognosis, we conducted this study based on the published data. Methods: We searched electronic databases (PubMed, EMBASE and Web of Science databases) (Jan 1, 2007 to Jun 1, 2018). The pooled sensitivity, specificity and area under the curve (AUC) of summary receiver operator characteristic (SROC) curve were used for diagnostic values, meanwhile the pooled hazard ration (HR) and 95% CI were used to explore the prognosis capacity of miR-372 and miR-373. In addition, the publication bias of the enrolled studies was tested and a sensitivity analysis of each study was performed to evaluate the stability of the pooled result. Results: A total of eleven eligible studies containing six eligible studies containing 870 participants for diagnosis and 1218 cancer cases for prognosis were selected for this study. For diagnosis, the pooled results revealed that the miR-371 (sensitivity: 0.85, specificity: 0.92, AUC: 0.92) and miR-373 (sensitivity: 0.81, specificity: 0.93, AUC: 0.93) could be used as diagnostic biomarkers. For prognosis, we observed that elevated miR-372 indicated poor prognosis (HR=2.31, 95% CI: 1.04-5.14), especially in the cutoff value subgroup of median (HR=2.62, 95% CI: 1.54-4.46). In addition, pooled results showed that expression of miR-373 was not related to prognosis because of the significant heterogeneity, and the high miR-373 expression presented favorable prognosis in Asians (HR=0.34, 95% CI: 0.23-0.50) after omitting the study of heterogeneity origin. Conclusion: The current studies demonstrated that miR-371 and miR-373 could be predictive tumor diagnostic biomarkers and the expression of miR-372 and miR-373 may indicate prognosis of cancer patients.

Background: Large-cell lung carcinomas (LCLCs) were reclassified by the World Health Organization 2015 criteria. and remain fairly unknown at the molecular level and targeted-therapeutic options. Methods: Data of 184 lung cancer patients were retrieved from clinical records, of which 54 were found to be pathologically diagnosed as LCLC. The genetic alterations EGFR/KRAS/BRAF mutations, MET copy number, and exon 14 mutation, ALK and ROS1 rearrangements, and PDL1 expression were investigated using clinical technologies. The relationship between clinicopathologic and genetic features was analyzed, and the Kaplan-Meier method with log-rank test was used for analyzing patient survival. Results: Major events, including EGFR, KRAS, and BRAF mutations and MET copy-number gain, were found in 5.6%, 16.7%, 1.9%, and 18.5% in LCLC, respectively. No ALK or ROS1 translocation was detected. PDL1 expression in tumor cells and in tumor-infiltrating lymphocytes was observed in 24 (44.4%) and 16 (29.6%) patients. Kaplan-Meier analysis showed that patients with a KRAS mutation had ower 5-year overall survival than those with wild-type KRAS (25.4% vs 47.8%, P=0.028) and that patients with negative PDL1 stained in tumor cells but positive for tumor-infiltrating lymphocytes had significantly favorable overall survival compared to those with solitary and positive PDL1 stained in tumor cells (62.5% vs 20.6%, P=0.044). Conclusion: KRAS mutations and PDL1 expression can predict patient survival and be potential target options in LCLC.