Association between immune-related hub genes CD36, CXCL13, FGFR4, GABBR1, LAMP3, MMP12, and PPM1H and colorectal cancer prognosis.

The present study aims to identify immune-related prognostic genes in colorectal cancer (CRC), and to explore potential mechanisms through which these genes regulate CRC progression. We first constructed a prognostic risk model based on seven gene signatures [cluster of differentiation-36 (CD36), chemokine (C-X-C-motif) ligand 13 (CXCL13), fibroblast growth factor receptor 4 (FGFR4), gamma-amino-butyric acid type B receptor 1 (GABBR1), lysosome-associated membrane glycoprotein 3 (LAMP3), recombinant matrix metalloproteinase 12 (MMP12), and protein phosphatase 1H (PPM1H)] using integrated bioinformatic analyses. FGFR4, GABBR1, and LAMP3 were highly expressed in CRC cell lines (in comparison with a normal colonic epithelial cell line), while CD36, CXCL13, MMP12, and PPM1H were weakly expressed. These in vitro expression results were largely consistent with our bioinformatic analysis. A prognostic model was generated to identify a high-risk group with worse survival outcome based on Kaplan-Meier analysis. Our prognostic model showed superior accuracy in both the training and test cohorts. In addition, we found that the low-risk subgroup exhibited greater infiltration by M1 macrophages, CD8+ T cells, CD4+ T cells, and activated NK cells. In conclusion, our findings provide evidence that seven immune-related hub genes can be considered as gene signatures to predict CRC prognosis and to differentiate CRC patient benefit, ultimately serving as a guide for individualized immunotherapy.

Proteomic study on nintedanib in gastric cancer cells.

Background: Gastric cancer is a very common gastrointestinal tumor with a high mortality rate. Nintedanib has been shown to significantly reduce tumor cell proliferation and increase apoptosis in gastric cancer cells in vitro. However, its systemic action mechanism on gastric cancer cells remains unclear. A high-throughput proteomic approach should help identify the potential mechanisms and targets of nintedanib on gastric cancer cells. Methods: The effects of nintedanib on the biological behavior of gastric cancer cells were evaluated. A cytotoxic proliferation assay was performed to estimate the half maximal inhibitory concentration (IC50). AGS cells were divided into control, and nintedanib-treated groups (5 µM, 48 h), and differential protein expression was investigated using tandem mass tags (TMT) proteomics. The molecular mechanisms of these differentially expressed proteins and their network interactions were then analyzed using bioinformatics, and potential nintedanib targets were identified. Results: This study identified 845 differentially expressed proteins in the nintedanib-treated group (compared to the control group), comprising 526 up-regulated and 319 down-regulated proteins. Bioinformatics analysis revealed that the differentially expressed proteins were primarily enriched in biological pathways for branched-chain amino acid metabolism, steroid biosynthesis, propionate metabolism, fatty acid metabolism, lysosome, peroxisome, and ferroptosis. Key driver analysis revealed that proteins, such as enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH), isocitrate dehydrogenase 1 (IDH1), acyl-CoA oxidase 1 (ACOX1), acyl-CoA oxidase 2 (ACOX2), acyl-CoA oxidase 3 (ACOX3), and acetyl-CoA acyltransferase 1 (ACAA1) could be linked with nintedanib action. Conclusion: Nintedanib inhibits the proliferation, invasion, and metastasis of gastric cancer cells. The crossover pathways and protein networks predicted by proteomics should provide more detailed molecular information enabling the use of nintedanib against gastric cancer.

Deubiquitinase USP1 regulates sarbecovirus ORF6 protein function.

SARS-CoV-2 belongs to the subgenus Sarbecovirus, which universally encodes the accessory protein ORF6. SARS-CoV-2 ORF6 is an antagonist of the interferon (IFN)-mediated antiviral response and plays an important role in viral infections. However, the mechanism by which the host counteracts the function of ORF6 to restrict viral replication remains unclear. In this study, we found that most ORF6 proteins encoded by sarbecoviruses could be ubiquitinated and subsequently degraded via the proteasome pathway. Through extensive screening, we identified that the deubiquitinase USP1, which effectively and broadly deubiquitinates sarbecovirus ORF6 proteins, stabilizes ORF6 proteins, resulting in enhanced viral replication. Therefore, ubiquitination and deubiquitination of ORF6 are important for antagonizing IFN-mediated antiviral signaling and influencing the virulence of SARS-CoV-2. These findings highlight an essential molecular mechanism and may provide a novel target for therapeutic interventions against viral infections.IMPORTANCEThe ORF6 proteins encoded by sarbecoviruses are essential for effective viral replication and infection and are important targets for developing effective intervention strategies. In this study, we confirmed that sarbecovirus ORF6 proteins are important antagonists of the host immune response and identified the regulatory mechanisms of ubiquitination and deubiquitination of most sarbecovirus ORF6 proteins. Moreover, we revealed that DUB USP1 prevents the proteasomal degradation of all ORF6 proteins, thereby promoting the virulence of SARS-CoV-2. Thus, impeding ORF6 function is helpful for attenuating the virulence of sarbecoviruses. Therefore, our findings provide a deeper understanding of the molecular mechanisms underlying sarbecovirus infections and offer potential new therapeutic targets for the prevention and treatment of these infections.

Chiral hybrid waveguide-plasmon resonances.

We investigate the chiroptical responses of the hybrid systems consisting of metal-insulator-metal (MIM) gammadion arrays on top of a dielectric slab waveguide. We demonstrate that both the transverse magnetic (TM) and transverse electric (TE) waveguide modes could be coupled to the antisymmetric localized surface plasmon resonances (LSPRs) of the individual MIM-gammadions, leading to the formation of narrow hybrid waveguide-plasmon resonances (WPRs), of which the TM-WPR is less dependent while the TE-WPR is highly dependent on the handedness of the incident light. Associated with the excitation of the TE-WPRs, strong negative and positive circular dichroism (CD) peaks with high quality factors could be obtained on the short-wavelength and long-wavelength side of the LSPRs of the MIM-gammadion, respectively. Moreover, we show that the variation on either the lattice period or slab waveguide thickness allows for easily tuning the TE-WPRs based CD peaks over a relative wide spectral range. Our proposed hybrid system provides tunable and strong CD responses with narrow linewidth, which may have applications in chiral selective imaging, chiral plasmonic bio-sensing and spectroscopy.

Deubiquitinase ubiquitin-specific protease 3 (USP3) inhibits HIV-1 replication via promoting APOBEC3G (A3G) expression in both enzyme activity-dependent and -independent manners.

BACKGROUND: Ubiquitination plays an essential role in many biological processes, including viral infection, and can be reversed by deubiquitinating enzymes (DUBs). Although some studies discovered that DUBs inhibit or enhance viral infection by various mechanisms, there is lack of information on the role of DUBs in virus regulation, which needs to be further investigated. METHODS: Immunoblotting, real-time polymerase chain reaction, in vivo / in vitro deubiquitination, protein immunoprecipitation, immunofluorescence, and co-localization biological techniques were employed to examine the effect of ubiquitin-specific protease 3 (USP3) on APOBEC3G (A3G) stability and human immunodeficiency virus (HIV) replication. To analyse the relationship between USP3 and HIV disease progression, we recruited 20 HIV-infected patients to detect the levels of USP3 and A3G in peripheral blood and analysed their correlation with CD4 + T-cell counts. Correlation was estimated by Pearson correlation coefficients (for parametric data). RESULTS: The results demonstrated that USP3 specifically inhibits HIV-1 replication in an A3G-dependent manner. Further investigation found that USP3 stabilized 90% to 95% of A3G expression by deubiquitinating Vif-mediated polyubiquitination and blocking its degradation in an enzyme-dependent manner. It also enhances the A3G messenger RNA (mRNA) level by binding to A3G mRNA and stabilizing it in an enzyme-independent manner. Moreover, USP3 expression was positively correlated with A3G expression ( r  = 0.5110) and CD4 + T-cell counts ( r  = 0.5083) in HIV-1-infected patients. CONCLUSIONS: USP3 restricts HIV-1 viral infections by increasing the expression of the antiviral factor A3G. Therefore, USP3 may be an important target for drug development and serve as a novel therapeutic strategy against viral infections.

Comparison between laparoscopic uncut Roux-en-Y and Billroth II with Braun anastomosis after distal gastrectomy: A meta-analysis.

BACKGROUND: Conventional Billroth II (BII) anastomosis after laparoscopic distal gastrectomy (LDG) for gastric cancer (GC) is associated with bile reflux gastritis, and Roux-en-Y anastomosis is associated with Roux-Y stasis syndrome (RSS). The uncut Roux-en-Y (URY) gastrojejunostomy reduces these complications by blocking the entry of bile and pancreatic juice into the residual stomach and preserving the impulse originating from the duodenum, while BII with Braun (BB) anastomosis reduces the postoperative biliary reflux without RSS. Therefore, the purpose of this study was to compare the efficacy and safety of laparoscopic URY with BB anastomosis in patients with GC who underwent radical distal gastrectomy. AIM: To evaluate the value of URY in patients with GC. METHODS: PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, Chinese Biomedical Database, and VIP Database for Chinese Technical Periodicals (VIP) were used to search relevant studies published from January 1994 to August 18, 2021. The following databases were also used in our search: Clinicaltrials.gov, Data Archiving and Networked Services, the World Health Organization International Clinical Trials Registry Platform Search Portal (https://www.who.int/clinical-trials-registry-platform/the-ictrp-search-portal), the reference lists of articles and relevant conference proceedings in August 2021. In addition, we conducted a relevant search by Reference Citation Analysis (RCA) (https://www.referencecitationanalysis.com). We cited high-quality references using its results analysis functionality. The methodological quality of the eligible randomized clinical trials (RCTs) was evaluated using the Cochrane Risk of Bias Tool, and the non-RCTs were evaluated using the Newcastle-Ottawa scale. Statistical analyses were performed using Review Manager (Version 5.4). RESULTS: Eight studies involving 704 patients were included in this meta-analysis. The incidence of reflux gastritis [odds ratio = 0.07, 95% confidence interval (CI): 0.03-0.19, P < 0.00001] was significantly lower in the URY group than in the BB group. The pH of the postoperative gastric fluid was lower in the URY group than in the BB group at 1 d [mean difference (MD) = -2.03, 95%CI: (-2.73)-(-1.32), P < 0.00001] and 3 d [MD = -2.03, 95%CI: (-2.57)-(-2.03), P < 0.00001] after the operation. However, no significant difference in all the intraoperative outcomes was found between the two groups. CONCLUSION: This work suggests that URY is superior to BB in gastrointestinal reconstruction after LDG when considering postoperative outcomes.

The Deubiquitinase USP29 Promotes SARS-CoV-2 Virulence by Preventing Proteasome Degradation of ORF9b.

Ubiquitin signaling is essential for immunity to restrict pathogen proliferation. Due to its enormous impact on human health and the global economy, intensive efforts have been invested in studying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its interactions with hosts. However, the role of the ubiquitin network in pathogenicity has not yet been explored. Here, we found that ORF9b of SARS-CoV-2 is ubiquitinated on Lys-4 and Lys-40 by unknown E3 ubiquitin ligases and is degraded by the ubiquitin proteasomal system. Importantly, we identified USP29 as a host factor that prevents ORF9b ubiquitination and subsequent degradation. USP29 interacts with the carboxyl end of ORF9b and removes ubiquitin chains from the protein, thereby inhibiting type I interferon (IFN) induction and NF-κB activation. We also found that ORF9b stabilization by USP29 enhanced the virulence of VSV-eGFP and transcription and replication-competent SARS-CoV-2 virus-like-particles (trVLP). Moreover, we observed that the mRNA level of USP29 in SARS-CoV-2 patients was higher than that in healthy people. Our findings provide important evidence indicating that targeting USP29 may effectively combat SARS-CoV-2 infection. IMPORTANCE Coronavirus disease 2019 (COVID-19) is a current global health threat caused by SARS-CoV-2. The innate immune response such as type I IFN (IFN-I) is the first line of host defense against viral infections, whereas SARS-CoV-2 proteins antagonize IFN-I production through distinct mechanisms. Among them, ORF9b inhibits the canonical IκB kinase alpha (IKKɑ)/ß/γ-NF-κB signaling and subsequent IFN production; therefore, discovering the regulation of ORF9b by the host might help develop a novel antiviral strategy. Posttranslational modification of proteins by ubiquitination regulates many biological processes, including viral infections. Here, we report that ORF9b is ubiquitinated and degraded through the proteasome pathway, whereas deubiquitinase USP29 deubiquitinates ORF9b and prevents its degradation, resulting in the enhancement of ORF9b-mediated inhibition of IFN-I and NF-κB activation and the enhancement of virulence of VSV-eGFP and SARS-CoV-2 trVLP.

[Palmitic acid induces inflammation and transdifferentiation by activating cGAS/STING pathway in human renal tubular epithelial cells].

Objective To investigate the molecular mechanism of palmitic acid (PA) inducing inflammation and epithelial to mesenchymal transdifferentiation (EMT) in human renal tubular epithelial cells (RTECs). Methods The cell lipid accumulation model was prepared by RTECs and the cells were divided into blank control group, bovine serum albumin (BSA) group, PA group, and PA combined with stimulator of interferon genes (STING) specific inhibitor H151 group. The lipid accumulation of RTECs were detected by oil red O staining. Real-time quantitative PCR was used to detect the mRNA levels of interleukin 6 (IL-6), IL-8, transforming growth factor ß1 (TGF-ß1), and type 1 collagen alpha 1 chain (COL1A1) in RTECs. The protein expressions of STING, nuclear factor-κB p65 (NF-κB p65), phosphorylated NF-κB p65 (p-NF-κB p65), TGF-ß1, and type 1 collagen (Col1) were detected by Western blot and the expression and distribution of Col1 in RETCs were detected by immunofluorescence chemical staining. Results Compared with the control group, PA stimulated the lipid deposition, the expression of STING, and the phosphorylation of NF-κB p65 obviously, up-regulated the mRNA levels of IL-6, IL-8, TGF-ß1, and COL1A1 significantly, increased the protein expressions of TGF-ß1 and Col1 and the distribution of Col1 in RTECs; compared with those in the PA group, after H151 treatment, the expression of STING and the phosphorylation of NF-κB p65 decreased notably, the mRNA levels of IL-6, IL-8, TGF-ß1, and COL1A1 were down-regulated dramatically, and the protein expressions of TGF-ß1 and Col1 declined with reduced distribution of Col1. Conclusion PA induces lipid deposition, activated the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)/STING pathway, and caused inflammation and EMT in RTECs.

Identification of IMPA2 as the hub gene associated with colorectal cancer and liver metastasis by integrated bioinformatics analysis.

BACKGROUND AND OBJECTIVES: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide with high incidence and mortality rate, while colorectal liver metastasis (CRLM) is one of the major causes of cancer-related deaths. Therefore, the present study aims to identify the hub gene associated with CRC carcinogenesis and liver metastasis, and then explore its diagnostic and prognostic value as well as the potential regulation mechanism. METHODS: The overlapping differential co-expression genes among CRC, CRLM, and normal tissues were explored on the GSE49355 and GSE81582 datasets from the Gene Expression Omnibus (GEO) database by integrated bioinformatics analysis. Then, the hub prognostic genes were selected from the overlapping genes by univariate Cox proportional hazard analysis and online database Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Subsequently, the clinical value of the hub genes was evaluated in the TCGA and GSE39582 cohorts. Finally, the underlying mechanisms of the hub gene regulating CRC carcinogenesis and metastasis were explored by Gene function annotation and DNA methylation analysis. RESULTS: Inositol mono-phosphatase 2 (IMPA2) was identified as the hub gene associated with CRC carcinogenesis and liver metastasis. IMPA2 had an excellent diagnostic efficiency, and its expression was significantly decreased in CRC and liver metastasis samples, being positively correlated with poor prognosis. Moreover, its low expression was associated with AJCC stage III+IV, T4, N1+2, and M1. In addition, our results revealed that the potential mechanisms used by IMPA2 to mediate CRC carcinogenesis and metastasis could be associated with lipid metabolism and epithelial mesenchymal transition (EMT). Finally, IMPA2 expression could be regulated by DNA methylation. CONCLUSIONS: IMPA2 was identified and reported for the first time as a hub gene biomarker in the diagnosis and prognosis of CRC, which could regulate CRC carcinogenesis and liver metastasis through the regulation of lipid metabolism, EMT, and DNA methylation.

Synthesis and Characterization of Salinomycin-Loaded High-Density Lipoprotein and Its Effects on Cervical Cancer Cells and Cervical Cancer Stem Cells.

BACKGROUND: Cervical cancer stem cells (CCSCs), a small part of tumor population, are one of the important reasons for metastasis and recurrence of cervical cancer. Targeting CCSCs may be an effective way to eliminate tumors. Salinomycin (Sal) has been proved to be an effective anticancer drug in many studies, especially for cancer stem cells (CSCs). However, the cytotoxicity of salinomycin limits its further research as an anticancer drug. High-density lipoprotein (HDL) nanoparticles are an excellent drug carrier, which can reduce the toxicity of Sal, have a certain targeting effect and improve the clinical benefit of Sal. METHODS: Salinomycin-loaded high-density lipoprotein (S-HDL) was synthesized and characterized by various analytical techniques. CD44highCD24low CCSCs were isolated from HeLa cells by magnetic separation. The uptake of HDL nanoparticles was observed by laser confocal microscopy, and the effect of S-HDL on the proliferation of CCCs and CCSCs was detected by cell viability analysis. Genome-wide analysis was used to analyze the effects of S-HDL on the biological processes of CCCs and then cell apoptosis, cell cycle and cell migration were selected for verification. RESULTS: S-HDL had a particle size of 38.98 ± 1.78 nm and an encapsulation efficiency of 50.73 ± 4.29%. Cell uptake analysis showed that HDL nanoparticles could enhance the drug uptake of CCCs and CCSCs and may target CCCs and CCSCs. In cell viability analysis, CCCs and CCSCs showed high sensitivity to S-HDL. S-HDL can more efficiently prevent CCSCs from developing tumorspheres than Sal in tumorsphere formation study. S-HDL had stronger ability to induce cell cycle arrest, promote cell apoptosis and inhibit cell migration compared with free Sal, which was consistent with the results of Genome Wide analysis. CONCLUSION: S-HDL can effectively target and eliminate CCCs and CCSCs, which is a potential drug for the treatment of cervical cancer.

The Molecular Mechanism of Multiple Organ Dysfunction and Targeted Intervention of COVID-19 Based on Time-Order Transcriptomic Analysis.

Coronavirus disease 2019 (COVID-19) pandemic is caused by the novel coronavirus that has spread rapidly around the world, leading to high mortality because of multiple organ dysfunction; however, its underlying molecular mechanism is unknown. To determine the molecular mechanism of multiple organ dysfunction, a bioinformatics analysis method based on a time-order gene co-expression network (TO-GCN) was performed. First, gene expression profiles were downloaded from the gene expression omnibus database (GSE161200), and a TO-GCN was constructed using the breadth-first search (BFS) algorithm to infer the pattern of changes in the different organs over time. Second, Gene Ontology enrichment analysis was used to analyze the main biological processes related to COVID-19. The initial gene modules for the immune response of different organs were defined as the research object. The STRING database was used to construct a protein-protein interaction network of immune genes in different organs. The PageRank algorithm was used to identify five hub genes in each organ. Finally, the Comparative Toxicogenomics Database played an important role in exploring the potential compounds that target the hub genes. The results showed that there were two types of biological processes: the body's stress response and cell-mediated immune response involving the lung, trachea, and olfactory bulb (olf) after being infected by COVID-19. However, a unique biological process related to the stress response is the regulation of neuronal signals in the brain. The stress response was heterogeneous among different organs. In the lung, the regulation of DNA morphology, angiogenesis, and mitochondrial-related energy metabolism are specific biological processes related to the stress response. In particular, an effect on tracheal stress response was made by the regulation of protein metabolism and rRNA metabolism-related biological processes, as biological processes. In the olf, the distinctive stress responses consist of neural signal transmission and brain behavior. In addition, myeloid leukocyte activation and myeloid leukocyte-mediated immunity in response to COVID-19 can lead to a cytokine storm. Immune genes such as SRC, RHOA, CD40LG, CSF1, TNFRSF1A, FCER1G, ICAM1, LAT, LCN2, PLAU, CXCL10, ICAM1, CD40, IRF7, and B2M were predicted to be the hub genes in the cytokine storm. Furthermore, we inferred that resveratrol, acetaminophen, dexamethasone, estradiol, statins, curcumin, and other compounds are potential target drugs in the treatment of COVID-19.

Development and validation of prognostic model based on the analysis of autophagy-related genes in colon cancer.

BACKGROUND: Autophagy, a process of self-digestion, is closely related to multiple biological processes of colon cancer. This study aimed to construct and evaluate prognostic signature of autophagy-related genes (ARGs) to predict overall survival (OS) in colon cancer patients. MATERIALS AND METHODS: First, a total of 234 ARGs were downloaded via The Cancer Genome Atlas (TCGA) database. Based on the TCGA dataset, differentially expressed ARGs were identified in colon cancer. The univariate and multivariate Cox regression analysis was performed to screen prognostic ARGs to construct the prognostic model. The feasibility of the prognostic model was evaluated using receiver operating characteristic curves and Kaplan-Meier curves. A prognostic model integrating the gene signature with clinical parameters was established with a nomogram. RESULTS: We developed an autophagy risk signature based on the 6 ARGs (ULK3, ATG101, MAP1LC3C, TSC1, DAPK1, and SERPINA1). The risk score was positively correlated with poor outcome and could independently predict prognosis. Furthermore, the autophagy-related signature could effectively reflect the levels of immune cell type fractions and indicate an immunosuppressive microenvironment. CONCLUSION: We innovatively identified and validated 6 autophagy-related gene signature that can independently predict prognosis and reflect overall immune response intensity in the colon cancer microenvironment.

Evaluation of intra- and post-operative outcomes to compare robot-assisted surgery and conventional laparoscopy for gynecologic oncology.

OBJECTIVE: To compare robot-assisted surgery and conventional laparoscopy for gynecologic oncology regarding intra- and post-operative outcomes. METHODS: A retrospective study was performed on consecutive patients with gynecologic oncology from February 2014 to October 2017 at Gansu Provincial Hospital, China. Multivariable linear and logistic regression models were performed to explore the difference between two surgeries in the surgical outcomes after adjusting for potential confounders. RESULTS: 276 women were included in this study: 153 robot-assisted surgeries and 123 conventional laparoscopies. The multivariable linear regression model showed that robot-assisted surgery was longer operative time [coefficient (coef), 33.76; 95% CI, 12.47, 55.05; P = 0.002) ], higher lymph node yield (coef, 10.41; 95% CI, 7.47, 13.35; P < 0.001), shorter time to early post-operative feeding (coef, -1.09; 95% CI, -1.33, -0.84; P < 0.001) and less post-operative drainage volume (coef, -368.77; 95% CI, -542.46, -195.09; P < 0.001) than conventional laparoscopy. However, no difference was observed between the two surgeries regarding the estimated blood loss (P > 0.05). The multivariable logistic regression model showed that post-operative complications were similar between robot-assisted surgery and conventional laparoscopy (P > 0.05). CONCLUSION: Robot-assisted surgery was superior to conventional laparoscopy regarding intra- and post-operative outcomes for gynecologic oncology.

Long noncoding RNA NORAD regulates MPP+-induced Parkinson's disease model cells.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been demonstrated to play important roles in human diseases. Yet, the functions of lncRNAs in neurodegenerative disorders, such as Parkinson's disease (PD) are poorly understood. In this study, we used human neuroblastoma SH-SY5Y cell line as a cell-basedin vitro PD model, and investigated the role of lncRNA, Non-Coding RNA Activated By DNA Damage (NORAD) in 1-methyl-4-phenylpyridinium (MPP+)-induced PD-like cytotoxicity. METHODS: SH-SY5Y cells were culturedin vitro, and treated with MPP + at various concentrations, or of various durations of times to induce PD-like cytotoxic events. qRT-PCR was used to measure MPP+-induced NORAD expression changes. Lentiviral transduction was applied to stably upregulate or downregulate NORAD in SH-SY5Y cells. The effects of NORAD upregulation or downregulation on MPP+-induced cytotoxic events, including dose-dependent and time-dependent cell death, apoptosis, caspase 3/7, reactive Oxygen Species (ROS) and lactate dehydrogenase (LDH) activities, were quantitatively investigated. RESULTS: MPP + induced cytotoxicity, and downregulated NORAD in both dose- and time- dependent manners in SH-SY5Y cells. Lentiviral-induced NORAD upregulation was found to protect against MPP+-induced cytotoxicity in SH-SY5Y cells, as it rescued MPP+-induced cellular destruction and apoptosis, as well as decreased MPP+-induced caspase 3/7, ROS and LDH activities. Alternatively, NORAD downregulation was found to significantly deteriorate MPP+-induced cytotoxicity in SH-SY5Y cells. CONCLUSION: We presented a novel functional role of lncRNA NORAD in regulating human Parkinson's disease.

Safety and effectiveness of robotic hysterectomy versus conventional laparoscopic hysterectomy in patients with cervical cancer in China.

OBJECTIVE: The aim of this study was to compare the safety and effectiveness of robotic hysterectomy (RH) with conventional laparoscopic hysterectomy (LH) for the treatment of cervical cancer using multivariate regressions. METHODS: We designed a retrospective single-center study and consecutively collected patients with cervical cancer from February 2014 to October 2017. Data extraction was performed by two independent researchers. The surgical outcomes include operative time, estimated blood loss, number of lymph nodes, time to first flatus, time to a full diet, time to remove drainage tube, length of hospital stay, and postoperative complication. RESULTS: A total of 152 patients with cervical cancer were collected in our study including 92 patients who underwent RH and 60 patients who underwent LH. Both groups have similar characteristics. The RH group showed shorter operative time (Coe - 42.89; 95% CI - 74.39 to 11.39; P = 0.008) and more number of lymph nodes (Coe 6.06; 95% CI 2.46-9.66; p = 0.001) than the LH group. As for the postoperative parameters, the RH group showed shorter time to remove drainage tube (Coe - 0.89; 95% CI -1.62 to -0.15; p = 0.019) and length of hospital stay (Coe - 6.40; 95% CI - 10.19 to - 2.95; p = 0.001). No significant difference was found between the groups in estimated blood loss (Coe 34.64; 95% CI - 33.08 to 102.37; p = 0.314), time to first flatus (Coe 0.11; 95% CI - 0.38 to 0.61; p = 0.652), time to a full diet (Coe - 0.24; 95% CI - 0.54 to 0.06, p = 0.118), and postoperative complication (OR 0.84; 95% CI 0.35-1.98; p = 0.685). CONCLUSION: The results from this study suggest that RH is safe and effective as LH but robotic surgery significantly contributed to the feasibility of alternative treatment options for cervical cancer patients.