Association of sleep duration, sleep apnea, and shift work with risk of colorectal neoplasms: a systematic review and meta-analysis.

Background: Although studies have reported that certain sleep characteristics, such as sleep duration and sleep apnea, are linked to the risk of colorectal cancer (CRC), this link remains contentious because of the limited evidence from individual studies. Furthermore, evidence indicated that shift work involving circadian disruption as a probable human carcinogen. This systematic review and meta-analysis aimed to examine the associations between sleep duration, sleep apnea, and shift work with the risk of colorectal neoplasms, including CRC and colorectal adenoma (CRA). Methods: We conducted a comprehensive literature search in PubMed, Embase, and Web of Science databases. The inclusion criteria were determined using PICOS principles. Observational studies reporting associations of sleep duration, sleep apnea, or shift work with risk of CRC or CRA were included. We assessed the risk of bias on the basis of the Newcastle-Ottawa Scale. Results: A total of 18 observational studies were included. Of these studies, nine studies reported the effect of sleep duration on risk of colorectal neoplasms, five reported the effect of sleep apnea, and six reported the effect of shift work. The relative risk (RR) for colorectal neoplasms was 1.06 [95% confidence interval (CI): 0.94, 1.20] in the short sleep duration group compared with the moderate sleep duration group. Long sleep duration was associated with an increased risk of colorectal neoplasms (RR: 1.33, 95% CI: 1.07, 1.65). The pooled results showed that sleep apnea was associated with an increased risk of colorectal neoplasms (RR: 1.75, 95% CI: 1.56, 1.97). Furthermore, results showed that the association between shift work and the risk of colorectal neoplasms was not significant (RR: 1.06, 95% CI: 0.95, 1.17). No publication bias was observed in all the analyses (all P>0.05). The sensitivity analysis showed that no individual study substantially influenced the pooled RRs for colorectal neoplasms and CRC. Conclusions: Our findings suggest the significant positive association of long sleep duration and sleep apnea with risk of colorectal neoplasms and CRC. Given that sleep characteristics may be a potentially modifiable risk factor for colorectal neoplasms, further understanding of its role in carcinogenesis will provide valuable insight for cancer prevention.

Clinical symptoms between severe and non-severe COVID-19 pneumonia: A protocol for systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019, (COVID-19) is a major problem in public health in the world. Up to June, 2020, the number of infections arising to 8,690,000 and cause 410,000 deaths all over the world. Identification the clinical symptoms from non-severe to severe is important for clinician. This meta-analysis aimed to compare the clinical symptoms between severe and non-severe COVID-19 pneumonia. METHODS: Electronic databases including PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure database, Wanfang Database and Chinese Biomedical Literature Database were searched from its inception to June 21, 2020. We only included severe versus non-severe COVID-19 pneumonia patients and pooled results were summarized by STATA 12.0 software.Two researchers independently selected the study and assessed the quality of the included studies. The heterogeneity was measured by I tests (I < 50 indicates little heterogeneity, I≥50 indicates high heterogeneity). Publication bias was ruled out by funnel plot and statistically assessed by Begg test (P > .05 as no publication bias). RESULTS: Results will be published in relevant peer-reviewed journals. CONCLUSION: Our study aims to systematically present the clinical symptoms between non-severe and severe of COVID-19 patients, which will be provide clinical guidance for COVID-19 patients.

BMX-ARHGAP fusion protein maintains the tumorigenicity of gastric cancer stem cells by activating the JAK/STAT3 signaling pathway.

BACKGROUND: Cancer stem cells (CSCs), drug-resistant cancer cell subsets, are known to be responsible for tumor metastasis and relapse. The JAK/STAT pathway, activated by SH2 domain, is known to regulate the tumor growth in gastric cancer (GC). Now, this study was designed to examine whether BMX-ARHGAP affects the GC stem cell properties and the underlying regulatory network via JAK/STAT axis. METHODS: BMX-ARHGAP expression was characterized in GC tissues and cells by RT-qPCR and western blot assay. When BMX-ARHGAP was overexpressed or silenced via plasmids or siRNA transfection, the stem cell properties were assessed by determining stem cell markers CD133, CD44, SOX2 and Nanog, followed by cell sphere and colony formation assays. Subsequently, cell proliferation and invasion were examined by conducting EdU and Transwell assays. The JAK/STAT3 signaling pathway activation was inhibited using AG490. ARHGAP12, BMX exon 10-11, BXM-SH2, JAK2 and STAT3 expression patterns were all determined to examine the regulatory network. The stem cell property in nude mice was also tested. RESULTS: BMX-ARHGAP was determined to be enriched in the GC. Overexpression of BMX-ARHGAP resulted in increased expression of CD133, CD44, SOX2 and Nanog protein, and accelerated proliferation and invasion of CD133+CD44+ cells as well as facilitated self-renewal potential of GC cells. However, the inhibition of the JAK/STAT3 signaling pathway reversed the stimulating effect of BMX-ARHGAP on proliferative and invasion abilities of CD133+CD44+ cells. The overexpression of BMX-ARHGAP was suggested to increase the BMX-SH2 protein expression via ARHGAP 5'UTR, and activate the JAK/STAT3 signaling pathway. Also, BMX-ARHGAP promoted tumor growth in nude mice. CONCLUSIONS: The aforementioned results demonstrated that the BMX-ARHGAP-dependent SH2 domain-JAK/STAT3 axis mediates the maintenance of GC stem cells, benefiting the development of new potential therapeutic targets for GC.

Suppression of BMX-ARHGAP fusion gene inhibits epithelial-mesenchymal transition in gastric cancer cells via RhoA-mediated blockade of JAK/STAT axis.

Gastric cancer (GC) is one of the main causes of cancer-related mortality worldwide. Epithelial-mesenchymal transition (EMT) is an important biological process involving the process by which malignant tumor cells obtain the ability of migration, invasion, resistance of apoptosis, and degradation in the extracellular matrix. The current study aimed at investigating whether bone marrow X kinase Rho GTPase activating protein 12 (BMX-ARHGAP) fusion gene affects GC. First, short hairpin RNA (shRNA) against BMX-ARHGAP or BMX-ARHGAP were introduced to treat SGC-7901 cells with the highest BMX-ARHGAP among the five GC cell lines (SGC-7901, MKN-45, NCI-N87, SNU-5, and AGS). Next, cell vitality, drug resistance, migration, and invasion of SGC-7901 cells, activities of Rho and JAK/STAT axis, as well as EMT and lymph node metastasis (LNM) were evaluated. The survival rate of the mice was then determined through the transfection of the specific pathogen-free NOD-SCID mice with treated SGC-7901 cells. The results showed that BMX-ARHGAP expression was associated with the infiltration degree of GC tumor and poor prognosis for patients with GC. BMX-ARHGAP silencing was found to play an inhibitory role in the Rho and JAK/STAT axis to reduce cell vitality, drug resistance, migration and invasion, reverse EMT process, as well as inhibit LNM. BMX-ARHGAP overexpression was observed to have induced effects on GC cells as opposed to those inhibited by BMX-ARHGAP silencing. The survival rate of mice was increased after transfection with silenced BMX-ARHGAP. These findings provided evidence that the suppression of BMX-ARHGAP resulted in the inhibition of RhoA to restraint the development of GC cells by blocking the JAK/STAT axis.

Neurofibroma discharged from the anus with stool: A case report and review of literature.

Isolated neurofibromas that affect the gastrointestinal tract are rare and almost always manifest as neurofibromatosis type 1 or multiple endocrine neoplasia type 2b. In this paper, we present a case of a 24-year-old female with abdominal pain who discharged a neurofibroma in her stool without any blood on it. A colonoscopy showed multiple small polyps in the sigmoid colon and a nodule in the ileocecus. The pathology results and the immunohistochemical stains of the removed neoplasm from the ileocecus confirmed the diagnosis was a bowel neurofibroma. We report a rare case of ileocecal neurofibroma due to the patient's affected gastrointestinal tract, without any associated systemic syndrome other than a neurofibroma discharged in the stool.

Valence state parameters of all transition metal atoms in metalloproteins--development of ABEEMσπ fluctuating charge force field.

To promote accuracy of the atom-bond electronegativity equalization method (ABEEMσπ) fluctuating charge polarizable force fields, and extend it to include all transition metal atoms, a new parameter, the reference charge is set up in the expression of the total energy potential function. We select over 700 model molecules most of which model metalloprotein molecules that come from Protein Data Bank. We set reference charges for different apparent valence states of transition metals and calibrate the parameters of reference charges, valence state electronegativities, and valence state hardnesses for ABEEMσπ through linear regression and least square method. These parameters can be used to calculate charge distributions of metalloproteins containing transition metal atoms (Sc-Zn, Y-Cd, and Lu-Hg). Compared the results of ABEEMσπ charge distributions with those obtained by ab initio method, the quite good linear correlations of the two kinds of charge distributions are shown. The reason why the STO-3G basis set in Mulliken population analysis for the parameter calibration is specially explained in detail. Furthermore, ABEEMσπ method can also quickly and quite accurately calculate dipole moments of molecules. Molecular dynamics optimizations of five metalloproteins as the examples show that their structures obtained by ABEEMσπ fluctuating charge polarizable force field are very close to the structures optimized by the ab initio MP2/6­311G method. This means that the ABEEMσπ/MM can now be applied to molecular dynamics simulations of systems that contain metalloproteins with good accuracy.

Fusion between TMPRSS2 and ETS family members (ERG, ETV1, ETV4) in prostate cancers from northern China.

In this study we evaluated the frequency of fusion between TMPRSS2 and ETS family members (ERG, ETV1, ETV4) in prostate cancers in patients from northern China in order to explore differences in fusion rates among regions in northern and southern China, other parts of Asia, Europe, and North America. We examined 100 prostate cancer patients, diagnosed by means of prostate biopsy; fluorescence in situ hybridization (FISH) was used to detect the expression of TMPRSS2, ERG, ETV1 and ETV4 in cancer tissue. Differences in gene fusion rates among different ethnics groups were also analyzed. Of the 100 prostate cancer patients, 55 (55%) had the fusion gene. Among the patients with the fusion gene, 46 (83.6%) patients had the TMPRSS2:ERG fusion product, 8 (14.8%) patients had TMPRSS2:ETV1 fusion, 1 (1.6%) patient had TMPRSS2:ETV4.