Experimental Limits on Solar Reflected Dark Matter with a New Approach on Accelerated-Dark-Matter-Electron Analysis in Semiconductors.

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

[ANCA-negative granulomatosis with polyangiitis: a case report].

We reported a case of 73-year-old male with multiple pulmonary nodules and cavities. The patient was admitted with a chief complaint of "dry cough with shortness of breath for 3 months". Chest CT showed multiple irregular masses, nodules, and patchy lesions in both lungs, accompanied by the formation of cavities. He also had anemia and renal dysfunction. Despite given empirical anti-infective and anti-tuberculosis treatments, the pulmonary nodules progressed, and the cavities enlarged. Anti-neutrophil cytoplasmic antibodies (ANCA) were negative twice. Bronchoscopic biopsy was performed. The mucosal pathology of the right middle lobe lesion showed little necrosis, focal granulomatous structure formation, and relevant vasculitis and remaining vessel wall structure in the necrosis lesions by elastic fiber staining. A clinical diagnosis of ANCA-negative necrotizing granulomatous polyangiitis was made and the patient was treated with glucocorticoids and cyclophosphamide. The nodules and cavities shrank, and some lesions were absorbed.

[Clinical and genetic analysis of a patient with HUPRA syndrome due to missense variants of SARS2 gene and literature review].

Objective: To explore the clinical manifestations and genotype of an infant with hyperuricemia, pulmonary hypertension, renal failure in infancy, and alkalosis syndrome (HUPRAS). Methods: Clinical data of the patient were collected. Peripheral blood samples from the patient and his parents were acquainted for whole exome sequencing. The filtrated variants were verified by Sanger sequencing. The pathogenicity of the variants was predicted by bioinformatic tools. Results: The patient is a male infant of 6 months old, carrying two missense variants in the SARS2 allele: a paternal inherited c.1205G>A (p. Arg402His) and a maternal inherited c.680G>A (p. Arg227Gln). The two variants were in extremely low population frequencies. The pathogenetic prediction tools categorized them as deleterious. Arg402 and Arg227 were highly conserved in evolution. The variants led to changes in the hydrogen bonds and hydrophobicity of seryl-tRNA synthetase encoded by SARS2. Conclusions: c.1205G>A (p. Arg402His) and c.680G>A (p. Arg227Gln) are the possible causative variants of the HUPRA syndrome.

[Mechanism of upper airway muscles in the pathogenesis of obstructive sleep apnea and potential therapeutic strategy].

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a prevalent sleep disorder associated with multiple systemic health issues and has emerged as a major public health concern. It is critical to investigate personalized treatments for different subtypes based on distinct pathophysiological mechanisms. Upper airway muscle dysfunction is recognized as one of the key factors in the development of OSAHS. This article provided a comprehensive review of the various mechanisms and therapeutic approaches related to the upper airway dilator muscles in OSAHS, and proposed an innovative treatment strategy for this condition.

[Study on the association between air pollution and respiratory disease of primary school students in Chongqing City].

To analyze the association between exposure to air pollution and respiratory disease of primary school students in Chongqing City. Eight districts and counties were randomly selected based on the air pollution situation in Chongqing City. In each selected district and county, one primary school was randomly selected. A questionnaire survey was conducted on all primary school students in Grades 3-5 by the end of 2019. Air quality data from the nearest environmental monitoring sites were collected. A logistic regression model was used to analyze the impact of the living environment, lifestyle and air pollution on the respiratory disease of surveyed students. This study included 5 918 primary school students, with a prevalence rate of respiratory disease of 21.54%. The prevalence rates of boys and girls were 23.38% and 19.59%, respectively. The average Air quality index (AQI) of the surveyed school was 67, and the rates of exceeding standards of PM10, PM2.5, NO2 and O3 were 1.16%, 6.92%, 0.99% and 5.65%, respectively. The level of SO2 and CO did not exceed the standard. After adjusting for relevant factors, logistic regression analysis showed that primary school students in areas with high exposure to air pollution (OR=2.52), using air pollution related-chemicals at home (OR=1.47), passive smoking (OR=1.27), and keeping pets at home (OR=1.18) had a higher risk of respiratory disease (all P<0.05). In addition, the average annual values of AQI (OR=1.18), PM10 (OR=1.20), PM2.5 (OR=1.35), and NO2 (OR=1.11) increased the risk of respiratory diseases in primary school students (all P<0.05). In conclusion, the respiratory disease of primary school students in Chongqing City is related to the living environment, behavior habits and ambient air quality. The increased exposure concentration of PM10, PM2.5 and NO2 in air pollutants can lead to an increased risk of respiratory disease among primary school students.

Oral Chinese Medicine for the treatment of targeted therapy-induced diarrhea: a systematic review and meta-analysis.

OBJECTIVE: The treatment of targeted therapy-induced diarrhea, a common adverse reaction of targeted therapy, with traditional Chinese medicine (TCM) has unique advantages; however, a unified TCM prescription is currently missing in clinical practice, and objective outcome indicators are lacking. Here, we aimed to provide medical evidence for the use of oral TCM in the treatment of targeted therapy-induced diarrhea. To this end, we systematically reviewed the literature evaluating the clinical efficacy of oral TCM for the treatment of targeted therapy-induced diarrhea. MATERIALS AND METHODS: The Chinese National Knowledge Infrastructure, China Biology Medicine disc, Technology Journal Database, Wanfang Medical Network, PubMed, Cochrane Library, EMBASE, MEDLINE, and OVID databases were used for a literature search of clinical randomized controlled trials examining the use of oral TCM in the treatment of targeted therapy-induced diarrhea until February 2022. A meta-analysis was performed using RevMan 5.3 software. RESULTS: In total, 490 relevant studies were screened, 480 were excluded based on the inclusion and exclusion criteria, and 10 clinical studies were finally included. The 10 studies included a total of 555 patients: 279 in the treatment group and 276 in the control group. The improvements in total clinical efficiency, TCM syndrome score, and graded efficacy of diarrhea in the treatment group were better than those in the control group (p<0.01); however, there was no difference in the Karnofsky Performance Scale score between the groups. The funnel plot for total clinical efficiency was symmetrical, and the publication bias was found to be low. CONCLUSIONS: Oral TCM is an effective treatment for targeted therapy-induced diarrhea and can significantly improve the clinical symptoms and quality of life of patients.

[Hemophagocytic lymphohistiocytosis caused by hematogenous disseminated pulmonary tuberculosis: A case report].

Hemophagocytic lymphohistiocytosis (HLH) was a life-threatening syndrome due to the uncontrolled immune activation of cytotoxic T lymphocytes, natural killer (NK) cells, and macrophages. HLH is characterized by primary and secondary causes, the early diagnosis and treatment of patients are closely related to the prognosis and clinical outcome of patients. The clinical presentation is variable but mostly includes prolonged fever, splenomegaly, coagulopathy, hypertriglyceridemia, and hemophagocytosis, none of them is specific and particular for HLH. Tuberculosis (TB) infection is one of the causes of HLH. HLH caused by TB is very rare clinically, but it has a high mortality. For patients with fever of unknown origin, HLH-related clinical manifestations sometimes present before the final diagnosis of TB, and HLH is associated with the most significant mortality rate. This article is mainly about a 28-year-old patient with HLH who suffered from severe TB infection. The patient attended a hospital with a history of 2 months of prolonged fever, 10 days booger and subcutaneous hemorrhage in lower limbs. Before this, he was in good health and denied any history of tuberculosis exposure. Combined with relevant laboratory test results (such as splenomegaly, hemoglobin, platelet count, and hypertriglyceridemia) and clinical manifestations (e.g. fever), the patient was diagnosed with hemophagocytic lymphohistiocytosis, but the etiology of HLH remained to be determined. To confirm the etiology, the patient was asked about the relevant medical history (intermittent low back pain) and was performed chest CT scan, bone marrow biopsy, and fundus photography. Finally, he was diagnosed with hemophagocytic lymphohistiocytosis caused by hematogenous disseminated pulmonary tuberculosis. In response to this, intravenous methylprednisolone and anti-tuberculosis treatment (isoniazid, pyrazinamide, moxifloxacin, and amikacin) were administered to the patient. After more than a month of treatment, the patient recovered from HLH caused by severe TB infection. Therefore, this case suggests that we should be vigilant to the patient who admitted to the hospital with fever for unknown reasons, to diagnose HLH as early as possible and clarify its cause, then perform interventions and treatment, especially HLH secondary to tuberculosis. Also, cases of atypical TB and severe TB should be carefully monitored to achieve early diagnosis and early intervention.

Constraints on Sub-GeV Dark Matter-Electron Scattering from the CDEX-10 Experiment.

We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4 kg·day dataset from the CDEX-10 experiment. Using a novel calculation technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m_{χ} larger than 80 MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m_{χ} larger than 90 MeV/c^{2} with heavy mediators and m_{χ} larger than 100 MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.

Exotic Dark Matter Search with the CDEX-10 Experiment at China's Jinping Underground Laboratory.

A search for exotic dark matter (DM) in the sub-GeV mass range has been conducted using 205 kg day data taken from a p-type point contact germanium detector of the CDEX-10 experiment at China's Jinping underground laboratory. New low-mass dark matter searching channels, neutral current fermionic DM absorption (χ+A→ν+A) and DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), have been analyzed with an energy threshold of 160 eVee. No significant signal was found; thus new limits on the DM-nucleon interaction cross section are set for both models at the sub-GeV DM mass region. A cross section limit for the fermionic DM absorption is set to be 2.5×10^{-46} cm^{2} (90% C.L.) at DM mass of 10 MeV/c^{2}. For the DM-nucleus 3→2 scattering scenario, limits are extended to DM mass of 5 and 14 MeV/c^{2} for the massless dark photon and bound DM final state, respectively.

[Real-world data analysis of 3012 patients undergoing laparoscopic radical gastrectomy in a single center over the past 12 years].

Objective: To Summarize the safety, clinical outcome and technical evolution of laparoscopic gastric cancer surgery. Methods: A retrospective cohort study was carried out. Clinical data of 3012 patients who underwent laparoscopic radical gastrectomy for gastric cancer from January 2010 to March 2022 at Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University were retrospectively collected and analyzed. Case inclusion criteria were gastric malignancies confirmed by pathology, without distant metastasis by examination before operation and exploration during operation, patients undergoing laparoscopic radical gastrectomy, intact function of important organs and with complete data. Exclusion criteria were patients who underwent emergency gastric cancer resection due to gastric bleeding, perforation or obstruction, etc., tumor found to invade adjacent organs such as pancreas or transverse colon during the operation, conversion to open surgery during the operation, those who had other malignant tumors (except thyroid cancer) within 5 years, and those had severe cardiopulmonary, liver, or kidney insufficiency before surgery. Outcomes included: (1) baseline information of patients; (2) trend of the quantity of laparoscopic radical gastrectomy year by year; (3) evolution of the mode of digestive tract reconstruction; (4) periopertive outcome short-term complication was defined as complication occurring within 30 days after operation and classified accordiny to the clavien-Dindo criteria; and (5) 5-year overall survival. SPSS software was used for statistical analysis. Continuous variables that obeyed the normal distribution were expressed in the form of Mean±SD. Days of hospital stay that did not follow a normal distribution were expressed as median (Q1,Q3), and the Mann-Whiney U test was used for comparison. Discrete variables were expressed as cases (%), and chi-square test or rank sum test was used for comparison between groups. Linear regression analysis was used to analyze the relationship between the amount of surgery and the year of surgery. Kaplan-Meier method and log-rank test were used for survival analysis. Two-tailed P<0.05 was considered as statistically significant. Results: Among the 3012 cases, 2114 were male and 898 were female. The patients' average age at surgery was (61.1±10.7) years old. According to the number of cumulative cases, the patients were divided into three groups: early, intermediate and late, with 1004 patients in each group. The early group consisted of patients undergoing operation from January 2010 to October 2018, the intermediate group consisted of patients undergoing operation from October 2018 to January 2021, and the late group consisted of patients undergoing operation from January 2021 to March 2022. (1) General information: There were 691 (68.8%), 699 (69.6%) and 724 (72.1%) male patients in early, intermediate and late groups respectively; the average age increased from 56.6 years in 2010 to 62.8 years in March 2022. As for the tumor stage T1, T2, T3, T4, there were 49.0%, 14.4%, 23.9% and 12.6% in the early group; 47.5%, 12.9%, 26.9% and 12.6% in the intermediate group; 39.7%, 14.6%, 30.0%, and 15.6% in the late group, respectively. Patients with N0, N1, N2, N3a, N3b stage were 56.8%, 13.7%, 13.4%, 11.0%, and 5.0% in the early group; 55.7%, 12.9%, 12.8%, 11.6%, and 6.9% in the intermediate group; 51.0%, 16.1%, 12.8%, 12.5%, and 7.5% in the late group, respectively. (2) Year-by-year change in the number of gastric cancer operations: From 19 cases per year in 2010 to 786 per year in 2021, the annual number of gastric cancer operations was proportional to the year of operation (y=47.505x, R2=0.67). The proportion of patients with stage I disease showed a fluctuating downward trend over time, while the proportion of patients with stage III disease increased slightly, accounting for 34% until March 2022. (3) Evolution of digestive tract reconstruction methods: Except in 2010, the digestive tract reconstruction method of distal gastrectomy focused on Billroth-II+Braun anastomosis among patients undergoing laparoscopic gastric cancer surgery in other years, whose proportion had gradually increased from less than 20% in 2016 to about 70% after 2021; the gastrointestinal reconstruction methods after total gastrectomy had gradually increased in π anastomosis and overlap anastomosis since 2016, of which π anastomosis reached about 65% in 2019, and overlap anastomosis reached almost 30% in 2020; the anastomosis methods after proximal gastrectomy had been mainly double-channel anastomosis (54%) and esophagogastric anastomosis (30%) since 2016, and double-channel anastomosis accounted for up to 70% in 2019. (4) Operation time: The operation time of early, intermediate and late group was (193.3±49.8) min, (186.9±44.3) min and (206.7±51.4) min respectively. Intermediate group was significantly shorter than early group (t=3.005, P=0.003), while late group was significantly longer than early group (t=5.875, P<0.001) and intermediate group (t=9.180, P<0.001). (5) Postoperative hospital stay: The median length of hospital stay for gastric cancer patients in early, intermediate and late groups was 9 (8, 11) d, 8 (7, 10) d, and 8 (7.5, 10) d respectively. The postoperative hospital stay of intermediate group and late group was significantly shorter than that of early group (Z=-12.467, Z=-5.981, both P<0.001), but there was no significant difference between intermediate group and late group (Z=0.415,P=0.678). (6) Postoperative complication: The morbidity of short-term complication in early, intermediate and late group was 20.4% (205/1004), 16.2% (163/1004), and 16.2% (162/1004) respectively, and above morbidity of intermediate group and late group was significantly lower than that of early group (χ2=5.869, P=0.015; χ2=6.165, P=0.013), while there was no significant difference between intermediate group and late group (χ2=0.004,P=0.952). The morbidity of short-term complication of grade IIIor higher was 8.0% (80/1004), 7.6% (76/1004), and 4.9% (49/1004) in early, intermediate and late group respectively, and above morbidity of late group was significantly lower than that of early and intermediate group (χ2=7.965, P=0.005; χ2=6.219,P=0.013), while there was no significant difference between intermediate group and early group (χ2=0.111,P=0.739). (7) Survival analysis: The follow-up deadline for survival data was December 31, 2021, and the median follow-up time was 29.5 months. The overall 5-year survival rate of all the patients was 74.7%. The 5-year survival rates of stage I, II and III patients were 92.0%, 77.2%, and 40.3% respectively and 5-year survival rates of patients with stage IA, IB, IIA, IIB, IIIA, IIIB and IIIC were 93.2%, 87.8%, 81.1%, 72.7%, 46.2%, 37.1%, and 34.0% respectively. Conclusions: The number of laparoscopic gastric cancer operation in our center is increasing year by year. With the maturity of laparoscopic technology, the morbidity of complication in laparoscopic gastric cancer surgery is decreasing.

Simulated global climate change benefits the nutritive value of oat grass.

Numerous data demonstrate that global climate change affects crop yield and quality. However, the effect of climate change on the nutritive value of forage crops remains unclear. Oat grass (Avena sativa L.) was used as a representative forage crop to understand changes in yield and chemical composition. The growth of oat grass under elevated temperature and CO2 conditions was simulated in a 51-day growth experiment inside OTCs. The oat grass was harvested during the heading period and yield, nutrient content, macro- and micro-mineral content and in vitro dry matter digestibility (IVDMD) determined. The fresh and dry yield, mineral P and Fe content and IVDMD of oat grass increased under increased CO2 concentrations (P < 0.05). As temperature increased, dry matter yield and soluble sugar content decreased and the content of Na, Mg, P, S, Ca, Mn, Fe, Cu and Zn increased (P < 0.05), while IVDMD was not significantly affected. Under the interaction of increasing CO2 and temperature, the content of Mg, P, S, Ca, Mn and IVDMD of oat grass increased (P < 0.05); however, there was no significant effect on yield. Climate change may result in oat grass containing more digestible nutrients and minerals for ruminants.

The neuroprotective effects of Galectin-1 on Parkinson's Disease via regulation of Nrf2 expression.

OBJECTIVE: Parkinson's disease (PD) is one of the neurodegenerative diseases. Galectin-1 (Gal-1) is expressed in the central nervous system. Our study sought to explore the neuroprotective effect of Gal-1 in 1­methyl­4­phenyl pyridine ion (MPP+)-induced cytotoxicity on SH-SY5Y cells. MATERIALS AND METHODS: SH-SY5Y cells were cultured in vitro, pretreated with Gal-1, and then exposed to MPP+. Thereafter, the generation of reactive oxygen species (ROS) in SH-SY5Y cells was investigated. The effects of Gal-1 on DNA breakage, cell damage (release of lactate dehydrogenase (LDH)), viability, and apoptosis in SH-SY5Y cells were examined by comet assay, LDH assay, WST-1 assay, and flow cytometry, respectively. Additionally, the regulatory effect of Gal-1 on Nrf2 expression was examined by western blot. Zebrafish embryos were pretreated with Gal-1 and then exposed to MPP+. The locomotor ability of zebrafish larvae was then investigated. RESULTS: MPP+ induced the production of ROS in cells, which can be alleviated by pretreatment with Gal-1. Gal-1 protected cells from MPP+-induced cytotoxicity by preventing DNA breakage and cell injury. Gal-1 inhibited apoptosis in SH-SY5Y cells. The neuroprotective effect of Gal-1 could be abolished when Nrf2 expression knockdown. Moreover, exposure to MPP+ decreased the locomotor activity of zebrafish, which was attenuated by pretreatment with Gal-1. CONCLUSIONS: Our study demonstrated that the administration of Gal-1 could protect neurons from cellular stress by preventing apoptosis and eliminating ROS. Moreover, the neuroprotective effect of Gal-1 in neuronal cells could be related to the activation of Nrf2 expression. Therefore, Gal-1 could be a promising strategy for treating PD.

[Roles and mechanisms of m6A modification regulating RP11-426A6.5 in laryngeal squamous cell carcinoma].

Objective: To investigate the roles of N6-methyladenosine (m6A) modification in regulating RP11-426A6.5 in the development of laryngeal squamous cell carcinoma (LSCC). Methods: The methylation and expression levels of lncRNAs were identified and important lncRNAs were screened utilizing long non-coding RNA (lncRNA) m6A methylation microarray. Cancer and para cancer tissue samples were taken from 48 LSCC patients hospitalized to the Department of Otolaryngology-Head and Neck Surgery of the Second Affiliated Hospital of Harbin Medical University between January and September 2017. Expression profiling microarray was performed in 3 of 48 LSCC samples, and methylated RNA immunoprecipitation-quantitative PCR (MeRIP-qPCR) and quantitative real-time fluorescent PCR (qRT-PCR) were performed in the remaining 45 LSCC samples to verify the m6A modification and expression levels of RP11-426A6.5. Correlations between RP11-426A6.5 and clinical factors were anlysed. Laryngeal cancer cell line with low expression of RP11-426A6.5 was created in vitro using RNA interference (RNAi) technology. The 5-Ethynyl-2'-deoxyuridine (EdU) cell proliferation experiment, wound healing experiment, and transwell invasion experiment were used respectively to measure the proliferation, migration, and invasion of LSCC cells. The effect of RP11-426A6.5 down-regulation on the growth of transplanted tumors in vivo was verified by nude mice tumorigenesis assay. The Cancer Genome Atlas (TCGA) database and sequence-based RNA adenosine methylation site predictor (SRAMP) website were used to predict the enzymes and corresponding methylation sites. MazF digestion was chosen to validate the binding sites. RNAi technology was used to observe the changes in cell function after interfering with the expression of the corresponding genes of the modified enzymes. MeRIP-qPCR was used to detect the level of RP11-426A6.5 m6A cell line treated with actinomycin D was used to observe the stability of RP11-426A6.5. Results: RP11-426A6.5 methylation and expression levels were significantly higher in LSCC tissues than those in paracancerous tissues (methylation levels: 23.828±4.975 vs 20.280±3.607; expression levels: 1.197±0.314 vs 1.015±0.170, all P values<0.05). RP11-426A6.5 expression levels were closely correlated with T stage (T1-2: 1.081±0.298 vs T3-4: 1.306±0.292, χ2=5.35, P<0.05). The postoperative survival of patients with high RP11-426A6.5 expressions was significantly lower than that of patients with low RP11-426A6.5 expression (P=0.046). Assays in vitro and in vivo showed that the downregulation of RP11-426A6.5 significantly decreased the proliferation, migration, and invasion abilities of LSCC cells and the growth of transplanted tumors. The binding of methyltransferase-like 3 (METTL3), an m6A-modified enzyme, to the corresponding methylation site of RP11-426A6.5 enhanced its stability and mediated its regulation of malignant behaviors of LSCC cells. Conclusions: RP11-426A6.5 can regulate the malignant behaviors of LSCC cells, which is mediated by the m6A modification process involving in the methyltransferase METTL3.

LINC00958/miR-3174/PHF6 axis is responsible for triggering proliferation, migration and invasion of endometrial cancer.

OBJECTIVE: To reveal the role of LINC00958 in the progression of endometrial cancer (EC) and the underlying molecular mechanism. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was conducted to detect relative level of LINC00958 in EC specimens and cell lines. Its prognostic potential in EC was analyzed by Kaplan-Meier method. After in vitro knockdown of LINC00958, cell proliferative, migratory and invasive abilities in KLE and Ishikawa cells were evaluated by Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) and transwell assay. Dual-Luciferase reporter assay was carried out to identify the LINC00958/miR-3174/PHF6 axis, and their expression interaction was determined by Pearson correlation test. The role of miR-3174 in influencing LINC00958-induced phenotype changes of EC cells was determined through rescue experiments. RESULTS: LINC00958 was abnormally upregulated in EC specimens and cell lines, which was unfavorable to the prognosis of EC. Knockdown of LINC00958 reduced proliferative, migratory and invasive rates in KLE and Ishikawa cells. MiR-3174 shared a binding site in the 3'-untranslated region (3'-UTR) to that of LINC00958, which was lowly expressed in EC specimens and negatively linked to LINC00958 level. Overexpression of miR-3174 partially abolished the role of LINC00958 in accelerating the malignant phenotypes of EC cells. PHF6 was the downstream target of miR-3174 and it was upregulated in EC specimens. CONCLUSIONS: LINC00958 is upregulated in EC specimens, which is a prognostic factor of EC. It stimulates EC to proliferate, migrate and invade through the miR-3174/PHF6 axis.

[Effect of high-fat diet on respiratory function and diaphragm fibers in mice and its mitochondrial mechanism].

Objective: To investigate the effect of high-fat diet (HFD) on respiratory function and its mitochondrial mechanism in mice. Methods: Twenty 4-week-old healthy male C57BL/6 mice were divided by simple random grouping into two groups, 10 mice for each group. Mice were raised with normal diet (NFD) and HFD for 16 weeks, respectively, and weighed once every two weeks. At the end of the intervention, respiratory parameters were measured by whole-body plethysomography, serum and diaphragm tissue lipid species were measured, diaphragm tissue was stained to observe diaphragmmatic morphology, muscle fiber phenotype and mitochondrial ultrastructure. Real-time fluorescence quantitative PCR and immunoblotting were used to detect myosin heavy chain(MHC) and mitochondrial dynamics-related genes and protein expression. Results: The baseline body weights of NFD and HFD mice were (19.17±0.59) and (19.12±0.64) g, respectively, with no statistically significant differences (P=0.857). After 16 weeks of feeding, the body weight of mice in the HFD group was (41.28±2.21) g, which was higher than NFD group [(27.14±0.53) g, P<0.001]. The peak inspiratory flow rate, tidal volume and minute ventilation of mice in the HFD group were (5.72±0.64) ml/s, (0.23±0.04) ml and (97.49±21.68) ml, respectively, which were lower than NFD group [(7.70±1.52) ml/s, (0.31±0.07) ml and (129.99±28.87) ml, respectively, all P values<0.05]. Penh value was 1.16±0.07, which was higher than NFD group (0.98±0.09, P<0.001). The diaphragmatic triglyceride content of mice in the HFD group was (20.43±6.36) mmol/mg, which was higher than NFD group [(11.62±1.78) mmol/mg] (P=0.003), and lipid droplets were deposited in the diaphragm fibers. The percentage of MHC-Ⅰ muscle fibers in the diaphragm of mice in the HFD group was 13.33%±2.95%, which was lower than NFD group (19.20%±1.23%, P=0.034). The mitochondria of the diaphragm in the NFD group were arranged in rows with clear structures, while in the HFD group showed swelling, cristae breakage and vacuoles. The relative expression level of mitochondrial fusion protein 2 in the diaphragm of the HFD group was 0.61±0.16, which was lower than NFD group (1.28±0.03, P<0.001); the relative expression of mitochondrial dynamin-related protein 1 were 1.18±0.06 and 0.91±0.11, respectively, both higher than NFD group (0.61±0.07 and 0.60±0.04, respectively, P<0.001). Conclusion: HFD impairs respiratory function in mice by the mechanism associated with the MHC-Ⅰ muscle fibers decrease and the mitochondrial dynamics imbalance of diaphragm.

LINC00665 knockdown protects against cerebral ischemia-reperfusion injury.

LINC00665 has been reported to participate in several human diseases. However, the role of LINC00665 in cerebral ischemia-reperfusion (CI/R) is still unknown. This study is designed to investigate the role of LINC00665 in rats with CI/R injury. We established middle cerebral artery occlusion/ reperfusion (MCAO/R) rats model in vivo. PC12 cells treated with oxygen-glucose deprivation/reperfusion (OGD/R) were used to establish in vitro I/R model. RT-qPCR assay was adopted to assess the mRNA expression of LINC00665 and miR-744-5p. MTT assay was used to determine cell viability. The protein expression of Bax and Bcl-2 were detected by Western blot assay. The relationship between LINC00665 and miR-744-5p was confirmed by dual luciferase reporter assay and RNA immunoprecipitation (RIP). In this study, we found that LINC00665 was sharply up regulated in MCAO/R rats and PC12 cells treated with I/R. Functionally, LINC00665 knockdown attenuated oxidative damage in PC12 cells treated with I/R. Moreover, LINC00665 knockdown promoted cell viability, while inhibited cell apoptosis in PC12 cells treated with I/R. In addition, miR-744-5p was confirmed to be a target of LINC00665. LINC00665 knockdown was validated to project CI/R injury by sponging miR-744-5p expression.

[The function and mechanism of long non-coding RNA RP11-159K7.2 in sinonasal squamous cell carcinoma].

Objective: To explore the role and mechanism of long non-coding RNA RP11-159K7.2 in the progression of sinonasal squamous cell carcinoma (SNSCC). Methods: Sixty-five cases of SNSCC tissues and adjacent tissues were selected from the Department of Otorhinolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Harbin Medical University from 2009 to 2014. The expression of RP11-159K7.2 in SNSCC and adjacent tissues was detected by RNAscope in situ hybridization to observe its association with prognosis. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated proteins 9 (CRISPR/Cas9) was used to knockout the expression of RP11-159K7.2 in RPMI-2650 cells (SNSCC cell line). Cell counting kit-8 (CCK-8), wound healing and Transwell were performed to observe the changes of proliferation, migration and invasion of SNSCC cells in vitro after down-regulation of RP11-159K7.2. Moreover, the growth of xenograft in nude mice after down-regulation of RP11-159K7.2 was examined in vivo. Mechanically, the protein chip, Western blot and RNA immunoprecipitation were performed to identify the proteins bound by RP11-159K7.2. SPSS 17.0 was used for statistical analysis. Results: The expression of RP11-159K7.2 in SNSCC tissue was significantly higher than that in adjacent tissues. RP11-159K7.2 expression was closely related with T grade, nodal metastasis and differentiation of SNSCC (χ2 value was 4.697, 4.235 and 10.753, respectively, all P<0.05). The five-year survival rate of RP11-159K7.2 high expression patients was significantly lower than that of RP11-159K7.2 low expression ones (P=0.013 7). After the down-regulation of RP11-159K7.2, the proliferation, migration and invasion ability of SNSCC cells decreased significantly, and the growth of SNSCC xenograft was significantly inhibited. There were 31 candidate proteins that may bind to RP11-159K7.2. RP11-159K7.2 directly bound to nuclear factor-κB (NF-κB) in SNSCC cells, and the regulation of RP11-159K7.2 on the proliferation and invasion of SNSCC cells depended on NF-κB. Conclusion: The increased expression of RP11-159K7.2 in SNSCC may serve as a potential molecular marker for SNSCC prognosis assessment. It is currently considered that the carcinogenic mechanism of RP11-159K7.2 in SNSCC is related to the regulation of NF-κB protein.