[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.

[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.

[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.

[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.

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.

[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.

[A multi-center retrospective study of perioperative chemotherapy for gastric cancer based on real-world data].

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.

LncRNA PRNCR1 aggravates the malignancy of oral squamous cell carcinoma by regulating miR-326/FSCN1 axis.

OBJECTIVE: The important regulatory mechanism of lncRNA PRNCR1 has been emphasized in malignant tumors. However, the role of lncRNA PRNCR1 remains unclear in oral squamous cell carcinoma (OSCC). The purpose of this study is to reveal the role of lncRNA PRNCR1 in OSCC. PATIENTS AND METHODS: RT-qPCR was used to detect mRNA expression. The functional mechanism of lncRNA PRNCR1 in OSCC was investigated by CCK-8, transwell and Luciferase reporter assays. RESULTS: LncRNA PRNCR1 was upregulated in OSCC and promoted cell proliferation, migration and invasion. LncRNA PRNCR1 directly binds to miR-326. The mutual inhibition between the expressions of lncRNA PRNCR1 and miR-326 was identified in OSCC. In addition, miR-326 restrained cell proliferation, migration and invasion in OSCC. Further, miR-326 directly targets FSCN1. FSCN1 expression was positively regulated by lncRNA PRNCR1 in OSCC. And FSCN1 promoted the progression of OSCC and aggravated the carcinogenic effect of lncRNA PRNCR1 in OSCC. CONCLUSIONS: LncRNA PRNCR1 promotes the progression of OSCC by functioning as a miR-326 'sponge' to upregulate FSCN1 expression.

[Lung cancer screening in urban Beijing from 2014 to 2019].

Objective: To analyze the current status of lung cancer screening among residents in Urban Beijing Cancer Screening Program, 2014-2019. Methods: Based on an on-going cancer screening program launched by the National Urban Cancer Screening Program, residents aged 40 to 69 were recruited from 80 streets in six districts of Beijing (Dongcheng, Xicheng, Chaoyang, Haidian, Fengtai, and Shijingshan District) by using a cluster sampling method. Subjects who were evaluated as high-risk individuals by using the questionnaire received Low-Dose spiral Computed Tomography (LDCT) screening in designated hospitals. All participants were followed up annually using active and passive follow-up methods to obtain their health outcomes (diagnosed with lung cancer or not). The proportion of high-risk cases evaluated by using the questionnaire, clinical recall rate for receiving LDCT screening, the proportion of cases with positive pulmonary node, incidence rate, cumulative incidence rate, and the proportion of patients with stage 0 or Ⅰ were calculated. Cox proportional hazard regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (95%CI) among individuals who experienced different screening scenarios. Results: A total of 88 044 residents with the age of (57.4±7.4) with completed high-risk assessment were included in the analysis. 23.14% of participants were evaluated as high-risk individuals by using the questionnaire. The clinical recall rate was 52.26% among the high-risk individuals. The positive rate of pulmonary node detected by LDCT was 10.99%. The incidence rate of lung cancer among males and females aged 40-69 years were 172.82/100 000 person-years and 133.52/100 000 person-years, respectively after 3 years follow-up. The incidence rates increased with age (Ptrend<0.001). The incidence rate of lung cancer among high-risk individuals was 259.22/100 000 person-years, with the HR (95%CI) about 2.27 (1.83-2.81) when compared with that among low-risk individuals. The incidence rate and cumulative incidence rate of lung cancer among individuals with positive pulmonary node detected by LDCT were 1 825.03/100 000 person-years and 4 615.38/100 000, respectively, with the HR (95%CI) about 13.80 (8.91-21.36) when compared with that among individuals with no or negative pulmonary node. The early diagnosis rate among individuals who received LDCT screening was 70.21%, which was higher than that among individuals with no LDCT screening (45.45%). Conclusion: Individuals with a high risk of lung cancer in Beijing have a better recall rate of receiving LDCT screening. Using LDCT screening among high-risk individuals is an effective strategy to detect lung cancer cases and improve the early detection rates of lung cancer in Beijing, China.

MiR-20b is implicated in preeclampsia progression via the regulation of myeloid cell leukemin-1.

Preeclampsia (PE) may induce gestational failure, threatening a significant number of pregnant women. Recently, microRNAs (miRNAs) have been reported to participate in PE progression, whereas the precise functions and potential mechanisms of miR-20b in placental trophoblast cells as well as in PE progression remain poorly understood. In the present study, real-time quantitative polymerase chain reaction (RT-qPCR) analysis was used to detect expressions of miR-20b and myeloid cell leukemin- 1(MCL-1) mRNA. Cell viability was investigated by cell counting kit-8(CCK-8) assays. Cell invasion and migration abilities were determined by Transwell assays. Western blot was performed to detect MCL-1 protein expressions. The interaction between miR-20b and MCL-1 was investigated by bioinformatics analysis and luciferase activity assay. The results of the study demonstrated that miR-20b was highly expressed in placental tissues of patients with PE. Moreover, miR-20b overexpression inhibited HTR8/ SVneo cell proliferation, invasion and migration. Furthermore, MCL-1 was targeted by miR-20b, and MCL-1 restoration could partially attenuate the effect of miR-20b on HTR8/SVneo cells. In conclusion, the results indicate that miR-20b may contribute to PE through inhibiting proliferation, invasion and migration of placental trophoblast cells by targeting MCL-1. Therefore, miR-20b may be used as a notable biomarker for the diagnosis, prevention, and treatment of PE. MiR-20b targeting MCL-1 deserves further investigation in order to explore their potential role in PE.

Long noncoding RNA CASC2c inhibited cell proliferation in hepatocellular carcinoma by inactivated ERK1/2 and Wnt/ß-catenin signaling pathway.

PURPOSE: Long non-coding RNAs (lncRNAs) have been shown to play important roles in tumorigenesis, but their biological functions and the underlying molecular mechanisms remain unclear. Alternative splicing of five exons results in three transcript variants of cancer susceptibility 2 (CASC2): the lncRNAs CASC2a, CASC2b, and CASC2c. CASC2a/b have been found to have crucial regulatory functions in a number of malignancies, but few studies have examined the effects of CASC2c in cancers. The objective of the study was to investigate the role of CASC2c in the proliferation and apoptosis of hepatocellular carcinoma (HCC) cells. METHODS: This study first investigated the expression levels of CASC2c in tumor tissues, corresponding non-tumor tissues and cells using quantitative real-time polymerase chain reaction. The function and underlying molecular mechanism of CASC2c in human HCC were investigated in QGY-7703 cell line, as well as in gastric cancer (GC) cell and colorectal cancer (CRC) cell. RESULTS: In the present work, we observed that CASC2c was significantly down-regulated in HCC tissues and cells. Moreover, its overexpression remarkably inhibited the growth, migration, and invasion of HCC cells in vitro and promoted their apoptosis. Furthermore, we demonstrated that CASC2c overexpression decreased p-ERK1/2 levels in HCC, GC, and CRC cells. Interestingly, while overexpression of CASC2c decreased ß-catenin expression in HCC and GC cells, it increased that in CRC cells. CONCLUSION: The lncRNA-CASC2c has a vital role in tumorigenesis and cancer progression, and may serve as a biomarker or therapeutic target in cancer treatment via down-regulation of the ERK1/2 and Wnt/ß-catenin signaling pathways.

Correlations between the level of antibody against peptide of glutamate receptor NR3B subunit in the CSF and cognitive comorbidities of patients with epilepsy.

OBJECTIVE: Autoimmune epilepsy is an under-recognized condition, and the mechanisms of antibody-mediated epileptogenesis are unknown. The N-methyl-D-aspartate (NMDA) receptor subunit 3 peptide B (NR3B) modulates Mg2+ sensitivity and Ca2+ mobilization of glutamate responses in the central nervous system (CNS). The levels of antibodies against NR3B (NR3B Ab's) in the cerebrospinal fluid (CSF) and the correlations between NR3B Ab's and cognitive comorbidities of epilepsy patients remain unclear. PATIENTS AND METHODS: CSF samples were collected from 36 patients with consecutive epilepsy and 17 healthy controls. The levels of NR3B Ab's in the CSF were measured by ELISA. The cognitive function was assessed by Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). RESULTS: The results showed that the levels of NR3B Ab's were significantly higher in patients with epilepsy than those in the controls (p<0.01). Thirteen of 36 patients had higher levels of NR3B Ab's exceeding mean+ 2SD of all patients, and the scores of MMSE and MoCA of these 13 patients were significantly lower than the other 23 patients and controls (p<0.01; p<0.001). However, there were no significant differences in the scores of MMSE and MoCA between the 23 patients and the controls. Correlation analysis indicated a significant negative correlation between the levels of NR3B Ab's and the scores of MMSE (correlation coefficient: r=-0.543; p<0.01) or the scores of MoCA (correlation coefficient: r=-0.548; p<0.01). CONCLUSIONS: We suggest that some patients with epilepsy may have immune process after onset and the presence of NR3B Ab's may be associated with cognitive comorbidities in patients with epilepsy.

Downregulation of HOTTIP regulates insulin secretion and cell cycle in islet ß cells via inhibiting MEK/ERK pathway.

OBJECTIVE: To investigate the effect of long non-coding RNA (lncRNA) HOTTIP on islet ß cells and its underlying mechanism. MATERIALS AND METHODS: The expressions of HOTTIP in different organs of db/db mice and C57BL/6J mice were detected by quantitative Real-time polymerase chain reaction (qRT-PCR). Effects of HOTTIP on the proliferation, insulin secretion and apoptosis of islet ß cells transfected with lentivirus were detected by cell counting kit-8 (CCK-8) assay, enzyme-linked immunosorbent assay (ELISA) and flow cytometry, respectively. We also assessed the protein expressions of key genes in MEK/ERK pathway by using Western blot. RESULTS: HOTTIP was upregulated in normal islet tissues of C57BL/6J mice but downregulated in islet tissues of diabetic mice. Inhibition of HOTTIP attenuated insulin secretion and reduced expressions of Pdx1 and MafA. Downregulation of HOTTIP also inhibited cell proliferation and reduced expressions of CyclinDl, CyclinD2, CyclinE1 and CyclinE2. Moreover, islet ß cells were arrested in G0/G1 phase after HOTTIP knockdown. Our data showed that the biological function of HOTTIP in regulating insulin secretion and cell cycle in islet ß cells might be related to the MEK/ERK pathway. CONCLUSIONS: Downregulation of HOTTIP inhibits insulin secretion and cell cycle in islet ß cells via MEK/ERK pathway.

[Smoking abstinence rate and its associated factors between abrupt and gradual smoking cessation].

Objective: To analyze and compare the abstinence rate of smoking quitting methods and its associated factors between abrupt and gradual smoking cessation in smokers with drug-based therapy. Methods: A prospective clinical study was conducted in patients undergoing quitting smoking intervention in Ruijin Hospital smoking cessation clinic between June 2013 and May 2016. All the subjects were randomized in a 1∶1 ratio into the abrupt smoking cessation group (smoking as usual over 3 weeks before a planned quit day, and then stopping smoking abruptly) and the gradual smoking cessation group (gradually reducing tobacco use over 3 weeks before a planned quit day, and then stopping smoking totally). The primary outcome was the complete abstinence rate, and the secondary outcomes included 1-month, 3-month and 6 month 7-day point prevalence of abstinence rates and 3 month sustained abstinence rates. Changes of body weight and drug adverse events were also compared. Results: A total of 314 moderate to severe nicotine-dependent patients were admitted in the study, including 157 patients in the abrupt smoking cessation and 157 patients in the gradual smoking cessation group. Fourteen patients fell off during the follow-up. For the complete abstinence rate, the gradual smoking cessation group was higher than the abrupt smoking cessation group(55.0% vs. 36.9%, χ(2)=9.841, P=0.002) .For 7-d smoking abstinence rate in the 1st, 3rd, 6th month, there was no significant difference between the 2 groups (all P>0.05). As for the 3-month sustained abstinence rate, a higher smoking quitting rate was seen in the gradual smoking cessation group compared to the abrupt smoking cessation group in the 6-month follow-up (17.9% vs.8.7%, χ(2)=5.441, P=0.020). The adverse drug reaction incidence was higher in the abrupt smoking cessation group than the gradual smoking cessation group (Gastrointestinal discomfort: 39.2% vs. 17.7%, χ(2)=12.336, P=0.000; Dreaminess: 40.2% vs. 13.3%, χ(2)=20.172, P=0.000). Conclusions: For moderate to severe nicotine-dependent patients, the gradual smoking cessation could serve to enhance the abstinence rate and mitigate the withdrawal symptoms.