Objective To investigate the expression and role of the DNA repair and recombination protein RAD54-like(RAD54L)in oral squamous cell carcinoma(OSCC).Methods Using OSCC-related data from The Cancer Genome Atlas(TCGA)database,the difference in RAD54L expression between OSCC and control samples was analysed using the Mann-Whitney rank sum test,and the potential value of RAD54L mRNA in OSCC diagnosis was assessed using the receiver operator characteristic curve.The correlation between RAD54L expression levels and clinicopathological data of OSCC patients was analysed using the chi-square test.Once OSCC samples were divided into two groups of high and low expression based on the median value of RAD54L mRNA expression,Cox regression analysis was used to compare the prognostic differences between the two groups.The differentially expressed genes between the groups were subse-quently screened using the DESeq2 package,and KEGG pathway enrichment analysis was performed using the cluster-Profiler package.The correlation between RAD54L mRNA and gene expression in the homologous recombination repair pathway was demonstrated by Spearman correlation analysis.After clarifying the bioinformatics significance of RAD54L,RAD54L knockdown experiments were performed in human oral squamous carcinoma cell line HSC-3,and the knock-down efficiency was verified through real-time quantitative polymerase chain reaction.After transfection,the changes in proliferation,migration,apoptosis,and cycle of HSC-3 cells were assessed by CCK-8,5-ethynyl-2'-deoxyuridine(EdU)staining,wound healing,apoptosis,and cell cycle assays.Results Bioinformatics analysis showed that the expression of RAD54L mRNA was higher in OSCC than in normal controls(P＜0.001)and had a high value in predicting poor prognosis(AUC=0.927).The high RAD54L expression group was associated with an increased proportion of male pa-tients(P=0.032),having a higher T-stage(P=0.040),clinical stage(P=0.027),and pathological grading(P=0.013).Once OSCC samples were divided into two groups of high and low expression using the median value of RAD54L mRNA expression,the prognosis of the group with high expression of RAD54L was poorer than that of the group with low expression(P=0.049).The differentially expressed genes between the high and low RAD54L expression groups two groups were mainly enriched in neuroactive ligand-receptor interactions,cytokine-cytokine receptor interactions,calci-um signaling pathway,cell cycle,gastric cancer,extracellular matrix receptor interactions,chemical carcinogenesis-DNA adducts,DNA replication,homologous recombination,and mismatch repair pathways(P＜0.05).In the homolo-gous recombination repair pathway,the expression of RAD54L was positively correlated with the expression of BRCA1,BLM,EME1,XRCC2,POLD1,TOPBP1,RAD51,BRIP1,RAD54B,BRCA2,and SYCP3(P＜0.05),and was strongly positively correlated with the expression of BRCA1,BLM,and EME1(R＞0.8,P＜0.05).The results of in vitro experi-ments showed that RAD54L expression was knocked down to approximately 25％in HSC-3 cells(P＜0.001).Compared with the control group,the RAD54L knockdown group showed a lower proliferation rate(P＜0.05),a lower proportion of EdU-positive cells(P＜0.001),a lower proportion of wound closure(P＜0.001),a higher proportion of G1-phase cells(P＜0.001),a lower proportion of S-phase cells(P＜0.001),and a higher proportion of apoptotic cells(P＜0.001).Conclusion RAD54L is highly expressed in OSCC and correlates with poor prognosis.Down-regulation of RAD54L expression inhibits the proliferation and migration of HSC-3 cells,promotes apoptosis,and impedes cell cycle progres-sion.

Background Exposure to air pollutants O₃ and PM_2.5 is closely related to population mortality. Most of the domestic research findings are for residents in coastal areas, and less for those in the central and western regions. Objective To investigate the acute effects of O₃ and PM_2.5 on the mortality of residents in a city of central China. Methods Data were collected on atmospheric pollutants, meteorological data, and population mortality in a city of central China from January 1, 2015 to June 30, 2021. Meteorological data included daily average temperature, air pressure, and relative humidity. Atmospheric pollution data included daily mean concentrations of PM_2.5, PM₁₀, SO₂, NO₂, and CO and maximum 8 h O₃. Generalized additive model with Poisson distribution was used for estimating the relationships between air pollutants (O₃ and PM_2.5) and population mortality, and further stratified by age, gender, and education. Results The daily maximum 8 h average concentration of O₃ in the city during the study period was 94.38 μɡ·m⁻³ and the daily average concentration of PM_2.5 was 55.56 μɡ·m⁻³. In the single-pollutant model, the correlations between O₃ concentration and total deaths as well as deaths due to respiratory, circulatory, hypertension, coronary heart disease, and stroke were strongest at lag02, lag2, lag02, lag0, lag02, and lag0, and for every 10 μɡ·m⁻³ increase in concentration of O₃, the associated ER (95%CI) values of daily mortality were increased by 0.09% (−0.08%–0.25%), 0.35% (0–0.71%), 0.43% (0.18%–0.68%), 0.45% (0.02%–0.91%), 0.59% (0.16%–1.02%), and 0.33% (0.01%–0.65%), respectively. The effect of O₃ on total mortality was not statistically significant (P>0.05). The correlations between PM_2.5 concentration and total deaths, as well as deaths due to respiratory, circulatory, hypertension, coronary heart disease, and stroke were strongest at lag1, lag5, lag01, lag05, lag04, and lag01, and for every 10 μɡ·m⁻³ increase in concentration of PM_2.5, the associated ER (95%CI) values of daily mortality increased by 0.02% (−0.09–0.13%), 0.25% (0.01%–0.50%), 0.35% (0.16%–0.54%), 1.18% (0.59%–1.77%), 0.17% (−0.13%–0.40%), and 0.65% (0.38%–0.92%), respectively, with no statistically significant effects of PM_2.5 on total mortality and mortality due to coronary heart disease (P>0.05). During warm season (from May to October), the ER (95%CI) values of total deaths per 10 μɡ·m⁻³ increase in O₃ in male, people aged 6~65 years, people aged >65 years, and people below high school education were 0.46% (0.16%–0.75%), 0.38% (0.08%–0.68%), 0.41% (0.14%–0.66%), and 0.38% (0.14%–0.61%), respectively, while the O₃ effect was not statistically significant (P>0.05) during cool season (from November to April). Conclusions Atmospheric pollutants (O₃ and PM_2.5) have acute effects on mortality in the city, with the elderly, people with less than a high school education, and those with circulatory disease being more sensitive to O₃ and PM_2.5 exposures.

Objective To identify the potential long non-coding RNA (lncRNA) expressed in rheumatoid arthritis (RA) synovium key to RA onset and investigate its association with immune cell infiltration. Methods RA synovium data were downloaded from the GEO database and normalized. The lncRNAs key to RA onset were identified using multiple machine learning methods. Infiltration of 22 immune cell populations in RA synovium was measured by cell-type identification by estimating relative subsets of RNA transcripts (CIBER-SORT). The relationship between the key lncRNA and infiltrating immune cells was analyzed. Finally, real-time quantitative PCR was applied to validate the expression of the key lncRNA in RA synovial cells. Results lncRNA human leukocyte antigen complex P5(HCP5) was identified as the key lncRNA associated with RA onset. Infiltration analysis revealed increased abundance of CD8⁺ T cells, γδ T cells, and M1 macrophages while decreased abundance of M2 macrophages in RA synovial tissue. Correlation analysis demonstrated that the lncRNA HCP5 expression was positively associated with the infiltration abundance of CD8⁺ T cells, γδ T cells, and M1 macrophages in RA synovial tissue. Furthermore,the expression of lncRNA HCP5 in RA synovial cells was up-regulated. Conclusion lncRNA HCP5 expression is up-regulated in RA synovial tissue and potentially associated with immune cells infiltration.
Humans ; Arthritis, Rheumatoid ; CD8-Positive T-Lymphocytes ; HLA Antigens/metabolism* ; RNA, Long Noncoding/metabolism* ; Synovial Membrane/metabolism*

Objective To investigate the efficacy and safety of programmed death receptor-1 (PD-1) inhibitor combined with transarterial chemoembolization (TACE) and anti-angiogenic drug tyrosine kinase inhibitor (TKI) versus TACE combined with TKI in the treatment of advanced hepatocellular carcinoma (HCC) and related influencing factors for prognosis. Methods An analysis was performed for all patients who received TACE+TKI+PD-1 inhibitor and some patients who received TACE+TKI in The First Affiliated Hospital of Air Force Medical University from June 2018 to July 2021. Related clinical data were collected, and propensity score matching (PSM) was used to balance the baseline characteristics between groups. The chi-square test was used for comparison of categorical data between two groups; the Wilcoxon rank-sum test was used for comparison of the number of TACE procedures between two groups; the Kaplan-Meier method was used to analyze overall survival (OS), and univariate and multivariate Cox regression models were used to analyze the influencing factors for prognosis. Results A total of 181 patients with advanced HCC were screened out, among whom 50 patients were treated with TACE+TKI+PD-1 inhibitor; after PSM, 40 patients treated with TACE+TKI+PD-1 inhibitor were enrolled as observation group and 40 patients treated with TACE+TKI were enrolled as control group. At the end of follow-up, the median follow-up time was 28.6 (95% confidence interval [ CI ]: 22.1-35.1) months, and the median OS was 15.9 (95% CI : 7.5-24.2) months in the observation group and 11.2 (95% CI : 5.0-17.5) months in the control group. The Cox regression analysis showed that the application of PD-1 inhibitor (hazard ratio [ HR ]=0.42, 95% CI : 0.23-0.80, P =0.008), the number of TACE procedures ( HR =0.67, 95% CI : 0.46-0.99, P =0.043), Child-Pugh class ( HR =2.40, 95% CI : 1.15-5.00, P =0.019), and vascular invasion ( HR =3.42, 95% CI : 1.11-9.42, P =0.031) were independent influencing factors for prognosis. The incidence rate of grade > 2 adverse events was 40% for both the observation group and the control group, and there was no significant difference between the two groups ( P =0.818). Conclusion Compared with TACE+TKI, TACE+TKI+PD-1 inhibitor can significantly prolong the OS of patients in advanced HCC, with relatively controllable adverse events.

Background In recent years, our country's atmospheric particulate matter pollution has improved significantly, while ozone (O₃) pollution has become increasingly serious. As a secondary pollutant, O₃ is closely related to human health. Objective To study the effect of short-term exposure to ozone in ambient air on population mortality in China. Methods A computer search with key words of "ozone or O₃", "death", and "time series" in Chinese or "ozone", "mortality", and "China" in English was performed in Web of Science, PubMed, China National Knowledge Infrastructure, Wanfang, and VIP databases to find literature on effects of short-term ozone exposure on population mortality covering a time period from January 1, 1990 to December 31, 2021. According to a set of inclusion and exclusion criteria developed for this study, literaturescreening, quality evaluation, andrelevant data extraction were carried out. Finally, R 4.1.2 software was used to perform meta-analysis to estimate target effect sizes. Results A total of 978 articles were retrieved. According to the inclusion and exclusion criteria, 18 articles were finally included, including 39 effect size estimates. The results showed that every 10 μɡ·m⁻³ increase in ambient ozone concentration was associated with an increase of 0.45% (95%CI: 0.39%-0.51%), 0.50% (95%CI: 0.33%-0.68%), and 0.60% (95%CI: 0.48%-0.72%) in total, respiratory, and cardiovascular disease mortalities , respectively. The results of subgroup analysis by age, sex, and season showed that when ozone concentration increased 10 μɡ·m⁻³, an increase of 0.34% (95%CI: 0.17%-0.51%) in mortality was observed in the ≥ 65-year-old population, higher than 0.09% (95%CI: −0.21%-0.39%) increase in the <65-year-old population; the mortality increase in females [0.44% (95%CI: 0.30%-0.58%)] was greater than that in males [0.35% (95%CI: 0.22%-0.48%)]; compared with the warm season [0.29% (95%CI: 0.16%-0.42%)], mortality increase was higher in the cold season [1.03% (95%CI: 0.71%-1.35%)]. Conclusion Ambient ozone is an important factor affecting population mortality. The elderly and women ≥ 65 years old in China are more sensitive to ozone, and the impact of ozone exposure on population mortality is greater in cold season.

Objective To explore the therapeutic effect of pedicled nasal septum mucosal flap on high-flow cerebrospinal fluid leakage in transsphenoidal approach. Methods The clinical data of 31 patients with high-flow cerebrospinal fluid leakage during neuroendoscope transsphenoidal approach from January 2012 to April 2018 were analyzed retrospectively. Among them, skull base of 18 patients was reconstructed with pedicled nasal septum mucosal flap technique (observation group), and skull base of 13 patients was reconstructed with the'sandwich'method (control group). The postoperative cerebrospinal fluid leakage and complications were compared between 2 groups. Results Postoperative cerebrospinal fluid leakage occurred in 6 cases in control group, and 1 case in observation group, and there was statistical difference between 2 groups (P<0.05). Postoperative olfactory loss occurred in 2 cases in control group, and 3 cases in observation group, and there was no statistical difference between 2 groups (P>0.05). Conclusions Multilayer skull base reconstruction with pedicled nasal septum mucosal flap can significantly reduce the incidence of cerebrospinal fluid leakage after transsphenoidal tumor resection, and is a safe and reliable method to treat the high flow cerebrospinal fluid leakage in operation.

Objective To invstigate the effect of ultrasound microbubble mediated miRNA delivery on mi-gration,invasion and cloning ability of human hepatoma HepG2 cells. Methods The migration,invasion and col-ony forming ability of HepG2 cells were measured after transfection with antisense miRNA-21/221 and miRNA-199a mimic via the optimal ultrasound microbubble transfection method. Results Compared with the control group ,the migration ,invasion and cloning ability of cells were significantly inhibited after transfection with miRNA mimics(P < 0.05,respectively),especially for miR-199a(relative cell migration rate was 31.05%,the number of invasive cells were 38.67 ± 4.51 and the number of clones were 105.67 ± 5.86). Conclusion The pres-ent study may provide new ideas and clues for gene therapy and prognosis of hepatocell ular carcinoma through ana-lyzing the effect of miRNAs on the biological characteristics of human hepatoma HepG2 cells.

Objective: To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m², 10 mg/m² or 12 mg/m² as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) . Methods: A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m²) as induction chemotherapy in newly diagnosed patients of adult AML. Results: Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m² group and IDA 12 mg/m² group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m² group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m² was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m² when compared with the IDA 8 mg/m² was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×10⁹/L in IDA 8 mg/m² group, IDA 10 mg/m² group and IDA 12 mg/m² group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×10⁹/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) . Conclusions For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m² is clinically superior to IDA 8 mg/m² and IDA 12 mg/m² in favorable intermediate AML subgroup. However, idarubicin 12 mg/m² is more suitable to adverse AML subgroup.

OBJECTIVETo evaluate the value of en-bloc mesogastric excision (EME) in the treatment of advanced gastric cancer.

METHODSA retrospective analysis on clinical data of 98 gastric cancer patients who underwent total gastrectomy in China-Japan Union Hospital of Jilin University from January 2013 to December 2015 was carried out, including EME group of 48 cases (according to the mesangial space) and D2 radical group of 50 cases(D2 lymphadenectomy according to the vascular markers). Operations were performed by the same single surgeon team. Surgical indexes and recent efficacy indexes were compared between two groups.

RESULTSGeneral informations pertaining to two groups were comparable (P>0.05). All the operations were performed successfully. Compared with D2 radical group, EME group had a shorter operative time [(155.3±13.6) vs. (171.2±14.9) minutes, P=0.012] and less intraoperative blood loss [(95.1±19.5) vs.(122.6±28.0) milliliters, P=0.011]. There were no significant differences in the number of harvested lymph node (30.8±3.9 vs. 31.5±4.7, P=0.675), time to postoperative bowel function return [(3.2±1.2) vs.(3.9±1.4) days, P=0.179], postoperative hospital stay [(10.9±2.7) vs.(11.3±3.2) days, P=0.788], and the incidence of postoperative complication [8.3% vs. 10.0%, P=0.775]. During the follow-up of 1 year, all the patients had no long-term complications, no tumor recurrence or death.

CONCLUSIONSFor advanced gastric cancer, EME result in the same clinical efficacy compared with standard D2 resection. At the same time, EME can shorten the operative time and reduce the intraoperative blood loss, which is a new technology and worthy promoting.

Aged ; Blood Loss, Surgical ; Defecation ; Female ; Gastrectomy ; methods ; Humans ; Laparoscopy ; Length of Stay ; Lymph Node Excision ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Operative Time ; Postoperative Complications ; Postoperative Period ; Retrospective Studies ; Stomach Neoplasms ; surgery ; Treatment Outcome

Objective To investigate the extent of pancreatic and liver function damage of acute necrotizing pancreatitis (ANP) rats under altitude hypoxia environment,and to provide a reference for better diagnosis and treatment of severe acute pancreatitis (SAP) in the plateau region.Methods Ninety-six specific pathogen free (SPF) Wistar male rats were involved in 1 500 meters,3 300 meters and 4 300 meters altitude.The model of ANP was established by using pancreatic capsule injection of sodium taurocholate (NaTc).In the sham operation group,the rats' belly was opened and closed after only flipping its pancreas several times.Rats in sham group were sacrificed at 6 h,and ANP group were sacrificed at 6,12,24 h after modeling.Serum amylase activity was measured,and pancreas and liver tissue were harvested for pathological examination and score.Results Serum amylase activity in sham operation group rats was not remarkably changed,and pathological changes of pancreas and liver were not obvious.At same altitude,serum amylase activity,pancreas and liver pathology score of ANP rats at each time point were significantly higher than those in the sham operation group;and serum amylase activity,pancreas and liver pathology scores of ANP 12,24 h group rats were significantly higher than those of ANP 6h group;and the difference was statistically significant (P ＜ 0.05).At 3 300 meters,4 300 meters altitude,the pancreas and liver pathology scores of ANP rats at each time point were significantly higher than those at 1 500 meters altitude,and the differences were statistically significant (P ＜ 0.05),but the difference in serum amylase activity was not statistically significant.Conclusions With the increase of altitude,pancreatic and liver pathological damage of ANP rats shows continuing aggravation.