Objective To map the genome-wide distribution profile of histone H3K27me3 modification in diffuse gastric cancer tissues,identify target genes regulated by H3K27me3,and primarily explore the potential mechanism of its modification reprogramming in the occurrence and development of the tumor.Methods Normal gastric mucosal tissues and diffuse gastric cancer tissues were harvested from the patients who underwent examinations or treatments in the departments of gastroenterology and gastrointestinal surgery of our medical center between 2021 and 2023.There were 14 patients in the normal group(6 males and 8 females,average age of 46 years)and 14 patients in the gastric cancer group(8 males and 6 females,average age of 63 years).Cleavage under target and tagmentation(CUT&Tag)technology was employed to capture genomic regions modified by H3K27me3,and analyze the reprogramming characteristics of these modifications.RNA sequencing data,data from high-throughput chromosome conformation capture(Hi-C)technology,and publicly available single-cell data were integrated to investigate the target genes regulated by the reprogramming of H3K27me3 modifications in diffuse gastric cancer cells.Results The quality of the CUT&Tag and RNA sequencing data met the standards required for subsequent analysis.Histone H3K27me3 modifications in normal gastric mucosa and diffuse gastric cancer tissues were primarily distributed in distal intergenic regions and intronic regions.In gastric cancer tissues,compared to normal tissues,there was significant reprogramming of H3K27me3 modifications,characterized by a marked reduction in overall H3K27me3 signal intensity.The loss of 2 912 H3K27me3 signal peaks might lead to the up-regulation of 822 tumor-associated genes.Among them,56 genes displayed the most significant up-regulation(fold change in signal intensity≥2,P<0.05),with notable enrichment in the mammalian target of rapamycin complex 1(mTORC1)signaling pathway.Specifically,the methionine transporter SLC7A5 and the cystine transporter SLC7A11 were found to have the highest expression levels in gastric cancer tissues.Single-cell data revealed that the abnormal overexpression of SLC7A11 in diffuse gastric cancer was primarily observed in tumor epithelial cells.Further validation using public data and immunohistochemical experiments confirmed the elevated expression of SLC7A11 in diffuse gastric cancer,which is associated with poor prognosis in gastric cancer patients.Conclusion The reprogramming of histone H3K27me3 modification is an important epigenetic characteristic in diffuse gastric cancer.Loss of H3K27me3 signal peaks may up-regulate the expression of SLC7A11 in diffuse gastric cancer cells,and thereby promote tumor progression.

Objective To draw the genome-wide distribution and remodeling characteristics of H3K27me3 silencers in signet-ring cell carcinoma of the stomach(SRCC)through epigenetic sequencing technology,and to investigate their roles in transcriptional regulation in order to elucidate the regulatory mechanism of SRCC malignant progression.Methods The study was conducted on 35 gastric samples obtained by gastroendoscopic biopsy(15 normal and 20 SRCC tissues)from Department of Gastroenterology of Army Medical Center of PLA between January 2021 and December 2023.Multi-omics analyses,including assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq),cleavage under targets and tagmentation(CUT&Tag)and transcriptome sequencing(RNA-seq),were performed to identify chromatin accessibility,H3K27me3 silencer regions,and transcriptional changes,with aid of Illumina NovaSeq 6000.H3K27me3 related differentially expressed genes(|Log2FC|>1,FDR<0.05)were screened using DESeq2.Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were employed to analyze the enrichment function,and Homer was employed to identify transcription factor motifs.A regulatory network was constructed using Cytoscape,and then validated using immunohistochemistry to explore its regulatory mechanism.Results H3K27me3 silencers were primarily located in distal intergenic regions(37.06%)in SRCC.Compared with the normal tissues,SRCC showed a significant reduction in H3K27me3 silencer signals(95%CI:1.34～2.30,P=0.007)with 6 257 lost sites(FDR<0.01).Integrating CUT&Tag and RNA-seq revealed 380 up-regulated immune-related genes,particularly in T cell receptor signaling(OR=4.2,95%CI:2.8～6.3,P=0.002).Immunohistochemistry confirmed elevated expression of transcription factor EHF(P<0.05).Conclusion There is the remodeling of H3K27me3 silencers in SRCC,and EHF may potentially play a crucial role in the SRCC malignant progression.

A virus was successfully isolated from a sick cat exhibiting clinical signs such as oral mu-cosal ulceration,nasal mucosal redness,and increased nasal secretions utilizing F81 cells.Through a comprehensive analysis as such PCR amplication,sequencing,morphology,serology,and animal re-gression tests,the virus was identified as a feline calicivirus and named FCV-BJ,an inactivated vac-cine was developed from this isolated strain its safety and efficacy were assessed.The results re-vealed that the isolated FCV-BJ strain exhibited characteristic serological and morphological fea-tures consistent with caliciviruses.Furthermore,inoculation of cats with the FCV-BJ demonstrated the strain is highly virulent and the cats manifested the clinical signs of feline calicivirus infection.For the vaccination trial,domestic cats were immunized with inactivated fifth-generation virus cell culture at varying dilutions,followed by a booster immunization after 21 days.Fourteen days after the challenge with the virus,cats immunized with 107.0 TCID50/mL or higher remained largely healthy,while all cats in the control group developed clinical signs of FCV.These findings suggest that the inactivated vaccine derived from the FCV-BJ isolate exhibits strong immunogenicity and protective efficacy at a minimum immunization dose of 107.0 TCID50/mL.This strain holds promise as a candidate for vaccine production,providing a valuable reference and foundation for future re-search and development of feline calicivirus vaccines.

Objective To systematically assess the clinical efficacy of estrogen combined with antidepressants in the treatment of perimenopause-related depression in our country by meta analysis.Methods The electronic databases of CBMdisc,CNKI,VIP,Wanfang,PubMed,Cochrane Library and Google Scholar were retrieved by computer.The subject terms were set for retrieving the literatures on the effect evaluation of estrogen combined with antidepressants in treating perimenopause-related depression in our country published at home and abroad from January 1980 to February 2016.The study data and results of included literatures were performed the meta analysis by using the RevMan 5.1 software.Results Fifteen articles conforming to the inclusion standard were included.The data merged results showed that compared with single estrogen use group,in the aspects of the effective rate(RR=1.46,95%CI=1.29-1.66,P<0.004),HAMD score(WMD=-4.61,95%CI=-5.63——3.59,P<0.01)and KMI score(WMD=-5.83,95%CI=-11.12——0.53,P<0.01),the estrogen combined with antidepressants group had statistically significant difference.Conclusion The treatment and alleviating effect of estrogen substitution therapy combined with antidepressants for treating perimenopause symptoms and depression is superior to that of single estrogen use substitution therapy.

Objective: To observe the expression of long non-coding RNA myocardial infarction associated transcript (LncRNA-MIAT) in tumor necrosis factor-α (TNF-α) induced endothelial cells (ECs) inflammation in vitroand to study the impact of LncRNA-MIAT on inflammatory regulation. Methods: LncRNA-MIAT expression in ECs was induced by TNF-α at different time and concentration. Expressions of intercellular adhesion molecule-1 (ICAM-1) and LncRNA-MIAT in inflammatory ECs were examined by quantitative real time polymerase chain reaction (qRT-PCR) and Western blot analysis. Moreover, ECs was transfected by siRNAMIAT to observe the effect of LncRNA-MIAT knock-down on ICAM-1 expression. Results: LncRNA-MIAT expression showed the increasing trend by elevated time and concentration of TNF-stimulation. Compared with TNF-α stimulation at 0h, 6h and 12h, LncRNA-MIAT expressions were increased at 24h and 48h of TNF-αstimulation respectively, allP<0.05; compared with TNF-α concentration at 0ng/ml and 0.125ng/ml, LncRNA-MIAT expressions were elevated by TNF-α stimulation at 1.000ng/ml and 10.000ng/ml respectively, allP<0.05. With siRNAMIAT knock-down, TNF-α induced ICAM-1 protein expression was significantly reduced in ECs,P<0.05. Conclusion: LncRNA-MIAT might be involved in ECs inflammatory response and it may play a role to promote inflammation.

China ; Humans ; Streptococcus pneumoniae

BACKGROUND:Elderly patients with degenerative lumbar degeneration often appear insufficient holding power of pedicle screw in spine surgery, which is prone to occur de-pinning and leads to insecure fixation. How to increase the holding power of screws has become a hot research. OBJECTIVE:To observe the early clinical effect of pedicle screws with cement augmentation for treating lumbar degenerative diseases in elderly patients. METHODS:A total of 65 old patients with lumbar degenerative diseases received a treatment between August 2012 and April 2014, and were divided into two groups according to the treatment strategy:treatment group (n=24;internal fixation of pedicle screws with cement augmentation) and control group (n=41;routine internal fixation of pedicle screws). General conditions of patients in two groups were observed and compared. Visual analog scale (VAS) and Japanese Orthopaedic Association (JOA) score system were used for evaluating the lumbar and back pain, and restoration of neurological function in lower limbs respectively. RESULTS AND CONCLUSION:Al of the patients successful y received the surgery and then were fol owed up from 3 to 20 months. The anterioposterior and lateral X-ray film revealed no loosening, loss, fracture of the screws, and no loss of intervetebral space height was found. There was no significant difference in the blood loss and hospital stay between two groups (P>0.05). JOA at postoperative 3 and 6 months, and VAS score at postoperative 3 months were significantly improved after the treatment of pedicle screws with cement augmentation, when compared to control group (P<0.05). VAS scores showed no difference at 6 months postoperatively in two groups (P>0.05). Pedicle screws with cement augmentation for treating lumbar degenerative diseases have the advantages of improving the screws holding strength, reconstructing the stability of lumbar vertebra and obtaining clinical efficacy on degenerative spine.

Background and objectiveA common consensus has been reached regarding ifrst- and second-line therapies for advanced non-small cell lung cancer (NSCLC). The newest guideline from National Comprehensive Cancer Network (NCCN) also provides recommendations for third-line therapy. This study focused on fourth-line and enhanced treatments for advanced NSCLC. Treatment results and impact factors were analyzed and discussed.MethodsA total of 140 patients with advanced NSCLC were selected and their data were analyzed. Response rate, survival rate, and prognostic factors were evaluated.Results Among the 140 patients, 12.9% (18 cases) showed partial response, 25.7% (36 cases) suffered from a stable disease, and 38.6% (54 cases) exhibited a disease control rate. Median overall survival (OS) and fourth-line therapy OS were 31 months and 10.1 months, respectively. The median progression free survival (PFS) of fourth-line therapy was 2.6 months. Univariate and multivariate analyses indicated different therapy regimens and suggested whether or not patients should undergo follow-up treatments. These parameters were independent prognostic factors of the OS of the fourth-line therapy; by contrast, no independent impact factor of PFS was found. Chemotherapy resulted in better median OS in fourth-line therapy than in targeted therapy (11.7 monthsvs 7.1 months,P=0.013). Considering the median OS of fourth-line therapy, we observed that single agent therapy did not signiifcantly differ from double agent therapy; likewise, we found that ifrst-time usage did not signiifcantly differ from multiple usage of epidermal growth factor receptor tyrosine kinase inhibitor.Conclusion Fourth-line therapy is recommended to increase the survival of advanced NSCLC patients. Nevertheless, the role of fourth-line therapy in advanced NSCLC should be further assessed in clinical trials.

ObjectiveTo investigate the effect of dexmedetomidine on tracheal extubation response in patients undergoing thyroid surgery after general anesthesia.Methods Forty-two patients who ASA classification Ⅰ - Ⅱ,were performed thyroid surgery under total intravenous anesthesia.They were divided into dexmedetomidine group and control group by random number table with 21 cases each.Both groups patients anesthesia induction and maintenance with the same methods,dexmedetomidine group patients at 15 min before anesthesia induction with venous infusion dexmedetomidine 0.6 μ g/kg(finished 10 min infusion),followed by 0.4 μ g/(kg · h) continuous infusion,control group patients with pump equivalent in 0.9％ sodium chloride injection in the same way.Systolic blood pressure (SBP),diastolic blood pressure (DBP) and heart rate (HR),surgery time,recovery time,extubation time,orientation recovery time,modified Aldrete score ≥9 scores time,rate of recovery from restlessness,tolerance score and recovery from any adverse effects were recorded.ResultsThere were no significant differences between two groups in surgery time,recovery time,extubation time,orientation recovery time,modified Aldrete score ≥ 9 scores time (P ＞0.05).SBP,DBP,HR at immediately and after extubation with 1,3,5 min of dexmedetomidine group were lower than those of control group(P ＜ 0.05 or ＜ 0.01 ).Tolerance score excellent rate of dexmedetomidine group was higher than that of control group[95.2％ (20/21) vs.28.6％ (6/21)] (P ＜ 0.05),the rate of recovery from restlessness of dexmedetomidine group was lower than that of control group[0 vs.28.6％(6/21 ) ] (P ＜ 0.05).ConclusionBefore anesthesia induction in patients with venous infusion dexmedetomidine 0.6 p g/kg(finished 10 min infusion),followed by 0.4 p g/(kg·h) continuous infusion can effectively reduce the patients' cardiovascular response to extubation,strengthen the patients' tolerance to endotracheal tube,reduce the patients' agitation and recover consciousness comfortable.

ObjectiveTo compare the efficacy of intravenous infusion of dexmedetomidine and midazolam for premedication in children.MethodsNinety-two ASA Ⅰ or Ⅱ children (46 cases aged 1-3 yr and 46 cases aged 4-6 yr) scheduled for elective general or urologic surgeries,were enrolled in this study.The children were randomly divided into 2 groups (n =46 each):midazolam group (group M) and dexmedetomidine group (group D).The children accompanied by their parents were admitted to the anesthesia preparation room at about 20 min before induction of anesthesia,and midazolam 0.1 mg/kg òr dexmedetomidine 1 μg/kg was infused intravenously over 10 min.Anesthesia was induced with proporol-rocuroniume-remifentanil,and maintained with sevoflurane-remifentanil-rocuroniume.Modified Yale Preoperative Anxiety Scale (mYPAS) score,sedation score,HR,mean arterial pressure (MAP),respiratory rate (RR) and SpO2 were recorded before premedication (T1),before separation from their parents (T2) and when entering the operating room (T3).The incidence of sleep (a sedation score of 4) was recorded at T2,3.The end-tidal concentration of sevoflurane,infusion rate of remifentanil,laryngeal air way removal time,emergence time,duration of stay at the recovery room,incidence of delirium during recovery period,the percentage of patients requiring rescue analgesic,and adverse effects were also retorded.ResultsCompared to that at T1,the mYPAS score was significantly decreased at T2,3,and the sedation score was significantly increased at T2,3 in both groups ( P ＜ 0.05),HR at T2 and MAP at T2,3 were significantly decreased in group D,and HR at T3 was significantly increased in group M ( P ＜ 0.05 ).Compared to group M,the sedation scores and the incidence of sleep were significantly increased at T2,3,and the HR was significantly decreased at T2 in group D ( P ＜ 0.05).There was no significant difference in the mYPAS score,RR,MAP,SpO2,end-tidal concentration of sevoflurane,infusion rate of remifentanil,laryngeal air way removal time,emergence time,duration of stay at the recovery room,incidence of delirium during recovery period,the percentage of patients requiting rescue analgesic,and incidence of adverse effects between D and M groups ( P ＞ 0.05).ConclusionThe sedative efficacy of iv dexmedetomidine is superior to that of iv midazolam when infused for premedication in children,but it exerts much influence on hemodynamics,and the changes in hemodynamics should be noted.