Objective To explore the role and possible molecular mechanism of Isocitrate dehydrogenase 1(IDH1) gene in proliferation and migration of intrahepatic cholangiocarcinoma (iCCA) cell HuCCT1. Methods HuCCT1 cells with IDH1 gene knockout (HuCCT1^IDH1-/-) were constructed by CRISPR/Cas9 gene editing technology. To investigate the capacities of proliferation, migration and invasion of HuCCT1^WT (HuCCT1 cells with wild-type IDH1 gene) and HuCCT1^IDH1-/- cells, assays of CCK-8, clone formation, scratch and transwell were performed. Western blotting was used to detect the expression levels of epithelial-mesenchymal transition(EMT) associated proteins E-cadherin, N-cadherin, Vimentin, MMP-9, Wnt3a and β-catenin in two groups of cells. The transcriptome sequencing data of HuCCT1^WT and HuCCT1^IDH1-/-cells were analyzed by bioinformatics methods, Western blotting was used to verify the expression of signaling pathway-related proteins. Results Compared with HuCCT1^WT cells, HuCCT1^IDH1-/- cells showed the number of proliferation and clone formation significantly reduced (P<0.05), the proportion of cells blocked in G₂/M phase was significantly increased (P<0.01), the rate of scratch healing was significantly decreased (P<0.01), and the number of migrated cells (P<0.001) and invaded cells (P<0.05) was significantly reduced. qRT- PCR assay showed that the expression levels of IDH1, Vimentin, MMP-9 and genes related to the regulation of G₂/M cycle proliferation, Cyclin A2, Cyclin B1 and CDK1 mRNA were down-regulated in HuCCT1^IDH1-/- cells (P<0.05), and the expression of CDH1 mRNA encoding E-cadherin was up-regulated (P<0.01); Western blotting assay showed that the expression level of E-cadherin in HuCCT1^IDH1-/- cells was significantly increased (P<0.05), and the expression level of N-cadherin, Vimentin and MMP-9 protein was significantly decreased (P<0.05) than that in HuCCT1^WT cells. Data of transcriptome sequencing revealed 1476 differentially expressed genes (DEGs) between two groups of HuCCT1 cells. Go enrichment analysis showed the DEGs were significantly enriched in cell biological processes associated with inflammatory response, cell signaling and cell metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that the DEGs may be involved in some signaling pathways such as Wnt,MAPK, Rap1, Hippo and TNF, which are closely related to the regulation of proliferation and invasion of tumor cells. Western blotting verification results showed that compared with HuCCT1^WT cells, the relative expression of Wnt3a and β‑catenin proteins of HuCCT1^IDH1-/- cells was significantly decreased (P<0.05). Conclusions IDH1 gene may participate in the control of biological functions of HuCCT1 cells, including cell proliferation, migration, invasion and epithelial mesenchymal transition.The mechanism may be related to the activation of the Wnt/β-catenin signaling pathway.

Objective To investigate the effect and mechanism of transplantation of neuregulin1 (NRG1) gene-modified bone marrow mesenchymal stem cells (BMSCs) on the repair of hemi-transected spinal cord injury (SCI) in rats. Methods Isolated and cultured rat BMSCs, followed by transfection with the NRG1 gene. The levels of NRG1 in BMSCs lysate and culture supernatant was deected by ELISA method, and the proliferation activity of the BMSCs was detected by cell counting method. Forty-three healthy 8-week-old SD rats were randomly divided into control group (n=10), SCI model group (n=10), BMSCs group (n=10), and NRG1-BMSCs group (n=13). After establishing the spinal cord hemisection model, animals received in-situ transplantation of BMSCs or NRG1-BMSCs. On the 1, 7, 14, 21, and 28 days after transplantation, the hind limb motor function was evaluated using BBB score and inclined plate test; on the 7th day after transplantation, the migration and distribution of transplanted cells was monitored using a fluorescence microscope; on the 28th day after transplantation, the pathological changes of rat spinal cord tissues was examined using HE staining and Nissl staining; cell apoptosis using TUNEL staining, and levels of endoplasmic reticulum stress-related proteins X-box binding protein 1 (XBP1), C/EBP homologous protein (CHOP), activating transcription factor 4 (ATF4), ATF6, glucose-regulated protein 78 (GRP78)] and apoptosis-related proteins [B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated protein X (Bax)] in rat spinal cord tissues using Western blotting. Results BMSCs were successfully isolated, cultured, and transfected with the NRG1 gene. ELISA method results showed that the NRG1 contents in the NRG1-BMSCs lysate and culture supernatant were significantly higher than that of BMSCs in a time-dependent manner (P<0.05). The proliferation activity of NRG1-BMSCs was significantly higher than that of BMSCs (P<0.05). On the 21 and 28 days after transplantation, the BBB score and the slope angle of the inclined plate in NRG1-BMSCs group were higher than those in SCI model group or BMSCs group (P<0.05). However, it did not reverse to the level in control group (P<0.05). On the 28th day after transplantation, compared with the SCI model group and BMSCs group, neuronal pyknosis reduced, the Nissl body density increased, the expression levels of XBP1, CHOP, ATF4, ATF6, GRP78, and Bax, and the rate of TUNEL-positive cells significantly reduced in NRG1-BMSCs group (P<0.05), and the expression level of Bcl-2 significantly increased (P<0.05). Conclusion Transplantation of NRG1 gene-modified BMSCs can alleviate SCI and improve the recovery of motor function in rats. The mechanism may be related to promoting the proliferation activity of BMSCs, inhibiting cell apoptosis, and mitigating endoplasmic reticulum stress.

Objective To evaluate the characteristics of different antigen-specific T cell immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after inoculation with 2 doses of SARS-CoV-2 inactivated vaccine for 12 months. Methods Fifteen healthy adults were enrolled in this study and blood samples collected at 12 months after receiving two doses of SARS-CoV-2 inactivated vaccine. The level and phenotypic characteristics of SARS-CoV-2 antigen-specific T lymphocytes were detected by activation-induced markers (AIM) based on polychromatic flow cytometry. Results After 12 months of inoculation with 2 doses of SARS-CoV-2 inactivated vaccine, more than 90% of adults had detectable Spike and Non-spike antigen-specific CD4⁺ T cells immune responses (Spike: 14/15, P=0.0001; Non-spike: 15/15, P<0.0001). 80% of adults had detectable Spike and Non-spike antigen-specific CD8⁺ T cells immune responses (Spike: 12/15, P=0.0463; Non-spike: 12/15, P=0.0806). Antigen-specific CD4⁺ T cells induced by SARS-CoV-2 inactivated vaccination after 12 months were composed of predominantly central memory (CM) and effector memory 1 (EM1) cells. On the other hand, in terms of helper subsets, antigen-specific CD4⁺ T cells mainly showed T helper 1/17 (Th1/17) and T helper 2 (Th2) phenotypes. Conclusions SARS-CoV-2 inactivated vaccination generates durable and extensive antigen-specific CD4⁺ T cell memory responses, which may be the key factor for the low proportion of severe coronavirus disease 2019 (COVID-19) infection in China.

Objective To analyze the correlation between the ELL2 gene 1119 T>C polymorphism and the susceptibility to pleomorphic adenoma of the salivary gland. Methods The pedigree of the pleomorphic adenoma family of salivary gland was drawn. The exons of ELL2 gene in 5 members of salivary pleomorphic adenoma family were sequenced. A case-control study was conducted. One hundred and twelve patients with pleomorphic adenoma of the salivary gland who visited the Department of Oral and Maxillofacial Surgery of Shanxi Bethune Hospital from January 2016 to July 2020 were taken as case group, and 176 healthy examinees from January 2019 to January 2020 were taken as control group with age and sex as matching conditions. The 1119 T>C polymorphism of ELL2 genes in the two groups were detected with high resolution melting (HRM) curve. Chi-square test was adopted to analyze the correlation between gene polymorphism and the occurrence of pleomorphic adenoma of the salivary gland, stratified analysis was performed to evaluate the synergistic effect of smoking and genotype, and real time quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression level of ELL2 in individuals with different genotypes. Results The 1119 T>C polymorphism site existed in the exon 8 of ELL2 gene in a family with pleomorphic adenoma of salivary gland. The results of case-control study showed that the genotype frequency of homozygous CC was significantly higher in patients with pleomorphic adenoma of salivary gland than that in the controls (24.1% vs. 11.9%, P=0.002). Homozygous CC was associated with increased risk for developing pleomorphic adenoma of salivary gland (OR=3.059, 95%CI 1.494-6.263) in this cohort. Stratification analysis showed that smoking and 1119C allele cooperated to increase the risk of pleomorphic adenoma of salivary gland (OR=3.200, 95%CI 1.460-7.014). The expression level of ELL2 mRNA in CC genotype was significantly higher than that in individuals with CT or TT genotype (P<0.05). Conclusion The genetic variation of ELL2 may play an important role in the occurrence of pleomorphic adenoma of salivary gland, and smoking combined with the 1119C allele increased the risk of this disease.

Objective To investigate the effect of different doses of statins on the clinical efficacy and safety outcome of intravenous thrombolytic therapy of urokinase in patients with acute ischemic stroke (AIS). Methods Based on a large prospective, multicenter study, the Chinese Intravenous Thrombolysis Registry for AIS within 4.5 h of onset (INTRECIS) database, clinical data of 898 patients with urokinase intravenous thrombolysis for AIS were retrospectively analyzed. According to the amount of statin used during hospitalization, the patients were divided into 132 patients in no-statin group, 591 patients in conventional statin group and 175 patients in intensive statin group. Clinical outcome measures included 14-day improvement in the National Institutes of Health Stroke Scale (NIHSS) and 90-day excellent prognosis (improved Rankin score ≤1 point). Safety measures included recurrent stroke, bleeding events, and 90-day all-cause mortality. Results After adjusting for differences in baseline characteristics (age, coronary heart disease, diabetes, atrial fibrillation, systolic blood pressure, OTT, DNT, previous anti-plate use, blood glucose, and treatment in Class A hospitals), NIHSS scores improved at 14 days after admission and excellent prognosis at 90 days after admission in convention-dose and intensive statin groups were superior to those in no-statin group (P<0.05); Univariate and multivariate analysis of safety outcome indicators showed no statistically significant differences in stroke recurrence and bleeding events among the three groups (P>0.05); The 90-day all-cause mortality was significantly higher in no-statin group (10.6%) than in convention-dose statin group (2.0%) and intensive dose statin group (2.9%) (P<0.01). Conclusions In patients with AIS who were treated with intravenous urokinase thrombolytic therapy, intensive statin use was associated with improved 14-day NIHSS score and near-term prognosis without increasing the risk of stroke recurrence and bleeding events. Statin use is beneficial to reduce mortality.

Objective To analyze the correlation between irritable bowel syndrome (IBS) as well as its subtypes and gallbladder stone. Methods Collected the clinical data of 556 patients who were treated in Department of Gastroenterology of the Sixth Medical Center of Chinese PLA General Hospital from January 2019 to March 2023. The patients were divided into IBS group (n=161) and non-IBS group (n=395). The subjects were investigated by questionnaire, physical examination and blood examination, and the data of gender, age, height, weight, blood pressure and blood biochemical indexes were obtained and compared between two groups. The relation between gallbladder stone and IBS were evaluated by logistic regression analysis. Results There were 90 cases of gallbladder stone in the total population, accounting for 16.2%, including 37 cases of gallbladder stone in IBS group (23.0%) and 53 cases in non-IBS group (13.4%). The prevalence rate of gallbladder stone in IBS group was significantly higher than that in non-IBS group (P<0.05). There were 6 cases of gallbladder muddy stones (3.7%) in IBS group and 3 cases (0.8%) in non-IBS group. And the prevalence rate of gallbladder muddy stones in IBS group was also significantly higher than that in non-IBS group (P<0.05). Logistic regression analysis showed that the age, BMI, total bile acids (TBA), total cholesterol (TC) and combined IBS were independently related to the occurrence of gallbladder stone (P<0.05). In the 161 IBS patients, there were 114 cases of diarrhea-predominant IBS (IBS-D group), including 26 cases (22.8%) of gallbladder stone in IBS-diarrhea (IBS-D, n=114) group and 47 cases of constipation-predominant IBS (IBS-C group), including 11 cases (23.4%) of gallbladder stone. And there were 53 cases (13.4%) of gallbladder stone in the non-IBS group (n=395). Further analysis showed that the prevalence rate of gallbladder stone in IBS-D group was significantly higher than that in non-IBS group (P<0.05). There was no significant difference in gallbladder stone prevalence rate between IBS-C group and non-IBS group (P>0.05). Conclusions There is a correlation between IBS and gallbladder stones. In addition, among the two subtypes of IBS, IBS-D patients may have an increased risk of gallbladder stone compared with non-IBS patients.

The electroencephalography (EEG) is an important method to evaluate epileptic seizure and brain functions, and it is of great significance for screening aircrew with potential risks of seizure and thus reducing the incidence of airborne incapacitation events. There are cases of epileptic seizure and seizure attack during flight among military aircrew both at home and abroad. However, currently there is no detailed EEG standards for the selection of aircrew applicants and physical examination of military aircrew. This consensus of Chinese experts on electroencephalographic examination and identification criteria for military aircrew was compiled jointly by experts in the fields of aeromedicine, neurology, epilepsy, and neuro-electrophysiology, from Xijing Hospital of Air Force Military Medical University and PLA General Hospital. This consensus was formulated based on 287 relevant literatures from PubMed, CNKI, Wanfang Data and VIP, combined with guidelines in the fields of epilepsy and EEG and the clinical experiences of Chinese experts. The objectives of the consensus are to further clarify the definition of "normal EEG", "borderline EEG" and "abnormal EEG" for military aircrew, unify the criteria of EEG identification for military aircrew with high risk of incapacitation, and standardize the criteria of EEG examination for aeromedical identification for military aircrew. This consensus includes four sections: applicable population and quality requirements for EEG monitoring, standards for EEG interpretation, standards for medical decision based on EEG, and the treatment of "temporarily unqualified" aircrew, which aim to literature supports and practical expert opinions for the standardization and accuracy of aeromedical qualification of EEG in military aircrew.

When refractory diarrhea comes on, it greatly affects the life and daily work of patients, and there is no unified treatment. Patients with refractory diarrhea have varying degrees of intestinal flora disorder, so rebuilding the intestinal micro ecosystem may be an effective way to treat refractory diarrhea. Fecal microbiota transplantation (FMT) has the potential to be an effective treatment for refractory diarrhea as a therapy that reconstructs normal intestinal flora. In recent years, FMT has been applied to the treatment of some refractory diarrhea related to intestinal flora imbalance, such as recurrent clostridium difficile infection, inflammatory bowel disease, irritable bowel syndrome, and has achieved good results, but some problems have not been properly solved so far. This article reviews the mechanism of action of FMT in the treatment of refractory diarrhea, its clinical application, research progress and current problems.

Objective To report a case of synovial sarcoma of the liver and review the literature for improving the understanding of the disease. Methods The clinical data of a patient with liver synovial sarcoma admitted to the First Affiliated Hospital of Henan University were analyzed retrospectively. The imaging, pathological features, treatment and prognosis of this disease were summarized by searching the database (CNKI, Wanfang Data, PubMed, untill July 2022) and the literature results analyzed comprehensively. Results The patient was a 71-year-old female who was admitted to the hospital due to abdominal pain. Computed tomography (CT) scan showed a mass with mixed density in the right lobe and caudate lobe of the liver. The large cross section size was about 115 mm×87 mm and the mass showed continuous heterogeneous enhancement, being considered as malignant hepatic tumors with multiple metastasis of the liver and lung. Ultrasound-guided needle biopsy was performed, and microscopy showed the tumor cells were obvious atypical, and some were spindle-shaped. Immunohistochemistry showed that the patient was positive for vimentin (VIM), epithelial membrane antigen (EMA), methylation of histone at lysine 27 (H3K27Me3), and negative for pan cytokeratin (CK-pan) and S-100, and pathological diagnosis of synovial sarcoma was made. The patient did not undergo subsequent treatment and was lost to follow-up after discharge. A total of 12 cases of hepatic synovial sarcoma were reported after searching the database. The clinical manifestations were abdominal pain or distention. The lesions were mostly located in the right lobe of the liver, usually large, heterogeneous density, and heterogeneous enhancement on enhanced CT or magnetic resonance imaging (MRI). Spindle-shaped cells were found at histopathologic examination. Immunohistochemistry showed the patient was positive for VIM, EMA, H3K27Me, B-cell leukemia/lymphoma-2 (BCL-2) and transducer-like enhancer of split 1 (TLE1). SS18-SSX fusion gene or SS18 gene isolation were detected. Eleven patients received surgical treatment, 5 received adjuvant chemotherapy, and 4 had recurrence or metastasis during the follow-up period. Conclusions Synovial sarcoma of the liver is a rare malignant tumor of the liver. The clinical and imaging features are not specific. The diagnosis depends on pathology. At present, the main treatment is surgery, and comprehensive treatment such as adjuvant chemotherapy can be performed. The prognosis of the patient is poor.

Objective To investigate the predictive value of new simplified insulin resistance (IR) assessment indexes in identifying subclinical left ventricular systolic function impairment in patients with type 2 diabetes mellitus (T2DM). Methods A total of 150 T2DM patients with preserved left ventricular ejection fraction (LVEF≥50%) who were admitted to Department of Endocrinology of the First Affiliated Hospital of Air Force Medical University from June 2021 to December 2021 were retrospectively analyzed. All patients underwent two-dimensional speckle tracking echocardiography to measure left ventricular global longitudinal strain (GLS). According to GLS value, the subjects were divided into the normal group (GLS≥18% group, n=80) and the impaired group (GLS<18% group, n=70). Some new simplified IR assessment indicators were calculated and compared between the two groups, including body mass index (BMI), TG/HDL‑C ratio, triglyceride-glucose (TyG) index, TyG‑BMI index, TyG‑WHR and metabolic score for IR (METS‑IR). Correlation between the GLS and the new simplified IR assessment indexes was analyzed. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of different simplified IR assessment indexes, with the area under the curve (AUC) calculated. Furthermore, according to whether the subjects were complicated with hypertension, binary logistics regression analysis was performed to explore the independent correlation between the simplified IR assessment index and GLS <18%. Results Total 150 were included with aged (54.5±13.7) years with 96 (64.0%) men and 54 (36.0%) women. Compared with the GLS≥18% group, the TG/HDL‑C ratio, TyG index, TyG‑BMI, and METS‑IR of subjects in the GLS<18% group were significantly increased (P<0.05). Pearson correlation analysis showed that TG/HDL‑C ratio, TyG index, TyG‑BMI, TyG‑WHR, and METS‑IR were negatively correlated with GLS (P<0.05). ROC analysis showed that TyG index had a certain predictive value for the evaluation of GLS<18% (AUC=0.678, 95%CI 0.591-0.765, P<0.001). Stratification based on hypertension and further adjusting for confounding factors, TyG index remains significantly associated with GLS<18% (OR=3.249, 95%CI 1.045-10.103, P=0.042). Conclusions The novel simplified insulin resistance evaluation indexes are closely associated with left ventricular subclinical systolic dysfunction in T2DM patients with preserved ejection fraction. TyG index is an effective index to identify left ventricular subclinical dysfunction in these populations.