Objective To investigate the therapeutic effects of Isaria felina derived from Cordyceps sinensis combined with cyclophosphamide(CTX)in hepatoma H22 tumor-bearing mice.Methods An H22 tumor-bearing mouse model was established and mice were divided randomly into a normal control group(NC group,distilled water),model control group(MC group,distilled water),positive control group(CTX group,25 mg/kg),Isaria felina group(IF group,400 mg/kg),and combined administration group(IF+CTX group,IF 400 mg/kg+CTX 25 mg/kg),with 5 mice in each group.Distilled water and IF were administered by gavage,and CTX was administered by intraperitoneal injection.The administration cycle was 10 days.At the end of the experiment,the mean tumor volume and weight,tumor inhibition rate,q value,and immune organ index were calculated,and routine blood indexes and cytokine levels were determined.Histopathological changes in tumor tissues were observed by HE staining.Results The tumor volume and mass were significantly lower in mice in each treatment group compared with those in mice in the MC group(P＜0.05).The tumor inhibition rates in the CTX,IF,and IF+CTX groups were 49.3%,34.2%,and 72.8%,respectively,and the q value was 1.09.The numbers of white blood cells,Lymph,and platelets were significantly higher in the IF+CTX group than in the CTX group(P＜0.05).The spleen index was significantly higher in the MC group compared with that in the NC group,and significantly lower in the IF+CTX group compared with that in the MC group(P＜0.05).Serum interferon-γ levels were significantly lower in the MC group than in the NC group,and were significantly higher in the IF and IF+CTX groups compared with those in the MC and CTX groups(P＜0.05).Pathologically,tumor cells in the MC group grew well and were numerous and closely arranged,while cells in the CTX,IF,and IF+CTX groups were arranged loosely,with focal necrosis and nuclear pyknosis of necrotic cells in many places.Conclusions The combination of IF and CTX has an additive anti-tumor effect on H22 tumor-bearing mice,which can alleviate immunosuppression and have an immunomodulatory function.

Objective:To analyze the gene mutation type and clinical phenotype of patients with PRRT2 mutation, and explore their relations with prognosis. Methods:A total of 18 patients with PRRT2 gene mutation (1 patient with novel mutation in PRRT2 gene, and 17 probands in 17 families with PRRT2 gene mutation) were enrolled in Department of Neurology, First Affiliated Hospital of Air Force Medical University from January 2018 to July 2023. Serum of the patients was collected for whole exon sequencing, and mutation sites and types of PRRT2 gene were analyzed. SWISS-MODEL website was used to predict the changes in protein structure caused by PRRT2 gene mutation. The relations of gene mutation type and clinical phenotype with prognosis of these patients were analyzed. Results:(1) All 18 patients with PRRT2 gene mutation were heterozygous mutation, including 12 frameshift mutations, 5 missense mutations, and 1 integer mutation. The clinical phenotype included benign familial infantile epilepsy (BFIE) in 5 patients, epilepsy in 6 patients, exercise-induced paroxysmal kinesigenic dyskinesia (PKD) in 5 patients, and infantile convulsion and choreoathetosis (ICCA) in 2 patients. A total of 8 mutation sites were found in 18 patients with PRRT2 gene mutation, of which 3 mutation sites have been reported, and 5 mutation sites have not been reported, including c.647(exon2)C>A, c.647(exon2)C>G, c.170(exon2)delC, c.981(exon3)C>G, and lossl(EXON: 2)(all). (2) Eighteen patients mainly accepted oxcarbazepine, levetiracetam, and sodium valproate in combination or monotherapy. Among them, 5 BFIE patients, 2 ICCA patients and 3 epilepsy patients were seizure-free after treatment. PKD patients did not respond well to oxcarbazepine. (3) Three frameshift mutations (mutation sites: c.649 [exon2]_c.650 [exon2] insC, c.640 [exon2]_c.641 [exon2] insC, and c.170 [exon2] delC) led to premature termination of protein translation, resulting in significant changes in protein structure. Four missense mutations (mutation sites: c.640[exo2]G>C, c.647[exon2]C>A, c.647[exon2]C>G, and c.981[exon3]C>G) had little effect on protein structure changes. No relation was found between changes of protein structure caused by different mutation types and prognosis. Conclusion:PRRT2 gene mutation patients with clinical phenotypes of BFIE and ICCA have good prognosis, but the mutation type is not related with the prognosis of patients.

Objective:To report the clinical phenotype and mutation site of a patient with grey matter heterotopia caused by a de novo heterozygous missense mutation in the TUBB2B gene, and to expand the phenotypic and mutational spectrum of TUBB2B mutations. Methods:One patient with TUBB2B mutation who presented to the Department of Neurology, the First Affiliated Hospital of Air Force Medical University in July 2017 was collected and analyzed for clinical features and mutation site, and a review of previous studies was performed. Results:The male patient started at the age of 18 and presented mainly with seizures, poor left-handed fine motor skills and poor spatial imagination. Magnetic resonance imaging showed nodular grey matter heterotopia in the right cerebral hemisphere, right frontoparietal-temporal localized cerebral gyrus, and cerebral sulcus shallow flat.The whole exon gene test suggested a heterozygous missense mutation in the TUBB2B gene: c.776 C>T (p.Pro259Leu), which was wild-type in both of his parents. The mutation site was located between the tubulin and tubulin-c structural domains and did not affect the function of the essential structural domain. After treatment with magnesium valproate in combination with levetiracetam, the patient′s seizure symptoms were significantly controlled and he has been seizure-free for 3 years now. Conclusions:The TUBB2B gene c.776 C>T (p.Pro259Leu) heterozygous missense mutation is a novel missense mutation causing grey matter heterotopia. The patient had a good prognosis, and the combination of two antiepileptic drugs resulted in complete seizure control.

Objective:To evaluate the long-term efficacy of laparoscopic-assisted natural orifice specimen extraction surgery (NOSES) colectomy using Cai tube for treating left-sided colorectal cancer.Methods:This was a randomized controlled trial. Inclusion criteria were as follows: preoperative pathological diagnosis of left-sided colorectal adenocarcinoma (rectal, sigmoid colon, descending colon, or left transverse colon cancer with the caudad margin ≥8 cm from the anal margin); preoperative abdominal and pelvic computed tomography (or magnetic resonance imaging) showing maximum tumor diameter <4.5 cm; and BMI <30 kg/m 2. Patients with synchronous multiple primary cancers or recurrent cancers, a history of neoadjuvant chemoradiotherapy, preoperative evidence of significant local infiltration, distant metastasis, or complications such as intestinal obstruction and intestinal perforation, or who were not otherwise considered suitable for laparoscopic surgery were excluded. A random number table was used to randomize sequential patients to NOSES surgery using Cai tube (non-assisted incision anal sleeve: patent number ZL201410168748.2) (NOSES group) or traditional laparoscopic-assisted surgery (CLS group). Relevant clinical data of the two groups of patients were analyzed, the main outcomes being disease-free survival, overall survival, overall recurrence rate, and local recurrence rate 5 years after surgery. Results:Patients in both study groups completed the surgery successfully with no requirement for additional surgery. After mean 70 (7–83) months postoperative follow-up, the 5-year overall postoperative survival in the NOSES and CLS groups was 90.0% and 83.3%, respectively ( P=0.455); disease free survival was 90.0% and 83.3%, respectively ( P=0.455); overall recurrence rate 6.6% and 10.0%, respectively ( P=0.625); and local recurrence rate both were 3.3% ( P=0.990), respectively. None of these differences was statistically significant. Conclusions:NOSES and CLS have similar long-term efficacy, and NOSES deserves to be used in clinical practice.

Objective:To evaluate the long-term efficacy of laparoscopic-assisted natural orifice specimen extraction surgery (NOSES) colectomy using Cai tube for treating left-sided colorectal cancer.Methods:This was a randomized controlled trial. Inclusion criteria were as follows: preoperative pathological diagnosis of left-sided colorectal adenocarcinoma (rectal, sigmoid colon, descending colon, or left transverse colon cancer with the caudad margin ≥8 cm from the anal margin); preoperative abdominal and pelvic computed tomography (or magnetic resonance imaging) showing maximum tumor diameter <4.5 cm; and BMI <30 kg/m 2. Patients with synchronous multiple primary cancers or recurrent cancers, a history of neoadjuvant chemoradiotherapy, preoperative evidence of significant local infiltration, distant metastasis, or complications such as intestinal obstruction and intestinal perforation, or who were not otherwise considered suitable for laparoscopic surgery were excluded. A random number table was used to randomize sequential patients to NOSES surgery using Cai tube (non-assisted incision anal sleeve: patent number ZL201410168748.2) (NOSES group) or traditional laparoscopic-assisted surgery (CLS group). Relevant clinical data of the two groups of patients were analyzed, the main outcomes being disease-free survival, overall survival, overall recurrence rate, and local recurrence rate 5 years after surgery. Results:Patients in both study groups completed the surgery successfully with no requirement for additional surgery. After mean 70 (7–83) months postoperative follow-up, the 5-year overall postoperative survival in the NOSES and CLS groups was 90.0% and 83.3%, respectively ( P=0.455); disease free survival was 90.0% and 83.3%, respectively ( P=0.455); overall recurrence rate 6.6% and 10.0%, respectively ( P=0.625); and local recurrence rate both were 3.3% ( P=0.990), respectively. None of these differences was statistically significant. Conclusions:NOSES and CLS have similar long-term efficacy, and NOSES deserves to be used in clinical practice.

Objective: To analyze the epidemiological characteristics of latent syphilis in Yancheng City from 2016 to 2020, so as to provide insights into syphilis control. Methods: All reported cases with latent syphilis in Yancheng City from 2016 to 2020 was collected from the Communicable Disease Report System of China Disease Prevention and Control Information System, and the prevalence of latent syphilis was estimated and standardized by the seventh population census data in Yancheng City. The trends in the incidence of latent syphilis were evaluated using annual percent change (APC), and the temporal, regional and human distributions of latent syphilis patients were descriptively analyzed. In addition, the spatial clusters of latent syphilis incidence were identified using spatial autocorrelation analysis. Results: A total of 7 790 cases with latent syphilis were reported in Yancheng City from 2016 to 2020, and the standardized incidence of latent syphilis increased from 15.35/105 in 2016 to 28.70/105 in 2020 (APC=17.54%, t=5.357, P=0.013). Latent syphilis cases were reported in each month, and no obvious seasonable characteristics were seen. During the period from 2017 to 2020, the highest incidence of latent syphilis was seen in residents at ages of 70 to 79 years, with incidence rates of 41.71/105, 43.04/105, 75.79/105 and 72.94/105, respectively, and most cases were farmers (4 711 cases, 60.47%). The three highest incidence of latent syphilis was reported in Funing County (191.40/105), Tinghu District (137.13/105) and Yandu District (126.23/105). There was a positive spatial correlation of latent syphilis incidence in Yancheng City from 2016 to 2020 (Moran's I=0.23, Z=4.457, P=0.001), and two high-high clusters were identified in 14 townships (streets) of Funing County, Binhai County, Tinghu District, Sheyang County and Yandu District and 3 low-low clusters in 7 townships (streets) in Jianhu County, Tinghu District, Dongtai City and Sheyang County. Conclusions The incidence of latent syphilis appeared a tendency towards a rise, and there were remarkable spatial clusters identified in latent syphilis incidence in Yancheng City from 2016 to 2020. The elderly people and farmers are at high risk of latent syphilis.

Lung cancer is currently one of the most common malignant tumors in the world. The occurrence and development of lung cancer, especially non-small cell lung cancer (NSCLC), are closely related to the abnormal expression of long non-coding RNA (lncRNA). lncRNA with a transcript of more than 200 nucleotides is involved in chromatin modification, transcription activation, transcription interference and other regulatory processes, and has varying degrees of regulation on the proliferation, migration, and invasion of tumor cells. It is characterized by up-regulation or down-regulation of expression. At present, there are a large number of studies on lncRNA, because lncRNA has considerable application prospects in the diagnosis, clinical treatment, drug resistance research and prognosis evaluation of NSCLC. In this paper, the overview of lncRNA, the up-regulation or down-regulation of NSCLC-related lncRNA expression, NSCLC clinical treatment and drug-resistant lncRNA were summarized.

Objective:To investigate optimal antiplatelet therapy options based on the CYP2C19 genotype in elderly patients with acute coronary syndrome(ACS).Methods:Elderly patients with ACS admitted to our hospital from January 2018 to March 2019 were enrolled and received CyP2C19 gene testing.Patients with the intermediate metabolic genotype of CYP2C19 were randomly divided into two groups: the Ticagrelor group and the double-dose Clopidogrel group.After a one-year follow-up, the risk of bleeding and incidences of cardiovascular events in the two groups were analyzed.Results:468 elderly patients meeting the criteria, 214 had the intermediate metabolic genotype of CYP2C19, accounting for 45.7% of the total, and were randomly divided into the ticagrelor treatment group( n=107)and the double-dose Clopidogrel treatment group( n=107). There were significant differences between the Ticagrelor treatment group and the double-dose Clopidogrel treatment group in incidences of minor bleeding, massive hemorrhage, recurrent angina and recurrent acute myocardial infarction(11.2% vs.22.4%, 2.8% vs. 9.4 %, 4.7% vs.13.1%, 3.7% vs. 11.2%, P<0.05). The double-dose Clopidogrel group not only had a higher risk of cardiovascular events, but also a higher risk of bleeding. Conclusions:For elderly ACS patients with the intermediate metabolic genotype of CYP2C19, a standard dose of ticagrelor is recommended.

[Abstract] Objective: To investigate the effect of Tim-4 on invasion and migration of cervical cancer cells and its underlying mechanisms. Methods：The expression levels of Tim-4 in cervical cancer cell lines Siha, Hela and cervical epithelial immortalized cell line H8 were detected by Real-time PCR. The Tim-4 lentiviral vector was transfected into Siha cell line. The over-expression of Tim-4 in Siha cell line was detected by fluorescence microscopy. The effects of Tim-4 on the invasion and migration of cervical cancer cell line were detected by Transwell and scratches methods. The changes of MMP2, MMP9, E-cadherin and N-cadherin in Siha cells were detected by Western blotting. Results：The expression of Tim-4 was higher in Siha and Hela cell lines compared to that in the H8 cell line. The Siha cell line burdening Tim-4 lentiviral vector was successfully constructed. Over-expression of Tim-4 significantly inhibited the migration and invasion of cervical cancer cell line, and affected the expression of MMP2, MMP9, N-cadherin and E-cadherin. Conclusion：Over-expression of Tim-4 promotes the invasion and migration by regulating the EMT transformation in cervical cell carcinoma.

Objective An interaction network among PD-1-ligands and other proteins were built to add deeper understanding of PD-1 signal pathway and to supply the theoretical data on the clinical application study of PD-1 and its ligands.Methods Searching the literature about PD-1 and its ligands in the PubMed,the result of which would be used to summarize the proteins that had been reported to have interactions with PD-1 and its ligands,and then,quadratic search would be performed on these proteins.Finally,the software Cytoscape would be used to build and analyze the interaction network and verified by PCR.Results There were 122 and 126 nodes in the PD-1/PD-L1 network and PD-1/PD-L2 network respectively.These proteins were involved in TCR signal path-way,cell adhesion,JAK-STAT signal pathway and interaction between cytokines.Meanwhile,a perspective that PD-L1 may influ-ence on CXCR4 through JAK-STAT pathway based on the network which had been supported by qPCR.Conclusion The bioinfor-matics suggested that there are differences between the mechanism of PD-1/PD-L1 and PD-1/PD-L2.Additionally,the method, which was based on the literature mining and bioinformatics,is good to put the biological literature to rational utilization and to pro-vide guidance for experiments.