Originating but free from chromosomal DNA, extrachromosomal circular DNAs (eccDNAs) are organized in circular form and have long been found in unicellular and multicellular eukaryotes. Their biogenesis and function are poorly understood as they are characterized by sequence homology with linear DNA, for which few detection methods are available. Recent advances in high-throughput sequencing technologies have revealed that eccDNAs play crucial roles in tumor formation, evolution, and drug resistance as well as aging, genomic diversity, and other biological processes, bringing it back to the research hotspot. Several mechanisms of eccDNA formation have been proposed, including the breakage-fusion-bridge (BFB) and translocation-deletion-amplification models. Gynecologic tumors and disorders of embryonic and fetal development are major threats to human reproductive health. The roles of eccDNAs in these pathological processes have been partially elucidated since the first discovery of eccDNA in pig sperm and the double minutes in ovarian cancer ascites. The present review summarized the research history, biogenesis, and currently available detection and analytical methods for eccDNAs and clarified their functions in gynecologic tumors and reproduction. We also proposed the application of eccDNAs as drug targets and liquid biopsy markers for prenatal diagnosis and the early detection, prognosis, and treatment of gynecologic tumors. This review lays theoretical foundations for future investigations into the complex regulatory networks of eccDNAs in vital physiological and pathological processes.
Male ; Female ; Animals ; Humans ; Swine ; DNA, Circular/genetics* ; Genital Neoplasms, Female ; Semen ; DNA ; Reproduction

Objective:To explore the characteristics of intestinal flora in female patients with type 2 diabetes mellitus (T2DM) with comorbid coronary heart disease.Methods:Female patients with T2DM from September 2019 to November 2020 were enrolled in this study and divided into 2 groups stratified by coronary heart disease: 22 patients with coronary heart disease(T2DM+ CHD group) and 49 patients with simple T2DM group(T2DM group). Thirty-one healthy females were selected as the normal control group(NC group). The abundance of intestinal flora, the difference in intestinal flora and its relationship with indicators such as glycosylated hemoglobin and fasting blood glucose was analyzed by the real-time fluorescent quantitative PCR detection technology in the three groups.Results:The abundance of Prevotella in the T2DM group was lower, and Roseburia inulinivorans and Faecalibacterium prausnitzii in the T2DM+ CHD group were lower, while Bacteroides and Enterococcus spp in the T2DM+ CHD group were higher compared with NC group, respectively( P<0.05). The abundance of Bacteroides and Enterococcus spp in the T2DM+ CHD group was lower than that in the T2DM group( P<0.05). Spearman correlation analysis showed that the abundance of Faecalibacterium prausnitzii and Eubacterium rectale was negatively correlated with obesity while abundance of Bacteroides and Enterococcus spp was positively correlated with HbA 1C and fasting blood glucose. The abundance of Bacteroides was positively correlated with TCH and TG(all P<0.05). Logistic regression analysis showed that Bacteroides and Enterococcus spp were independent influencing factor of the development of female patients with T2DM and CHD. Conclusion:Female T2DM and T2DM with CHD had intestinal flora imbalance, which was related to a variety of glucose and lipid metabolism indicators, and might be closely related to the occurrence of T2DM and CHD. Bacteroides and Enterococcus spp were independent influencing factors of the development of female patients with T2DM and CHD. Regulating the intestinal flora can provide ideas for the prevention and treatment of T2DM with CHD in female.

OBJECTIVES: To investigate the level and significance of serum γ-glutamyl transferase-to-platelet ratio (GPR) and monocyte count to high-density lipoprotein ratio (MHR) in patients with essential hypertension (EH) and unstable angina (UA). METHODS: A total of 218 patients with coronary angiography aged ≥60 years, who were admitted to the EH hospital of the Department of Cardiac Medicine, Affiliated Hospital of Chengde Medical College, were selected from September 2018 to September 2019. They were divided into an EH+UA group ( RESULTS: Compared with the control group, patients in the EH+UA group and the EH group had higher body mass index (BMI), tyiglyceride (TG), GPR, and MHR, and lower high-density lipoprotein-cholesterol (HDL-C) (all CONCLUSIONS There is a correlation between GPR, MHR and EH combined with UA pectoris, and the combined detection of the two indicators has adjuvant diagnostic value for elderly EH combined with UA.
Aged ; Angina, Unstable ; Cholesterol, HDL ; Coronary Angiography ; Essential Hypertension ; Humans ; Lipoproteins, HDL ; Monocytes

Objective:To investigate the correlation of the gamma-glutamyl transpeptidase to platelet ratio(GPR)and monocyte count to high-density lipoprotein cholesterol(HDL-C)ratio(MHR)with the severity of coronary artery disease in elderly patients with essential hypertension(EH)combined with unstable angina pectoris(UA).Methods:A total of 218 EH patients aged 60 years and over undergoing coronary arteriography admitted to cardiology department of our hospital were enrolled from September 2018 to September 2019.They were divided into the EH plus UA group(n=113)and the simple EH group(n=105)according to whether UA was combined.In addition, 106 patients with normal coronary angiography who were suspected with coronary heart disease were selected as the healthy group.General data of patients between three groups were compared.Severity of coronary artery disease was evaluated using a Gensini score.The correlation of GPR and MHR with coronary Gensini scores was analyzed in the EH plus UA group.Patients in the EH plus UA group were sub-grouped into the single-, double- and triple-vessel disease groups according to the number of disease branches.Differences in coronary Gensini scores, GPR and MHR were compared among subgroups.A receiver operating characteristic(ROC)curve was used to evaluate the auxiliary diagnostic efficacy of GPR, MHR and the combined GPR and MHR in the EH plus UA group.Results:Compared with the healthy group, both EH plus UA group and EH group showed that the BMI(25.8±3.4 kg/m 2, 25.4±3.6 kg/m 2vs.24.2±2.3 kg/m 2), triglyceride(1.9±1.2, 2.0±1.2 vs.1.5±1.1 mmol/L), and MHR(6.6±1.4, 5.8±1.7 vs.4.9±1.7)were increased, and the HDL-C(1.1±0.2 mmol/L, 1.1±0.3 mmol/L vs.1.3±0.3 mmol/L)were reduced( P<0.05), and only EH plus UA group showed that white blood cells(6.7±1.5×10 9/L vs.6.1±1.8×10 9/L), LDL-C(2.3±0.6 mmol/L vs.2.1±0.6 mmol/L)and GPR(0.3±0.1 vs.0.2±0.1)were higher than in the healthy group( P<0.05). Compared with the EH group, the EH plus UA group showed that the GPR(0.3±0.1 vs.0.2±0.1), and MHR(6.6±1.4 vs.5.8±1.7)were increased( P<0.05). The correlation analysis showed that the levels of GPR and MHR were positively correlated with Gensini scores in the EH plus UA group( r=0.537, 0.333, P<0.05), and the correlation was better along with the increased number of diseased branches( P<0.05). The ROC curve analysis showed that GPR had a high specificity and positive predictive value with the specificity of 68.9% and the area under the ROC curve( AUC)of 0.842, while MHR had a high sensitivity with the sensitivity of 92.9%.The combined detection of GPR and MHR had a higher specificity and positive predictive value with a specificity of 84.0% and the AUC of 0.871. Conclusions:The increase of GPR and MHR can be used as a marker to assist the diagnosis of EH combined with UA, and to assess the severity of coronary artery disease in the elderly.

Objective    To evaluate the security and outcomes of thoracolaparoscopic esophagectomy (TLE) versus open approach (OA) for thoracic esophageal squamous cell carcinoma. Methods    From June 2014 to June 2015, 125 patients with thoracic esophageal squamous cell carcinoma underwent esophagectomy through McKeown approach, including TLE (a TLE group, 107 patients, 77 males and 30 females) and OA (an OA group, 18 patients, 13 males and 5 females). The data of operation and postoperative complications of the two groups were analyzed retrospectively. Results    There was no statistical difference in the duration of operation and ICU stay and resected lymph nodes around laryngeal recurrent nerve between the TLE group and the OA group (333.58±72.84 min vs. 369.17±91.24 min, P=0.067; 2.84±1.44 d vs. 6.44±13.46 d, P=0.272; 4.71±3.87 vs. 3.89±3.97, P=0.408) . There was a statistical difference in blood loss, total resected lymph nodes and resected lymph nodes groups between TLE group and OA group (222.62±139.77 ml vs. 427.78±276.65, P=0.006; 19.62±9.61 vs. 14.61±8.07, P=0.038; 3.70±0.99 vs. 3.11±1.13, P=0.024). The rate of postoperative complications was 32.7% in the TLE group and 38.9% in the OA group (P=0.608). There was a statistical difference (P=0.011) in incidence of pulmonary infection (2.8% in the TLE group and 16.7% in the OA group). Incidences of complications, such as anastomotic leakage, cardiac complications, left-side hydrothorax, right-side pneumothorax, voice hoarse and incision infection, showed no statistical difference between two groups. Conclusion    For patients with thoracic esophageal squamous cell carcinoma, TLE possesses advantages of more harvested lymph nodes, less blood loss and less pulmonary infection comparing with open approach, and is complied with the principles of security and oncological radicality of surgery.

Primary intrahepatic cholangiocarcinoma (ICC) is the second frequent malignant tumor in adult liver,and appears an increasing tendency worldwide.Gross type is frequently mass-forming and a tubular adenocarcinoma is shown as the typical histopathological appearance.Surgical resection is the only curative treatment,and liver transplantation is selected for the patients with early ICC.Rediofrequency ablation,transcatheter arterial chemoembolization or molecular targeted therapies should be considered in the treatment of the unresectable or recurrent patients.

BACKGROUNDChemoresistance is common among patients with esophageal squamous cell carcinoma (ESCC). We investigated the effect and mechanism of insulin on enhancing anticancer functions of cisplatin in human esophageal cancer cell line EC9706.

METHODSThe viability of EC9706 cells exposed to cisplatin was assessed using MTT assay. The times T1, when the number of living cells reached a plateau and T2, when the number of living cells reached a new plateau after the addition of insulin were found. T1 and T2 plateau cells were stained by Annexin V-FITC/PI and monodansylcadaverin (MDC). Fluorescent microscopy was used to observe the expression of apoptosis and autophagy intuitively. Apoptotic ratio and fluorescent intensity were analysed by flow cytometry (FCM) quantitatively. Western blotting analysis was used to estimate the protein expression levels of AKT, mTOR, PI3K, PTEN, autophage related indicator LC3-II and autophage related protein Beclin1 changes that occurred in the course of treatment.

RESULTSA larger number of typical autophagosomes were detected in EC9706 cells exposed to cisplatin. Insulin can increase the apoptosis induced by cisplatin. Apoptotic ratio of T1 plateau cells ((32.6 ± 4.3)%) is significantly less than T2 plateau ((47.5 ± 5.6)%). MDC fluorescent intensity at T1 plateau (104.9 ± 13.2) was significantly higher than intensity at T2 plateau (82.6 ± 10.3). After cotreatment with insulin, the expression level of LC3-II, Beclin1 and PTEN in T2 plateau cells were significantly downregulated, but AKT, mTOR and PI3K expressions significantly upregulated compared with T1 plateau.

CONCLUSIONSInsulin could enhance cisplatin-induced apoptosis in human esophageal squamous cell carcinoma EC9706 cells related to inhibition of autophagy. The activation of PI3K/Akt/mTOR signaling pathway induced by insulin resulted in the suppression of autophagy in EC9706 cells, which may be attributed to the anticancer effects of cisplatin.

Apoptosis ; drug effects ; Autophagy ; drug effects ; Carcinoma, Squamous Cell ; metabolism ; Cell Line, Tumor ; Cell Survival ; drug effects ; Cisplatin ; pharmacology ; Esophageal Neoplasms ; metabolism ; Humans ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction ; drug effects

Objective To evaluate the effects of percutaneous cholecystostomy (PCT) for the treatment of acute cholecystitis (AC) in poor-risk patients.Methods A retrospective clinical analysis was undertaken in poor-risk AC patients receiving PCT or emergency cholecystectomy (CCY) from April 2007 to December 2012.The success rate,complications,hospital stay and mortality,and readmission rate were compared between PCT and CCY groups.Results Of the 51 poor-risk acute cholecystitis patients,25 underwent PCT drainages and 26 received emergency CCY at an average age of 75 and 74 years respectively.The average intensive care unit length of stay was 13 days in PCT group and 5 days in CCY group (t =5.175,P =0.001).The mean hospital length of stay in PCT patients (21.3 days) was longer than that in CCY patients (9.8 days) (t =3.213,P =0.002).However,there was no significant difference in the overall hospital mortality,complications and successful rate between the two groups.No recurrence was observed in 19 out of 25 PCT cases after removing PCT catheter.The remaining six patients were readmitted for recurrent AC.Three of them were conservatively treated,while another 3 patients had PCT drainage anew and one of the three underwent delayed CCY 4 weeks after PCT replacement.The overall successful rate of PCT treatment was 76％.Conclusions Compared with emergency CCY,PCT has similar treatment effects in the successful rate of surgical management,morbidity,and overall hospital mortality although it is associated with longer hospital stays and higher readmission rate,which indicated that PCT is a convenient,safe and effective treatment option for poor-risk AC patients.

Objective To investigate the effect of epidermal growth factor receptor 2 (ErbB2) expression on invasion ofglioma cells and its possible mechanism.Methods Glioma TJ905 cells were cultured in vitro; and ErbB2 shRNA and overexpression vectors were constructed and transfected into Glioma T J905 cells to down-regulate and up-regulate the ErbB2 expression levels; empty vector plasmid was also transfected into the TJ905 cells as control group.Invasive ability changes of T J905 cells were measured by Transwell assay,and the expression levels of matrix metalloprotease (MMP)-2 and MMP-9 were identified by Western blotting.Results As compared with the ErbB2,MMP-2 and MMP-9 protein expression levels in the control group (62.34±5.72,62.34±5.72 and 69.76±6.25),those in the ErbB2 shRNA group were significantly decreased (34.82±4.91,58.73±4.48 and 52.32±5.23),while those in the ErbB2 overexpression group were significantly increased (69.76±6.25,87.34±7.96 and 94.39±6.12),with significant differences (P＜0.05).The mean cells crossing Matrigel in the ErbB2 shRNA group (28.5 cells/field) were obviously decreased,and those in the ErbB2 overexpression group were increased (82 cells/field) as compared with those in the control group (70 cells/field),with significant differences (P＜0.05).Conclusion ErbB2 expression can affect the invasiveness ofglioma cells,which might be related to the expression changes of MMP-2 and MMP-9.