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 screen the prescription and preparation method of Bupleurum nanoemulsion, and evaluate its quality, study the antipyretic effect. METHODS The emulsifier and co-emulsifier of the nanoemulsion were preliminarily screened, and then the prescription was screened by pseudo-ternary phase diagram. The quality evaluation of the appearance, particle size distribution, structure type, stability and content of the prepared Bupleurum nanoemulsion was performed. Wistar rats were further randomly divided into blank control group, model control group, positive control group(aspirin group), Bupleurum nanoemulsion high-dose, medium-dose and low-dose groups(18.00, 9.00, 3.00 g·kg−1). Except for the blank control group, the pathological model of fever rats was prepared in the other groups. According to the scheduled experimental requirements, rats in each group were given the corresponding drugs. And the temperature changes of rats in each group were recorded at 0.5, 1, 1.5, 2, 3 h to observe the antipyretic effect of Bupleurum nanoemulsion. RESULTS The best prescription of Bupleurum nanoemulsion: Tween-80 6 g and n-butanol 3 g, Bupleurum extract dissolved in pure water as water phase 20 mL, Bupleurum oil as oil phase 2 g. At room temperature, the Bupleurum nanoemulsion was a yellow-brown clear and transparent liquid, O/W nanoemulsion, with an average particle size of (77.21±3.66)nm, polydispersity index of 0.28±0.04, Zeta potential of (–18.81±1.42)mV, and saikosaponin content of 3.071 mg·mL−1, with good stability. In animal experiments, compared with the model control group, the rectal temperature of aspirin group and Bupleurum nanoemulsion high-dose group was significantly lower after the first administration(P<0.01), the rectal temperature of Bupleurum nanoemulsion middle-dose group was significantly lower after the first administration 2, 3 h(P<0.01). CONCLUSION The Bupleurum nanoemulsion is transparent and stable, and it has good antipyretic effect on fever rat model.

A new class of potent liver injury protective compounds, phychetins A-D ( 1- 4) featuring an unique 6/6/5/6/5 pentacyclic framework, were isolated and structurally characterized from a Chinese medicinal plant Phyllanthus franchetianus. Compounds 2- 4 are three pairs of enantiomers that were initially obtained in a racemic manner, and were further separated by chiral HPLC preparation. Compounds 1- 4 were proposed to be originated biosynthetically from a coexisting lignan via an intramolecular Friedel-Crafts reaction as the key step. A bioinspired total synthesis strategy was thus designated, and allowed the effective syntheses of compounds 2- 4 in high yields. Some of compounds exhibited significant anti-inflammatory activities in vitro via suppressing the production of pro-inflammatory cytokine IL-1β. Notably, compound 4, the most active enantiomeric pair in vitro, displayed prominent potent protecting activity against liver injury at a low dose of 3 mg/kg in mice, which could serve as a promising lead for the development of acute liver injury therapeutic agent.

OBJECTIVE To study the efficacy of sinapine thiocyanate dissoluble microneedle （ST-DMN） for acupoint administration against bronchial asthma （BA）. METHODS The network pharmacology and molecular docking techniques were used to screen the core targets of sinapine thiocyanate （ST） against BA， and the pharmacodynamics of the top 3 core targets was studied. Firstly， ST-DMN was prepared （drug loading of ST was 1 mg/tablet）； secondly， 30 rats were divided into blank control group， model control group， blank microneedle group， Sinapine powder plaster group （positive control group） and ST-DMN group. Except for the blank control group， rats of other groups were sensitized with 10% ovalbumin （containing aluminum hydroxide adjuvant） and nebulized with 1% ovalbumin to induce the BA model. After modeling， blank control group did not receive any intervention； normal saline was applied to the Feishu acupoint and Dazhui acupoint of the rats in the model control group， while the blank microneedle group， Sinapine powder plaster group and ST-DMN group were given blank microneedle， Sinapis alba powder （plaster， 1.5 g） and ST-DMN （3 tablets at 2 acupoints） at same acupoint， once a day， for 28 consecutive days. After administration， the general symptoms were observed and the body mass of the rats was measured.pathological changes of lung tissues in rats was observed； the levels of prostaglandin endoperoxide synthase 2 （PTGS2）， GNYL matrix metalloproteinase-9 （MMP-9） and interleukin-2 （IL-2）in serum， bronchoalveolar lavage fluid （BALF） and lung tissues were determined. RESULTS Results of network pharmacology and molecular docking showed that the key targets of ST against BA were identified as PTGS2， MMP-9， IL-2， epidermal growth factor receptor， heat shock protein90AA1， etc. Pharmacodynamic experiments showed that compared with model control group， relieved cough， restored hair color， sensitive behavior， stable respiration and increased body weight were all found in ST-DMN group； the histopathological changes as the structure of lung tissue， infiltration of alveolar epithelial cells and pulmonary interstitial inflammatory cells were improved to different extent； the levels of PTGS2， MMP-9 and IL-2 in serum， BALF and lung tissue were significantly reduced （P＜0.05 or P＜0.01）. CONCLUSIONS The anti-BA effect of ST-DMN acupoint administration is good， the mechanism of which may be associated with decreasing the levels of PTGS2， MMP-9 and IL-2 in serum， BALF and lung tissue.

Objective:To investigate the clinical value of imaging features of primary lesions combined with venous phase CT value in predicting central group lymph node (LN) metastasis in patients with papillary thyroid carcinoma (PTC) .Methods:Clinical data of 170 PTC patients who underwent central group LN dissection in the First People's Hospital of Handan City of Hebei Province from January 2017 to June 2020 were retrospectively analyzed. All patients were divided into different groups according to whether central group LN metastasis or not, and there were 89 patients with central group LN metastasis and 81 patients without central group LN metastasis. The CT value and imaging features of primary lesions in different periods were analyzed, and the imaging features of primary lesions combined with venous phase CT values to predict the central group LN metastasis were evaluated by the receiver operating characteristic (ROC) curve.Results:There were no statistically significant differences in CT value in plain scan phase and CT value, net increased CT value, standardized CT value in arterial phase between patients with and without central group LN metastasis (all P>0.05) . The CT value, net increased CT value and standardized CT value in venous phase of patients with central group LN metastasis were (113.84±22.95) HU, (59.05±12.10) HU and 0.72±0.14 respectively, which were significantly higher than those of patients without central group LN metastasis [ (103.99±17.67) HU, (51.29±14.45) HU and 0.59±0.10] ( t=3.26, P<0.001; t=3.81, P<0.001; t=3.67, P<0.001) . ROC curve analysis showed that the area under the curve for diagnosing central group LN metastasis of PTC patients was 0.75, 0.70 and 0.76 when the cut-off values of CT value, net increased CT value and standardized CT value in venous phase were 115.78 HU, 62.37 HU and 0.75 respectively. There were statistically significant differences in the diameter of primary focus and the contact area of thyroid capsule between patients with and without central group LN metastasis ( Z=-2.34, P=0.019; Z=-2.08, P=0.037) . There were no statistically significant differences between calcification and primary lesion location (both P>0.05) . Lesion diameter >2 cm (87.73%) and capsule contact range ≥1/2 (92.17%) had the highest specificity in predicting central group LN metastasis. The imaging features of primary lesion combined with standardized CT value in venous phase was in good agreement with histopathological diagnosis results in predicting central group LN metastasis (Kappa=0.475) , and the sensitivity and specificity were 73.12% and 82.75% respectively. Conclusion:The imaging features of the primary lesion combined with CT value in venous phase have a good clinical value in predicting central group LN metastasis in PTC patients. Patients with primary lesion diameter >2 cm, capsule contact range ≥1/2 and the standardized CT value in venous phase >0.75 are more likely to have central group LN metastasis.

Objective To develop a new method to expose the stellate ganglion to increase the success rate of establishing a dog model of atrial fibrillation indinced by sympathetic stimulation .Methods A total of 28 adult dogs were randomly divided into traditional group and improvement group , 14 dogs in each group .The stellate ganglions were separated by the two different methods , respectively , to establish a sympathetic stimulation induced atrial fibrillation model in all the dogs .Changes of vital signs , survival rate of the dogs and the voltage required to stimulate the stellate ganglion were recorded intraoperatively .Changes of cardiac electrophysiology were recorded before and after electric stimulation . The levels of released neurotransmitters were detected by immunohistochemistry . Results The survival rate of the improvement group was 100%(14/14), significantly higher than the 64.3%(9/14) of the traditional group (P<0.05). The operation time of the improvement group was 122.71 ±3.62 min, significantly shorter than the 269.44 ±8.79 min of the traditional group (P<0.05).The threshold voltage of the improvement group was significantly lower than that of the traditional group ( P<0.05) .Conclusions Our modified surgical procedure can effectively reduce the mortality of dogs , significantly shorten the operation time , and reduce the intraoperative blood loss , keeping a more intact stellate ganglion , and maintains a more stable voltage of electric stimulation , Therefore, it is a new method more suitable for establishment of a sympathetic stimulation induced atrial fibrillation model in dogs .

Objective To investigate the efficacy and safety of Tripterygium wilfordii Hook F (TwHF) combined with renin-angiotensin system (RAS) blockers in chronic kidney disease (CKD) stages 2~3 of IgA nephropathy. Methods 109 patients were randomized into the observation group and the control group. On the basis of taking RAS blockers, patients in the observation group received TwHF, and patients in the control group received methylprednisolone. The proteinuria, renal function and adverse effect were observed during treatment. Results At 3, 6, 9 and 12 months of treatment, proteinuria in the two groups was lower than the baseline(P <0.05). During follow-ups, there was no significant difference of eGFR between the two groups and baseline (P >0.05). Besides, there was no significant difference in terms of proteinuria, eGFR and effective rate in the two groups. The occurrence rate of adverse effects was 9.8% vs 27.4% and there was significant difference in the two groups (P < 0.05). Conclusions TwHF combined with RAS blockers can decrease proteinuria, protect renal function and have less adverse effects, and it is a useful therapeutic options for CKD stages 2 ~ 3 of IgAN.

ObjectiveTo investigate the effect and safety of endoscopic injection of cyanoacrylate in the treatment of esophageal and gastric variceal bleeding (EGVB) in children. MethodsThe clinical data of 35 children with acute EGVB who were treated with endoscopic injection of cyanoacrylate in Children′s Hospital of Baoji Maternal and Child Health Care Hospital from August 2010 to August 2015 were analyzed retrospectively. The emergency response rate, rebleeding rate, and incidence of complications after the treatment were analyzed statistically. ResultsThirty-five patients received 46 times of endoscopic injection of cyanoacrylate in total. The response rate to the initial injection was 95.6% (44/46). The volume of cyanoacrylate injected was 0.2-0.6 ml, with a mean volume of 0.4±0.2 ml. The emergency hemostasis rate was 93.4% (43/46), the rebleeding rate was 11.4% (4/35), and the cycle for 4 patients with the recurrence of bleeding to be cured was 1.2-23.0 months (mean 121±10.9 months). One patient experienced abdominal pain, and no patients experienced ectopic embolism. Two patients died after injection. ConclusionFrequent, small-volume endoscopic injection of cyanoacrylate is an effective and convenient therapeutic method for EGVB in children, has few complications, and holds promise for clinical application.

Objective To conduct a prospective,randomly controlled trial,evaluating the combination of tacrolimus,corticosteroids and entecavir for the treatment of adult patients with biopsyproven hepatitis B virus-associated membrane nephropathy (HBV-MN).Methods A total of 38 patients with biopsy-confirmed HBV-MN were randomized to the tacrolimus group (n=19) and the control group (n=19).Patients in tacrolimus group received combination therapy of tacrolimus (0.05 mg·kg-1 · d-1),corticosteroids (prednisone acetate,0.5 mg· kg-1 · d-1) and entecavir (0.5 mg/d),whereas patients in control group received entecavir mono-therapy (0.5 mg/d).The primary end point was the percentage of patients reaching complete remission (CR) or partial remission (PR).Results The probability of remission in the treatment group was 88.89％ and 94.44％ after 6 and 12 months,but only 38.89％ and 58.82％ in the control group,respectively.The decrease in proteinuria was significantly greater in the treatment group.Entecavir was used for the treatment of hepatitis in all patients,which caused the disappearance of serum hepatitis B viral DNA(HBV-DNA) and the normalization of ALT and AST levels in 3 months.Notably,two patients in the control group and one patient in the treatment group reached the secondary end point.One patient in the tacrolimus-treated group showed a relapse during the taper period.Conclusion This treatment protocol not only can control the replication of HBV-DNA but also can reduce proteinuria and preserve renal function,it is one of useful therapeutic options for patients with HBV-MN.

Objective To analyse distribution and antibacterial resistance of common pathogenic bacteria of clinical infectious diseases and provide scientific basis for the treatment of infectious diseases ,rational use of antibacterial agents and nosocomial infec‐tion control .Methods The distribution and antibacterial resistance of common pathogens clinically isolated from inpatients and out‐patients from August 2012 to July 2013 were analyzed .Bacterial identification and drug susceptibility test were carried out by using MicroScan WorkAway 40 automated bacterial identification and drug‐susceptibility analyzer ,and the results of drug susceptibility test were analysed by using the WHONET5 .5 software .Results A total of 1 434 strains of pathogenic bacteria were isolated ,and gram‐negative bacteria ,gram‐positive bacteria and other pathogenic bacteria accounted for 53 .8% ,28 .1% and 18 .1% respectively . The detection rate of methicillin‐resistant Staphylococcus aureus and methicillin‐resistant coagulase negative Staphylococcus were 31 .6% and 57 .4% respectively .No strains of vancomycin‐resistant Staphylococcus were found ,while strains of vancomycin‐resist‐ant Enterococcus faecium accounted for 8 .8% .The detection rate of extended‐spectrum beta‐lactamases producing Escherichia coli and Klebsiella pneumoniae were 47 .2% and 12 .2% respectively .Isolates of Staphylococcus and Enterococcus faecium were sensi‐tive to vancomycin ,linezolid and moxifloxacin ,and the resistance rates were less than 10 .0% .While isolates of Staphylococcus were resistant to the penicillin ,macrolides ,quinolones ,tetracycline ,cephalosporin ,and the resistance rates were more than 30 .0% .Most isolates of gram‐negative bacteria were sensitive to ertapenem ,imipenem ,amikacin ,meropenem ,piperacillin/tazobactam ,ticarcillin/clavulanic acid and levofloxacin ,and the resistance rates were less than 10 .0% .Conclusion It is necessary to enhance monitoring of distribution and antibacterial resistance of pathogenic bacteria ,so as to provide references for guiding rational use of antibacterial a‐gents in different departments .