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 evaluate the feasibility of indocyanine green fluorescence imaging technology applied in thyroid surgery to identify parathyroid gland.Methods:From Oct 2021 to May 2022, data of 42 patients undergoing thyroidectomy via gasless unilateral axillary approach in Zhejiang Provincial Hospital of Traditional Chinese Medicine were retrospectively analyzed. Cases using intraoperative fluorescence imaging technology(42 cases) were compared with conventional laparocopic approach.Results:The number of parathyroid glands dissected in the study group 1.57±0.61 was higher than that in the control group 0.56± 0.59 ( t=-5.472, P<0.05). The PTH value of the study group was (2.88±1.23)pmol/L on the first day after operation, which was higher than that of the control group (2.16±0.10)pmol/L ( t=-1.844, P<0.05). The blood parathyroid hormone value on the third day(3.22±1.31)pmol/L was higher than that of the control group (2.55±0.81) pmol/L ( t=-2.041, P<0.05). There were 2 cases of hypoparathyroidism in the study group, less than 5 cases in the control group, but there was no significant difference between the two groups( χ2=0.942, P>0.05). There was 1 case of hypocalcemia in the study group and 3 cases in the control group ( χ2=0.731, P>0.05). Conclusion:Using indocyanine green fluorescence imaging technology to identify parathyroid gland is feasible, simple, fast, safe and effective.

Objective:To analyze the clinical characteristics and genetic variation of 2 children with developmental and epileptic encephalopathy 8 (DEE8).Methods:Whole-exome sequencing (WES) was performed to determine the potential variants in the probands. Candidate variants identified by WES were validated by Sanger sequencing and quantitative real-time polymerase chain reaction. X chromosome inactivation (XCI) detection was performed in the proband 1′s mother and proband 2 to detect the allelic expression difference of ARHGEF9. Results:Both of the cases showed global developmental delay. Proband 1 presented with delayed motor and speech development, intellectual disability, and seizures. Electroencephalography of proband 1 showed slow background activity, with spikes, spike and waves in bilateral frontal and midline regions during sleep. While proband 2 showed delay in acquisition of language, motor skills, and cognition, but no seizures. It was identified that proband 1 carried a novel maternally derived heterozygous splicing variant (c.925-2A>T) in ARHGEF9 by WES, which was verified in Sanger sequencing. The XCI in proband 1′s mother was observed, and the expression ratio of mutant ARHGEF9 and wild-type was 0∶100%. A novel exon 3-10 heterozygous deletion of ARHGEF9 was identified in proband 2, and this variant was not found in his unaffected parents. Conclusions:DEE8 disorders are relatively rare. Most of the patients have varying degrees of neurodevelopmental phenotype, but epilepsy is not a specific clinical manifestation. ARHGEF9 gene deletion and splicing variation may be the genetic cause of the 2 probands, and above findings have enriched the spectrum of variation and phenotype of DEE8.

Purpose: This study was performed to analyze the rule of confluence of the caudate lobe bile duct (CLD) into the left hepatic duct (LHD) and to discuss the protective strategy during left hemihepatectomy. Methods: MRI of 400 patients and T-tube angiography images of 100 patients were collected, and the imaging rules of the confluence of the CLD into the LHD were summarized. The clinical data of 33 patients who underwent left hemihepatectomy using the protective strategy were analyzed. Results: MRI and T-tube angiography images showed that the length from the confluence point of the CLD into the LHD to the confluence of the left and right hepatic ducts was 1.19 ± 0.40 cm and 1.26 ± 0.39 cm, respectively. The average angle between the longitudinal axis of the 2 bile ducts was 68.27° ± 22.59° and 66.58 ± 22.88°, respectively. Coronal and cross-sectional images showed that inflow from the foot side to the cranial side was noted in 79.8% and 82.0% of patients, respectively, and inflow from the dorsal to the ventral side was observed in 84.5% and 88.0%, respectively. Based on these imaging rules, the safe transection length and plane were summarized, and the CLD was effectively protected in 33 cases of left hemihepatectomy. Conclusion In left hemihepatectomy, the LHD should be transected at least 1.5 cm away from the confluence of the left and right hepatic ducts, and the plane of transection should be oblique to the dorsal side at an angle of 45° with the LHD, these parameters represent an effective strategy to protect the CLD.

Human dental pulp stem cells (DPSCs) have emerged as an important source of stem cells in the tissue engineering, and hypoxia will change various innate characteristics of DPSCs and then affect dental tissue regeneration. Nevertheless, little is known about the complicated molecular mechanisms. In this study, we aimed to investigate the influence and mechanism of miR-140-3p on DPSCs under hypoxia condition. Hypoxia was induced in DPSCs by Cobalt chloride (CoCl
Cell Differentiation ; Histone-Lysine N-Methyltransferase ; Humans ; Hypoxia ; Methyltransferases ; MicroRNAs

OBJECTIVE: To investigate the prevalence and risk factors of multi-site work-related musculoskeletal disorders(WMSDs) among workers in the industry of electronic equipment manufacturing. METHODS: A total of 815 workers in three factories of electronic equipment manufacturing in Guangdong Province were selected as study subjects by convenience sampling. The prevalence of multi-site WMSDs in the past year was investigated using Musculoskeletal Disorders Investigating Questionnaire and the influencing factors were analyzed. RESULTS: The total prevalence of WMSDs was 69.4%(566/815). The prevalence of multi-site WMSDs was 54.5%(444/815), and the prevalence of one-site WMSDs was 15.0%(122/815). Multiple logistic regression showed that female workers had higher prevalence of multi-site WMSDs than males [odds radio(OR) and 95% confidence interval(CI): 1.59(1.12-2.26), P<0.05]. The prevalence of multi-site WMSDs in left-handed workers was lower than that of right-handed workers [OR(95% CI): 0.42(0.19-0.91), P<0.05]. The longer service of current position and the more neck forward movement, the higher prevalence of multi-site WMSDs [OR(95% CI) were 1.33(1.09-1.63) and 1.62(1.23-2.15), P<0.01]. The workers who had long-time sitting at work, adopted uncomfortable working posture, could decide when to work on their own, kept head down for a long time, or often bending wrists up/down had higher prevalence of multi-site WMSDs [OR(95% CI) were 1.41(1.16-1.73), 1.82(1.40-2.38), 1.79(1.16-2.75), 1.92(1.38-2.69) and 1.60(1.14-2.24), respectively, P<0.01]. The workers who could take turns with colleagues to finish work or had enough rest time had lower prevalence of multi-site WMSDs [OR(95% CI): 0.57(0.41-0.78) and 0.67(0.48-0.92), P<0.05]. The workers who worked >10 h per day had lower prevalence of multi-site WMSDs than those who worked ≤8 h per day [OR(95% CI): 0.57(0.37-0.87), P<0.05]. CONCLUSION: Multi-site WMSDs were more common than one-site WMSDs among workers in the industry of electronic equipment manufacturing, and the prevalence of multi-site WMSDs was high. The risk factors include personal factors, work organization and adverse ergonomic factors.

Objective:To explore the clinical efficacy and adverse reactions of the combination of external beam radiotherapy followed by three-dimensional intracavitary brachytherapy in patients with inoperable locally advanced rectal cancer.Methods:Clinical data of 11 patients with inoperable locally advanced rectal cancer, 7 male and 4 female, admitted to China-Japan Union Hospital of Jilin University from 2013 to 2015 were retrospectively analyzed. All patients received pelvic external irradiation (50 Gy in 25 fractions), followed by a three-dimensional intracavitary brachytherapy boost (15-20 Gy in 3-4 fractions, 1 fraction/week). External beam radiotherapy was used to boost the dose to the perirectal lymph nodes (60-66 Gy in 30-33 fractions). All patients received concurrent chemotherapy with Capecitabine during external beam radiotherapy. Efficacy evaluation was performed using the RECIST standard. Survival and local control rates were calculated using the Kaplan- Meier method. Early and late radiotherapy responses were assessed using the RTOG lesion grading criteria. Results:The CTV D 90% EQD 2 Gy of HDR 3D-ICBT among 11 patients was (21.3±1.60) Gy. The complete response (CR) and partial response (PR) rates were 64% and 27%, respectively, yielding an objective response rate (CR+PR) of 91%. With a median follow-up time of 36 months, the 1-, 2-, and 3-year overall survival rates were 82%, 64% and 46%, respectively. The 1-, 2-, 3-year disease-free survival rates were 64%, 45% and 27%, respectively. The 3-year local control rate was 46%. One patient presented with lung metastases after 8 months, 7 patients experienced grade 1-2 acute intestinal reactions and 5 patients developed grade 1-2 acute bladder reactions, only one patient had grade 2 myelosuppression; long-term grade 1-2 intestinal reactions occurred in 5 patients, and 1 patient had long-term grade 1-2 bladder reaction. All the radiation-induced toxicities were alleviated by medication administration. Conclusions:External beam radiotherapy followed by three-dimensional intracavitary brachytherapy can be a safe and effective surrogate in patients with inoperable locally advanced rectal cancer, which yields reliable clinical efficacy and tolerable adverse reactions.

In China, COVID-19 epidemic is currently showing a sporadic state, and the task of epidemic prevention is still arduous. Brachytherapy (BT) plays a critical role in the treatment of cancer. For some cancer receiving radiotherapy, use of BT can not be replaced or excessively delayed. Nevertheless, the recommendations or guidelines regarding the application of BT during COVID-19 epidemic have been rarely reported. In this article, a few recommendations on the application of BT during COVID-19 epidemic were retrieved and the work experience of Department of Radiation Oncology, China-Japan Union Hospital of Jilin University in the early epidemic period was summarized, aiming to provide relevant reference for the use of high-dose-rate BT for malignant tumor patients during COVID-19 epidemic.

OBJECTIVETo investigate the efficacy of single-hand four-needle suture with sled-shaped needle three-tail fixed stitch in closure of pesudohernia sac of direct hernia under transabdominal preperitoneal (TAPP) inguinal hernia repair.

METHODSA randomized controlled trail was conducted on adult patients with unilateral direct inguinal hernia undergoing laparoscopic TAPP repair from January 2014 to January 2018 at the Sixth Affiliated Hospital of Sun Yat-sen University. A total of 156 patients were enrolled prospectively in the study and were randomly divided into single-hand four-needle suture group (trial group, 76 cases) and traditional tacking group (control group, 80 cases). In trial group, sled-shaped needle three-tail knot-free stitch was applied to the continuous four-needle suture. The sled-shaped needle three-tail fixed stitch was made as follows: straighten the tail of a 3-0, 1/2-circle looper VICRYL Rapide into a sled shape; use suture overlap method to make and tighten a single knot; thread the end of the needle into the single knot loop;knot two ends of the thread next to the first knot; tighten the second knot, leaving about 12 cm to the end of the needle;cut the end of the loop (leaving about 0.6 cm) and the other end of the thread(leaving about 1.5 cm). In the control group, a hernia repair tack was used to fix the pseudohernia sac on pectineal ligament. This study was approved by the Hospital Ethics Committee(approval number: L2014ZSLYEC-016). Operation time, pseudoherina sac closure time, hospitalization cost, morbidity of postoperative complication, VAS score and postoperative recurrence were compared between two groups.

RESULTSAll the patients completed operations successfully. There were no significant differences between trial group and control group in age [(60.2±0.4) years vs. (61.1±0.7) years)], gender (male ratio 93.4% vs. 92.5%), BMI [(25.1±0.2) kg/m vs. (24.9±0.2) kg/m ], defection area [(16.1±0.4) cm vs. (15.7±0.7) cm ] (all P > 0.05). As compared to control group, trial group had longer operative time[(34.2±1.9) minutes vs. (30.3±1.1) minutes, t=5.484, P=0.045], longer closure time of psudohernia sac [(4.2±0.5) minutes vs. (1.8±0.7) minutes, t=7.423, P=0.031], but lower VAS score (3.2±0.1 vs. 5.3±0.6, t=-3.186, P=0.015) and lower total cost [(9 897.3±104.4) yuan vs. (12 325.6±169.7) yuan, t=-3.972, P=0.023]. No severe complication and death were found in either groups intra-operatively and postoperatively. No mesh infection and relapse occurred during postoperative follow-up of 1-24 (12.0±1.2) months. During follow-up, seroma occurred in 2 cases (2.6%) of trial group and 3 cases (3.8%) of control group without significant difference (χ =1.284, P=0.799), and all were absorbed and disappeared within 30 days after local application of mirabilite.

CONCLUSIONCompared to tack fix method, single-hand four-needle suture with sled-shaped needle three-tail fixed stitch can effectively close pseudohernia sac, reduce hospitalization cost and ameliorate postoperative pain in TAPP repair, which is worth promotion.

Hernia, Inguinal ; surgery ; Herniorrhaphy ; methods ; Humans ; Laparoscopy ; Male ; Middle Aged ; Surgical Mesh ; Suture Techniques ; Sutures ; Treatment Outcome

Objective To explore the clinical efficacy of laparoscope-assisted transanal total mesorectal excision (La-TaTME) for middle-low rectal cancer.Methods The retrospective cross-sectional study was conducted.The clinical data of 16 patients with middle-low rectal cancer who underwent La-TaTME in the Peking University Third Hospital from August 2015 to August 2016 were collected.Sequential surgery of La-TaTME was applied to patients in the same team,with laparoscopic surgery first and then transanal surgery.Observation indicators:(1) operation and postoperative recovery situations:conversion to open surgery,anastomosis method,operation time,volume of intraoperative blood loss,intraoperative complications,time for out-of-bed activity,time for liquid diet intake,postoperative complications and duration of postoperative hospital stay.(2) postoperative pathological situations:length of surgical specimen,tumor diameter,distance from tumor to resected distant intestinal canal,complete degree of mesorectum,circumferential resection margin,pathological T stage,pathological N stage,number of lymph node detected and tumor cell differentiation.(3) follow-up.Patients in stage Ⅲ-ⅣV of TNM stage of RC underwent postoperative adjuvant chemotherapy.Follow-up using outpatient examination was performed once every 3 months postoperatively to detect the patients' survival and tumor recurrence up to December 2016.Measurement data were represented as M (range).Results (1) Operation and postoperative recovery situations:all the 16 patients underwent successful La-TaTME without conversion to open surgery,including 10 with colorectal anastomosis,3 with colon-canalis analis anastomosis and 3 with permanent colostomy.Operation time and volume of intraoperative blood loss were 290 minutes (range,215-420 minutes) and 50 mL (range,30-100 mL),respectively.One patient had intraoperative complication,showing broken ends ischemia of sigmoid colon after dragging out resected rectum from the anus,following free splenic flexure of colon,about 5 cm ischemic sigmoid colon were resected,and descending colon-rectum anastomosis was performed.Time for out-of-bed activity and time for liquid diet intake were 1 days (range,1-3 days) and 2 days (range,1-9 days),respectively.Among 3 patients with postoperative complications (Ⅱ stage of ClavienDindo),2 with incomplete intestinal obstruction were improved by gastrointestinal decompression and total parenteral nutrition,and 1 with presacral infection was improved by drainage and antibiotic therapy.Duration of postoperative hospital stay was 7 days (range,5-21 days).(2) Postoperative pathological situations:length of surgecal specimen,tumor diameter and distance from tumor to resected distant intestinal canal were respectively 18.0 cm (range,12.0-24.0 cm),3.5 cm (range,0.5-6.8 cm) and 2.5 cm (range,1.0-5.0 cm).Evaluation of mesorectum of surgical specimen:14 patients had complete mesorectum of surgical specimen and 2 had nearly complete mesorectum.There was no residual tumor at circumferential resection margin,proximal and distal ends.Pathological T stage of 16 patients:T0 (pathological complete response after neoadjuvant therapy),T1,T2 and T3 stages were found in 1,1,4 and 10 patients,respectively.Pathological N stage:12,2 and 2 patients were detected in N0,N1 and N2 stages,respectively.Number of lymph node detected was 16 (range,6-32).Tumor cell differentiation:no tumor cell (pathological complete response after neoadjuvant therapy),high-,moderateand low-differentiated tumors were respectively detected in 1,2,7 and 6 patients.(3) Follow-up.All the patients were followed up for 12 months (range,4-16 months).There were no local tumor recurrence or distant metastasis and death.Conclusion La-TaTME may be a new,safe and effective resection for middle-low rectal cancer.