Bowel wall thickness measured by MRI is useful for early diagnosis of bowel endometriosis.

OBJECTIVE: To evaluate MRI features of bowel endometriosis (BE) and verify its clinical significance compared with pathological diagnosis. MATERIALS AND METHODS: Since 2018, patients clinically diagnosed with deep endometriosis (DE) and planned to undergo surgery were enrolled prospectively. MRI parameters including traction, thickening sign of the rectum, obliteration of the Douglas Pouch, sign of adenomyosis, and pelvic adhesion were extracted. Uni- and multi-variate analyses were performed to explore their association with pathological diagnosis of BE. ROC curve was utilized to ascertain the appropriate cutoff value for predicting the presence and assessing the severity of BE. RESULTS: A total of 226 patients with DE were recruited, and 154 BE cases were pathologically confirmed. Logistic regression analysis revealed that thickness of the rectal wall, traction sign of the rectum, and obliteration of the Douglas Pouch were independent factors to predict the presence of BE with the OR 1.59 (95% CI: 1.29-1.96), 0.24 (95% CI: 0.09-0.67), and 0.17 (95% CI: 0.07-0.40), respectively (p all < 0.01). A cutoff value of 6.0 mm for the thickness of rectal wall resulted in the highest predictive value of BE (specificity: 90.3%; sensitivity: 78.6%). For patients with measured thickness of the rectal wall over 6.0 mm, 72.1% (93/129) was confirmed BE with lesions infiltrated more than muscular layer. CONCLUSION: This prospective study indicates that based on precise definition of visualized features on MRI images, BE could be recognized pre-operatively. DE patients with thickness of rectal wall exceeding 6.0 mm have a greater probability of BE. CLINICAL RELEVANCE STATEMENT: Based on precise definition of visualized features and accurate measurement on MRI images, bowel infiltrating among deep endometriosis patients could be recognized pre-operatively. KEY POINTS: • Precise definition of measurable MRI parameters made it possible for early detection of bowel endometriosis. • Thickening sign, traction sign of the rectum, and obliteration of the Douglas Pouch were typical radiological indicators for bowel endometriosis. • Bowel involvement is more sensitive to be detected among pelvic deep endometriosis patients with the thickness of the rectal wall over 6.0 mm.

The efficacy of GnRH-a followed by SanJieZhenTong capsules in long-term management of endometriosis: Study protocol for a multicenter, double-blinded, double-dummy randomized clinical trial.

Background: Endometriosis is a common benign gynecological disorder with high risk of recurrence and adverse impact on fertility-sparing. This study aims to evaluate the effectiveness and safety of SanJieZhenTong Capsules, a traditional Chinese medicine, in the long-term management of endometriosis postoperatively. Methods: and analysis: A prospective, double-blinded, double-dummy parallel-group randomized controlled trial will be conducted at three university-based medical centers in China. A total of 600 patients with rAFS III-IV endometriosis diagnosed by laparoscopy will be enrolled. After fundamental treatment (gonadotropin-releasing hormone agonists injection starts on the first day of menstruation postoperatively, and repeats 3 times every 28 days), participants will be randomly allocated to the oral contraceptive group (oral contraceptive + dummy A) or SanJieZhenTong Capsules group (SanJieZhenTong Capsules + dummy B) in a 1:1 ratio. All participants will be treated and followed up for 52 weeks. The primary outcome is a recurrence rate based on endometriosis-related symptoms, physical examination, and/or ultrasound/MRI findings. The secondary outcome includes changes in quality of life and organic function outcome via the 36-item Short-Form scores and gastrointestinal function score. Conclusion: The current trial could provide rigorous evidence on SanJieZhenTong Capsules application in the long-term management of advanced-stage endometriosis.

Single-Cell RNA Sequencing: Technological Progress and Biomedical Application in Cancer Research.

Single-cell RNA-seq (scRNA-seq) is a revolutionary technology that allows for the genomic investigation of individual cells in a population, allowing for the discovery of unusual cells associated with cancer and metastasis. ScRNA-seq has been used to discover different types of cancers with poor prognosis and medication resistance such as lung cancer, breast cancer, ovarian cancer, and gastric cancer. Besides, scRNA-seq is a promising method that helps us comprehend the biological features and dynamics of cell development, as well as other disorders. This review gives a concise summary of current scRNA-seq technology. We also explain the main technological steps involved in implementing the technology. We highlight the present applications of scRNA-seq in cancer research, including tumor heterogeneity analysis in lung cancer, breast cancer, and ovarian cancer. In addition, this review elucidates potential applications of scRNA-seq in lineage tracing, personalized medicine, illness prediction, and disease diagnosis, which reveals that scRNA-seq facilitates these events by producing genetic variations on the single-cell level.

Targeted DNA demethylation of the Arabidopsis genome using the SunTag-dCpf1-TET1cd system.

DNA methylation is a stable and heritable epigenetic mark, and it plays an important role in regulation of gene expression and transposon silencing. Here we developed a CRISPR/dCpf1-based targeted demethylation system using the catalytic domain of the human demethylase TEN-ELEVEN TRANSLOCATION1 (TET1cd) and a SunTag system. The SunTag-dCpf1-TET1cd system is able to achieve targeted DNA demethylation and up-regulate gene expression when guided to the FWA or CACTA1 loci in Arabidopsis thaliana . Our study provides tools for targeted removal of DNA cytosine methylation, and activation of protein-coding genes or transposons expression.

The application of antidepressant drugs in cancer treatment.

Antidepressants refer to psychotropic drugs which are used to treat mental illness with prominent emotional depression symptoms. It was reported that antidepressants had associated with anti-carcinogenic function which was associated with various signaling pathways and changing of microenvironment. Its mechanism includes cell apoptosis, antiproliferative effects, mitochondria-mediated oxidative stress, DNA damaging, changing of immune response and inflammatory conditions, and acting by inhibiting multidrug resistance of cancer cells. Accumulated studies showed that antidepressants influenced the metabolic pathway of tumor cells. This review summarized recent developments with the impacts and mechanisms of 10 kinds of antidepressants in carcinostasis. Antidepressants are also used in combination therapy with typical anti-tumor drugs which shows a synergic effect in anti-tumor. By contrast, the promotion roles of antidepressants in increasing cancer recurrence risk, mortality, and morbidity are also included. Further clinical experiments and mechanism analyses needed to be achieved. A full understanding of the underlying mechanisms of antidepressants-mediated anticarcinogenic effects may provide new clues for cancer prevention and clinical treatment.

Combination Therapies against COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of Coronavirus disease 2019 (COVID-19), which was announced as a pandemic leading to devastating economic and medical burden worldwide. The virus attacks the organ system across the body by binding to its receptor (for example, angiotensin converting enzyme 2) on the surface of the host cell of various organs. The patients present with a variety of pathological symptoms ranging from fever, cough and cytokine storm to acute respiratory distress syndrome (ARDS). Many combination therapies have been developed to combat the disease, via blocking one or more processes of the viral life cycle and/or relieving host complications simultaneously. In this review, the progress of those combination therapies containing at least one small molecule is updated. We believe it'll provide significant inspiration for further development of treatment strategy against SARS-CoV-2, especially its mutant variants.

Reproductive and postsurgical outcomes of infertile women with deep infiltrating endometriosis.

BACKGROUND: This study aimed to summarize and analyze clinical characteristics and reproductive outcomes in postoperative deep infiltrating endometriosis (DIE). METHODS: This retrospective cohort study included 55 reproductive-aged patients who were diagnosed with DIE, wished to conceive and underwent resection surgery at the Obstetrics and Gynecology Hospital, Fudan University, from January 2009-June 2017. Those with any plausible infertility factor or abnormalities in the partner's semen analysis were excluded. Patient characteristics, preoperative symptoms, infertility history, intraoperative findings and reproductive outcomes were followed up and recorded. Risk factors for reproductive outcomes were identified for women who became pregnant versus those who did not by univariate logistic regression. Additionally, pre- and postoperative endometriosis health profile questionnaire-30 (EHP-30), Knowles-Eccersley-Scott Symptom questionnaire (KESS), Cox Menstrual Symptom Scale (CMSS) and Female Sexual Function Index (FSFI) scores were used to evaluate the effect of DIE surgery on quality of life. RESULTS: The average age was 30.22 ± 3.62 years, with no difference between the pregnancy and nonpregnancy groups. The average follow-up time was 26.57 ± 14.51 months. There were 34 pregnancies (61.82%): 24 (70.59%) conceived spontaneously and 10 (29.41%) by in vitro fertilization (IVF). Twenty-eight patients (82.35%) had term deliveries. The interval between operation and pregnancy was 10.33 ± 5.6 (1-26) months. Univariate analysis showed that a lower endometriosis fertility index (EFI) score (EFI < 8) was a risk factor for infertility (OR: 3.17 (1.15-10.14), p = .044). For patients with incomplete surgery, postoperative gonadotropin-releasing hormone agonist (GnRHa) administration improved the pregnancy rate (p < 0.05). Regarding quality of life, there was significant improvement (p < 0.05) in the postoperative EHP-30, KESS and CMSS scores compared with preoperative scores in both groups. Although there was no obvious difference in FSFI scores, significant improvement in dyspareunia was observed (p < 0.05). CONCLUSIONS: Overall, the postoperative pregnancy rate of DIE patients was 61.82%. Surgical management of DIE for patients with complaints of pain and with pregnancy intentions was feasible and effective. Long-term expectant treatment should not be advised for patients with lower EFI scores (EFI < 8), and postoperative IVF-ET may be a good choice. More cases should be enrolled for further study, and randomized studies are required.

Laparoscopic blockage of uterine artery in the management of large cornual pregnancy.

OBJECTIVE: To present a technique of temporary uterine artery clamping before laparoscopic surgery for prevention of blood loss in cornual ectopic pregnancy. DESIGN: Step-by-step explanation of the entire surgical procedure using video and still images (Canadian Task Force classification III). SETTING: Tertiary university-based hospital. PATIENT(S): A 37-year-old woman who presented with amenorrhea of 55 days and extremely high ß-hCG level of 281,400 mIU/mL. Transvaginal ultrasound examination revealed a 7 cm mass with ample blood supply invading the muscularis layer around the right uterine cornua. INTERVENTION(S): Institutional Review Board and Ethics Committee approval was obtained. After pelvic adhesiolysis, retroperitoneum was dissected and the bilateral uterine arteries were exposed. To reduce the possibility of massive hemorrhage, titanium clips were used to temporarily block the bilateral uterine arteries. Laparoscopic inspection showed the mass as dark and blue, consistent with the diagnosis of cornual pregnancy. After removal of the cornual lesion, 2-0 Vicryl was used to reconstruct the uterine cornua. At the end of the surgery, the titanium clips were removed to reverse the uterine blood supply. MAIN OUTCOME MEASUREMENT(S): The surgery lasted for about 2 hours, with estimated blood loss of only 50 mL. The patient recovered completely and was discharged 2 days postoperatively, without any further bleeding or postoperative complications. The pathological examination confirmed the diagnosis of cornual pregnancy. RESULT(S): One month later, the ß-hCG levels decreased to within normal range. At 6-month postoperative follow-up, ultrasound examination showed a normal size uterus. CONCLUSION(S): Temporary blockage of the uterine artery during surgery could prevent heavy blood loss, especially in difficult surgeries such as myomectomy for complex uterus fibromas or adenomyomectomy. Moreover, this technique would be feasible for emergent cases, including conservative surgery for cesarean scar pregnancy, and could also replace traditional uterine artery embolization for treating cornual pregnancy.

Establishment of patient-derived xenograft model in ovarian cancer and its influence factors analysis.

AIM: Patient-derived xenograft (PDX) model has been applied to the study of breast cancer, lung cancer, colon cancer and other cancers. However, its feasibility in ovarian cancer has not been understood. This study aimed to establish ovarian cancer PDX model and reveal its influence factors. METHODS: In this study, 27 patients in Obstetrics and Gynecology Hospital affiliated to Fudan University from May 2015 to May 2016 were employed to explore the method of PDX model in ovarian cancer and verify its feasibility. RESULTS: Finally, five cases of PDX models were successfully established, and the tumor formation rate (TFR) was 18.52%. In addition, immunohistochemistry and transcriptome sequencing analysis showed that tumor of PDX model have similar gene expression, gene splicing, gene fusion and single nucleotide polymorphisms with primary tumor (R2 = 0.741). Furthermore, it was revealed that compared to epithelial ovarian cancer, the TFR of PDX models with nonepithelial ovarian cancer was higher, while other factors such as the initiation site of tumor, the degree of tumor malignancy, the stage of tumor, the type of tumor and the species of experimental animals were not associated with the TFR. CONCLUSION: Ovarian cancer PDX model, as a new scientific research model, can better keep the biological characteristics of primary tumor, which has great research value in ovarian cancer.

Simultaneous determination of saflufenacil and three metabolites in five agriculture products using liquid chromatography-Tandem mass spectrometry.

A reliable and efficient method was firstly established for the simultaneous determination of saflufenacil and its metabolites (M800H02, M800H11 and M800H35) in cereals (soybean and corn) and fruits (apple, grape and orange), based on a triple quadrupole liquid chromatography mass spectrometer. The four target compounds were extracted with acetonitrile and purified by Florisil or Florisil with octadecylsilane from the cereals and fruits. Determination of the targets was achieved within 3.5 min by using Shim-pack GIST C18 column connected to an electrospray ionization source (ESI- mode). The method showed excellent linearity (R2  > 0.9984), and the limits of quantitation were 1 µg/kg for all compounds. Average recoveries were in the range of 74.6%-108.1%, with an intra-day relative standard deviation between 0.9% and 18.3%. The inter-day relative standard deviation was less than 13.8%. The results demonstrate that this method is convenient for monitoring the residues of saflufenacil and its metabolites in food matrices. PRACTICAL APPLICATIONS: Saflufenacil controls many common annual broadleaf weed efficiently, it has been developed and launched into the market by domestic enterprises. Consequently, an analysis method for monitoring saflufenacil in food sample will be urgently needed in China over the next few years. This method provides separation with good specificity within 3.5 min, which is less than previous studies. For the five matrixes, the method presented satisfactory validation parameters in terms of good linearity, low limit of quantitations, and satisfactory accuracy and precision. Therefore, the method established in this study is a valuable tool to overcome gaps in determining saflufenacil and its metabolites in cereals and fruits, in order to accurate evaluation of risk and ensure food safety.

Human health safety studies of a new insecticide: Dissipation kinetics and dietary risk assessment of afidopyropen and one of its metabolites in cucumber and nectarine.

To preliminarily study the law of natural dissipation and the relation to human health of a new insecticide (afidopyropen), the QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method and a UHPLC-MS/MS system were used to extract and detect the afidopyropen and its metabolite (M440I007) from cucumber and nectarine. The limits of quantitation (LOQs) of both target compounds in two matrixes were reduced to 0.0001 mg/kg. Dissipative dynamics experiments indicated that afidopyropen residue dissipation is more consistent with a two-compartment kinetic model than a first-order kinetic model whether in cucumber or nectarine. The half-lives were less than 1.1 and 2.0 days in the distribution phase and up to 9.9 and 27.7 days in the elimination phase in cucumber and nectarine, respectively. The correlation coefficients were 0.9620, 0.9391, and 0.9923 for cucumber and 0.9676 and 0.9985 for nectarine from different locations. M440I007 initially increased rapidly, reached a maximum at 2 days, and then decreased gradually over time. Finally, dietary risk assessment indicated that the mixed residues of afidopyropen and M440I007 at the recommended dosage would not cause health concerns in population.

Rectovaginal fistula following surgery for deep infiltrating endometriosis: Does lesion size matter?

Objective This study was performed to identify risk factors for postoperative rectovaginal fistula (PRF) in patients with deep infiltrating endometriosis (DIE). Methods Data were retrospectively obtained from the medical records of 104 patients with DIE, and statistical analysis was used to detect risk factors for PRF. Results Five of 104 (4.8%) patients developed PRF from 5 to 16 days postoperatively. The operative procedures included 84 (80.8%) superficial excisions, 6 (5.8%) full-thickness disc excisions, and 14 (13.5%) bowel resections. Most lesions were located in the cul-de-sac, and the mean lesion size was 2.6 cm (range, 0.5-7.0 cm). The univariate analysis showed that lesion location, larger lesion size, and surgical technique were statistically significant risk factors for PRF. Conclusion Surgical procedures should be very carefully executed in patients with DIE lesions of ≥4 cm.

Current Updates on Salpingectomy for the Prevention of Ovarian Cancer and Its Practice Patterns Worldwide.

A paradigm shift of the origin of ovarian cancer to fallopian tube has brought more focus on bilateral salpingectomy as a preventive method for ovarian cancer. Bilateral salpingectomy has shown a dramatic reduction in the risk of ovarian cancer. Bilateral salpingo-oophorectomy has been a long-used practice to prevent ovarian cancer, but it brings surgical menopause and an increased mortality rate to women undergoing such a surgery at the age of <47.5. With the prophylactic bilateral salpingectomy, however, the ovarian function remains unaltered. Recent studies have shown that prophylactic salpingectomy was helpful not only in preventing high-grade serous type ovarian cancer, but also in decreasing adnexal pathologies. With the publication of committee opinion, more practitioners have accepted this proposal, but some are more concerned about its disadvantages. This review illustrates the latest updates on salpingectomy as a preventive method for ovarian cancer, including its advantages and disadvantages, clinicians' opinions, public opinions, so as to find out Obstetricians' and Gynecologists' practice pattern related to opportunistic salpingectomy worldwide.

Retrospective analysis of the clinicopathologic and prognostic characteristics of stage I placental site trophoblastic tumor in China.

OBJECTIVE: To investigate clinicopathologic features and identify prognostic factors of placental site trophoblastic tumor (PSTT). METHODS: In a retrospective study, data were analyzed from patients with stage I PSTT treated at a tertiary hospital in Shanghai, China, from January 2007 to May 2013. Univariate log-rank tests were used to examine the association between clinicopathologic characteristics and overall survival and disease-free survival (DFS). RESULTS: In total, seven patients had stage I PSTT. Mean age was 31.6 years (range 22-42). Four patients had term delivery as the outcome of their antecedent pregnancy. Six had a ß-human chorionic gonadotropin (ß-hCG) serum concentration of less than 10 000 mIU/mL. Among five patients who underwent hysterectomy combined with chemotherapy, one had recurrent disease. One patient received fertility-preserving therapy and achieved complete remission. The mean 5-year overall survival and DFS were 100% and 86%, respectively. Maximum ß-HCG concentration of at least 10 000 mIU/mL and a mitotic index of more than 5 mitotic counts per 10 high-power fields were associated with disease recurrence (both P=0.014). CONCLUSION: Pretreatment ß-hCG concentration and mitotic index might be predictors of recurrence among patients with PSTT. Fertility-preserving therapy might be practical in some patients.

Induction of autophagy contributes to cisplatin resistance in human ovarian cancer cells.

Cisplatin resistance is a major challenge in the clinical treatment of ovarian cancer, of which the underlying mechanisms remain unknown. The aim of the present study was to explore the role of autophagy in cisplatin resistance in ovarian cancer cells. A2780cp cisplatin-resistant ovarian carcinoma cells and the A2780 parental cell line, were used as a model throughout the present study. The cell viability was determined using a water soluble tetrazolium salt-8 assay, and western blot analysis was performed to determine the protein expression levels of microtubule-associated protein 1 light chain 3 (LC3 I and LC3 II), and Beclin 1. Beclin 1 small interfering (si)RNA and 3-methyladenine (3-MA) were used to determine whether inhibition of autophagy may re-sensitize cisplatin-resistant cells to cisplatin. The ultrastructural analysis of autophagosomes was performed using transmission electron microscopy, and apoptosis was measured by flow cytometry. In both A2780cp and A2780 cells, cisplatin induced the formation of autophagosomes and upregulated the expression levels of autophagy protein markers, LC3 II and Beclin 1. However, the levels of autophagy were significantly higher in A2780cp cells, as compared with the A2780 cells. The combined treatment of cisplatin with 3-MA, the autophagy pharmacological inhibitor, increased the cell death rate, but had no effects on apoptosis, as compared with cisplatin treatment alone in A2780cp cells. However, inhibition of autophagy by siRNA knockdown of Beclin 1 expression enhanced cisplatin-induced cell death and apoptosis. The findings of the present study suggest that autophagy has a protective role in human ovarian cancer cells, and that targeting autophagy may promote chemotherapeutic sensitivity.

Nrf2 induces cisplatin resistance through activation of autophagy in ovarian carcinoma.

UNLABELLED: Cisplatin resistance is a major problem affecting ovarian carcinoma treatment. NF-E2-related factor 2 (Nrf2), a nuclear transcription factor, plays an important role in chemotherapy resistance. However, the underlying mechanism by which Nrf2 mediates cisplatin chemoresistance is unclear. METHODS: The human ovarian carcinoma cell line, A2780, and its cisplatin-resistant variant, A2780cp were cultivated. Cell viability was determined with WST-8 assay. Western blot was applied to detect the expression of Nrf2, Nrf2 target genes, and autophagy-related proteins. RNA interference was used to knock down target genes. Annexin V and propidium iodide (PI) staining was utilized to quantify apoptosis. The ultrastructural analysis of autophagosomes was performed by transmission electron microscopy (TEM). RESULTS: Nrf2 and its targeting genes, NQO1 and HO-1, are overexpressed in A2780cp cells compared with A2780 cells. Knocking down Nrf2 sensitized A2780cp cells to cisplatin treatment and decreased autophagy-related genes, Atg3, Atg6, Atg12 and p62 in both mRNA and protein levels. Furthermore, we demonstrated that in both cell lines cisplatin could induce the formation of autophagosomes and upregulate the expression of autophagy-related genes Atg3, Atg6 and Atg12. Treatment with an autophagy inhibitor, 3-Methyladenine (3-MA), or beclin 1 siRNA enhanced cisplatin-induced cell death in A2780cp cells, suggesting that inhibition of autophagy renders resistant cells to be more sensitive to cisplatin. Taken together, Nrf2 signaling may regulate cisplatin resistance by activating autophagy. CONCLUSIONS: Nrf2-activated autophagy may function as a novel mechanism causing cisplatin-resistance.