Maternal inheritance of glucose intolerance via oocyte TET3 insufficiency.

Diabetes mellitus is prevalent among women of reproductive age, and many women are left undiagnosed or untreated1. Gestational diabetes has profound and enduring effects on the long-term health of the offspring2,3. However, the link between pregestational diabetes and disease risk into adulthood in the next generation has not been sufficiently investigated. Here we show that pregestational hyperglycaemia renders the offspring more vulnerable to glucose intolerance. The expression of TET3 dioxygenase, responsible for 5-methylcytosine oxidation and DNA demethylation in the zygote4, is reduced in oocytes from a mouse model of hyperglycaemia (HG mice) and humans with diabetes. Insufficient demethylation by oocyte TET3 contributes to hypermethylation at the paternal alleles of several insulin secretion genes, including the glucokinase gene (Gck), that persists from zygote to adult, promoting impaired glucose homeostasis largely owing to the defect in glucose-stimulated insulin secretion. Consistent with these findings, mouse progenies derived from the oocytes of maternal heterozygous and homozygous Tet3 deletion display glucose intolerance and epigenetic abnormalities similar to those from the oocytes of HG mice. Moreover, the expression of exogenous Tet3 mRNA in oocytes from HG mice ameliorates the maternal effect in offspring. Thus, our observations suggest an environment-sensitive window in oocyte development that confers predisposition to glucose intolerance in the next generation through TET3 insufficiency rather than through a direct perturbation of the oocyte epigenome. This finding suggests a potential benefit of pre-conception interventions in mothers to protect the health of offspring.

The Scheduling Mode of Anesthesia Nurses Affects Postanesthesia Care Unit Efficiency: A Single-Center Retrospective Study From China.

PURPOSE: Anesthesia nurses play an important postsurgical role during the anesthesia recovery period, which is characterized by a high incidence of complications related to anesthesia and surgery. Strengthening staff allocation and skill management in the postanesthesia care unit (PACU) is therefore particularly important in managing length of stay. We aimed to investigate the effect of two schedule modes for anesthesia nurses on PACU efficiency. DESIGN: A retrospective observational cohort study. METHODS: We conducted a retrospective study in a large tertiary academic medical center. In 2018, the PACU operated with traditional scheduling and the nurse-to-patient ratio was 1.2:1. The PACU implemented intensive scheduling and this ratio was adjusted to 1:1 in 2019 by adjusting the anesthesia nurse allocation scheme. We compared the number of admitted patients, length of PACU stay, the incidence of anesthesia-related complications, and nurse satisfaction with the two modes. FINDINGS: The total number of admitted patients was 10,531 in 2018 and 10,914 in 2019. PACU admitted 401 more patients in 2019 than in 2018, even with two fewer nurses per day. Nevertheless, the median length of PACU stay in 2019 was statistically significantly shorter than in 2018 (29 [22-40] vs 28 [21-39], P < .001], while the incidence of anesthesia-related complications including postoperative pain, nausea and vomiting, hypertension, and shivering were comparable in the 2 years (P > .091). The intensive scheduling implemented in 2019 received more satisfaction from nurses than the traditional scheduling applied in 2018 (P < .01). CONCLUSIONS: The scheduling of anesthesia nurses affects PACU efficiency. The intensive scheduling mode implemented in 2019 resulted in a comparable number of admitted patients, a better quality of care, and higher nurse satisfaction than those under the traditional scheduling mode.

KRT18 regulates trophoblast cell migration and invasion which are essential for embryo implantation.

Female infertility is a worldwide concern that impacts the quality of life and well-being of affected couples. Failure of embryo implantation is a major cause of early pregnancy loss and is precisely regulated by a programmed molecular mechanism. Recent studies have shown that proper trophoblast adhesion and invasion are essential for embryo implantation. However, the potential regulatory mechanism involved in trophoblast adhesion and invasion has yet to be fully elucidated. KRT18 has been reported to play a critical role in early embryonic development, but its physiological function in embryo implantation remains unclear. In the present study, we revealed that KRT18 was highly expressed in trophoblast cells and that knockdown of KRT18 in mouse embryos inhibited embryo adhesion and implantation. In vitro experiments further showed that silencing KRT18 disturbed trophoblast migration and invasion. More importantly, we provide evidence that KRT18 directly binds to and stabilizes cell surface E-cadherin in trophoblast cells through microscale thermophoresis (MST) analysis and molecular biology experiments. In brief, our data reveal that KRT18, which is highly expressed in trophoblast cells, plays an important role in the regulation of trophoblast invasion and adhesion during embryo implantation by directly binding to E-cadherin.

MicroRNA-122-5p alleviates endometrial fibrosis via inhibiting the TGF-ß/SMAD pathway in Asherman's syndrome.

RESEARCH QUESTION: What is the effect of miR-122 on the progression and recovery of fibrosis in Asherman's syndrome? DESIGN: Endometrial tissue was collected from 21 patients, 11 with intrauterine adhesion (IUA) and 10 without IUA. Quantitative real-time polymerase chain reaction, immunofluorescence and Western blot were applied to observe the expression of mRNAs/miRNAs and protein, respectively. The endometrial physical injury was carried out in C57BL/6 mice to create an endometrial fibrosis model, with intrauterine injection of adenovirus to compare the antifibrosis and repair function of miR-122 on endometrium. The morphology of the uterus was observed using haematoxylin and eosin staining, and fibrosis markers were detected by immunohistochemistry. RESULTS: miR-122 expression was reduced in patients with IUAs, accompanied by fibrosis. MiR-122 overexpression reduced the degree of fibrosis in endometrial stromal cells. Further molecular analyses demonstrated that miR-122 inhibited fibrosis through the TGF-ß/SMAD pathway by directly targeting the 3' untranslated region of SMAD family member 3, suppressing its expression. Notably, miR-122 promoted endometrial regeneration and recovery of pregnancy capacity in a mouse endometrial injury model. CONCLUSIONS: miR-122 is a critical regulator for repair of endometrial fibrosis and provided new insight for the clinical treatment of intrauterine adhesions.

CircRNA CircABCB1 Diminishes the Sensitivity of Breast Cancer Cells to Docetaxel by Sponging MiR-153-3p.

Resistance to docetaxel is a major problem to the success of docetaxel-based therapies for breast cancer. The present study was to identify the role of circABCB1 in altering the docetaxel resistance properties. Reverse transcription-quantitative PCR (qRT-PCR) was performed to quantify circABCB1 and miR-153-3p. The effects of circABCB1 on the viability, apoptosis and migration/invasion of docetaxel-resistant and -sensitive cells were investigated by cell function experiments, including Cell Counting Kit-8 and Transwell assays. Correlation between circABCB1 and the docetaxel-treated outcome was analyzed by multivariate Cox regression analysis, in addition to Kaplan-Meier analysis of time to treatment failure (TTF). The targeting relationship between circABCB1 and miR-153-3p was predicted and verified by dual-luciferase reporter assay and RNA immunoprecipitation. CircABCB1 was highly expressed in cancerous tissues, as well as the docetaxel-sensitive group and cells. The overexpression of circABCB1 contributed to cell viability, docetaxel-resistance and migration/invasion, but inhibited apoptosis. CircABCB1 can sponge miR-153-3p. CircABCB1 contributed to the docetaxel resistance of breast cancer, maybe via the miR-153-3p.

Intrauterine administration of G-CSF for promoting endometrial growth after hysteroscopic adhesiolysis: a randomized controlled trial.

STUDY QUESTION: Does intrauterine infusion of granulocyte colony-stimulating factor (G-CSF) prevent adhesion reformation and promote endometrial growth after hysteroscopic adhesiolysis? SUMMARY ANSWER: Intrauterine perfusion of G-CSF can increase endometrial thickness but does not prevent the recurrence of intrauterine adhesions (IUAs) in patients with Asherman syndrome (AS) after surgery. WHAT IS KNOWN ALREADY: Intrauterine infusion of G-CSF has been used in attempts to treat patients with recurrent miscarriage and an idiopathic thin endometrium for either fresh or frozen-thawed embryo transfer cycles but without uniform efficacy. There have been no reports on the effect of G-CSF on the recurrence of IUAs, endometrial regrowth or pregnancy results in specific populations with AS. STUDY DESIGN, SIZE, DURATION: This two-center prospective double-blind randomized controlled trial ran between April 2016 and August 2021. In it, 245 patients with moderate to severe AS were randomized to G-CSF and control groups at a 1:1 ratio; 229 women were included in the adhesion recurrence analysis; and 164 patients were analyzed for pregnancy outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: All eligible patients received the first hysteroscopic adhesion separation and balloon placement procedure. Patients who met our inclusion and exclusion criteria were randomized after surgery. These patients returned for balloon removal and underwent intrauterine perfusion with 300 µg (1.8 ml) G-CSF or 1.8 ml normal saline according to randomization at 7 days after surgery. A second-look hysteroscopy was carried out 1-2 months later. The primary outcome was the rate of formation of new adhesions at the second hysteroscopy. The secondary outcomes included endometrial thickness in the periovulatory period after surgery, as well as the clinical pregnancy and live birth rates. MAIN RESULTS AND THE ROLE OF CHANCE: Age, menstrual cycle characteristics, pregnancy history and IUA score before surgery were similar between groups. There were no statistically significant differences in the adhesion reformation rate or median adhesion score reduction. However, G-CSF perfusion significantly improved endometrial thickness (7.91 ± 2.12 mm vs 7.22 ± 2.04 mm; P = 0.019, 95% CI for difference: -1.26 to -0.12), as well as cumulative pregnancy and live birth rate over time (P = 0.017 and P = 0.042). Furthermore, multivariate logistic regression analysis showed that postoperative endometrial thickness was an independent prognostic factor for pregnancy and live birth rates. LIMITATIONS, REASONS FOR CAUTION: These results cannot be extended to older patients or those without AS, as our subjects had moderate or severe AS and were aged <40 years. The low number of patients included in the fertility analysis could lead to biased results. WIDER IMPLICATIONS OF THE FINDINGS: Intrauterine perfusion of G-CSF could be an effective adjuvant therapy for patients with AS to increase endometrial thickness. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the National Key Research and Development Program of China (2018YFC1004800), the National Natural Science Foundation of China (82001624 and 81871209), the Natural Science Foundation of Zhejiang Province (LQ20H040004) and the provincial and ministerial construction project of Zhejiang Province (2017 WKJ-ZJ-1721). The authors declare that they have no conflicts of interest regarding this work. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT02855632). TRIAL REGISTRATION DATE: 4 March 2016. DATE OF FIRST PATIENT'S ENROLMENT: 13 April 2016.

Synthesis and radioprotective effects of novel hybrid compounds containing edaravone analogue and 3-n-butylphthalide ring-opening derivatives.

As the potential risk of radiation exposure is increasing, radioprotectors studies are gaining importance. In this study, novel hybrid compounds containing edaravone analogue and 3-n-butylphthalide ring-opening derivatives were synthesized, and their radioprotective effects were evaluated. Among these, compound 10a displayed the highest radioprotective activity in IEC-6 and HFL-1 cells. Its oral administration increased the survival rates of irradiated mice and alleviated total body irradiation (TBI)-induced hematopoietic damage by mitigating myelosuppression and improving hematopoietic stem/progenitor cell frequencies. Furthermore, 10a treatment prevented abdominal irradiation (ABI)-induced structural damage to the small intestine. Experiment results demonstrated that 10a increased the number of Lgr5+ intestinal stem cells, lysozyme+ Paneth cells and Ki67+ transient amplifying cells, and reduced apoptosis of the intestinal epithelium cells in irradiated mice. Moreover, in vitro and in vivo studies demonstrated that the radioprotective activity of 10a is associated to the reduction of oxidative stress and the inhibition of DNA damage. Furthermore, compound 10a downregulated the expressions of p53, Bax, caspase-9 and caspase-3, and upregulated the expression of Bcl-2, suggesting that it could prevent irradiation-induced intestinal damage through the p53-dependent apoptotic pathway. Collectively, these findings demonstrate that 10a is beneficial for the prevention of radiation damage and has the potential to be a radioprotector.

Association between hepatitis B and E virus infection and hepatocellular carcinoma risk.

The role of hepatitis E virus (HEV) in developing hepatocellular carcinoma (HCC) is unclear. Our study aimed to investigate the role of HE infection in HCC development and the effect of hepatitis B virus (HBV) and HEV coinfection on HCC risk. A hospital-based case-control study was conducted. A total of 474 eligible HCC cases and 586 control patients were successfully recruited. The fasting venous blood was collected from the patients at the first visited to hospital and HBV infection and HEV infection were examined within 5 days. Crude and adjusted odd ratios (ORs) with 95% confidence interval (95% CI) were estimated by using logistic regression model. HBV infection (OR: 63.10, 95% CI: 42.02-97.26) rather than HEV infection (OR: 1.08, 95% CI: 0.721-1.65) was associated with an increased risk of HCC after adjustment for confounders. The association between HBV infection and HCC risk was more remarkable in male (OR: 72.61, 95% CI: 45.10-121.38) than in female (OR: 61.89, 95% CI: 25.74-169.26). In comparison with patients who infected with neither HEV nor HBV, those who infected with only HBV (OR: 69.62, 95% CI: 40.90-123.52) and who coinfected with HEV and HBV (OR: 67.48, 95% CI:37.23-128.19) were significantly associated with an increased risk after adjustment for potential confounders. The results showed that HBV infection rather than HEV infection was associated with an increased risk of HCC, and the HEV infection may alleviate the promoting impact of HBV on HCC development.

Pregnancy-related complications and perinatal outcomes following progesterone supplementation before 20 weeks of pregnancy in spontaneously achieved singleton pregnancies: a systematic review and meta-analysis.

BACKGROUND: Progesterone supplementation is widely performed in women with threatened miscarriage or a history of recurrent miscarriage; however, the effects of early progesterone supplementation on pregnancy-related complications and perinatal outcomes in later gestational weeks remain unknown. METHODS: Ovid MEDLINE, the Cochrane Library, Embase and ClinicalTrials.gov were searched until April 3rd, 2021. Randomized controlled trials regarding spontaneously achieved singleton pregnancies who were treated with progestogen before 20 weeks of pregnancy and were compared with those women in unexposed control groups were selected for inclusion. We performed pairwise meta-analyses with the random-effects model. The risk of bias was assessed according to the Cochrane Collaboration tool. The primary outcomes included preeclampsia (PE), and gestational diabetes mellitus (GDM), with the results presented as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: We identified nine eligible studies involving 6439 participants. The pooled OR of subsequent PE following early progestogen supplementation was 0.64 (95% CI 0.42-0.98, moderate quality of evidence). A lower OR for PE was observed in the progestogen group when the subgroup analysis was performed in the vaginal subgroup (OR 0.62, 95%CI 0.40-0.96). There was insufficient evidence of a difference in the rate of GDM between pregnant women with early progestogen supplementation and unexposed pregnant women (OR 1.02, 95% CI 0.79-1.32, low quality of evidence). The pooled OR of low birth weight (LBW) following oral dydrogesterone was 0.57 (95% CI 0.34-0.95, moderate quality of evidence). The results were affected by a single study and the total sample size of enrolled women did not reach the required information size. CONCLUSION: Use of vaginal micronized progesterone (Utrogestan) in spontaneously achieved singleton pregnancies with threatened miscarriage before 20 weeks of pregnancy may reduce the risk of PE in later gestational weeks. Among spontaneously achieved singleton pregnancies with threatened miscarriage or a history of recurrent miscarriage, use of oral dydrogesterone before 20 weeks of pregnancy may result in a lower risk of LBW in later gestational weeks. However, the available data were not sufficient to reach definitive conclusions, which highlighted the need for future studies.

Luteal phase support for in vitro fertilization/intracytoplasmic sperm injection fresh cycles: a systematic review and network meta-analysis.

BACKGROUND: Various luteal phase supports (LPSs) have been proven to increase the pregnancy rate in fresh cycles of in vitro fertilization or intracytoplasmic sperm injection; however, there is still significant debate regarding the optimal use of LPS. METHODS: A systematic review with the use of a network meta-analysis was performed via electronic searching of Ovid MEDLINE, the Cochrane Library, Embase, Web of Science, ClinicalTrials.gov and Google Scholar (up to January 2021) to compare the effectiveness and safety of various LPSs, as well as to evaluate the effects of different initiations of LPSs on pregnancy outcomes. The primary outcomes included live birth and ongoing pregnancy, with the results presented as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Eighty-nine randomized controlled trials with 29,625 women comparing 14 interventions or placebo/no LPS treatments were included in the meta-analyses. No significant differences were found in terms of the pregnancy outcomes when LPS was started within 48 h after oocyte retrieval versus a delayed initiation between 48 h and 96 h after oocyte retrieval. The addition of gonadotropin-releasing hormone (GnRH) agonists to progesterone vaginal pessaries showed a significant benefit in terms of live birth (OR 1.39, 95% CI 1.08 to 1.78). Only human chorionic gonadotropin (HCG) was found to be more efficacious than the placebo/no LPS treatment in terms of live birth (OR 15.43, 95% CI 2.03 to 117.12, low evidence). Any active LPSs (except for rectal or subcutaneous progesterone) was significantly more efficacious than the placebo/no LPS treatment in terms of ongoing pregnancy, with ORs ranging between 1.77 (95% CI 1.08 to 2.90) for the vaginal progesterone pessary and 2.14 (1.23 to 3.70) for the intramuscular progesterone treatment. Among the comparisons of efficacy and tolerability between the active treatments, the differences were small and very uncertain. CONCLUSION: Delays in progesterone supplementation until 96 h after oocyte retrieval does not affect pregnancy outcomes. The safety of GnRH agonists during the luteal phase needs to be evaluated in future studies before the applications of these agonists in clinical practice. With comparable efficacy and acceptability, there may be several viable clinical options for LPS.

HucMSC-Derived Exosomes Mitigate the Age-Related Retardation of Fertility in Female Mice.

In mammals, resting primordial follicles serve as the ovarian reserve. The decline in ovarian function with aging is characterized by a gradual decrease in both the quantity and quality of the oocytes residing within the primordial follicles. Many reports show that mesenchymal stem cells have the ability to recover ovarian function in premature ovarian insufficiency (POI) or natural aging animal models; however, the underlying mechanism remains unclear. In this study, using exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-exos), we found the specific accumulation of exosomes in primordial oocytes. The stimulating effects of exosomes on primordial follicles were manifested as the activation of the oocyte phosphatidylinositol 3-kinase (PI3K)/mTOR signaling pathway and the acceleration of follicular development after kidney capsule transplantation. Further analysis revealed the stimulatory effects of HucMSC-exos on primordial follicles were through carrying functional microRNAs, such as miR-146a-5p or miR-21-5p. In aged female mice, the intrabursal injection of HucMSC-exos demonstrated the recovery of decreased fertility with increased oocyte production and improved oocyte quality. Although assisted reproductive technologies have been widely used to treat infertility, their overall success rates remain low, especially for women in advanced maternal age. We propose HucMSC-exos as a new approach to mitigate the age-related retardation of fertility in women.

Feasibility of modified radical mastectomy with nipple-areola preservation combined with stage I prosthesis implantation using air cavity-free suspension hook in patients with breast cancer.

BACKGROUND: Mastoscopic surgery is proven to have lower incidence of postoperative complications and better postoperative recovery than traditional breast cancer surgery. This study aimed to examine the feasibility of mastoscopic modified radical mastectomy (MRM) with skin nipple-areola preservation under air cavity-free suspension hook and stage I silicone prosthesis implantation (SMALND) compared with routine MRM. METHODS: This was a retrospective study of patients who underwent MRM for breast cancer at the Shengjing Hospital Affiliated to China Medical University between January 1, 2019, and June 30, 2019. Surgical outcomes, complications, satisfaction, and quality of life (Functional Assessment of Cancer Therapy-Breast [FACT-B] [Chinese version]) were compared between the two groups. RESULTS: A total of 87 patients were enrolled, with 30 underwent SMALND and 57 underwent routine MRM. The intraoperative blood loss in the SMALND group was lower than in the control group (165.3±44.1 vs. 201.4±52.7 ml, P=0.001), the operation time was longer (220.5±23.9 vs. 155.6±9.2 min, P<0.001), daily axillary drainage volume was smaller (20.2±3.6 vs. 24.1±3.0 ml, P<0.001), daily subcutaneous drainage volume was smaller (15.5±2.3 vs. 19.3±3.5 ml, P<0.001), the discharge time was shorter (7.5±1.6 vs. 9.0±1.8 days, P<0.001), and FACT-B scores were higher (83.8±5.6 vs. 72.1±4.6, P<0.001). The overall satisfaction was higher in the SMALND group than in the controls (76.7% vs. 54.4%, P=0.041). Compared with the controls, the occurrence rates of nipple and flap necrosis, upper limb edema, and paraesthesia in the SMALND group were lower within 6 months (all P<0.05). CONCLUSIONS: Compared with traditional MRM, SMALND had better surgical outcomes, higher satisfaction, higher quality of life, and lower complication rates.

Endometrial preparation for frozen-thawed embryo transfer cycles: a systematic review and network meta-analysis.

PURPOSE: To compare the effects of different endometrial preparation protocols for frozen-thawed embryo transfer (FET) cycles and present treatment hierarchy. METHODS: Systematic review with meta-analysis was performed by electronic searching of MEDLINE, the Cochrane Library, Embase, ClinicalTrials.gov and Google Scholar up to Dec 26, 2020. Randomised controlled trials (RCTs) or observational studies comparing 7 treatment options (natural cycle with or without human chorionic gonadotrophin trigger (mNC or tNC), artificial cycle with or without gonadotropin-releasing hormone agonist suppression (AC+GnRH or AC), aromatase inhibitor, clomiphene citrate, gonadotropin or follicle stimulating hormone) in FET cycles were included. Meta-analyses were performed within random effects models. Primary outcome was live birth presented as odds ratio (OR) with 95% confidence intervals (CIs). RESULTS: Twenty-six RCTs and 113 cohort studies were included in the meta-analyses. In a network meta-analysis, AC ranked last in effectiveness, with lower live birth rates when compared with other endometrial preparation protocols. In pairwise meta-analyses of observational studies, AC was associated with significant lower live birth rates compared with tNC (OR 0.81, 0.70 to 0.93) and mNC (OR 0.85, 0.77 to 0.93). Women who achieved pregnancy after AC were at an increased risk of pregnancy-induced hypertension (OR 1.82, 1.37 to 2.38), postpartum haemorrhage (OR 2.08, 1.61 to 2.78) and very preterm birth (OR 2.08, 1.45 to 2.94) compared with those after tNC. CONCLUSION: Natural cycle treatment has a higher chance of live birth and lower risks of PIH, PPH and VPTB than AC for endometrial preparation in women receiving FET cycles.

Artificial Intelligence Medical Ultrasound Equipment: Application of Breast Lesions Detection.

Breast cancer ranks first among cancers affecting women's health. Our work aims to realize the intelligence of the medical ultrasound equipment with limited computational capability, which is used for the assistant detection of breast lesions. We embed the high-computational deep learning algorithm into the medical ultrasound equipment with limited computational capability by two techniques: (1) lightweight neural network: considering the limited computational capability of ultrasound equipment, a lightweight neural network is designed, which greatly reduces the amount of calculation. And we use the technique of knowledge distillation to train the low-precision network helped with the high-precision network; (2) asynchronous calculations: consider four frames of ultrasound images as a group; the image of the first frame of each group is used as the input of the network, and the result is respectively fused with the images of the fourth to seventh frames. An amount of computation of 30 GFLO/frame is required for the proposed lightweight neural network, about 1/6 of that of the large high-precision network. After trained from scratch using the knowledge distillation technique, the detection performance of the lightweight neural network (sensitivity = 89.25%, specificity = 96.33%, the average precision [AP] = 0.85) is close to that of the high-precision network (sensitivity = 98.3%, specificity = 88.33%, AP = 0.91). By asynchronous calculation, we achieve real-time automatic detection of 24 fps (frames per second) on the ultrasound equipment. Our work proposes a method to realize the intelligence of the low-computation-power ultrasonic equipment, and successfully achieves the real-time assistant detection of breast lesions. The significance of the study is as follows: (1) The proposed method is of practical significance in assisting doctors to detect breast lesions; (2) our method provides some practical and theoretical support for the development and engineering of intelligent equipment based on artificial intelligence algorithms.

Enhanced preoperative education about continuous femoral nerve block with patient-controlled analgesia improves the analgesic effect for patients undergoing total knee arthroplasty and reduces the workload for ward nurses.

BACKGROUND: Total knee arthroplasty (TKA) is the most common treatment for end-stage knee osteoarthritis and continuous femoral nerve block (CFNB) has become the gold standard for analgesia. But the lack of knowledge about CFNB and patient-controlled analgesia (PCA) often leads to inappropriate dose of medications and increased workload for ward nurses. METHODS: After retrospectively registering to http://www.chictr.org.cn (ChiCTR1800018957), 60 patients undergoing unilateral TKA were randomly divided into groups A and B (n = 30 each). Patients in group B and their families received a nurse-led preoperative visit the day before surgery focusing on PCA educational pamphlets for postoperative pain management. Before returning to the ward, patients and their families in both groups received face-to-face PCA pump operation training. The usual postoperative follow-up was performed by nurse anesthetists for 2 consecutive days. Visual Analogue Scale (VAS) scores at rest and during movement, knowledge of the PCA evaluated by a ten-question questionnaire, knee flexion angles, and the number of PCA-related nurse calls were recorded. RESULTS: The VAS scores at rest and during movement of the patients in group B were both significantly lower than in group A on postoperative days 1 and 2. The questionnaire scores of the patients in group B were much higher than those in group A on postoperative day 1, but not on day 2. Patients in the 2 groups had similar knee flexion on postoperative days 1 and 2. Patients in group B asked for assistance from the ward nurses with the PCA fewer times than those in group A, and the ward nurses were more satisfied with the analgesic protocol in group B. CONCLUSIONS: Enhanced preoperative education for CFNB with PCA can provide patients with a better grasp of postoperative pain management, improve the postoperative analgesic effect after TKA, and reduce the PCA-related workload for ward nurses. TRIAL REGISTRATION: This study was retrospectively registered to ChiCTR (identifier: ChiCTR1800018957 ) on October 18, 2018.

Ultrasonic Diagnosis of Breast Nodules Using Modified Faster R-CNN.

Breast cancer has become the biggest threat to female health. Ultrasonic diagnosis of breast cancer based on artificial intelligence is basically a classification of benign and malignant tumors, which does not meet clinical demand. Besides, the current target detection method performs poorly in detecting small lesions, while it is clinically required to detect nodules below 2 mm. The objective of this study is to (a) propose a diagnostic method based on Breast Imaging Reporting and Data System (BI-RADS) and (b) increase its detectability of small lesions. We modified the framework of Faster R-CNN (Faster Region-based Convolutional Neural Network) by introducing multi-scale feature extraction and multi-resolution candidate bound extraction into the network. Then, it was trained using 852 images of BI-RADS C2, 739 images of C3, and 1662 images of malignancy (BI-RADS 4a/4b/4c/5/6). We compared our model with unmodified Faster R-CNN and YOLO v3 (You Only Look Once v3). The mean average precision (mAP) is significantly increased to 0.913, while its average detection speed is slightly declined to 4.11 FPS (frames per second). Meanwhile, its detectivity of small lesions is effectively improved. Moreover, we also tentatively applied our model on video sequences and got satisfactory results. We modified Faster R-CNN and trained it partly based on BI-RADS. Its detectability of lesions, as well as small nodules, was significantly improved. In view of wide coverage of dataset and satisfactory test results, our method can basically meet clinical needs.

Smoking cessation sharply reduced lung cancer mortality in a historical cohort of 3185 Chinese silicotic workers from 1981 to 2014.

BACKGROUND: Population-based studies showed an over 50% decrease in lung cancer risk after quitting smoking for 5-6 years, but the beneficial effect in silicotics remains unknown. We aimed to rectify this knowledge gap using a large historical cohort of 3185 Chinese silicotics since 1981 and followed-up till 2014. METHODS: Baseline information on workers' socio-demographics, smoking habits, occupational history, and medical history was collected. Smoking status was reassessed during follow-up. Multiple Cox proportional hazards model was performed to evaluate the impact of smoking cessation on lung cancer mortality. RESULTS: Overall, 1942 deaths occurred and 188 lung cancer deaths were identified. Compared with never quitters, silicotics who were new quitters had almost halved their lung cancer risk [hazard ratio (HR) = 0.51, 95%CI: 0.34-0.76], while persistent quitters had a 53% risk reduction (HR = 0.47, 95%CI: 0.33-0.66). Lung cancer mortality approximately halved after quitting smoking for 10 years. While the risk kept decreasing with years since cessation, it did not reverse back to that of never smokers. Persistent quitters with small opacities tended to have higher beneficial effects than those with large opacities. CONCLUSIONS: Smoking cessation for 10 years halved lung cancer mortality among silicotics, while the beneficial effect was prominent for patients with small opacities.

Endometrial stem cell-derived granulocyte-colony stimulating factor attenuates endometrial fibrosis via sonic hedgehog transcriptional activator Gli2.

Intrauterine adhesion (IUA) is characterized by endometrial fibrosis, which ultimately leads to menstrual abnormalities, infertility, and recurrent miscarriages. The Shh/Gli2 pathway plays a critical role in tissue fibrogenesis and regeneration; Gli2 activation induces profibrogenic effects in various tissues, such as the liver and kidney. However, the role of Gli2 in endometrial fibrosis remains unknown. The purpose of this study was to test the hypothesis that activated Gli2 promotes endometrial fibrosis. Endometrial samples from moderate and severe IUA patients exhibited significantly enhanced expression of Gli2 compared with normal endometrial samples and mild IUA samples. Transfection with overactive Gli2 plasmids induced higher fibrosis-related protein expression, while blocking Gli2 signaling with cyclopamine caused the opposite effect in endometriotic stromal cells (ESCs), including inducing cell-cycle arrest. Menstrual-derived stem cell conditioned medium (MenSCs-CM) reduced endometrial fibrosis by reducing Gli2 protein levels and causing cell-cycle arrest in ESCs through granulocyte-colony stimulating factor (G-CSF). The effect was weakened after neutralization with a G-CSF antibody. Gli2 overexpression reduced the effects of MenSC-CM and G-CSF on fibrosis and cell-cycle progression in vitro. The antifibrotic effect of G-CSF was also observed in murine model. These findings demonstrate that Gli2 signaling promotes endometrial fibrosis, and the inhibition of Gli2 through MenSCs-secreted G-CSF may be of therapeutic value for managing endometrial fibrosis.

Cornual Suture at the Time of Laparoscopic Salpingectomy Reduces the Incidence of Interstitial Pregnancy after In Vitro Fertilization.

STUDY OBJECTIVE: To investigate the effect of cornual suture at the time of laparoscopic salpingectomy on the incidence of interstitial pregnancy (IP) after in vitro fertilization (IVF). DESIGN: Single-center, retrospective review (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Patients with hydrosalpinx who were treated with salpingectomy before IVF-embryo transfer and managed in our center were included in this study. INTERVENTIONS: A total of 542 patients who underwent laparoscopic salpingectomy from April 2011 to March 2014 comprised group A. A total of 502 patients who underwent cornual suture at the time of laparoscopic salpingectomy from April 2014 to February 2016 comprised group B. MEASUREMENTS AND MAIN RESULTS: The overall IP rate was significantly lower in group B (7/293, 2.39%) than in group A (27/373, 7.24%; p < .05). The intrauterine pregnancy and ongoing pregnancy/live birth rates were significantly higher in group B than in group A (both p < .05). All 34 patients with IP underwent laparoscopic cornuostomy and cornual repair. Seven of 11 patients with combined interstitial and intrauterine pregnancies carried the intrauterine pregnancy to term and delivered via cesarean section, whereas 4 patients underwent inevitable miscarriage. IP rupture occurred in 8 of 34 patients at a mean of 23.43 ± 2.77 days after embryo transfer. The earliest time of rupture was on day 20 after embryo transfer. CONCLUSION: An optimized salpingectomy technique plays an important role in pretreatment before embryo transfer in patients with hydrosalpinx. Cornual suture at the time of salpingectomy helps reduce the risk of IP.