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Any abnormality of the uterine cavity can result in reduced endometrial receptivity, which negatively affects embryo implantation and leads to lower clinical pregnancy rates. The effects of improved uterine cavity environment on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)-embryo transfer (ET) treatment outcome are unclear. This study aimed to investigate the impact of improved uterine cavity abnormalities on the pregnancy outcomes of infertile patients undergoing IVF/ICSI-ET.Retrospective study.Single-center.Women with infertility who underwent fresh cycles of IVF/ICSI-ET.We retrospectively analyzed the clinical data of 31 057 cycles of women with infertility undergoing IVF/ICSI-ET with hysteroscopy and treated at the First Affiliated Hospital of Zhengzhou University Reproductive Medicine Center from August 2009 to May 2018. According to the previous condition of their uterine cavity, patients were divided into the normal uterine cavity, single uterine cavity abnormality, and complex uterine cavity abnormality groups. Differences in general conditions and pregnancy-assisted outcomes were compared among the groups, which were screened according to propensity score matching.In 3005 cycles after propensity score matching screening, there were no statistically significant differences in the implantation and clinical pregnancy rates of patients with successfully treated uterine cavity abnormalities and lesions (p.05). The miscarriage rate was significantly higher in the complex uterine cavity abnormality group than in the normal (p = .001) and single uterine cavity abnormality groups (p = .002). Logistic regression analysis showed that the female partner's age (adjusted odds ratio, 1.12; 95% confidence interval, 1.05-1.19; p = .001) and history of intrauterine adhesions (adjusted odds ratio, 1.44; 95% confidence interval, 1.12-1.85; p = .005) were independent risk factors for miscarriage.The age of the female partner and history of intrauterine adhesions increased the miscarriage rate in patients undergoing IVF/ICSI-ET.

Familial celiac disease syndrome (FCS) is a form of hypertriglyceridemia (HTG) caused by the accumulation of celiac particles. Currently, volanesorsen is considered to be used to treat patients with FCS and HTG to improve symptoms. To evaluate the effect of volanesorsen on lipid metabolism in patients with FCS, we performed a systematic evaluation and meta-analysis.A systematic search of PubMed, Embase, ClinicalTrials.gov, and the Cochrane Library was conducted, and the bibliographies of original articles were checked manually. The quality of the studies was assessed using the Cochrane Risk of Bias tool.Four randomized, controlled trials involving 246 patients were analyzed in this study. Patients treated with volanesorsen showed (MD = -78.85%; 95% CI = -96.04 to -61.65, P = 0.67, I

Oral hypoglycemic drugs for the treatment of gestational diabetes mellitus (GDM) are still controversial because they can pass through the placenta. The purpose of this meta-analysis is to evaluate the safety and effectiveness of oral hypoglycemic drugs.PubMed, Ovid Embase, Web of Science, and Cochrane databases were systematically searched (inception to 20 April 2021). Rev Man 5.0 was used to analyze the data. A random-effects model was used to compute the summary risk estimates.There were 26 randomized controlled trials (RCTs) involving 4921 GDM patients which were included in this meta-analysis. Compared with metformin, insulin had a significant increase in the risk of preeclampsia (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.06 to 2.45; IMetformin is comparable with insulin in glycemic control and neonatal outcomes and has the potential to replace insulin therapy in clinical practice. Glyburide is behind metformin and insulin, and more RCTs are needed to verify its safety.

Objective To evaluate whether the change in endometrial thickness from progesterone administration day to transfer day is related to pregnancy outcomes in single frozen-thawed euploid blastocyst transfer cycles. Design Observational cohort study. Setting Single reproductive medical center. Patient(s) All patients were transferred with a single biopsied euploid blastocyst, and their endometrium was prepared with hormone replacement therapy (HRT). Intervention(s) The endometrial thickness on the day of blastocyst transfer and progesterone administration was measured by transvaginal ultrasound, and the difference between them and the change ratio were calculated. Main Outcome Measure(s) Clinical pregnancy rates and live birth rates. Result(s) Endometrial ultrasound images of 508 euploid blastocyst transfer cycles using HRT were evaluated by transvaginal ultrasound. Overall, pregnancy outcomes were comparable in different groups of endometrial thickness changes. The results of multiple logistic regression showed that the clinical pregnancy rate and live birth rate did not significantly increase with the increase in endometrial thickness change ratios (per 10%) in the fully adjusted model as a continuous variable. In the adjustment model as a categorical variable, there was no statistical difference in pregnancy outcomes among the groups with changes in endometrial thickness. Interaction analysis showed that after adjusting for confounders, there was no statistically significant interaction between the endometrial thickness change ratio and pregnancy outcomes in all subgroups. Conclusion(s) In the euploid blastocyst transfer cycle of preparing the endometrium with HRT, the endometrial thickness change ratio after progesterone administration was not related to pregnancy outcomes.

Resistance to epidermal growth factor receptor-tyrosin kinase inhibitors (TKIs, e.g. icotinib) remains a major clinical challenge. Non-small cell lung cancer patients with wild-type EGFR and/or K-RAS mutation are primary resistance to EGFR-TKIs. Berberine has been found to have potent anticancer activities via distinct molecular mechanism. In this study, we sought to investigate the therapeutic utility of BBR in combination with icotinib to overcome icotinib resistance in NSCLC cells, and explore the molecular mechanism of synergism of icotinib and BBR to EGFR-resistant NSCLC cells. We used the two EGFR-resistant NSCLC cell lines H460 and H1299 for testing the inhibitory effect of icotinib and/or BBR on them. Moreover, xenograft mouse model was applied for assessing the anti-tumor activities of BBR and icotinib in combination. Results showed that BBR and icotinib have a synergistic inhibitory effect on H460 and H1299 cells through induction of autophagic cell death and apoptosis. Accordingly, the anti-cancer effect of BBR plus icotinib was further confirmed in the NSCLC xenograft mouse models. Combination of BBR and icotinib significantly inhibited the protein expression and the activity of EGFR by inducing autophagic EGFR degradation. BBR plus icotinib resulted in intracellular ROS accumulation, which could mediated autophagy and apoptosis and involved in the suppression of cell migration and invasion. In conclusions, combination application of BBR and icotinib could be an effective strategy to overcome icotinib resistance in the treatment of NSCLC.

Polycystic ovary syndrome (PCOS) is a multifactorial reproductive and endocrine disease, believed to be caused by aberrant steroid biosynthesis pathways involving cytochrome P450, 17α-hydroxylase (CYP17A1). This meta-analysis aimed to evaluate the association between CYP17A1 polymorphism rs743572 and PCOS risk. Studies on the CYP17A1 gene were retrieved by searching PubMed, Embase and Web of Science and statistical analyses were performed by STATA software. Fifteen eligible studies were included, dated from January 1994 to 19 November 2020, involving 2277 patients with PCOS and 1913 control individuals. Overall, the results showed that the rs743572 T>C mutation was most likely to be associated with PCOS risk under the recessive model, which was further confirmed by heterogeneity analysis and publication bias detection (CC versus CT + TT, odds ratio [OR] 1.24, 95% confidence interval [CI] 1.02–1.50, P = 0.028, I² = 35.9%). Moreover, subgroup analysis by ethnicity demonstrated that Caucasian but not Asian women carrying the CC genotype of rs743572 had an elevated risk of PCOS (CC versus CT + TT, OR 1.45, 95% CI 1.03–2.06, P = 0.035, I² = 15.10%, six studies). In conclusion, rs743572 is highly likely to be a risk factor for PCOS, and the mutant genotype CC may increase susceptibility to PCOS in Caucasians rather than Asians.

Background With the onset of the coronavirus disease 2019 (COVID‐19) pandemic, many experts expected that asthma‐associated morbidity because of severe acute respiratory syndrome coronavirus 2 infection would dramatically increase. However, some studies suggested that there was no apparent increasing in asthma‐related morbidity in children with asthma, it is even possible children may have improved outcomes. To understand the relationship between the COVID‐19 pandemic and asthma outcomes, we performed this article. Methods We searched PubMed, Embase, and Cochrane Library to find literature from December 2019 to June 2021 related to COVID‐19 and children's asthma control, among which results such as abstracts, comments, letters, reviews, and case reports were excluded. The level of asthma control during the COVID‐19 pandemic was synthesized and discussed by outcomes of asthma exacerbation, emergency room visit, asthma admission, and childhood asthma control test (c‐ACT). Results A total of 22,159 subjects were included in 10 studies. Random effect model was used to account for the data. Compared with the same period before the COVID‐19 pandemic, asthma exacerbation reduced (odds ratio [OR] = 0.26, 95% confidence interval [CI] = [0.14–0.48], Z = 4.32, p

OBJECTIVE: To develop the birth weight curves of the Chinese Han (26-41 weeks of gestation) and Zhuang (28-41 weeks of gestation) singleton neonates in 11 cities of China, as well as the birth weight means of full-term neonates of 14 Chinese ethnic groups. METHODS: The live singleton neonates who were born in 11 maternal and child health care hospitals from 11 cities of China between January 2017 and December 2020 were classified according to the mother's ethnic group. Birth weight means were calculated for the full-term neonates of each ethnic group. For the Han and Zhuang singleton neonates with a large sample size, the Lambda-Mu-Sigma (LMS) method was used to establish the birth weight percentile curves of the Han and Zhuang singleton neonates with different gestational ages. RESULTS: A total of 105 365 live singleton neonates were included, among whom the Han neonates had the highest number of 84 851 (26-41 weeks of gestation), followed by the Zhuang neonates (12 803 neonates with a gestational age of 28-41 weeks). The neonates of the other Chinese ethnic groups enrolled were live full-term singleton neonates, with a sample size of more than 100 neonates for each ethnic group. The 3rd-97th percentile curves of birth weight were established for the Han singleton neonates with a gestational age of 26-41 weeks and the Zhuang singleton neonates with a gestational age of 28-41 weeks. The birth weight curves of the Han singleton neonates at each gestational age were higher than those of the Zhuang singleton neonates. Birth weight means (3 199-3 499 g) and standard deviations were determined for 14 Chinese ethnic groups, i.e., Li, Mulao, Zhuang, Yao, Dong, Miao, Han, Buyi, Mongolian, Tujia, Yi, Hui, Man, and Korean ethnic groups. The Li ethnic group had the lowest birth weight, followed by the Mulao, Zhuang, Yao, Dong, Miao, Han, Buyi, Mongolian, Tujia, Yi, Hui, Man, and Korean ethnic groups. CONCLUSIONS: The 3rd-97th percentile curves of birth weight are developed for the Han (26-41 weeks of gestation) and Zhuang (28-41 weeks of gestation) singleton neonates in 11 cities of China, and birth weight means are determined for the full-term neonates of 14 Chinese ethnic groups in 11 cities of China, which provides a reference for evaluating the intrauterine growth of neonates in these ethnic groups.

Background The dual inhibitors of receptor interacting protein kinase-1 and -3 (RIP1 and RIP3) play an important role in cell death processes and inflammatory responses. White matter injury (WMI), a leading cause of neurodevelopmental disabilities in preterm infants, which is characterized by extensive myelination disturbances and demyelination. Neuroinflammation, leads to the loss and differentiation-inhibition of oligodendrocyte precursor cells (OPCs), represents a major barrier to myelin repair. Whether the novel RIP1/RIP3 dual inhibitor ZJU-37 can promote transplanted OPCs derived from human neural stem cells (hOPCs) survival, differentiation and myelination remains unclear. In this study, we investigated the effect of ZJU-37 on myelination and neurobehavioral function in a neonatal rat WMI model induced by hypoxia and ischemia. Methods In vivo, P3 rat pups were subjected to right common carotid artery ligation and hypoxia, and then treated with ZJU-37 or/and hOPCs, then OPCs apoptosis, myelination, glial cell and NLRP3 inflammasome activation together with cognitive outcome were evaluated at 12 weeks after transplantation. In vitro, the effect of ZJU-37 on NLRP3 inflammasome activation in astrocytes induced by oxygen–glucose deprivation (OGD) were examined by western blot and immunofluorescence. The effect of ZJU-37 on OPCs apoptosis induced by the conditioned medium from OGD-injured astrocytes (OGD-astrocyte-CM) was analyzed by flow cytometry and immunofluorescence. Results ZJU-37 combined with hOPCs more effectively decreased OPC apoptosis, promoted myelination in the corpus callosum and improved behavioral function compared to ZJU-37 or hOPCs treatment. In addition, the activation of glial cells and NLRP3 inflammasome was reduced by ZJU-37 or/and hOPCs treatment in the neonatal rat WMI model. In vitro, it was also confirmed that ZJU-37 can suppress NLRP3 inflammasome activation in astrocytes induced by OGD. Not only that, the OGD-astrocyte-CM treated with ZJU-37 obviously attenuated OPC apoptosis and dysdifferentiation caused by the OGD-astrocyte-CM. Conclusions The novel RIP1/RIP3 dual inhibitor ZJU-37 may promote OPC survival, differentiation and myelination by inhibiting NLRP3 inflammasome activation in a neonatal rat model of WMI with hOPC graft.

To develop the birth weight curve of twin neonates with a gestational age of 25-40 weeks, and to investigate the regional differences of the birth weight curve.A total of 11 maternal and child health care hospitals with more than 7 000 neonates delivered annually were selected in 11 cities of China (Haikou, Guangzhou, Liuzhou, Guilin, Quanzhou, Shenzhen, Chongqing, Chengdu, Changsha, Ningbo, and Lianyungang), and all live twin neonates delivered in the 11 hospitals from January 1, 2017 to December 31, 2020 were enrolled for the development of birth weight curves.A total of 17 256 twin neonates with a gestational age of 25-40 weeks from the 11 cities were included in the study. The reference values of the 3rd-97th percentiles of birth weight of twin neonates for the total of the 11 cities and for each of the 11 cities in China were established, and the birth weight percentile curves were drawn. The birth weight curve level of twin neonates in Liuzhou was lower than the average level of the 11 cities; the birth weight curve level of twin neonates in Ningbo was higher than the average level of the 11 cities; the birth weight curve level of twin neonates in Lianyungang was obviously higher than the average level of the 11 cities; the birth weight curve level of twin neonates in other 8 cities was almost the same as the average level of the 11 cities.The reference values of the 3rd-97th percentiles of birth weight of twin neonates for the total of the 11 cities and for each of the 11 cities are developed, which can be used as a reference for evaluating the intrauterine growth of twin neonates in the region. The level of intrauterine growth of twin neonates in some cities is different from the average level of the 11 cities of China.

We aimed to analyze whether elevated progesterone levels on the day before ovulation affected pregnancy outcomes in natural cycles of frozen thawed embryo transfer (NC-FET).A retrospective analysis was conducted in a public university hospital. Data on clinical pregnancy, live birth, ectopic pregnancy, and miscarriage rates were collected, along with other patient data. Patients were divided into two groups according to their progesterone levels the day before ovulation: the progesterone elevation (PE) group (progesterone level1.0 ng/mL) and the normal progesterone (NP) group (progesterone level ≤1.0 ng/mL). We assessed the effect of elevated progesterone levels in NC-FET by performing multivariate logistic regression analysis.Overall 1159 women with tubal factor infertility who underwent NC-FET were enrolled, including 666 women who received cleavage-stage embryo transfers and 493 women who received blastocyst embryo transfers. When two cleavage-stage embryos were transferred, the clinical pregnancy rate was significantly higher in the PE than in the NP group following NC-FET (The results showed that in patients undergoing cleavage-stage NC-FET, progesterone levels1.0 ng/mL improved the clinical pregnancy rates. However, the level of progesterone had no effect on the clinical pregnancy rate for patients undergoing blastocyst-stage NC-FET.

Abnormalities of the insulin‑like growth factor 2

ObjectiveThis study aimed to evaluate potential predictors for recovery time in pregnant patients with moderate to severe ovarian hyperstimulation syndrome (OHSS).MethodsA total of 424 pregnant patients with moderate to severe OHSS who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) were retrospectively identified. The clinical features and laboratory findings within 24 h after admission were collected. Treatment for OHSS was carried out according to standard procedures, including fluid replacement therapy, human albumin, aspirin, low-molecular-weight heparin, and paracentesis, when necessary. Patients were discharged from the hospital when the tmorning hematocrit was ResultsThe median recovery time of these patients was 11 days. In Spearman’s correlation test, leukocytes, hemoglobin, platelets, hematocrit, creatinine, prothrombin time (PT), fibrinogen (Fib), D-dimer, and fibrinogen degradation products (FDPs) were positively correlated with recovery time. On the other hand, albumin and thrombin time (TT) were negatively correlated with recovery time. Multiple linear regression analysis showed that polycystic ovary syndrome (PCOS), hemoglobin, platelets, albumin, and Fib were significantly associated with the recovery time of patients with OHSS (p = 0.023, p p = 0.007, p p = 0.019, respectively).ConclusionsIn pregnant patients with OHSS, PCOS and hypoalbuminemia were associated with a significantly longer recovery time. Meanwhile, the recovery time was longer when patients have high levels of hemoglobin, platelets, and Fib.

Renal risk score (RRS) and chronicity score (CS) are both newly proposed tools to predict end stage renal disease (ESRD) which could be applicable in antineutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis patients. Their predictive value has not been fully studied and compared.252 patients with newly biopsy-proven ANCA-associated renal vasculitis were retrospectively studied at the Department of Nephrology, Ruijin Hospital, China. Patients were evaluated with RRS and CS for clinical factors, pathological lesions and outcome. Their predictive value of renal survival was also compared.The median RRS score point at diagnosis was 6 (interquartile range [IQR] 0-9) and CS score point was 4 (IQR 3-7). In accordance with severity of RRS category and CS grade, percentage of hypertensive patients, dialysis dependency, and level of proteinuria increased accordingly. Significant differences were found regarding dialysis dependency within RRS and CS groups (p0.001 and p0.01 respectively). The addition of RRS or CS scoring scheme to the base model of dialysis dependency significantly improved discrimination. The C statistic, integrated discrimination improvement and net reclassification improvement were significantly increased by adding either RRS/CS or both. Furthermore, RRS had better ROC.Among ANCA associated renal vasculitis patients, RRS and CS achieved similar discrimination, but the discrimination of RRS was superior.

To investigate whether the ratio of the serum progesterone level on the day of human chorionic gonadotrophin (hCG) administration to the basal serum progesterone level (PA total of 12,708 cycles were performed in 9747 patients between 19 and 36 years of age who were undergoing controlled ovarian stimulation from October 2011 to July 2016 for their first or second attempts at IVF followed by fresh embryo transfer (ET). hCG was administered 36 h before oocyte retrieval to trigger final oocyte maturation. The serum progesterone level was measured on menstrual cycle days 2-4 (basal progesterone, PThe average age of the patients recruited was 29.9 years. The average basal progesterone level was 0.8 ng/ml, while the average progesterone level on the day of hCG administration was 0.9 ng/ml. The live birth rates (according to the abovementioned ordinal PP

Background Unroofed coronary sinus syndrome (UCSS) is rare and often associated with the left superior vena cava (LSVC). We report our experience of the clinical features, diagnosis, associated anomalies, surgical procedures, and late outcomes of UCSS during a 20-year period. Methods One hundred and fifty-nine patients with UCSS were treated surgically and followed up between May 1998 and May 2019. UCSS was confirmed by preoperative echocardiography or computerized tomography (CT) scan in 97 patients and by the surgeons intraoperatively in 62 cases, and 100 cases were associated with LSVC. Among these patients, eight cases underwent ligation, and the intracardiac tunnel or baffle was reconstructed in 71 cases to ensure drainage of the LSVC into the right atrium (RA), and the extracardiac procedure was to lead the LSVC into the RA in three patients. Coronary sinus opening was diverted to the RA by the atrial septal patch in three cases. Thirteen patients underwent the reroof procedures, and two patients had untreated LSVC. The associated cardiac lesions were corrected concomitantly. Results There were five in-hospital deaths. Follow-up of 143 patients of early survivors was done, and no deaths were reported. No serious complications were observed, with the exception of avulsion of the internal tunnel patch in one patient. Conclusion UCSS is often misdiagnosed during preoperative evaluation of congenital heart diseases. Preoperative transthoracic echocardiography remains the most important method in the diagnosis of UCSS. We adopted multiple surgical approaches to manage the different types of UCSS with LSVC with good results.

Fms-like tyrosine kinase 3 (FLT3) mutation has been strongly associated with increased risk of relapse, and the irreversible covalent FLT3 inhibitors had the potential to overcome the drug-resistance. In this study, a series of simplified 4-(4-aminophenyl)-6-methylisoxazolo[3,4-b] pyridin-3-amine derivatives containing two types of Michael acceptors (vinyl sulfonamide, acrylamide) were conveniently synthesized to target FLT3 and its internal tandem duplications (ITD) mutants irreversibly. The kinase inhibitory activities showed that compound C14 displayed potent inhibition activities against FLT3 (IC

ObjectiveTo investigate the effect of BMI in male and/or female partners on embryo development and clinical pregnancy outcome during ART.MethodsData of 11,130 cycles between January 2018 and December 2020 were retrospectively analyzed. They were divided into Group A, B, C, and D based on couples’ BMI values, also were divided into Group I, II, III and IV in IVF cycles and Group i, ii, iii, and iv in ICSI cycles. After grouping, inter-group indicators comparisons and logistic regression analysis were performed.ResultsIn IVF cycles, CPR in Group I and Group III were higher than Group IV. In Group III, it was higher than Group II. The AR in Group IV was higher, but the LBR was lower than Group I, Group II, and Group III. Logistic regression analysis results suggested that AR in Group IV was higher than that in Group I in IVF cycles, whereas LBR was lower.In ICSI cycles, high-quality embryo rate in Group i and Group ii were both higher than that in Group iii and Group iv. The CPR in Group i was higher than Group ii and Group iv, and in Group iii was higher than Group ii and Group iv. The AR in Group i was lower than Group iii and Group iv, and AR in Group ii was lower than Group iv. LBR, in Group I it was higher than Group ii, Group iii, and Group iv. Logistic regression analysis results suggested CPR in Group ii was significantly lower than that in Group i. AR in Group iii was considerably higher than that in Group i. LBR in Group ii and Group iv were significantly lower than that in Group i.ConclusionFemale higher BMI was not conducive to the formation of high-quality embryos in ICSI cycle. Female and/or male BMI affected AR and LBR more than CPR not only in IVF cycles, but also in ICSI cycles.

Background Axillary vein/subclavian vein (AxV/SCV) and Internal jugular vein (IJV) are commonly used for implantable venous access port (IVAP) implantation in breast cancer patients for chemotherapy. Previous research focused on comparison of complications while patient comfort was ignored. This study aims to compare patient comfort, surgery duration and complications of IVAP implantation between IJV and AxV/SCV approaches. Methods Two hundred forty-eight breast cancer patients were enrolled in this randomized controlled study from August 2020 to June 2021. Patients scheduled to undergo IVAP implantation were randomly and equally assigned to receive central venous catheters with either AxV /SCV or IJV approaches. All patients received comfort assessment using a comfort scale table at day 1, day 2 and day 7 after implantation. Patient comfort, procedure time of operation as well as early complications were compared. Results Patient comfort was significantly better in the AxV/SCV group than that of IJV group in day 1 (P P P = 0.023). Procedure duration in AxV/SCV group was slightly but significantly shorter than IJV group (27.14 ± 3.29 mins vs 28.92 ± 2.54 mins, P P = 0.019). No difference of complications of artery puncture, pneumothorax or subcutaneous hematoma between these two groups but significantly more catheter misplacement in AxV/SCV group than IJV group (6/124 vs 0/124, P = 0.029). Absolutely total risk of complications was rather low in both groups (8.87% in AxV/SCV group and 1.61% in IJV group). Conclusions Our study indicates that patients with AxV/SCV puncture have higher comfort levels than IJV puncture. AxV/SCV puncture has shorter procedure duration but higher risk of early complications, especially catheter misplacement. Both these two approaches have rather low risk of complications. Consequently, our study provides an alternative choice for breast cancer patients to reach better comfort.

Background Infliximab was the first approved biologic treatment for moderate to severe Crohn's disease (MS-CD) in China. However, the cost-effectiveness of infliximab maintenance therapy (IMT) for MS-CD relative to conventional maintenance therapy remained unclarified. Aim To assess the cost-effectiveness of IMT for MS-CD in Chinese patients from the perspective of Chinese public insurance payer. Methods A cohort of MS-CD patients managed in a Chinese tertiary care hospital was created to compare IMT with conventional maintenance therapy (CMT) for clinical outcomes and direct medical costs over a 1-year observation time using conventional regression analyses. A decision-analytic model with the generated evidence was constructed to assess the cost-effectiveness of IMT relative to CMT using reimbursed medical costs. Results Based on the included 389 patients, IMT was associated with significantly higher disease remission chance [odds ratio: 4.060, P = 0.003], lower risk of developing new complications (odds ratio: 0.527, P = 0.010), higher utility value for quality of life (coefficient 0.822, P = 0.008), and lower total hospital costs related to disease management (coefficient -0.378, P = 0.008) than CMT. Base-case cost-effectiveness analysis estimated that IMT could cost Chinese health insurance payers ¥55260 to gain one quality-adjusted life year (QALY). The cost-effectiveness of IMT was mainly driven by the estimate of quality of life, treatment efficacy of maintenance therapy, mortality risk associated with active disease, and unit price of infliximab. The probability that IMT was cost-effective at a willingness-to-pay threshold of three times gross domestic product [2018 Chinese gross domestic product per capita (GDPPC)] was 86.4%. Conclusion IMT significantly improved real-world health outcomes and cost the Chinese public health insurance payers less than one GDPPC to gain one QALY in Chinese MS-CD patients.

Proteasome inhibitors, bortezomib (BTZ), and carfilzomib (CFZ) are approved drugs for hematological malignancies, but lack anticancer activities against most solid tumors. Small cell lung cancer (SCLC) is a very aggressive neuroendocrine carcinoma of the lungs demanding effective therapy. In this study we investigated whether BTZ or CFZ combined with obatoclax (OBX), an antagonist for MCL-1 and a pan-BCL family inhibitor, could cause synergistic growth inhibition of SCLC cells. We showed that combined application of BTZ or CFZ with OBX caused synergistic growth inhibition of human SCLC cell lines (H82, H526, DMS79, H196, H1963, and H69) than single agent alone. Both BTZ-OBX and CFZ-OBX combinations displayed marked synergism on inducing apoptosis (~50% increase vs BTZ or CFZ alone). A comprehensive proteomics analysis revealed that BTZ preferentially induced the expression of MCL-1, an antiapoptotic protein, in SCLC cells. Thus, proteasome inhibitor-OBX combinations could specifically induce massive growth inhibition and apoptosis in SCLC cells. Subsequent proteome-wide profiling analysis of activated transcription factors suggested that BTZ- or CFZ-induced MCL-1 upregulation was transcriptionally driven by FOXM1. In nude mice bearing in SCLC H82 xenografts, both BTZ-OBX, and CFZ-OBX combinations exhibited remarkable antitumor activities against SCLC tumors evidenced by significant reduction of tumor size and the proliferation marker Ki-67 signals in tumor tissues as compared with single agent alone. Thus, proteasome inhibitor-OBX combinations are worth immediate assessments for SCLC in clinical settings.

Background Internal jugular vein (IJV) and axillary vein/subclavian vein (AxV/SCV) are commonly used for implantable venous access port (IVAP) implantation in breast cancer (BC) patients with chemotherapy. Previous studies focused on complications between these different approaches and ignored patient comfort. In this study, we aim to compare patient comfort between IJV and AxV/SCV approaches, as well as surgery duration and complications. Methods This is a single-center prospective randomized controlled clinical trial. A total of 200 patients diagnosed with invasive BC will be enrolled in this study. After signing written informed consent, patients schedule to undergo IVAP implantation will be randomized at a 1:1 ratio to receive central venous catheters (CVC) with either IJV or AxV/SCV approaches. Baseline as well as demographic data and procedure time of port implantation will be recorded. All patients will receive assessment of comfort with a comfort scale table at days 1, 2 and 7 after implantation surgery. Patients will be followed up and complications will be recorded until devices are removed at the end of the treatment period, or in case of complications. Patient comfort, procedure time of implantation and complications will be compared and analyzed between these two arms. Discussion To the best of our knowledge, this is the first study to compare patient comfort as primary outcome measure between IJV and AxV/SCV puncture. This study will further confirm the benefits of ultrasound guidance and may provide a better choice of IVAP implantation for BC patients. Trial registration This study has been registered at Chinese Clinical Trial Registry (ChiCTR, www. chictr.org.cn) and Chinese Ethics Committee of Registering Clinical Trials (No. ChiCTR2000034986).

We aimed to evaluate the efficacy and safety of percutaneous mechanical thrombectomy (PMT) in treating acute iliofemoral deep vein thrombosis (DVT).We retrospectively analyzed the clinical data of 82 acute iliofemoral DVT patients between November 2017 and December 2018. The therapeutic effects were evaluated based on the thrombus removal rate and circumference changes 10 cm above the affected knee. Incidence rates of pulmonary embolism were evaluated to determine the safety of the procedure. During follow-up, the incidence of postthrombotic syndrome (PTS) was evaluated using the Villalta score, whereas the patency rate of the iliac vein was evaluated via duplex ultrasonography and venography.The surgical success rate was 100%. We identified 48 patients with iliac vein compression syndrome (IVCS) intraoperatively: three of these underwent stent implantation and the others underwent percutaneous transluminal angioplasty (PTA). Grade II and III thrombus removal was achieved in 32.9% (27/82) and 67.1% (55/82) patients, respectively. Postoperative venography revealed that four patients had many floating thrombi under their inferior vena cava filters, which were not removed. The circumference 10 cm above the affected knee decreased from 50.3 ± 3.5 cm preoperatively to 46.3 ± 3.3 cm postoperatively (P 0.05). During follow-up, a PTS incidence rate of 9.8% was observed. The patency rate of the iliac vein was 66.6% after stent implantation and 93.3% after PTA.PMT is feasible, safe, and effective for acute iliofemoral DVT. With regard to IVCS, we suggest PTA alone as a one-stage surgery, and the need of secondary stent implantation should be determined based on follow-up results.

Background The blastocyst morphology provided valuable roles for predicting pregnancy and live birth, but was still not fully understood for evaluating miscarriage. The aim of this study was to explore the association between blastocyst morphologic evaluation and first trimester miscarriage combined with karyotype of miscarried conceptus. Methods This retrospective cohort study included a total of 2873 clinical pregnancy cycles with single blastocyst transfer performed from January 2013 to April 2019. Chromosome karyotype of miscarried conceptus was analyzed via single nucleotide polymorphism array analysis. Miscarriage and karyotype of miscarried conceptus associated with blastocyst morphology were analyzed by chi-square and logistic regression analysis. Results A total of 354 (12.3%) cycles resulted in first trimester miscarriage. Miscarriage rates increased with trophectoderm (TE) grade from A to C (P = 0.012), while three morphologic parameters (blastocoele expansion degree, inner cell mass (ICM) and TE) showed no statistical significance with miscarriage after multivariable analysis. The rate of aneuploidy was 47.7% (83 of 174) in total miscarried conceptuses. For euploid miscarriages, the grade B of ICM occupied a higher proportion compared with aneuploidy, with OR of 2.474, (95% CI, 1.311–4.699), P = 0.005. Conclusions Chromosomal aberration of embryo is an important genetic factor for first trimester miscarriage, and the quality of ICM is a potential indicator for euploid miscarriage. Blastocysts with grade A of ICM should be given priority during single blastocyst transfer to reduce potential miscarriage.

Eicosapentaenoic acid (EPA)-enriched phosphoethanolamine plasmalogens (EPA-PlsEtns) might be retained in the intestine rich in gut microbiota for a long time after treatment. It reminded us that EPA-PlsEtns might affect intestinal microbiota composition and its metabolites, which have been identified as a contributing factor in the development of cardiovascular diseases. In the present study, EPA-PlsEtn administration for 8 weeks significantly reduced the atherosclerotic lesion area in low-density lipoprotein receptor deficient (LDLR

Vascular endothelial growth factor (VEGF) plays important roles in the pathogenesis of polycystic ovary syndrome (PCOS). Several single nucleotide polymorphisms (SNP) of the VEGF gene have been identified and are associated with the aberrant secretion of VEGF protein. This meta-analysis aimed to evaluate the impact of the VEGF +405G>C (rs2010963), -460C>T (rs833061) and -2578A>C (rs699947) polymorphisms on PCOS susceptibility. A systematic search of the Embase, PubMed, Web of Science and Wanfang databases was carried out to identify relevant studies published before 19 July 2019. Seven eligible studies were included in this meta-analysis involving 1100 patients with PCOS and 1141 control individuals. The pooled analysis revealed no significant association between PCOS risk and the +405G>C (rs2010963), -460C>T (rs833061) or -2578A>C (rs699947) polymorphisms in women. Subgroup analysis by ethnicity indicated that Asian women carrying the VEGF +405C allele had a lower risk of PCOS (C versus G: odds ratio [OR] 0.731, 95% confidence interval [CI] 0.544-0.982, P C (rs2010963) may protect Asian women from PCOS.

Oocyte retrieval is a routine procedure during the application of assisted reproduction technology. However, technical difficulties experienced during oocyte retrieval and the subsequent unsatisfactory number of oocytes obtained are rarely reported. The current study included 10,624 oocyte retrieval cycles from April 2015 to June 2018, and patients were followed up until February 2019. Patients were divided into two groups depending on whether the oocyte number obtained reached the >14-mm follicle number on the day of hCG administration. In the oocyte retrieval not satisfactory (ORNS) group, there were 1,294 cycles, and in the oocyte retrieval satisfactory (ORS) group, there were 9,330 cycles. ORNS patients were older, had a longer duration of infertility, had higher follicle-stimulating hormone, and were more likely to have endometriosis. The ORS group had a higher rate of the use of a follicular phase long-acting gonadotropin-releasing hormone (GnRH) agonist long ovarian stimulation protocol and a lower rate of the use of a luteal phase short-acting GnRH agonist long protocol. The ORNS group had fewer total number of days of FSH stimulation. On human chorionic gonadotropin day, the ORNS group had higher luteinizing hormone (LH), lower estradiol, and lower progesterone levels. After oocyte retrieval, the oocyte quality and fresh cycle transplantation rate were higher in the ORNS group. An unsatisfactory oocyte retrieval number did not influence the clinical pregnancy rate, miscarriage rate, or live birth rate during the fresh cycles. The cumulative pregnancy rate and the live birth rate were lower in the ORNS group. In conclusion, with a similar number of matured follicles, ORNS was more likely to occur in ovarian dysfunction patients. The follicular phase long-acting GnRH agonist long protocol had lower oocyte retrieval difficulty during IVF/ICSI. ORNS does not affect embryo quality or the fresh cycle pregnancy rate, but it significantly reduces the cumulative pregnancy rate and the live birth rate.

To explore the therapeutic effect of acupuncture combined with thunder-fire moxibustion on cervical spondylotic radiculopathy of wind-cold-damp type and its impacts on the conduction velocity of F wave of median nerve and ulnar nerve, as well as hypersensitive C-responsive protein (hs-CRP), interleukin 6 (IL-6), IL-1β and tumor necrosis factor α (TNF-α) in serum.A total of 94 patients with cervical spondylotic radiculopathy of wind-cold-damp type were randomly divided into a control group and a combined therapy group, 47 cases in each group. In the control group, acupuncture was applied to Fengchi (GV20), Tianzhu (BL10), Neck-Jiaji (EX-B5), Dazhui (GV14) and others, 30 min each time, once daily, 5 times a week, totally for 4 weeks. In the combined therapy group, on the base of the treatment as the control group, the thunder-fire moxibustion was adopted over GV20, EX-B5, GV14, Jianjing (ST21) and Tianzong (SI11), 20 min each time, once every other day, for 4 weeks in total. After the treatment, the curative effect was compared in the patients between two groups. The short-form McGill pain questionnaire (SF-MPQ), the neck specificity scale and the MOS 36-item short form health survey (SF-36) were scored. The conduction velocity of F wave in median nerve and ulnar nerve was detected by electromyography. The expression of hs-CRP was measured by immunoturbidimetry. IL-6, IL-1β and TNF-α in serum were determined by enzyme linked immunosorbent assay.The total effective rate in the combined therapy group was 95.7% (45/47), which was higher than 80.9% (38/47) in the control group (Acupuncture combined with thunder-fire moxibustion relieves the clinical symptoms of cervical spondylotic radiculopathy of wind-cold-damp type.

Nonalcoholic steatohepatitis (NASH) is a severely inflammatory subtype of nonalcoholic fatty liver. Endoplasmic reticulum stress (ERS) and oxidative stress (OS) cause metabolic abnormalities, promote liver steatosis and inflammation, and are central to the development of NASH. Dihydroartemisinin (DHA) is a compound extracted from Artemisia annua that is often used in the treatment of malaria. Recent studies have shown that DHA also has a wide range of pharmacological effects, acting on various organs throughout the body to exert anti-inflammatory, antioxidant, and anti-fibrotic effects. In this study, we demonstrated in vitro that the anti-inflammatory effect of DHA is effective against NASH and reduces liver steatosis. DHA treatment decreased the synthesis of lipids, such as cholesterol and free fatty acids, and the expression of nuclear factor kappa-B. This is accomplished by inhibiting the unfolded protein response and reducing the production of reactive oxygen species, thereby inhibiting OS and ERS. This study reveals DHA's therapeutic effect and potential mechanism in NASH, implying that DHA could be a new and promising candidate for NASH therapy.

Among digestive system cancers, the extremely poor prognosis of pancreatic cancer (PC) is a pressing concern. Nonoperative treatments such as targeted and immunotherapy, have improved the current situation, however, the accompanying side effects of these chemicals should not be ignored. Here, we discovered a novel hydroxycinnamic acid named sinapic acid (SA) derived from fruits, vegetables, cereals, and oil crops as an effective anti-PC molecule. Both the in vitro and in vivo models we designed showed that SA exhibited anticancer activities but not apoptosis induction. Research on the underlying mechanisms illustrated that AKT phosphorylation was blocked by SA, and the downstream Gsk-3β was downregulated subsequently. Our study revealed the inhibitory activity and underlying mechanisms of SA, providing evidence that SA is a potential strategy for cancer research and can be a promising option of PC chemotherapy.

ObjectiveTo determine the effect of gender of reciprocal chromosomal translocation on blastocyst formation and pregnancy outcome in preimplantation genetic testing, including different parental ages.MethodsThis was a retrospective cohort study that enrolled 1034 couples undergoing preimplantation genetic testing-structural rearrangement on account of a carrier of reciprocal chromosomal translocation from the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2015 to December 2019. Group A represented 528 couples in which the man was the carrier of reciprocal translocation and group B represented 506 couples in which the woman was the carrier of reciprocal translocation. All patients were divided into two groups according to their age: female ageResultsThe blastocyst formation rate of group A (55.3%) is higher than that of group B (50%) and the results were statistically significant (PConclusionWhen the carrier of reciprocal translocation is male, the blastocyst formation rate is higher than that of female carrier. While there is no significant difference between the two in terms of fertilization rate, aeuploidy rate, clinical pregnancy rate, miscarriage rate and live birth rate.

Background: Triple-negative breast cancer (TNBC) is an aggressive disease. Nomograms can predict prognosis of patients with TNBC. Methods: A total of 745 eligible TNBC patients were recruited and randomly divided into training and validation groups. Endpoints were disease-free survival and overall survival. Concordance index, area under the curve and calibration curves were used to analyze the predictive accuracy and discriminative ability of nomograms. Results: Based on the training cohort, neutrophil-to-lymphocyte ratio, positive lymph nodes, tumor size and tumor-infiltrating lymphocytes were used to construct a nomogram for disease-free survival. In addition, age was added to the overall survival nomogram. Conclusion: The current study developed and validated well-calibrated nomograms for predicting disease-free survival and overall survival in patients with TNBC.

Background To investigate whether the endometrial thickness change ratio from the progesterone administration day to the blastocyst transfer day is associated with pregnancy outcomes in a single frozen-thawed euploid blastocyst transfer cycle. Methods All patients used natural cycles with luteal support for endometrial preparation and selected a single euploid blastocyst for transfer after a biopsy for preimplantation genetic testing. The endometrial thickness was measured by transvaginal ultrasound on the progesterone administration day and the transfer day, the change in endometrial thickness was measured, and the endometrial thickness change ratio was calculated. According to the change rate of endometrial thickness, the patients were divided into three groups: the endometrial thickness compaction group, endometrial thickness non-change group and endometrial thickness expansion group. Among them, the endometrial thickness non-change and expansion groups were combined into the endometrial thickness noncompaction group. Results Ultrasound images of the endometrium in 219 frozen-thawed euploid blastocyst transfer cycles were evaluated. The clinical pregnancy rate increased with the increase in endometrial thickness change ratio, while the miscarriage rate and live birth rate were comparable among the groups. The multiple logistic regression results showed that in the fully adjusted model a higher endometrial thickness change ratio (per 10%) was associated with a higher clinical pregnancy rate (adjusted odds ratio [aOR] 1.29; 95% confidence interval [CI], 1.01–1.64; P = .040). Similarly, when the patients were divided into three groups according to the change rate of endometrial thickness, the endometrial thickness noncompaction group had a significant positive effect on the clinical pregnancy rate compared with the endometrial thickness compaction group after adjusting for all covariates. Conclusions In frozen-thawed euploid blastocyst transfer cycles in which the endometrium was prepared by natural cycles with luteal support, the clinical pregnancy rate was higher in cycles without endometrial compaction after progesterone administration.

ObjectivesTo evaluate the combined impact of male and female BMI on cumulative pregnancy outcomes after the first ovarian stimulation.DesignRetrospective cohort study.SettingUniversity-affiliated reproductive medicine center.PatientsA total of 15,972 couples undergoing their first ovarian stimulations from June 2009 to June 2016 were included. During the follow-up period between June 2009 and June 2018, 14,182 couples underwent a complete ART cycle involving fresh embryo transfer and subsequent frozen embryo transfers (FETs) after their first ovarian stimulations. Patients with a BMI 2 served as the reference group. Patients with a BMI ≥ 24 kg/m2 were considered to be overweight, and those with a BMI ≥28 kg/m2 were considered to be obese.Intervention(s)None.Primary Outcome MeasureThe primary outcome was the cumulative live birth rate (CLBR), which defined as the delivery of at least one live birth in the fresh or in the subsequent FET cycles after the first ovarian stimulation.ResultsIn the analyses of females and males separately, compared with the reference group, overweight and obese females had a reduced CLBR (aOR 0.83, 95% CI 0.7.92 and aOR 0.76, 95% CI 0.64–0.90). Similarly, overweight males had a reduced CLBR (aOR 0.91, 95% CI 0.83–0.99) compared with that of the reference group. In the analyses of couples, those in which the male was in the reference or overweight group and the female was overweight or obese had a significantly lower CLBR than those in which both the male and female had a BMI 2.ConclusionsThe CLBR is negatively impacted by increased BMI in the female and overweight status in the male, both individually and together.

To compare the clinical therapeutic effect on diarrhea-predominant irritable bowel syndrome (IBS-D) of spleen deficiency and damp excess among fire needling therapy with filiform needle combined with acupoint application therapy, simple acupoint application therapy and pinaverium bromide tablets, and explore the mechanism on the improvements in IBS-D.A total of 150 patients with IBS-D of spleen deficiency and damp excess were randomized into a combined treatment group (50 cases, 14 cases dropped off), an acupoint application group (50 cases, 16 cases dropped off ) and a western medication group (50 cases, 13 cases dropped off ). In the western medication group, pinaverium bromide tablets were prescribed for oral administration, 50 mg per time, three times a day. In the acupoint application group, the herbal plaster ofExcept the score for abdominal pain in the acupoint application group and the scores for abdominal pain and abdominal distention in the western medication group after 7 days of treatment, the scores for abdominal pain, abdominal distention, defecation frequency, stool form and incomplete bowel movement after 7 and 28 days of treatment were all reduced as compared with those before treatment in each group separately (The combined treatment with the fire needling therapy with filiform needle and the acupoint application therapy effectively relieves the clinical symptoms, improves the quality of life and strengthens the immunity in the patients with IBS-D. The therapeutic effect of this combined regimen is better than either simple acupoint application therapy or the oral medication of pinaverium bromide. The mechanism may be related to the regulation of the levels of T lymphocyte subsets and the modulation of the expressions of 5-HT3R and 5-HT4R mRNA in colon tissue.

Purpose The present study attempted to identify 100 most cited articles on pancreatic neuroendocrine tumors and characterize them via bibliometric analysis whereby it would provide an insight into the progress and trend in this field. Methods Records regarding pancreatic neuroendocrine tumors and published between 2000 and 2020 were retrieved in 2021 through the Web of Science to identify the 100 most cited articles. Results The 100 articles were screened in 17 434 records. The number of citations of the top-cited articles ranged from 151 to 1867. These articles were published in 47 journals among which the Journal of Clinical Oncology produced the most articles (n = 10). The USA contributed most of the articles (n = 44). Articles enrolled came from 58 institutions; the University of California System of the USA came to the top (n = 7). More than half of the articles were clinical studies (n = 55), basic science research reports accounting for a quarter. In clinical topics (n = 73), treatment issues were the most concerned (n = 21), in which more articles focused on targeted inhibitors. Articles about gene mutation were cited most frequently in basic science topics (n = 27). Conclusions This bibliometric analysis reflected the brief the progress and highlighted current trend in pancreatic neuroendocrine tumor research, providing references for further study.

Global aridification is projected to intensify. Yet, our knowledge of its potential impacts on species ranges remains limited. Here, we investigate global aridity velocity and its overlap with three sectors (natural protected areas, agricultural areas, and urban areas) and terrestrial biodiversity in historical (1979 through 2016) and future periods (2050 through 2099), with and without considering vegetation physiological response to rising CO(2). Both agricultural and urban areas showed a mean drying velocity in history, although the concurrent global aridity velocity was on average +0.05/+0.20 km/yr(−1) (no CO(2) effects/with CO(2) effects; “+” denoting wetting). Moreover, in drylands, the shifts of vegetation greenness isolines were found to be significantly coupled with the tracks of aridity velocity. In the future, the aridity velocity in natural protected areas is projected to change from wetting to drying across RCP (representative concentration pathway) 2.6, RCP6.0, and RCP8.5 scenarios. When accounting for spatial distribution of terrestrial taxa (including plants, mammals, birds, and amphibians), the global aridity velocity would be -0.15/-0.02 km/yr(−1) (“-” denoting drying; historical), -0.12/-0.15 km/yr(−1) (RCP2.6), -0.36/-0.10 km/yr(−1) (RCP6.0), and -0.75/-0.29 km/yr(−1) (RCP8.5), with amphibians particularly negatively impacted. Under all scenarios, aridity velocity shows much higher multidirectionality than temperature velocity, which is mainly poleward. These results suggest that aridification risks may significantly influence the distribution of terrestrial species besides warming impacts and further impact the effectiveness of current protected areas in future, especially under RCP8.5, which best matches historical CO(2) emissions [C. R. Schwalm et al., Proc. Natl. Acad. Sci. U.S.A. 117, 19656–19657 (2020)].

N6-methyladenosine (m

Noonan syndrome (NS) is a genetic syndrome causing obstructive hypertrophic cardiomyopathy (HCM) in infants. Studies of cardiac surgery in pediatric HCM patients with NS (NS-HCM) are lacking. We aim to characterize the early disease course of young NS-HCM patients before adolescence and assess their complications and survival condition after septal myectomy. Pediatric obstructive HCM patients who underwent septal myectomy at age 10 years or under were enrolled consecutively between 2009 and 2019. Ten patients with NS and 43 non-NS patients were enrolled in our study. NS-HCM patients were diagnosed at a younger age (5.00 ± 7.48 months vs. 18.73 ± 26.96 months) and more often had biventricular outflow tract obstruction (90.00% vs 30.23%). The surgical treatment can significantly reduce the pressure gradient of the outflow tract. More NS-HCM patients had biventricular reconstruction (70.00% vs 25.58%). The overall survival rates in all patients were 98.04% during 5-year follow-up, respectively. Complete heart block (CHB) was the most prevalent complication in patients with NS and tended to be more common than in non-NS patients (20% vs 7.32%). No sudden cardiac death (SCD) occurred in CHB patients who had pacemaker implantation. Biventricular reconstruction was the risk factor for CHB. Septal myectomy is safe and effective surgery to relieve obstruction in young age pediatric obstructive NS-HCM patients. Postoperative CHB is a common complication, especially in patients who underwent biventricular reconstruction. The implantation of pacemaker can protect CHB patients from SCD and improve their prognosis.

To explore the genetic etiology for a fetus with congenital orofacial cleft.Single nucleotide polymorphism microarray (SNP array) was carried out on skin tissues sampled from the fetus following induced abortion for the detection of copy number variation (CNVs). Pathogenicity of the candidate gene was validated through experiment.SNP array revealed that the fetus has carried a hemizygous 9.23Mb deletion at Xq21.31-q22.1(91 063 807-100 293 555), which was inherited from its mother. The region contained 13 OMIM genes and 1 ncRNA coding gene(MIR548M). Inhibiting of the expression of the MIR548M gene in oral epithelial celllines has resulted in up-regulation of the expression of SUMO1 gene which was known to involve in the pathogenesis of orofacial cleft.Dosage insufficiency of the MIR548M gene may underlie the etiology of orofacial cleft in this fetus.

Phosphatase and tensin homologue (PTEN) is frequently mutated in human cancer, but its roles in lymphopoiesis and tissue homeostasis remain poorly defined. Here we show that PTEN orchestrates a two-step developmental process linking antigen receptor and IL-23-Stat3 signalling to type-17 innate-like T cell generation. Loss of PTEN leads to pronounced accumulation of mature IL-17-producing innate-like T cells in the thymus. IL-23 is essential for their accumulation, and ablation of IL-23 or IL-17 signalling rectifies the reduced survival of female PTEN-haploinsufficient mice that model human patients with PTEN mutations. Single-cell transcriptome and network analyses revealed the dynamic regulation of PTEN, mTOR and metabolic activities that accompanied type-17 cell programming. Furthermore, deletion of mTORC1 or mTORC2 blocks PTEN loss-driven type-17 cell accumulation, and this is further shaped by the Foxo1 and Stat3 pathways. Collectively, our study establishes developmental and metabolic signalling networks underpinning type-17 cell fate decisions and their functional effects at coordinating PTEN-dependent tissue homeostasis.

Background Mediastinal lipoma/liposarcoma is a rare tumor of the mediastinum. Case presentation This article reported one case of giant anterior superior mediastinum well-differentiated liposarcoma involving the left thoracic cavity with symptom of dysphagia. The mediastinum liposarcoma was completely resected through a left thoracotomy. Histologic examination and molecular pathological test clarified the diagnosis as well-differentiated mediastinal liposarcoma. There has been no evidence of recurrence during the 8 months follow-up. Conclusion Molecular pathological examination of the MDM2, CDK4 and p16 gene in tumors provides the diagnostic gold standard in distinguishing well-differentiated liposarcoma from lipoma. Complete surgical resection is the first-line treatment choice for mediastinal lipoma/ liposarcoma.

BACKGROUND Patients with endometriosis (EMs) are routinely advised to take GnRH-a for 3-6 months to improve the internal reproductive environment, but this may not be necessary. MATERIAL AND METHODS This retrospective study examined the effects of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) with shortened (n=311) or conventional (n=213) long-term pituitary downregulation in EMs patients between January 2013 and July 2017. RESULTS The 2 groups showed no significant differences in gonadotropin (Gn) dose, number of oocytes retrieved, or miscarriage rate. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels on the initiation day and the LH level on human chorionic gonadotropin (hCG) day (1.22±1.39 vs. 0.74±0.55 P=0.0026) were higher in the study group than in the control group. The cumulative live birth rates in the second cycle were 69.13% in the study group (95% confidence interval (CI), 64-74.27%) vs. 68.54% in the control group (95% CI, 62.31-74.78%, P=0.88, respectively). CONCLUSIONS This study showed that the shortened regimen and the ultralong regimen did not produce different pregnancy outcomes after ART, and the single-application, long-term GnRH-a protocol may serve as a cost-effective and safe treatment protocol for EMs patients.

Background Recently, no relevant research has focused on the relationship between the clinical efficacy of da Vinci robotic distal pancreatectomy (RDP) and the number of mechanical arms and assistants used for RDP. The aim of this study was to evaluate the safety, efficacy, and advantages of RDP with the “3 + 2” mode. Methods Clinical data from 53 patients (observation group) who received RDP using the “3 + 2” mode in our department, from March 2016 to September 2018, were reviewed. An additional 53 patients who received RDP using the classical mode were chosen at random for the control group. Short‐term outcomes for the two groups were compared. Results There were no statistically significant differences between the two groups for estimated blood loss, postoperative day of flatus passage, postoperative hospital stay, and postoperative complication (P > 0.05). Compared with the control group, the observation group had a significantly shorter operative time (166.9 ± 13.3 vs 192.6 ± 11.1 minutes, P

Background A local coronavirus disease 2019 (COVID-19) case confirmed on June 11, 2020 triggered an outbreak in Beijing, China after 56 consecutive days without a newly confirmed case. Non-pharmaceutical interventions (NPIs) were used to contain the source in Xinfadi (XFD) market. To rapidly control the outbreak, both traditional and newly introduced NPIs including large-scale management of high-risk populations and expanded severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-based screening in the general population were conducted in Beijing. We aimed to assess the effectiveness of the response to the COVID-19 outbreak in Beijing’s XFD market and inform future response efforts of resurgence across regions. Methods A modified susceptible–exposed–infectious–recovered (SEIR) model was developed and applied to evaluate a range of different scenarios from the public health perspective. Two outcomes were measured: magnitude of transmission (i.e., number of cases in the outbreak) and endpoint of transmission (i.e., date of containment). The outcomes of scenario evaluations were presented relative to the reality case (i.e., 368 cases in 34 days) with 95% Confidence Interval (CI). Results Our results indicated that a 3 to 14 day delay in the identification of XFD as the infection source and initiation of NPIs would have caused a 3 to 28-fold increase in total case number (31–77 day delay in containment). A failure to implement the quarantine scheme employed in the XFD outbreak for defined key population would have caused a fivefold greater number of cases (73 day delay in containment). Similarly, failure to implement the quarantine plan executed in the XFD outbreak for close contacts would have caused twofold greater transmission (44 day delay in containment). Finally, failure to implement expanded nucleic acid screening in the general population would have yielded 1.6-fold greater transmission and a 32 day delay to containment. Conclusions This study informs new evidence that in form the selection of NPI to use as countermeasures in response to a COVID-19 outbreak and optimal timing of their implementation. The evidence provided by this study should inform responses to future outbreaks of COVID-19 and future infectious disease outbreak preparedness efforts in China and elsewhere. Graphical abstract

Research question Is there any difference in live birth rate between the natural cycle and hormone replacement therapy (HRT) endometrial preparation protocols for women with regular menstrual cycles undergoing their first single vitrified–warmed euploid blastocyst transfer? Design This was a retrospective cohort study that enrolled 722 women who underwent vitrified–warmed euploid blastocyst transfer at assisted reproductive technology (ART) centre of The First Affiliated Hospital of Zhengzhou University, from January 2013 to December 2019. Univariate and multivariate logistic regression models were used to analyse the relationship between the endometrial preparation protocols and live birth rates. Stratified analyses and sensitivity analyses were performed to ensure the reliability and stability of the results. Results A total of 722 single vitrified–warmed euploid blastocyst transfer cycles were included. Overall, the live birth rates were 50.00% (110/220) in the natural cycle group and 47.61% (239/502) in the HRT group. Multiple logistic regression analyses showed that there was no significant association (adjusted odds ratio 0.82; 95% confidence interval 0.56–1.20; P = 0.313) between natural cycle and HRT protocols and the live birth rate. Interaction analysis showed that there was no significant difference in live birth rates between the two groups for any subgroup after adjusting for confounding factors. Conclusions For single vitrified–warmed euploid blastocyst transfer, natural cycle and HRT endometrial preparation protocols result in similar live birth rates among women with regular menstrual cycles. Further studies are needed into the effects of endometrial preparation protocols on pregnancy outcomes.

Background Growing evidence indicates that systemic immune inflammation index (SII) can predict the prognosis of various solid tumors. The objective of this study aimed to investigate the efficacy of SII in predicting the prognosis of gallbladder carcinoma (GBC) patients after radical surgery. Methods A consecutive series of 93 patients with GBC who underwent radical resection were enrolled in the retrospective study. The cutoff value for the SII was calculated using the time-dependent receiver operating characteristic (ROC) curve analysis by overall survival (OS) prediction. The associations between the SII and the clinicopathologic characteristics were analyzed using Pearson's χ2 test and Fisher's exact test. Survival curves were calculated using the Kaplan-Meier method. Univariate analysis was performed to evaluate the prognostic relevance of preoperative parameters. The multivariate Cox regression proportional hazard model was used to assess variables significant on univariate analysis. Results The Kaplan-Meier survival analysis and the multivariate analysis of patients with GBC who received radical resection showed SII independently predicted OS. The univariate analysis showed that the TNM stage, SII, CA19-9, ALP, prealbumin, NLR, MLR, lymph node metastasis, and histopathological type were all associated with overall survival. In time-dependent ROC analysis, the area of the SII-CA19-9 under the ROC curve (AUC) was higher than that of the preoperative SII or CA19-9 levels for the prediction of OS. Conclusion Our results demonstrate that high SII was a predictor of poor long-term outcomes among patients with GBC undergoing curative surgery. SII-CA19-9 classification may be more effective in predicting the postoperative prognosis of GBC patients.

Purpose: To build a novel predictive model for hepatocellular carcinoma (HCC) patients based on DNA methylation data. Methods: Four independent DNA methylation datasets for HCC were used to screen for common differentially methylated genes (CDMGs). Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to explore the biological roles of CDMGs in HCC. Univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) Cox analysis were performed to identify survival-related CDMGs (SR-CDMGs) and to build a predictive model. The importance of this model was assessed using Cox regression analysis, propensity score-matched (PSM) analysis and stratification analysis. A validation group from the Cancer Genome Atlas (TCGA) was constructed to further validate the model. Results: Four SR-CDMGs were identified and used to build the predictive model. The risk score of this model was calculated as follows: risk score = (0.01489826 × methylation level of WDR69) + (0.15868618 × methylation level of HOXB4) + (0.16674959 × methylation level of CDKL2) + (0.16689301 × methylation level of HOXA10). Kaplan–Meier analysis demonstrated that patients in the low-risk group had a significantly longer overall survival (OS; log-rank P-value =0.00071). The Cox model multivariate analysis and PSM analysis identified the risk score as an independent prognostic factor (P Conclusion: Our DNA methylation-based prognosis predictive model is effective and reliable in predicting prognosis for patients with HCC.

Single-cell RNA sequencing is a powerful tool to study developmental biology but does not preserve spatial information about tissue morphology and cellular interactions. Here, we combine single-cell and spatial transcriptomics with algorithms for data integration to study the development of the chicken heart from the early to late four-chambered heart stage. We create a census of the diverse cellular lineages in developing hearts, their spatial organization, and their interactions during development. Spatial mapping of differentiation transitions in cardiac lineages defines transcriptional differences between epithelial and mesenchymal cells within the epicardial lineage. Using spatially resolved expression analysis, we identify anatomically restricted expression programs, including expression of genes implicated in congenital heart disease. Last, we discover a persistent enrichment of the small, secreted peptide, thymosin beta-4, throughout coronary vascular development. Overall, our study identifies an intricate interplay between cellular differentiation and morphogenesis., Using single-cell and spatial transcriptomics in chicken hearts, here, the authors generate a census of cellular interactions from early to late four-chambered heart stage, identifying a distinct epicardial-mesenchymal cell population with a migratory phenotype.

Water-soluble ions (WSI) and organic extract (OE) in traffic-related particulate matter with aerodynamic diameters ≤ 2.5 μm (TRPM