Objective:To analyse the clinical significance of selective single embryo transfer by time-lapse mo-nitoring(TLM)or conventional morphology assessment(CMA)in vitro fertilization/intracytoplasmic sperm in-jection and embryo transfer(IVF/ICSI-ET),and to initially explore the predictive value of Raman spectral analy-sis of embryo culture medium for clinical pregnancy rate.Methods:The study is a prospective randomized con-trolled clinical trial.We assigned 139 patients treated with IVF/ICSI-ET in Reproductive and Genetics Center of Suzhou Municipal Hospital from April 2019 to July 2020,which were randomly assigned to either the CMA or the TLM group.We performed selective single-embryo transfer(fresh cycle and FET)after selecting the optimal em-bryos with TLM or CMA respectively.If the patient's first embryo transfer was unsuccessful,a second one would be performed to compare the differences in the cumulative live birth rate of embryo transfer and other pregnancy outcomes between the two groups.Meanwhile,we collected 15 μl of embryo culture medium at day 3 after IVF/ISCI fertilization for Raman spectroscopy analysis.Results:There were no differences in cumulative live birth,cu-mulative clinical pregnancy,cumulative premature birth,cumulative early spontaneous abortion,cumulative ectopic pregnancy and LGA or SGA between TLM and CMA groups(P＞0.05).The Neonatal sex ratio in the TLM group was lower than that in the CMA group,but the difference was not significant(P＞0.05).Raman spectros-copy analysis of embryo culture medium predicted the clinical pregnancy rate with 67.21％accuracy.Conclu-sions:In young women with a good ovarian reserve,the advantage of using TLM to evaluate embryos is not obvi-ous,so we should remain vigilant that embryo selection based on morphokinetic parameters may affect the sex ratio.Raman spectroscopic analysis of embryo culture medium is not yet able to effectively predict the planting ability of embryos.

BACKGROUND: Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment. Our previous clinical trial demonstrated that berberine (BBR) hydrochloride might reduce the recurrence and canceration of colorectal adenoma (CRA). The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer (CRC). METHODS: We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial, and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction. We further performed ApcMin/+ animal intervention tests, RNA sequencing, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assays. RESULTS: The abundance of fecal Veillonella parvula ( V . parvula ) decreased significantly after BBR administration ( P = 0.0016) and increased through the development from CRA to CRC. Patients with CRC with a higher V. parvula abundance had worse tumor staging and a higher lymph node metastasis rate. The intestinal immune pathway of Immunoglobulin A production was activated, and the expression of TNFSF13B (Tumor necrosis factor superfamily 13b, encoding B lymphocyte stimulator [BLyS]), the representative gene of this pathway, and the genes encoding its receptors (interleukin-10 and transforming growth factor beta) were significantly upregulated. Animal experiments revealed that V. parvula promoted colorectal carcinogenesis and increased BLyS levels, while BBR reversed this effect. CONCLUSION: BBR might inhibit V. parvula and further weaken the immunomodulatory effect of B cells induced by V. parvula , thereby blocking the development of colorectal tumors. TRIAL REGISTRAION ClinicalTrials.gov, No. NCT02226185.
Animals ; Humans ; Berberine/therapeutic use* ; Carcinogenesis ; Veillonella ; Colorectal Neoplasms/genetics* ; Tumor Microenvironment

Objective:To explore the effects of cyclosporine A (CsA) on the clinical outcomes of patients with unexplained repeated implantation failure (URIF) undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. Methods:A retrospective cohort study was conducted, and the data of URIF patients at the Center for Human Reproduction and Genetics of the Affiliated Suzhou Hospital of Nanjing Medical University from April 2016 to March 2020 was analyzed. Totally 94 cycles with CsA application were enrolled, and 188 cycles of control group were selected according to age, body mass index (BMI), basal follicle-stimulating hormone (FSH), the number of high-quality embryos transferred and embryo stage matched with CsA group. The general conditions, characteristics of previous failed transfer cycles and the de novo transfer cycles, clinical outcomes, obstetric and neonatal complications were compared between the two groups, and regression analysis of CsA and clinical outcomes. Results:1) There were no statistical differences between the two groups in baseline characteristics such as age, BMI, basal FSH, duration of infertility, indications for IVF/ICSI, number of previous failed cycles, number of high-quality embryos and blastocyst transferred rate (all P>0.05). There were also no significant differences in the number of embryos transferred, the number of high-quality embryos, the rate of transferred blastocyst and the endometrial thickness on transfer day of the de novo transfer cycles (all P>0.05). 2) The embryo implantation rate, the clinical pregnancy rate and the live birth rate in CsA group [53.39% (63/118), 58.51% (55/94), 45.74% (43/94)] were distinctly higher than those of control group [38.43% (93/242), 45.74% (86/188), 33.51% (63/188)]. The differences were statistically significant ( P=0.007, P=0.043, P=0.046). While there were no differences in miscarriage rate and ectopic pregnancy rate between the two groups (all P>0.05). 3) The differences of the rates of preterm birth, multiple pregnancy, obstetric and neonatal complications were all not statistically significant between the two groups (all P>0.05). No birth defects were observed in both groups. 4) The multivariate logistic regression analysis showed that CsA was an independent promoter of clinical pregnancy (after adjusted OR=1.694, 95% CI:1.019-2.816, P=0.042) and live birth (after adjusted OR=1.700, 95% CI:1.012-2.853, P=0.045) in URIF patients after adjusting for age, BMI, basal FSH, the number of embryos transferred and the endometrial thickness on transfer day. Conclusion:CsA showed remarkably enhancement on embryo implantation rate, clinical pregnancy rate and live birth rate of de novo embryo transfer in patients with URIF, without increasing the risk of obstetric and pediatric complications. CsA application may be used as an effective treatment for URIF patients.

Objective:To explore the effects of cyclosporine A (CsA) on the clinical outcomes of patients with unexplained repeated implantation failure (URIF) undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. Methods:A retrospective cohort study was conducted, and the data of URIF patients at the Center for Human Reproduction and Genetics of the Affiliated Suzhou Hospital of Nanjing Medical University from April 2016 to March 2020 was analyzed. Totally 94 cycles with CsA application were enrolled, and 188 cycles of control group were selected according to age, body mass index (BMI), basal follicle-stimulating hormone (FSH), the number of high-quality embryos transferred and embryo stage matched with CsA group. The general conditions, characteristics of previous failed transfer cycles and the de novo transfer cycles, clinical outcomes, obstetric and neonatal complications were compared between the two groups, and regression analysis of CsA and clinical outcomes. Results:1) There were no statistical differences between the two groups in baseline characteristics such as age, BMI, basal FSH, duration of infertility, indications for IVF/ICSI, number of previous failed cycles, number of high-quality embryos and blastocyst transferred rate (all P>0.05). There were also no significant differences in the number of embryos transferred, the number of high-quality embryos, the rate of transferred blastocyst and the endometrial thickness on transfer day of the de novo transfer cycles (all P>0.05). 2) The embryo implantation rate, the clinical pregnancy rate and the live birth rate in CsA group [53.39% (63/118), 58.51% (55/94), 45.74% (43/94)] were distinctly higher than those of control group [38.43% (93/242), 45.74% (86/188), 33.51% (63/188)]. The differences were statistically significant ( P=0.007, P=0.043, P=0.046). While there were no differences in miscarriage rate and ectopic pregnancy rate between the two groups (all P>0.05). 3) The differences of the rates of preterm birth, multiple pregnancy, obstetric and neonatal complications were all not statistically significant between the two groups (all P>0.05). No birth defects were observed in both groups. 4) The multivariate logistic regression analysis showed that CsA was an independent promoter of clinical pregnancy (after adjusted OR=1.694, 95% CI:1.019-2.816, P=0.042) and live birth (after adjusted OR=1.700, 95% CI:1.012-2.853, P=0.045) in URIF patients after adjusting for age, BMI, basal FSH, the number of embryos transferred and the endometrial thickness on transfer day. Conclusion:CsA showed remarkably enhancement on embryo implantation rate, clinical pregnancy rate and live birth rate of de novo embryo transfer in patients with URIF, without increasing the risk of obstetric and pediatric complications. CsA application may be used as an effective treatment for URIF patients.

Objective To evaluate the diagnostic accuracy of dual source CT angiography (DSCTA) for coronary artery stenosis.Methods During the period from November 2012 to November 2013, a total of 210 patients with coronary artery disease underwent DSCTA and selective coronary arteriography (CAG). Taking CAG as the gold standard, the diagnostic accuracy of DSCTA for coronary artery stenosis was evaluated. Thirty patients receiving DSCTA and 30 patients receiving CAG were selected, and all of them underwent stent implantation in the anterior descending branch after imaging examination. The angiography positions, the used time of PCI and the used dosage of contrast agent were compared between the two groups. Results DSCTA was performed in 210 patients and a total of 2 630 segments of coronary stenosis or occlusion were detected. Compared with CAG, the diagnostic sensitivity, specificity, positive predictive value and negative predictive value of DSCTA were 95.4%, 96.2%, 91.3%and 100%respectively, which were not significantly different from those obtained by CAG (P=0.066). In performing DSCTA, 2-3 angiography positions were used (2-4 positions less than that of CAG), the used time of PCI was about 15 min (about 10 min less than that of CAG), and the mean used dosage of contrast agent was 48 ml (30-150 ml) (about half less than that of CAG). Conclusion DSCTA has higher accuracy in diagnosing coronary artery stenosis, quite similar to that of CAG. DSCTA is a safe, reliable and noninvasive examination method. Preoperative DSCTA can reduce exposure positions during angiography, can reduce the dosage of contrast agent, and can shorten the time of PCI as well, thus, iatrogenic radioactive radiation dose can be reduced.