Objective:To investigate the influencing factors and perinatal outcomes associated with monozygotic twins (MZT) following elective single embryo transfer (eSET) via in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). Methods:A retrospective cohort study was conducted on 12 079 patients who achieved pregnancy after undergoing IVF/ICSI-eSET at Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University between January 2015 and September 2023. Patients were stratified into two groups based on ultrasound findings 30 d post-transfer: singleton pregnancy group and MZT pregnancy group. Finally, 300 MZT and 1 500 single pregnancies, which were randomly matched according to 1∶5 were included by study period. General patients' characteristics, embryo-related factors, and perinatal outcomes were compared between the two groups. A multivariate logistic regression model was employed to identify risk factors for MZT after single embryo transfer, adjusting for potential confounding variables.Results:The incidence of twin pregnancy following single embryo transfer was 2.48% (300/12 079), which was higher than that of naturally conceived monozygotic twin pregnancy. No significant difference was found in baseline characteristics between the two groups (all P>0.05). The blastocyst transfer rate was higher in the MZT pregnancy group [93.3% (280/300)] than in the singleton pregnancy group [88.8% (1 332/1 500), P=0.022]. Multivariate logistic regression analysis also showed that blastocyst transfer was associated with an increased risk of MZT ( OR=0.552, P=0.016, 95% CI: 0.341-0.894). Analysis of blastocyst cycles showed that the risk of MZT was higher when transferring high-quality blastocysts [79.6% (223/280) vs. 67.8% (903/1 332), P<0.001], where as a trophectoderm (TE) grading of C [20.4% (57/280) vs. 32.2% (429/1 332), P<0.001] had a lower risk of MZT. After adjusting for confounding factors, the risk of MZT was found to increase with the transfer of blastocysts with a B-grade inner cell mass (ICM) ( OR=0.601, P=0.001, 95% CI: 0.442-0.819) and A/B grade TE (grade A: OR=2.951, P<0.001, 95% CI: 1.980-4.399; grade B: OR=1.840, P<0.001, 95% CI: 1.315-2.576). The risk of complications during pregnancy [47.7% (143/300) vs. 19.3% (289/1 500), P<0.001], preterm labor [55.1% (140/254) vs. 7.4% (101/1 368), P<0.001], and the risk of stillbirth [3.7% (11/300) vs. 1.5% (22/1 500), P=0.016] were significantly higher in the MZT pregnancy group than in the singleton pregnancy group. Conclusion:Assisted reproductive technology may contribute to the risk of MZT. Transfer of blastocysts, particularly those with loose ICM arrangement and dense TE arrangement, appears to increase the risk of MZT in patients undergoing eSET.

Objective To compare the clinical outcomes of the clomiphene citrate(CC)dual stimulation protocol and the luteal phase ovarian stimulation protocol after natural cycle oocytes retrieved in POSEIDON patients with low expected prognosis.Methods The clinical data from patients who underwent in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI)at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from May 2016 to December 2023 were analyzed retrospectively.According to the POSEI-DON criteria,including POSEIDON group 3 and group 4,which were treated with the CC dual stimulation protocol(the CC group)and the luteal-phase ovarian stimulation protocol after the natural cycle oocytes retrieval(the natural cycle group).The basic data and clinical outcomes of the two ovulation protocols were analyzed,and the main observations included the number of oocytes retrieved,the cumulative clinical pregnancy rate and the cumulative live birth rate,and explored the impact of ovulation promotion regimens on clinical outcomes through binary logis-tic regression.Results On the whole,there was no significant difference in the total number of oocytes retrieved,cumulative clinical pregnancy rate and live birth rate between the CC group and the natural cycle group(all P>0.05),And in POSEIDON group 4,the numbers of oocytes retrieved in the follicular phase of the CC group were higher than those in the natural cycle group,whereas the number of oocytes retrieved in the luteal phase of natural cycle group were higher,and the difference was statistically significant(P<0.05).After logistic regression analysis,the ovulation stimulation protocols did not affect the cumulative clinical pregnancy rate and live birth rate of POSEI-DON 3 and 4 group(P>0.05).Conclusions For the POSEIDON patients with a low expected prognosis,the clinical effectiveness of the luteal phase ovarian stimulation protocol after natural cycle oocytes retrieved is not inferior to that of the CC dual stimulation protocol.In POSEIDON group 4,on the premise that the AMH levels of patients in the natural cycle group were lower than those in the CC group,who underwent natural cycle ovulation followed by luteal phase induction achieved similar clinical outcomes to those of the CC dual stimulation protocol group.Therefore,the luteal phase ovarian stimulation protocol after natural cycle oocytes retrieved should be more clinically recommended for POSEIDON group 4 patients.

Objective To compare the clinical outcomes of the clomiphene citrate(CC)dual stimulation protocol and the luteal phase ovarian stimulation protocol after natural cycle oocytes retrieved in POSEIDON patients with low expected prognosis.Methods The clinical data from patients who underwent in vitro fertilization(IVF)or intracytoplasmic sperm injection(ICSI)at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from May 2016 to December 2023 were analyzed retrospectively.According to the POSEI-DON criteria,including POSEIDON group 3 and group 4,which were treated with the CC dual stimulation protocol(the CC group)and the luteal-phase ovarian stimulation protocol after the natural cycle oocytes retrieval(the natural cycle group).The basic data and clinical outcomes of the two ovulation protocols were analyzed,and the main observations included the number of oocytes retrieved,the cumulative clinical pregnancy rate and the cumulative live birth rate,and explored the impact of ovulation promotion regimens on clinical outcomes through binary logis-tic regression.Results On the whole,there was no significant difference in the total number of oocytes retrieved,cumulative clinical pregnancy rate and live birth rate between the CC group and the natural cycle group(all P>0.05),And in POSEIDON group 4,the numbers of oocytes retrieved in the follicular phase of the CC group were higher than those in the natural cycle group,whereas the number of oocytes retrieved in the luteal phase of natural cycle group were higher,and the difference was statistically significant(P<0.05).After logistic regression analysis,the ovulation stimulation protocols did not affect the cumulative clinical pregnancy rate and live birth rate of POSEI-DON 3 and 4 group(P>0.05).Conclusions For the POSEIDON patients with a low expected prognosis,the clinical effectiveness of the luteal phase ovarian stimulation protocol after natural cycle oocytes retrieved is not inferior to that of the CC dual stimulation protocol.In POSEIDON group 4,on the premise that the AMH levels of patients in the natural cycle group were lower than those in the CC group,who underwent natural cycle ovulation followed by luteal phase induction achieved similar clinical outcomes to those of the CC dual stimulation protocol group.Therefore,the luteal phase ovarian stimulation protocol after natural cycle oocytes retrieved should be more clinically recommended for POSEIDON group 4 patients.

OBJECTIVES: To compare the anti-inflammatory, antibacterial and analgesic effects of Yinqiao Powder (YQS) formulated granules and decoction. METHODS: We first evaluated the anti-inflammatory effects of the two dosage forms of YQS in a LPS-induced RAW 264.7 cell model using RT-qPCR and Western blotting. We further constructed zebrafish models of inflammation by copper sulfate exposure, caudal fin transection, or LPS and Poly (I:C) microinjection, and evaluated anti-inflammatory effects of YQS granules and decoction by examining neutrophil aggregation and HE staining findings. In a mouse model of acute lung injury (ALI) induced by intratracheal LPS instillation, the effects of YQS gavage at 10, 15, and 20 g/kg on lung pathologies were evaluated by calculating lung wet-dry weight ratio and using HE staining, ELISA and Western blotting. The microbroth dilution method was used to evaluate the antibacterial effect of YQS. Mouse pain models established by hot plate and intraperitoneal injection of glacial acetic acid were used to evaluate the analgesic effects of YQS at 10, 15, and 20 g/kg. RESULTS: Both YQS granules and decoction significantly reduced TNF-α, IL-6, and IL-1β expressions and p-STAT3 (Tyr 705) phosphorylation level in LPS-induced RAW 264.7 cells, and obviously inhibited neutrophil aggregation in the zebrafish models. In ALI mice, YQS granules and decoction effectively ameliorated lung injury, lowered lung wet-dry weight ratio, and reduced p-STAT3 (Tyr 705) expression and TNF-α and IL-6 levels. YQS produced obvious antibacterial effect at the doses of 15.63 and 31.25 mg/mL, and significantly reduced body torsion and increased pain threshold in the mouse pain models. CONCLUSIONS The two dosage forms of TQS have similar anti-inflammatory, antibacterial and analgesic effects with only differences in their inhibitory effect on TNF-α, IL-6 and IL-1β mRNA expressions in LPS-induced RAW 264.7 cells.
Animals ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Anti-Inflammatory Agents/pharmacology* ; Analgesics/pharmacology* ; RAW 264.7 Cells ; Zebrafish ; Anti-Bacterial Agents/pharmacology* ; Powders ; Tumor Necrosis Factor-alpha/metabolism* ; Acute Lung Injury/drug therapy* ; Interleukin-6/metabolism* ; Lipopolysaccharides

Objective:To investigate the influencing factors and perinatal outcomes associated with monozygotic twins (MZT) following elective single embryo transfer (eSET) via in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). Methods:A retrospective cohort study was conducted on 12 079 patients who achieved pregnancy after undergoing IVF/ICSI-eSET at Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University between January 2015 and September 2023. Patients were stratified into two groups based on ultrasound findings 30 d post-transfer: singleton pregnancy group and MZT pregnancy group. Finally, 300 MZT and 1 500 single pregnancies, which were randomly matched according to 1∶5 were included by study period. General patients' characteristics, embryo-related factors, and perinatal outcomes were compared between the two groups. A multivariate logistic regression model was employed to identify risk factors for MZT after single embryo transfer, adjusting for potential confounding variables.Results:The incidence of twin pregnancy following single embryo transfer was 2.48% (300/12 079), which was higher than that of naturally conceived monozygotic twin pregnancy. No significant difference was found in baseline characteristics between the two groups (all P>0.05). The blastocyst transfer rate was higher in the MZT pregnancy group [93.3% (280/300)] than in the singleton pregnancy group [88.8% (1 332/1 500), P=0.022]. Multivariate logistic regression analysis also showed that blastocyst transfer was associated with an increased risk of MZT ( OR=0.552, P=0.016, 95% CI: 0.341-0.894). Analysis of blastocyst cycles showed that the risk of MZT was higher when transferring high-quality blastocysts [79.6% (223/280) vs. 67.8% (903/1 332), P<0.001], where as a trophectoderm (TE) grading of C [20.4% (57/280) vs. 32.2% (429/1 332), P<0.001] had a lower risk of MZT. After adjusting for confounding factors, the risk of MZT was found to increase with the transfer of blastocysts with a B-grade inner cell mass (ICM) ( OR=0.601, P=0.001, 95% CI: 0.442-0.819) and A/B grade TE (grade A: OR=2.951, P<0.001, 95% CI: 1.980-4.399; grade B: OR=1.840, P<0.001, 95% CI: 1.315-2.576). The risk of complications during pregnancy [47.7% (143/300) vs. 19.3% (289/1 500), P<0.001], preterm labor [55.1% (140/254) vs. 7.4% (101/1 368), P<0.001], and the risk of stillbirth [3.7% (11/300) vs. 1.5% (22/1 500), P=0.016] were significantly higher in the MZT pregnancy group than in the singleton pregnancy group. Conclusion:Assisted reproductive technology may contribute to the risk of MZT. Transfer of blastocysts, particularly those with loose ICM arrangement and dense TE arrangement, appears to increase the risk of MZT in patients undergoing eSET.

Objective:To investigate the effect of drospirenone and ethinylestradiol in the treatment of ovulation induction in patients with premature ovarian insufficiency (POI).Methods:A randomized controlled clinical study analyzed the clinical data of 130 POI patients who underwent assisted reproductive treatment at the Department of Reproductive Medicine, Department of Obstetrics and Gynecology, the Seventh Medical Center and Department of Obstetrics and Gynecology, the Sixth Medical Center of Chinese people's Liberation Army General Hospital from December 2021 to November 2022. The subject-centered randomization method was used to conceal the allocation, and there was no blinding. The patients in experimental group was given drospirenone and ethinylestradiol as pretreatment, while control group was not treated. The main observation indicator of the follicle recovery growth rate and the secondary observation indicators of estradiol and follicle-stimulating hormone (FSH) levels before and after pretreatment, the number of eggs retrieved, the proportion of eggs retrieved, and other embryo laboratory-related indicators were compared between the two groups.Results:The recovery rate of follicular growth in the experimental group was significantly higher than that in control group, and the difference was statistically significant [50.77% (33/65) vs. 15.38% (10/65), P<0.001, rate difference =35.38%, 95% CI: 19.44%-48.98%]. The levels of FSH [17.70 (8.15, 27.00) U/L] decreased significantly and estradiol [24.00 (15.00, 90.47) ng/L] increased significantly in the experimental group after preconditioning with spironolone ethinylestradiol compared with those before preconditioning [30.30 (25.95, 48.05) U/L, P<0.001; 15.00 (15.00, 24.00) ng/L, P<0.001], the differences were statistically significant. Conclusion:The spironolone ethinylestradiol can effectively inhibit the level of FSH and increase the level of estradiol in patients with POI, and increase the probability of ovarian growth and development during ovulation induction therapy.

Objective:To investigate the effect of drospirenone and ethinylestradiol in the treatment of ovulation induction in patients with premature ovarian insufficiency (POI).Methods:A randomized controlled clinical study analyzed the clinical data of 130 POI patients who underwent assisted reproductive treatment at the Department of Reproductive Medicine, Department of Obstetrics and Gynecology, the Seventh Medical Center and Department of Obstetrics and Gynecology, the Sixth Medical Center of Chinese people's Liberation Army General Hospital from December 2021 to November 2022. The subject-centered randomization method was used to conceal the allocation, and there was no blinding. The patients in experimental group was given drospirenone and ethinylestradiol as pretreatment, while control group was not treated. The main observation indicator of the follicle recovery growth rate and the secondary observation indicators of estradiol and follicle-stimulating hormone (FSH) levels before and after pretreatment, the number of eggs retrieved, the proportion of eggs retrieved, and other embryo laboratory-related indicators were compared between the two groups.Results:The recovery rate of follicular growth in the experimental group was significantly higher than that in control group, and the difference was statistically significant [50.77% (33/65) vs. 15.38% (10/65), P<0.001, rate difference =35.38%, 95% CI: 19.44%-48.98%]. The levels of FSH [17.70 (8.15, 27.00) U/L] decreased significantly and estradiol [24.00 (15.00, 90.47) ng/L] increased significantly in the experimental group after preconditioning with spironolone ethinylestradiol compared with those before preconditioning [30.30 (25.95, 48.05) U/L, P<0.001; 15.00 (15.00, 24.00) ng/L, P<0.001], the differences were statistically significant. Conclusion:The spironolone ethinylestradiol can effectively inhibit the level of FSH and increase the level of estradiol in patients with POI, and increase the probability of ovarian growth and development during ovulation induction therapy.

Objective:To systematically evaluate the risk of hypotension induced by sodium-glucose transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus.Methods:Randomized controlled trials of SGLT2 inhibitors in the treatment of type 2 diabetes mellitus, in which hypotension were evaluated as an outcome indicator of adverse events, were collected by searching relevant databases at home and abroad (up to February 15, 2023). Cochrane risk of bias assessment tool was used to evaluate the quality of the included studies. Stata 15.1 software was used to conduct Bayesian network meta-analysis, including drawing the network evidence plot, the league map of pairwise comparison, and the surface under the cumulative ranking curve (SUCRA) for hypotension risk under different interventions of SGLT2 inhibitors, and ranking the risks of hypotension induced by different interventions of SGLT2 inhibitors. The effect sizes were expressed by relative risk ( RR) and its 95% confidence interval ( CI). Results:A total of 20 studies were included in the analysis, involving 22 525 patients with 15 260 in the trial group and 7 265 in the control group. Drugs that used in the trial group included dapagliflozin (in 1 517 patients), canagliflozin (in 6 053 patients), and ertugliflozin (in 7 690 patients); drugs that used in the control group included glimepiride (in 482 patients) and placebo (in 6 783 patients). The results of the network meta-analysis showed that the risk of hypotension was higher after treatment with 300 mg of canagliflozin, compared with those with 5 mg and 15 mg of ertugliflozin, and placebo ( RR=2.13, 95% CI: 1.31-3.47; RR=2.21, 95% CI: 1.35-3.61; RR=2.49, 95% CI: 1.62-3.82; all P<0.05); the risk of hypotension was higher after treatment with 100 mg of canagliflozin, compared with placebo ( RR=1.61, 95% CI: 1.04-2.50, P<0.05); the differences in comparison between any other 2 interventions with SGLT2 inhibitors were not statistically significant. According to the relative risks for hypotension of different interventions with SGLT2 inhibitors in the results of SUCRA, interventions were ranked as ertugliflozin 5 mg, placebo, dapagliflozin 2.5 mg, ertugliflozin 10 mg, ertugliflozin 15 mg, canagliflozin 50 mg, canagliflozin 100 mg, dapagliflozin 5 mg, dapagliflozin 10 mg, canagliflozin 150 mg, and canagliflozin 300 mg. Conclusions:Different treatment regimens with SGLT2 inhibitors had different risks of hypotension in patients with type 2 diabetes. The risk of hypotension caused by ertugliflozin is lower, especially at the dose of 5 mg. The risk of hypotension caused by canagliflozin is higher, especially at relatively high doses.

Objective: To investigate whether long non-coding RNA (lncRNA) Gm8097 (LncGm8097) is associated with male infertility. Methods: The expression and bilogical role of LncGm8097 were investigated. Results: LncGm8097 expression was down-regulated in the testis tissues with moderate and severe hypospermatogenesis compared with those with normal spermatogenesis and mild hypospermatogenesis (p<0.05). LncGm8097 down-regulation significantly promoted apoptosis and inhibited proliferation in GC1 and GC2 cells. In addition, LncGm8097 was significantly down-regulated in mouse model of hypospermatogenesis and correlated with cell apoptosis and proliferation. LncGm8097 was located immediately upstream of PRPS2, and correlated with Bcl-2/P53/caspase 6/caspase 9 signal pathway. Conclusion LncGm8097 down-regulation correlates with hypospermatogenesis, which may offer new insights into the pathogenesis of male infertility.

Objective To evaluate the cost-utility of tiotropium/olodaterol in treating Chinese patients with moderate to very severe chronic obstructive pulmonary disease(COPD)and to provide references for selecting more economical inhaled preparations in clinical practice.Methods A four-state lifetime Markov model was established with a 3-month cycle.The health outcomes included life years and quality-adjusted life years.Costs,including direct medical costs,were calculated from the perspective of the Chinese health system.Discontinuation rates were derived from the discontinuation curve using GetData Graph Digitizer.The main output indicator of the model was the incremental cost-utility ratio,which was calculated from the queue simulation results to judge the economy of tiotropium bromide/odataterol.The scenario analysis and sensitivity analyses were carried out to detect the robustness of the base case result.Results Compared with tiotropium bromide,the patient treated with tiotropium bromide/odataterol gained an additional 0.0846 life years,an additional cost of ￥3 201.50,and additional 0.029 6 QALY.The incremental cost-utility ratio was 108 140.11 yuan/QALY,lower than the willingness-to-pay threshold of three times China's per capita GDP in 2021.The costs of tiotropium bromide and tiotropium bromide/odataterol had the greatest impact on the result in the one-way sensitivity analysis.93.8%of the Chinese COPD population was willing to pay for tiotropium bromide/odataterol under the threshold in the probability sensitivity analysis.Conclusion Tiotropium/olodaterol is a cost-effective alternative compared to tiotropium for patients with moderate to very severe COPD in China and the results were robust in the sensitivity analyses.