Objective: To assess the association between the metabolic score for insulin resistance index (METS-IR) and overactive bladder (OAB) in the US population，so as to explore the potential of METS-IR as a predictive tool for OAB risk and to provide insights for early screening and intervention strategies. Methods: Based on the data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018，a cross-sectional design was employed，and multivariate logistic regression models were used to analyze the association between METS-IR and OAB. METS-IR was analyzed both as a continuous variable and categorized into quartiles. To further validate the association between METS-IR and OAB across diverse populations，subgroup analyses were conducted in participants stratified by clinical characteristics. Smooth curve fitting was employed to test the linearity of the METS-IR-OAB relationship. Results: Elevated METS-IR was associated with an increased risk of OAB (P<0.001)，and this positive correlation remained stable when METS-IR was categorized into quartiles (P<0.001). Subgroup analyses revealed that the association between METS-IR and OAB was more pronounced in females，participants younger than 55 years，and non-diabetic individuals (P<0.05). Furthermore，smooth curve fitting confirmed a linear positive correlation between METS-IR and OAB，with this linear relationship observed in both diabetic and non-diabetic groups. Conclusion: This study，based on the NHANES 2005-2018 database，found a linear positive correlation between METS-IR and OAB.

Energy metabolism is fundamental for life.It encompasses the utilization of carbohydrates,lipids,and proteins for internal processes,while aberrant energy metabolism is implicated in many diseases.In the present study,using three-dimensional(3D)printing from polycarbonate via fused deposition modeling,we propose a multi-nuclear radiofrequency(RF)coil design with integrated 1H birdcage and interchangeable X-nuclei(2H,13C,23Na,and 31P)single-loop coils for magnetic resonance imaging(MRI)/magnetic resonance spectroscopy(MRS).The single-loop coil for each nucleus attaches to an arc bracket that slides unrestrictedly along the birdcage coil inner surface,enabling convenient switching among various nuclei and animal handling.Compared to a commercial 1H birdcage coil,the proposed 1H birdcage coil exhibited superior signal-excitation homogeneity and imaging signal-to-noise ratio(SNR).For X-nuclei study,prominent peaks in spectroscopy for phantom solutions showed excellent SNR,and the static and dynamic peaks of in vivo spectroscopy validated the efficacy of the coil design in structural imaging and energy metabolism detection simultaneously.

Objective:To explore the variables associated with the severity of coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 omicron variant during the epidemic in patients with myeloproliferative neoplasms (MPN).Methods:A cross-sectional study. During the SARS-CoV-2 omicron variant pandemic from December 15, 2022, to March 15, 2023, COVID-19 related data for patients with MPN who were treated at Peking University People′s Hospital were collected through an online questionnaire-based survey. All questionnaires and clinical data were checked by medical assistants. Logistic multivariate analysis was used to explore the prevalence and variables associated with the severity of COVID-19 in patients with MPN.Results:A total of 239 patients with MPN, including 90 (37.7%) presenting with essential thrombocythemia (ET), 50 (20.9%) with polycythemia vera (PV), and 99 (41.4%) with myelofibrosis (MF), were enrolled in the study. The 99 patients with MF included 87 (87.9%) with primary MF, 5 (5.1%) with post-PV MF, and 7 (7.1%) with post-ET MF. Overall, 239 (100%) patients reported that they experienced COVID-19 during the pandemic. Of these, 226 (94.6%) had mild disease, 4 (1.7%) had moderate disease, 7 (2.9%) had severe disease, and 2 (0.8%) had critical disease. Two (0.8%) patients with severe COVID-19 died, one of which suffered from MT and the other from PV. Multivariate analysis showed that older age ( OR=2.36, 95% CI 1.24-4.49), MF ( OR=10.22, 95% CI 1.13-92.80), or comorbidity ( OR=5.25, 95% CI 1.25-22.03) were associated with a significantly higher risk of developing moderate, severe, or critical COVID-19. Among patients with MF, higher risk stratification reflected an increased risk of developing moderate, severe, or critical COVID-19 ( P=0.034). Conclusion:During the omicron pandemic, older age, MF (especially higher-risk categories), and comorbidity were associated with a higher risk of developing moderate, severe, or critical COVID-19.

Objective:To evaluate the effects of recombinant luteinizing hormone (rLH) and human menopausal gonadotropins (hMG) supplementation on pregnancy outcomes for suboptimal ovarian responders undergoing follicular phase long protocol.Methods:The data of infertile patients who underwent in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) for the first time with follicular phase long protocol from January 2017 to January 2020 in Reproductive Medicine Center of the First Affiliated Hospital of Nanjing Medical University Hospital were retrospectively cohort analyzed. Totally 2 336 patients with normal ovarian reserve were included in the study with suboptimal ovarian response to ovarian stimulation. According to the different exogenous LH supplementation, they were divided into hMG group ( n=1 558) and rLH group ( n=778). The clinical features and effects of ovulation induction were compared between the two groups and reproductive outcomes were compared in both fresh embryo transfer cycles and subsequent frozen-thawed embryo transfer (FET) cycles. Logistic regression analysis were performed to explore the relationship between different LH activity drugs supplementation and the cumulative live birth rate of suboptimal ovarian responders. Results:The basic characteristics such as age, infertility type and diagnosis, body mass index and biomarkers of ovarian reserve were comparable between the two groups (all P>0.05). Total dosage [(2 088.98±628.24) U] and duration [(12.22±2.29) d] of FSH used in the hMG group were significantly higher than those in the rLH group [(1 866.90±602.65) U, P<0.001; (11.89±2.37) d, P=0.001]. Total dosage [(537.30±484.49) U] and duration [(7.40±3.52) d] of LH used in the hMG group were significantly higher than those in the rLH group [(498.10±472.04) U, (5.67±3.78) d, P<0.001]. The serum LH levels on the first day [(0.78±0.77) U/L] and the sixth day [(0.81±0.49) U/L] of gonadotropin stimulation in the hMG group were higher than those in the rLH group [(0.67±0.32) U/L, P<0.001; (0.71±0.33) U/L, P=0.002]. However, the serum LH level was comparable on the trigger day between the two groups without significant difference ( P=0.303). The levels of serum estrodiol [(8 377.14±7 000.63) pmol/L] and progesterone [(3.84±2.18) nmol/L] on the trigger day were significantly higher in the hMG group than in the rLH group [(7 644.91±5 145.64) pmol/L, P=0.009; (3.14±1.80) ng/L, P<0.001]. The pregnancy outcomes including clinical pregnancy rates, abortion rates and live birth rates were comparable between the two groups in fresh embryo transfer cycles and the subsequent FET cycles (all P>0.05). The cumulative pregnancy rate (CPR) [89.46% (696/778)] and the cumulative live birth rate (CLBR) [78.02% (607/778)] in the rLH group were significantly higher than those in the hMG group [84.60% (1 318/1 558), P=0.001; 72.98% (1 137/1 558), P=0.008]. Multivariate logistic regression analysis showed that age was a risk factor for CLBR ( OR=0.930, 95% CI: 0.906-0.955, P<0.001) and antral follicle count ( OR=1.029, 95% CI: 1.005-1.054, P=0.018), total number of oocytes retrieved ( OR=1.064, 95% CI: 1.029-1.100, P<0.001), the number of embryos transferred ( OR=1.714, 95% CI: 1.293-2.272, P<0.001), the stage of embryos transferred ( OR=1.567, 95% CI: 1.243-1.975, P<0.001), endometrial thickness on transfer day ( OR=1.122, 95% CI: 1.077-1.170, P<0.001) and rLH supplementation ( OR=1.348, 95% CI:1.101-1.651, P=0.004) were protective factors for CLBR of suboptimal responders. Conclusion:For suboptimal ovarian responders with normal ovarian reserve, rLH supplementation may achieve a higher CLBR than hMG supplementation in follicular phase long protocol.

Objective:To explore the effect of clomiphene citrate (CC) with different dosages on the endometrial factor, number of oocytes retrieved, pregnancy outcomes and other factors in diminished ovarian reserve (DOR) patients with minimal stimulation/natural protocol.Methods:This was a retrospective cohort study. The patients who underwent minimal stimulation protocol of in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) were divided into 4 groups. Group A: the patients had CC 50 mg/d from the third day of menstruation to the trigger day (1 457 cycles); group B: the patients had 50 mg/d from the third day of menstruation for 3 d (1 533 cycles); group C: the patients had CC 25 mg/d from the third day of menstruation to the trigger day (345 cycles); group D: the patients had CC 25 mg/d for 3 d (319 cycles). The general data, clinical results, pregnancy and delivery outcomes were compared between group A and group B, as well as group C and group D. Results:In the treatment of IVF/ICSI, the dosage of gonadotropin (Gn) used, number of dominant follicles, estradiol level, luteinizing hormone level, progesterone level, number of oocytes retrieved, rate of oocytes retrieved, number of fertilizations, number of transplantable embryos and whole embryo freezing rate in patients of group A were significantly higher than those in group B (all P<0.05). The endometrial thickness [7.10 (5.40,8.65) mm] and the ratio of endometrial type (A/A-B) on trigger day [70.70% (888/1 256)] of group B were significantly better than those of group A [6.00 (4.70,8.00) mm, P<0.001; 63.62% (649/1 020), P<0.001], and the fresh embryo transfer rate of group B was significantly higher than that of group A [20.00% (259/1 295) vs. 42.94% (584/1 360), P<0.001]. There were no statistical differences in the number of high-quality embryos and the rate of no embryo transfer between the two groups (both P>0.05). In group C and group D, the Gn used dosage, the number of dominant follicles, the estradiol level on trigger day, number of oocytes retrieved, embryos/cycles were significantly increased (all P<0.05), the endometrial thickness on trigger day of group D [7.00 (5.40, 8.60) mm] was significantly higher than that of group C [6.10 (5.00,7.93) mm, P<0.001], but there was no statistical difference of the ratio of endometrial type (A/A-B) between the two groups ( P=0.739). In addition, the luteinizing hormone and progesterone values on the trigger day in group C were significantly higher than those in group D ( P=0.014, P=0.005), but there were no significant differences in pre-ovulation rate and all embryos frozen rate between the two groups (all P<0.05), and the rate of fresh embryo transfer in group C [26.04% (75/288)] was significantly lower than that in group D [38.80% (97/250), P<0.001]. Finally, there were no significant differences in cumulative clinical pregnancy rate and fresh/frozen embryo transfer outcome between group A and group B as well as group C and group D (all P>0.05). Conclusion:The use of low-dose and short-time CC in minimal stimulation protocol does not change the final pregnancy outcome, while saving patients' economic and time costs, so it could be an appropriate project for DOR patients.

Objective:To explore the effect of clomiphene citrate (CC) with different dosages on the endometrial factor, number of oocytes retrieved, pregnancy outcomes and other factors in diminished ovarian reserve (DOR) patients with minimal stimulation/natural protocol.Methods:This was a retrospective cohort study. The patients who underwent minimal stimulation protocol of in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) were divided into 4 groups. Group A: the patients had CC 50 mg/d from the third day of menstruation to the trigger day (1 457 cycles); group B: the patients had 50 mg/d from the third day of menstruation for 3 d (1 533 cycles); group C: the patients had CC 25 mg/d from the third day of menstruation to the trigger day (345 cycles); group D: the patients had CC 25 mg/d for 3 d (319 cycles). The general data, clinical results, pregnancy and delivery outcomes were compared between group A and group B, as well as group C and group D. Results:In the treatment of IVF/ICSI, the dosage of gonadotropin (Gn) used, number of dominant follicles, estradiol level, luteinizing hormone level, progesterone level, number of oocytes retrieved, rate of oocytes retrieved, number of fertilizations, number of transplantable embryos and whole embryo freezing rate in patients of group A were significantly higher than those in group B (all P<0.05). The endometrial thickness [7.10 (5.40,8.65) mm] and the ratio of endometrial type (A/A-B) on trigger day [70.70% (888/1 256)] of group B were significantly better than those of group A [6.00 (4.70,8.00) mm, P<0.001; 63.62% (649/1 020), P<0.001], and the fresh embryo transfer rate of group B was significantly higher than that of group A [20.00% (259/1 295) vs. 42.94% (584/1 360), P<0.001]. There were no statistical differences in the number of high-quality embryos and the rate of no embryo transfer between the two groups (both P>0.05). In group C and group D, the Gn used dosage, the number of dominant follicles, the estradiol level on trigger day, number of oocytes retrieved, embryos/cycles were significantly increased (all P<0.05), the endometrial thickness on trigger day of group D [7.00 (5.40, 8.60) mm] was significantly higher than that of group C [6.10 (5.00,7.93) mm, P<0.001], but there was no statistical difference of the ratio of endometrial type (A/A-B) between the two groups ( P=0.739). In addition, the luteinizing hormone and progesterone values on the trigger day in group C were significantly higher than those in group D ( P=0.014, P=0.005), but there were no significant differences in pre-ovulation rate and all embryos frozen rate between the two groups (all P<0.05), and the rate of fresh embryo transfer in group C [26.04% (75/288)] was significantly lower than that in group D [38.80% (97/250), P<0.001]. Finally, there were no significant differences in cumulative clinical pregnancy rate and fresh/frozen embryo transfer outcome between group A and group B as well as group C and group D (all P>0.05). Conclusion:The use of low-dose and short-time CC in minimal stimulation protocol does not change the final pregnancy outcome, while saving patients' economic and time costs, so it could be an appropriate project for DOR patients.

Objective:To evaluate the effects of recombinant luteinizing hormone (rLH) and human menopausal gonadotropins (hMG) supplementation on pregnancy outcomes for suboptimal ovarian responders undergoing follicular phase long protocol.Methods:The data of infertile patients who underwent in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) for the first time with follicular phase long protocol from January 2017 to January 2020 in Reproductive Medicine Center of the First Affiliated Hospital of Nanjing Medical University Hospital were retrospectively cohort analyzed. Totally 2 336 patients with normal ovarian reserve were included in the study with suboptimal ovarian response to ovarian stimulation. According to the different exogenous LH supplementation, they were divided into hMG group ( n=1 558) and rLH group ( n=778). The clinical features and effects of ovulation induction were compared between the two groups and reproductive outcomes were compared in both fresh embryo transfer cycles and subsequent frozen-thawed embryo transfer (FET) cycles. Logistic regression analysis were performed to explore the relationship between different LH activity drugs supplementation and the cumulative live birth rate of suboptimal ovarian responders. Results:The basic characteristics such as age, infertility type and diagnosis, body mass index and biomarkers of ovarian reserve were comparable between the two groups (all P>0.05). Total dosage [(2 088.98±628.24) U] and duration [(12.22±2.29) d] of FSH used in the hMG group were significantly higher than those in the rLH group [(1 866.90±602.65) U, P<0.001; (11.89±2.37) d, P=0.001]. Total dosage [(537.30±484.49) U] and duration [(7.40±3.52) d] of LH used in the hMG group were significantly higher than those in the rLH group [(498.10±472.04) U, (5.67±3.78) d, P<0.001]. The serum LH levels on the first day [(0.78±0.77) U/L] and the sixth day [(0.81±0.49) U/L] of gonadotropin stimulation in the hMG group were higher than those in the rLH group [(0.67±0.32) U/L, P<0.001; (0.71±0.33) U/L, P=0.002]. However, the serum LH level was comparable on the trigger day between the two groups without significant difference ( P=0.303). The levels of serum estrodiol [(8 377.14±7 000.63) pmol/L] and progesterone [(3.84±2.18) nmol/L] on the trigger day were significantly higher in the hMG group than in the rLH group [(7 644.91±5 145.64) pmol/L, P=0.009; (3.14±1.80) ng/L, P<0.001]. The pregnancy outcomes including clinical pregnancy rates, abortion rates and live birth rates were comparable between the two groups in fresh embryo transfer cycles and the subsequent FET cycles (all P>0.05). The cumulative pregnancy rate (CPR) [89.46% (696/778)] and the cumulative live birth rate (CLBR) [78.02% (607/778)] in the rLH group were significantly higher than those in the hMG group [84.60% (1 318/1 558), P=0.001; 72.98% (1 137/1 558), P=0.008]. Multivariate logistic regression analysis showed that age was a risk factor for CLBR ( OR=0.930, 95% CI: 0.906-0.955, P<0.001) and antral follicle count ( OR=1.029, 95% CI: 1.005-1.054, P=0.018), total number of oocytes retrieved ( OR=1.064, 95% CI: 1.029-1.100, P<0.001), the number of embryos transferred ( OR=1.714, 95% CI: 1.293-2.272, P<0.001), the stage of embryos transferred ( OR=1.567, 95% CI: 1.243-1.975, P<0.001), endometrial thickness on transfer day ( OR=1.122, 95% CI: 1.077-1.170, P<0.001) and rLH supplementation ( OR=1.348, 95% CI:1.101-1.651, P=0.004) were protective factors for CLBR of suboptimal responders. Conclusion:For suboptimal ovarian responders with normal ovarian reserve, rLH supplementation may achieve a higher CLBR than hMG supplementation in follicular phase long protocol.

OBJECTIVE: To explore the genetic etiology of recurrent hydatidiform mole (RHM) and provide accurate guidance for reproduction. METHODS: Peripheral venous blood samples of the probands with RHM and members from 5 unrelated pedigrees were collected. Genomic DNA was extracted by using routine method, and whole exome sequencing was carried out to detect variants of RHM-associated genes including NLRP7 and KHDC3L. Sanger sequencing and real-time quantitative PCR (RT-qPCR) were used to validate the candidate variants and delineate their parental origin. RESULTS: Homozygous or compound heterozygous variants of the NLRP7 gene were identified in four patients from three pedigrees, which included a homozygous deletion of exon 1 to 4 of NLRP7 in patient P1 and her elder sister, compound heterozygous variants of NLRP7 c.939delG (p.Q314Sfs*6) pat and c.1533delG (p.N512Tfs*4) mat in patient P2, and compound heterozygous variants of NLRP7 c.2389_2390delTC (p.A798Qfs*6) pat and c.2165A>G (p.D722G) mat in patient P4. All variants were interpreted as pathogenic or likely pathogenic according to the American College of Medical and Genomics (ACMG) guidelines. Among these, NLRP7 exons 1 to 4 deletion, c.939delG (p.Q314Sfs*6), c.1533delG (p.N512Tfs*4) and c.2389_2390delTC (p.A798Qfs*6) were unreported previously. CONCLUSION Variants of the NLRP7 gene probably underlay autosomal recessive RHM in the three pedigrees, and definitive molecular diagnosis is beneficial for accurate genetic counseling. Above finding has also enriched the spectrum of the NLRP7 variants underlying RHM.
Adaptor Proteins, Signal Transducing/genetics* ; Aged ; China ; Female ; Homozygote ; Humans ; Hydatidiform Mole/pathology* ; Mutation ; Pedigree ; Pregnancy ; Sequence Deletion

Objective To investigate chromosome abnormality rate and related factors of spontaneous abortion in early pregnancy. Methods A total of 831 tissue samples of spontaneous abortion in early pregnancy were collected from June 2015 to August 2018 in the First Affiliated Hospital of Nanjing Medical University. Chromosomal copy number was analyzed by next generation sequencing (NGS). The relationships between chromosome abnormality and maternal age, in vitro fertilization?embryo transfer (IVF?ET) pregnancy, number of previous spontaneous abortions, history of live birth were analyzed by statistical methods. Results Among 831 tissue samples of spontaneous abortion in early pregnancy, 461 (55.5%, 461/831) were found to have chromosome abnormalities. Maternal age (OR=1.107, 95%CI: 1.070-1.145) and history of live birth ( OR=1.909, 95%CI : 1.182-3.083) were the positive correlative factors of chromosome abnormality. Times of previous spontaneous abortion (OR=0.807, 95%CI: 0.702-0.928) and IVF?ET pregnancy ( OR=0.554, 95%CI : 0.404-0.760) were the negative correlative factors of chromosome abnormality. Conclusions Chromosome abnormality is an important cause of spontaneous abortion in early pregnancy. The rate of chromosome abnormality increases with the increase of maternal age and the history of live birth, and decreases with the increase of number of previous spontaneous abortion and IVF?ET pregnancy.

Objective: To investigate chromosome abnormality rate and related factors of spontaneous abortion in early pregnancy. Methods: A total of 831 tissue samples of spontaneous abortion in early pregnancy were collected from June 2015 to August 2018 in the First Affiliated Hospital of Nanjing Medical University. Chromosomal copy number was analyzed by next generation sequencing (NGS). The relationships between chromosome abnormality and maternal age, in vitro fertilization-embryo transfer (IVF-ET) pregnancy, number of previous spontaneous abortions, history of live birth were analyzed by statistical methods. Results: Among 831 tissue samples of spontaneous abortion in early pregnancy, 461 (55.5%, 461/831) were found to have chromosome abnormalities. Maternal age (OR=1.107, 95%CI: 1.070- 1.145) and history of live birth (OR=1.909, 95%CI: 1.182-3.083) were the positive correlative factors of chromosome abnormality. Times of previous spontaneous abortion (OR=0.807, 95%CI: 0.702-0.928) and IVF-ET pregnancy (OR=0.554, 95%CI: 0.404-0.760) were the negative correlative factors of chromosome abnormality. Conclusions Chromosome abnormality is an important cause of spontaneous abortion in early pregnancy. The rate of chromosome abnormality increases with the increase of maternal age and the history of live birth, and decreases with the increase of number of previous spontaneous abortion and IVF-ET pregnancy.