ObjectiveTo investigate the protective effect of Genistein against nonalcoholic fatty liver disease （NAFLD） in ovariectomized （OVX） mice and its mechanism. MethodsA total of 40 female C57BL/6 mice， aged 6 weeks， were used to establish an OVX mouse model， and then they were randomly divided into blank group， 4-week model group， 6-week model group， 8-week model group， and 10-week model group， with 8 mice in each group. Under the same environmental conditions， the mice were given high-fat diet for modeling， and pathological examination showed that NAFLD was successfully induced by 10-week high-fat diet. Another 40 female C57BL/6 mice， aged 6 weeks， were randomly divided into blank group， sham operation group （Sham group）， OVX group， OVX+L-Genistein （4 mg/kg body weight） group， and OVX+H-Genistein （8 mg/kg body weight） group. The mice in the Sham group were given the same procedure of OVX， without the ligation of the ovarian artery and the resection of the ovary. The mice in the blank group were given normal diet， and those in the other groups were given high-fat diet. Genistein was dissolved in DMSO， and the mice in the Sham group and the OVX group were treated with solvent solution alone by gavage， once a day for 10 consecutive weeks. Body weight and visceral index were recorded， and the mice were sacrificed to collect serum and liver tissue. Kits were used to measure the activity of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） and the serum levels of triglyceride （TG） and total cholesterol （TC）， and HE staining and oil red O staining were used to observe liver histopathology； Western blot was used to measure the protein expression levels of sterol regulatory element-binding protein 1c （SREBP-1c） and peroxisome proliferator-activated receptor alpha （PPARα） associated with lipid metabolism in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the Dunnett-t test was used for further comparison between two groups. ResultsAfter 10 weeks of high-fat diet， the OVX+L-Genistein group and the OVX+H-Genistein group had significantly lower body weight， liver index， and liver tissue weight （all P<0.05）. In addition， Genistein significantly downregulated the serum levels of TC and TG （P<0.05） and reduced the activities of serum AST and ALT （P<0.05）. HE and oil red O staining showed that compared with the OVX group， the OVX+L-Genistein group and the OVX+H-Genistein group had a significant reduction in the accumulation of lipid droplets. Western blot showed that after Genistein intervention， there was a significant reduction in the protein expression level of SREBP-1c and a significant increase in the protein expression level of PPARα （P<0.05）. ConclusionGenistein exerts a protective effect against NAFLD in OVX mice possibly by regulating the expression of SREBP-1c and PPARα， thereby promoting fatty acid oxidation and inhibiting liver lipid synthesis.

BACKGROUND:Bibliometrics and visual analyses based on thematic literature are particularly important for understanding the foundation and frontiers of postmenopausal osteoporosis research. OBJECTIVE:To perform bibliometric,citation,and visualization analyses of highly cited SCI papers in postmenopausal osteoporosis research over the last 20 years. METHODS:The top 100 highly cited papers on postmenopausal osteoporosis published between 2003 and 2022 included in SCI-EXPANDED catalog of the Web of Science database were obtained for bibliometric measure and visual analysis using CiteSpace software. RESULTS AND CONCLUSION:The top 100 highly cited papers have a total of 67 377 citations in the Web of Science Core Collection,with an annual average of 49.17 citations per paper.Postmenopausal osteoporosis research primarily involves medical,engineering,biological,and multidisciplinary fields.The subcategories are dominated by endocrinology and metabolism,and medicine:internal medicine.Stable and close cooperative network relationships have been formed globally.United States,University of California System,Cummings,and Steven R are the country,research institution,and author,respectively,with the most highly-cited publications.The frontiers of postmenopausal osteoporosis research mainly include calcium and vitamin D supplementation and fracture risk,clinical studies of bisphosphonates in the treatment of postmenopausal osteoporosis,atypical femur fracture,clinical studies of new drugs and sequential treatment of postmenopausal osteoporosis,predictors of fracture risk,mid-and long-term follow-up of osteoporotic vertebral compression fractures,genetic polymorphisms and hereditary factors,formulation and updating of clinical practice guidelines for postmenopausal osteoporosis.Large cohort studies,high-quality randomized controlled trials,systematic reviews,meta-analyses,and clinical practice guidelines are the great engines that drive the development of clinical research in postmenopausal osteoporosis.We should make efforts in the above areas to improve China's international influence in the field of osteoporosis.

Objective To analyze the current research application status and hotspots of nanoparticles in the treatment of non-small cell lung cancer (NSCLC) and predict the future development trend. Methods The Web of Science database was searched for literatures on nanoparticles use in the treatment of NSCLC from inception to November 2022. CiteSpace, VOSviewer and literature measurement analysis online platform (https://bibliometric.com/) were used for the visual analysis of the number of documents, source journals, authors, organizations, countries and keywords. Results A total of 742 English literatures were included. The results showed that the number of published literatures increased year by year from 2011 and reached the peak in 2020. Researches on nanoparticles and NSCLC treatment were mainly concentrated in China, the United States, India and Japan. China is a major research country in this field, but it lacked cooperation with other countries and related institutions. Among numerous research institutions, the Chinese Academy of Sciences was the authoritative and backbone force in this research field, with the number of published literatures ranking first and the research achievements outstanding. The keyword analysis found that "poly lactic-co-glycolic acid nanoparticles (PLGA NPs)" and "photothermal therapy" had become the latest breakout words since 2018. Moreover, the occurrence frequency of related keywords such as "drug delivery" increased significantly, indicating that the application of PLGA NPs in photothermal therapy might be the current research hotspot and future development trend of NSCLC treatment. Conclusion Currently, the domestic research on the treatment of nanoparticles and NSCLC is in a leading position in the world. The organic combination of nanoparticles with different materials and other NSCLC therapies is expected to improve the prognosis of NSCLC patients. In the future, attempts to develop nanoparticles with different sources and structures and combined with photothermal therapy for the treatment of NSCLC may become a research hotspot of nanoparticles in the treatment of NSCLC.

Objective To identify the independent risk factors of cognitive impairment(CI)in patients with cerebral small vessel disease(CSVD)and construct a clinical prediction model.Methods Patients with CSVD who were hospitalized in the First Affiliated Hospital of Xi'an Jiaotong University from January 1,2017 to December 31,2022 were retrospectively enrolled,and were divided into a group with cognitive impairment(CSVD-CI group,n=83)and a group without cognitive impairment(CSVD-NCI group,n=164)according to the mini-mental state examination(MMSE).The influence factors of cognitive impairment were screened by logistic regression.The clinical prediction model of the nomogram was further developed based on the screened factors,and the efficacy of the model was tested.Results Compared with patients in the CSVD-NCI group,patients in the CSVD-CI group had higher neutrophil/lymphocyte ratio(NLR)(3.03±2.56 vs 2.33±1.34)and(1.58±0.27 vs 1.49±0.28),and a lower estimated glomerular filtration rate[eGFR:88.59±16.59 ml/(min·1.73m2)vs 94.02±12.45 ml/(min·1.73m2)],with significant differences(t=2.282,2.426,2.689,all P＜0.05).Compared with patients in the CSVD-NCI group,patients in the CSVD-CI group had lower proportion of males(43.4％vs 67.7％)and level of education(2.13±1.50 vs 2.86),and the differences were significant(x2=13.516,t=4.283,all P＜0.05).NLR(OR:1.20,95％CI:1.01～1.43),sex(OR:0.43,95％CI:0.24～0.79),eGFR(OR:0.97,95％CI:0.95～0.99)and education degree(OR:0.72,95％CI:0.57～0.91)were the impact factors for cognitive impairment in CSVD patients.The nomogram prediction model based on these four factors had good efficacy in predicting cognitive impairment(AUC=0.704,95％CI:0.633～0.766).Conclusion The nomogram constructed in this study has moderate accuracy and clinical utility in predicting the occurrence of cognitive impairment in CSVD patients.

Objectives:To report the sexual functional outcomes of vaginal dilation therapy in Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome patients.Methods:From March 2020 to February 2023, 97 MRKH syndrome patients performed vaginal dilation therapy with guidance from Peking Union Medical College Hospital, and 45 of them engaged in penetrative intercourse and were included in this prospective cohort study. The Chinese version of female sexual function index (FSFI) was used to assess sexual function. Functional success was defined as FSFI>23.45. Forty age-matched healthy women were selected as controls. Kaplan-Meier survival analysis was used to calculate the median time to success. Pearson correlation analysis was used to explore the relationship between neovagina length and sexual function. Complications were collected using follow-up questionnaires.Results:The functional success rate of vaginal dilation therapy was 89% (40/45) with a median time to success of 4.3 months (95% CI: 3.0-6.1 months). Compared to controls, MRKH syndrome patients had significantly lower scores in the orgasm domain (4.72±1.01 vs 4.09±1.20; P=0.013) and pain domain (5.03±0.96 vs 4.26±0.83; P<0.001). However, there were no significant differences in the FSFI total score (26.77±2.70 vs 26.70±2.33; P=0.912), arousal domain (4.43±0.77 vs 4.56±0.63; P=0.422) and satisfaction domain (4.88±0.98 vs 4.65±0.86; P=0.269) between MRKH syndrome patients and controls. MRKH syndrome patients had significantly higher scores in the desire domain (3.33±0.85 vs 3.95±0.73; P<0.001) and lubrication domain (4.37±0.56 vs 5.20±0.67; P<0.001). The prevalence of sexual dysfunction in MRKH patients was non-inferior to controls: low desire [3% (1/40) vs 23% (9/40); P=0.007], arousal disorder [3% (1/40) vs 3% (1/40); P>0.999], lubrication disorder [5% (2/40) vs 25% (10/40); P=0.012], orgasm disorder [40% (16/40) vs 20% (8/40); P=0.051], sexual pain [30% (12/40) vs 15% (6/40); P=0.108]. Conclusions:MRKH syndrome patients undergoing non-invasive vaginal dilation therapy could achieve satisfactory sexual life. Given its high functional success rate and slight complication, vaginal dilation therapy should be recommended as the first-line option, reducing the need for unnecessary surgeries.

Objective:To explore the genetic etiology of two children with Spinal muscular atrophy with respiratory distress type 1 (SMARD1), and prevent the recurrence of birth defects.Methods:Two unrelated families who had visited the Obstetrics and Gynecology Medical Center of Drum Tower Hospital from August to November 2021 were selected as the study subjects. Copy number of SMN1 gene exon 7 for the probands and their parents was detected by multiple ligation-dependent probe amplification (MLPA). and whole exome sequencing (WES) was carried out to screen the variants in the probands. Sanger sequencing was used to validate the variants within the families. Pathogenecity of the variants were predicted by bioinformatic analysis. Based on the results, prenatal diagnosis was performed for the fetuses. Results:Both probands were found to harbor compound heterozygous variants of the IGHMBP2 gene, which were inherited from their parents. Among these, c. 1144C>T, c. 866delG and c. 1666C>G were previously unreported and respectively classified as pathogenic variant (PVS1+ PM2_Supporting+ PP3+ PP4), likely pathogenic variant (PM1+ PM2_Supporting+ PM4+ PP3+ PP4) and likely pathogenic variant (PM1+ PM2_Supporting+ PP2+ PP3+ PP4) based on the ACMG guidelines. Through preimplantation genetic testing for monogenic (PGT-M) and interventional prenatal diagnosis, transmission of the variants within the families was successfully blocked. Conclusion:The SMARD1 in both children may be attributed to the compound heterozygous variants of the IGHMBP2 gene, which has facilitated the genetic diagnosis and counselling, and provided reference for delineating the molecular pathogenesis of this disease.

Objective:To explore the clinical manifestations of two fetuses harboring heterozygous deletions of the SHOX gene. Methods:Two pregnant women who had presented at the Prenatal Diagnosis Center of Nanjing Drum Tower Hospital respectively on June 24, 2022 and July 27, 2022 were selected as the study subjects. In case 1, prenatal ultrasonography had shown short femur and intrauterine growth retardation of the fetus. Case 2 had a history of spontaneous abortions due to structural chromosomal aberrations. Fetus 1 had undergone a test for the FGFR3 gene, and both fetuses were subjected to single nucleotide polymorphism-based microarray (SNP array) analysis. Results:Affter excluding the influence of FGFR3 gene Fetus 1 was found to harbor a heterozygous 883 kb deletion at Xpter or Ypter, whilst fetus 2 was found to harbor a 5.75 Mb deletion in the Xpter region. Both deletions have encompassed the SHOX gene. The origin of the deletion in fetus 1 was unknown, whilst that in fetus 2 was inherited from its mother. Fetus 1 has been delivered at term with a normal phenotype, and fetus 2 was not born yet. Conclusion:The intrauterine and postnatal phenotypes of fetuses may be predicted by combining the ultrasound finding, parental phenotype and results of CMA, variant, and the results can facilitate genetic counseling and decision making over the pregnancy.

Objective:To explore the genetic characteristics of three fetuses with regions of homozygosity (ROH).Methods:Three fetuses with ROH diagnosed at Nanjing Drum Tower Hospital on December 2, 2020, March 19, 2021, and May 27, 2022, respectively were selected as the study subjects. Clinical data of the fetuses were collected. Chromosomal microarray analysis (CMA) was used to detect the ROH, and tandem repeat sequences (STR)-based multiplex PCR assay was used to identify the mosaicism status in fetus 1.Results:Partial maternal isodisomy (iUPD) (16) was found in fetus 1, for which trisomy rescue may be accountable. Meanwhile, the fetus also has confined placental mosaicism (CPM) but not true mosaicism. The formation mechanism of ROH for fetus 2 was identity by descent. Partial maternal iUPD (7) was found in fetus 3, which may be due to gametic recombination.Conclusion:The ROH of the three fetuses were inherited from both parents or the mother. Above findings suggested that it is justified to detect ROH on imprinting disorder-related chromosomes when potential uniparental disomy is suspected.

To examine the global research trends and emerging focal points in the field ofgeriatric interdisciplinary team (GIT) from 2000 to 2023, so as to offer insights and reference for related research in China.

Objective:To investigate the influence of maternal autoimmune diseases and anticoagulants, including low-molecular-weight heparin (LMWH) and aspirin, on the fetal fraction of maternal plasma cell-free DNA of non-invasive prenatal testing (NIPT).Methods:A prospective cohort study was conducted on women with singleton pregnancies receiving NIPT in the Nanjing Drum Tower Hospital from March 2021 to July 2022. NIPT was carried out using a polymerase chain reaction (PCR)-free amplification platform. In this study, four types of maternal autoimmune diseases, which were antiphospholipid syndrome, undifferentiated connective tissue disease, Sj?gren's syndrome, and systemic lupus erythematosus (SLE), and two anticoagulants, LMWH and aspirin, were studied. Univariate and multivariate linear regression models were used to analyze the factors influencing fetal fraction of maternal plasma cell-free DNA.Results:A total of 4 102 singleton pregnant women were enrolled in the prospective cohort, and 3 948 were finally included after excluding the cases with unclear dosing time of LMWH or aspirin, other autoimmune diseases, conceiving through ovulation induction alone, and having true positive or failed NIPT result. There were 96 cases with antiphospholipid syndrome, 35 with undifferentiated connective tissue disease, 34 with Sj?gren's syndrome, and 18 with SLE. A total of 108 patients only received LMWH treatment, 121 only received aspirin treatment, and 113 received both LMWH and aspirin treatment. Univariate linear regression analysis showed that maternal body mass index at blood collection ( B=－0.423), conceived by assisted reproductive technology ( B=－0.803), male fetus ( B=－0.458), undifferentiated connective tissue disease ( B=1.774), and SLE ( B=3.467) had influence on the fetal fraction (all P<0.05). Multivariate linear regression analysis showed that maternal body mass index at blood collection ( B=－0.415), conceived by assisted reproductive technology ( B=－0.585), male fetus ( B=－0.322), SLE ( B=3.347) and undifferentiated connective tissue disease ( B=1.336) were factors influencing fetal fraction (all P<0.05). Conclusions:Maternal use of LMWH or aspirin does not affect fetal fraction when performing NIPT on a PCR-free amplification platform, but undifferentiated connective tissue disease and SLE are the influencing factors. Therefore, pregnant women should be informed before the NIPT that the fetal fraction of maternal plasma cell-free DNA may be affected by maternal autoimmune diseases.