ObjectiveTo evaluate the pregnancy outcomes of assisted reproductive technology （ART） in women with a history of thyroid cancer who retained fertility intentions after completing cancer treatment. MethodsA retrospective analysis was performed on 61 patients with a history of thyroid cancer who underwent in vitro fertilization/intracytoplasmic sperm microinjection and embryo transfer （IVF/ICSI-ET）. These patients were included as the case group. A total of 122 non-cancer patients who received ART during the same period were selected as the control group using 1∶2 matching based on age and oocyte retrieval time. Baseline characteristics， outcomes of the first ART cycle， and cumulative pregnancy outcomes were compared between the two groups. ResultsThere was no significant difference in the basic data， the total amount of gonadotropin （Gn） and the days of use between the case group and the control group （P>0.05）. However， the case group had significantly fewer retrieved oocytes， mature oocytes （MII）， lower fertilization and cleavage rates， and fewer transferable and high-quality embryos， as well as fewer embryos transferred during the first cycle （P < 0.05）. However， there was no significant difference in the rate of first embryo implantation and first clinical pregnancy between the two groups （P>0.05）. In the analysis of cumulative outcomes， the two groups did not show statistically significant differences in the cumulative pregnancy rate， clinical pregnancy rate per transfer cycle， the number of oocyte retrieval cycles required per live birth， the number of embryo transfer cycles required per live birth， and the number of embryos used for each live birth （P>0.05）. However， the cumulative live birth rate was significantly lower in the case group compared to the control group （P=0.005）. ConclusionAfter treatment for thyroid cancer， when ART is used to help pregnant women， the pregnancy outcome is comparable to that of women without tumors. Individualized reproductive management and timely fertility preservation strategies are recommended to optimize reproductive outcomes in this population.

Objective:To explore the genetic etiology of two fetuses with Mosaic variegated aneuploidy syndrome (MVA) in a pedigree.Methods:A 30-year-old pregnant woman, who presented at the Center for Medical Genetics and Prenatal Diagnosis of Shandong Maternal and Child Health Care Hospital on November 16, 2023, was enrolled. Clinical data of the pedigree were collected, and peripheral blood samples from the parents and amniotic fluid samples from the two fetuses were obtained for genomic DNA extraction. Whole exome sequencing (WES) was performed on both fetuses, followed by Sanger sequencing for familial validation and pathogenicity analysis of candidate variants. Chromosomal karyotyping of the parents was conducted to quantify the proportion of premature chromatid separation (PCS). This study was approved by the Medical Ethics Committee of Shandong Maternal and Child Health Care Hospital (Ethics No. 2024-034).Results:① Both fetuses exhibited structural brain anomalies and developmental delays during the second trimester. Amniocyte karyotyping revealed low-level mosaic aneuploidy involving multiple chromosomes, while chromosomal microarray analysis (CMA) showed no abnormalities. Pregnancy termination was performed for fetus 1. ② WES identified compound heterozygous variants in BUB1B — c. 2363_2364del (p.S788Cfs*29) and ss804270619: G>A — in both fetuses. Sanger sequencing confirmed paternal inheritance of c. 2363_2364del and maternal inheritance of ss804270619: G>A. According to the American College of Medical Genetics and Genomics (ACMG) and Clinical Genome Resource(ClinGen) Standards and Guidelines for the Interpretation of Sequence Variants, the c. 2363_2364del variant was classified as likely pathogenic (PVS1 + PM2_Supporting). Parental karyotyping demonstrated PCS traits, with a higher proportion of abnormal metaphases in the father. Conclusion:The compound heterozygous variants c. 2363_2364del (p.S788Cfs*29) and ss804270619: G>A in BUB1B may constitute the genetic etiology of the two MVA fetuses in this pedigree.

Objective To screen antidepressant-active compounds from Polygonati Rhizoma and explore their effects and possible mechanisms against depression induced by simulated weightlessness.Methods A systems pharmacology approach was used to screen potential antidepressant-active compounds and their targets from Polygonati Rhizoma.The hindlimb unloading(HLU)rat model was employed for the study.Twenty-four healthy male Sprague-Dawley rats were randomly divided into three groups:control group(administered 0.5%carboxymethylcellulose by gavage),HLU group(hindlimb unloading),and HLU+treatment group(hindlimb unloading+active compound gavage),with 8 rats in each group.After 28 days of hindlimb unloading,depressive-like behaviors in rats were evaluated using the forced swimming test and tail suspension test.Hippocampal morphology was examined with H&E staining,and GO and KEGG enrichment analyses were conducted on the targets of active compounds.Results A total of 38 active compounds were screened from Polygonati Rhizoma,among which apigenin had an oral bioavailability of 23.06%and a drug-likeness score of 0.21.Compound-target network analysis indicated that apigenin had the highest degree and betweenness centrality values,suggesting it might be the key active component with antidepressant potential in Polygonati Rhizoma.In the forced swimming and tail suspension tests,rats in the HLU group showed a significant increase in immobility time compared to the control group,indicating successful establishment of the depression model.However,compared to the HLU group,rats in the HLU plus apigenin group exhibited significantly reduced immobility time.The H&E staining results of hippocampal tissue showed a significant reduction in the number of hippocampal neurons,along with numerous shrunken neurons and small vacuoles in nerve fibers in the HLU group.In contrast,the treatment group exhibited an increased number of hippocampal neurons,with improved cellular morphology.Target enrichment analysis indicated that apigenin targets were mainly involved in the regulation of apoptosis and cancer-related signaling pathways.Conclusion Apigenin significantly improved depressive-like behaviors in rats subjected to hindlimb unloading,and it has a protective effect on hippocampal tissue.It may provide a new natural active compound for the treatment of depression caused by spaceflight-induced weightlessness.

OBJECTIVE: To explore the genetic etiology of two fetuses with Mosaic variegated aneuploidy syndrome (MVA) in a pedigree. METHODS: A 30-year-old pregnant woman, who presented at the Center for Medical Genetics and Prenatal Diagnosis of Shandong Maternal and Child Health Care Hospital on November 16, 2023, was enrolled. Clinical data of the pedigree were collected, and peripheral blood samples from the parents and amniotic fluid samples from the two fetuses were obtained for genomic DNA extraction. Whole exome sequencing (WES) was performed on both fetuses, followed by Sanger sequencing for familial validation and pathogenicity analysis of candidate variants. Chromosomal karyotyping of the parents was conducted to quantify the proportion of premature chromatid separation (PCS). This study was approved by the Medical Ethics Committee of Shandong Maternal and Child Health Care Hospital (Ethics No. 2024-034). RESULTS: Both fetuses exhibited structural brain anomalies and developmental delays during the second trimester. Amniocyte karyotyping revealed low-level mosaic aneuploidy involving multiple chromosomes, while chromosomal microarray analysis (CMA) showed no abnormalities. Pregnancy termination was performed for fetus 1. WES identified compound heterozygous variants in BUB1B, i.e., c.2363_2364del (p.S788Cfs*29) and ss804270619: G>A, in both fetuses. Sanger sequencing confirmed paternal inheritance of c.2363_2364del and maternal inheritance of ss804270619:G>A. According to the American College of Medical Genetics and Genomics (ACMG) and Clinical Genome Resource (ClinGen) Standards and Guidelines for the Interpretation of Sequence Variants, the c.2363_2364del variant was classified as likely pathogenic (PVS1 + PM2_Supporting). Parental karyotyping demonstrated PCS traits, with a higher proportion of abnormal metaphases in the father. CONCLUSION The compound heterozygous variants c.2363_2364del (p.S788Cfs*29) and ss804270619: G>A in BUB1B may constitute the genetic etiology of the two MVA fetuses in this pedigree.
Humans ; Female ; Pregnancy ; Adult ; Mosaicism ; Protein Serine-Threonine Kinases/genetics* ; Chromosome Disorders/diagnosis* ; Pedigree ; Heterozygote ; Prenatal Diagnosis ; Aneuploidy ; Male ; Fetus ; Karyotyping

Objective:To observe changes in intestinal flora in children with anorexia and the effects of pediatric Tuina(Chinese therapeutic massage)on their intestinal flora,and to explore the relationship between alterations in intestinal flora and anorexia,as well as the therapeutic mechanisms of pediatric Tuina in treating children with anorexia.Methods:A total of 60 healthy children who underwent physical examinations were recruited as the blank group.One hundred and twenty children with anorexia were randomly divided into a Tuina group and a medication group,with 60 children in each group,according to the random number table method.The blank group received no intervention;the Tuina group was treated with pediatric Tuina therapy;the medication group was treated with Jian Wei Xiao Shi(stomach-invigorating and digestion-promoting)tablets.Both groups underwent continuous treatment for 7 d as one course,with a 1-day rest period between courses,for a total of 4 courses.Fecal samples were collected from the three groups.The intestinal flora was detected using the 16S rDNA method.Results:Before treatment,compared to the blank group,the abundance of Firmicutes in the Tuina and medication groups was significantly lower(P<0.05).After treatment,the abundance of Firmicutes in the Tuina group was significantly increased compared to before treatment(P<0.05),with no significant difference compared to the blank group(P>0.05);in the medication group,there was a trend of increased abundance of Firmicutes,but there was no significant difference compared to that before treatment in the same group(P>0.05),and the difference compared to the blank group remained significant(P<0.05).Before treatment,compared to the blank group,the abundance of Faecalibacterium prausnitzii(F.prausnitzii)in the Tuina and medication groups was significantly lower(P<0.05).After treatment,the abundance of F.prausnitzii in the Tuina group was significantly increased compared to before treatment(P<0.05),with no significant difference compared to the blank group(P>0.05);in the medication group,there was a trend of increased abundance of F.prausnitzii,but no significant difference was showed compared to before treatment in the same group(P>0.05),and the differences compared to the blank and Tuina groups were significant(P<0.05).Before treatment,compared to the blank group,the abundance of Eubacterium in the Tuina and medication groups was significantly lower(P<0.05);after treatment,the abundance of Eubacterium in both Tuina and medication groups was significantly increased compared to that before treatment(P<0.05),with no significant difference compared to the blank group(P>0.05).Before treatment,compared to the blank group,the abundance of Roseburia in the Tuina and medication groups was significantly lower(P<0.05);after treatment,the abundance of Roseburia in both Tuina and medication groups was significantly increased compared to that before treatment(P<0.05),with no significant difference compared to the blank group(P>0.05).Conclusion:The reduction of beneficial intestinal flora may be involved in the pathogenesis of pediatric anorexia.Pediatric Tuina can promote the recovery of intestinal flora balance by increasing the abundance of beneficial flora.

Objective:To explore the genetic etiology of two fetuses with Mosaic variegated aneuploidy syndrome (MVA) in a pedigree.Methods:A 30-year-old pregnant woman, who presented at the Center for Medical Genetics and Prenatal Diagnosis of Shandong Maternal and Child Health Care Hospital on November 16, 2023, was enrolled. Clinical data of the pedigree were collected, and peripheral blood samples from the parents and amniotic fluid samples from the two fetuses were obtained for genomic DNA extraction. Whole exome sequencing (WES) was performed on both fetuses, followed by Sanger sequencing for familial validation and pathogenicity analysis of candidate variants. Chromosomal karyotyping of the parents was conducted to quantify the proportion of premature chromatid separation (PCS). This study was approved by the Medical Ethics Committee of Shandong Maternal and Child Health Care Hospital (Ethics No. 2024-034).Results:① Both fetuses exhibited structural brain anomalies and developmental delays during the second trimester. Amniocyte karyotyping revealed low-level mosaic aneuploidy involving multiple chromosomes, while chromosomal microarray analysis (CMA) showed no abnormalities. Pregnancy termination was performed for fetus 1. ② WES identified compound heterozygous variants in BUB1B — c. 2363_2364del (p.S788Cfs*29) and ss804270619: G>A — in both fetuses. Sanger sequencing confirmed paternal inheritance of c. 2363_2364del and maternal inheritance of ss804270619: G>A. According to the American College of Medical Genetics and Genomics (ACMG) and Clinical Genome Resource(ClinGen) Standards and Guidelines for the Interpretation of Sequence Variants, the c. 2363_2364del variant was classified as likely pathogenic (PVS1 + PM2_Supporting). Parental karyotyping demonstrated PCS traits, with a higher proportion of abnormal metaphases in the father. Conclusion:The compound heterozygous variants c. 2363_2364del (p.S788Cfs*29) and ss804270619: G>A in BUB1B may constitute the genetic etiology of the two MVA fetuses in this pedigree.

Objective To elucidate the expression characteristics of the NUAK family SNF1-like kinase 2(NUAK2)in ovarian serous carcinoma and determine its regulatory roles in cell proliferation and apoptosis.Methods Fifty-seven patients with ovarian serous car-cinoma(observation group)and 57 patients with ovarian serous cystadenoma(control group)were selected from June 2019 to December 2022.The GEPIA database was used to assess the expression patterns of NUAK2 in ovarian serous carcinoma.Immunohistochemistry was used to detect the expression of NUAK2,proliferating cell nuclear antigen(PCNA),and B-cell lymphoma-associated X antigen(BAX).Western blotting was performed to evaluate the expression of NUAK2 in the human ovarian serous carcinoma cell lines(SKOV3)and the human ovarian surface epithelial cell lines(HOSEpiC).SKOV3 cells were transfected with the siRNA-NUAK2 plasmid to establish the si-NUAK2 group,or with the empty transfection vector(EV)or a blank solution(NC)to establish control groups.Western blotting was sub-sequently used to detect the expression of NUAK2,PCNA,and BAX.The CCK-8 method was used to assess cell proliferation activity,and flow cytometry was used to quantify apoptosis.Results The GEPIA database analysis showed a significant increasing trend in the expres-sion of NUAK2 in ovarian cancer(P<0.05).Immunohistochemical analysis revealed a significantly higher NUAK2 positive rate in ovarian serous carcinoma tissue than that in the control group.Moreover,significant differences in the expression of NUAK2 were observed across different lesion grades and maximum tumor diameters(P<0.05).A significant positive correlation was found between NUAK2 and PCNA(P<0.05),whereas a significant negative correlation was observed between NUAK2 and BAX(P<0.05)in ovarian serous carcinoma.In vitro cell culture experiments showed that the expression level of NUAK2 was significantly higher in SKOV3 cells than that in HOSEpiC cells(P<0.05).The si-NUAK2 group exhibited significantly lower cell proliferation activity and PCNA expression and significantly higher apoptosis rate and BAX expression than those in the EV and NC groups(P<0.05).Conclusion NUAK2 is overexpressed in ovarian serous carcinoma and promotes tumor progression by enhancing cell proliferation and suppressing apoptosis.

Objective:To develop and validate risk prediction models for hypertension comorbidity in community-dwelling patients with type 2 diabetes mellitus(T2DM).Methods:The health records of 2 979 T2DM patients from two community health service centers in Fengtai District of Beijing from January 2023 to January 2024 were collected,including 2 591 cases from Fangzhuang Center(model development group) and 388 cases from Youanmen Center(external validation group). Patients in model development group were randomly assigned in a training set( n=1 813) and an internal validation set(778 cases) at a ratio of 7∶3. The risk factors associated with hypertention comorbidity in T2DM patients were identified with LASSO regression analysis,based on which risk prediction models was developed using six machine learning algorithms,including logistic regression(LR),classification and regression tree(CART),random forest(RF),extreme gradient boosting(XGB),support vector machine(SVM) and artificial neural network(ANN). The internal and external validations of the prediction models were conducted. Results:Among 2 979 patients with T2DM,2 158(72.44%) had concurrent hypertension,with 1 572 in the development set,280 in the internal validation set,306 in the external validation set. The LASSO regression identified 14 risk factors: age,educational level,occupation,medical insurance type,alcohol consumption,exercise frequency,BMI,SBP,TG/HDL-C,METS-IR,FBG,eGFR,duration of T2DM,and dyslipidemia. The nomogram model based on 14 predictive factors was constructed with XGB algorithm showed the best performance in predicting risk of hypertention for T2DM patients,showing the highest area under the curve(AUC) of 0.694(95% CI: 0.524-0.810) and effective calibration(Brier Score=0.121). Decision curve analysis confirmed the clinical utility of the predictive model. Conclusion:The risk prediction models based on machine learning algorithms have been developed in the study,which show good prediction perfomance for hiypertention comorbidity in community-dwelling T2DM patients.

Background Previous studies have demonstrated that the vagus nerve stimulation improves upper limb function in patients with stroke sequelae(six month-two years).This study aimed to investigate whether the auricular intradermal acupuncture(AIA)acted on the auricular branch of the vagus nerve can facilitate the recovery of upper limb motor function and expedite the effects and characteristics of rehabilitation processes in flaccid phase after stroke in Phase Brunnstrom Ⅰ.Methods This study utilized a randomized controlled single-blinded clinical design.Patients with ischemic stroke in Phase Brunnstrom Ⅰ were randomly assigned to the auricular intradermal acupuncture(AIA)group(AIA,standard rehabilitation,conventional acupuncture)or the sham auricular intradermal acupuncture(sham AIA)group(the sham AIA,standard rehabilitation,conventional acupuncture)for 6 days of 1 week(6 times).Primary outcome measures:Brunnstrom(Ueda Assessment),Fugl-Meyer assessment of the upper extremity(FMA-UE)and its subtype score(FMA-UEFS,FMA-UEES),Wolf motor function test scale(WMFT).Secondary outcome measures:Upper limb active range of joint motion(AROM),manual muscle test(MMT)of upper limb muscles,Barthel index(BI).Results Of the 332 patients who were screened,70 patients met the criteria and were recruited.There were 35 patients in the AIA group,1 patient was fall off,34 patients were actually completed;35 patients in the sham AIA group had no falling off case.Primary outcome measures:The upper Ueda assessment of the AIA group were better than those of the sham AIA group after treatment on days 3 and 6(P<0.05,P<0.001,respectively).The FMA-UEFS score on days 6 of the AIA group were significantly better than those of the sham AIA group(P<0.05).FMA-UEES of the AIA group was more associated with FMA-UE than FMA-UEFS with FMA-UE after treatment on day 6(FMA-UEFS:r=0.728,P<0.001;FMA-UEES:r=0.744,P<0.001).After 3 days and 6 days of treatment,the AIA group of the WMFT were significantly improved in the sham AIA group(P<0.05,P<0.001,respectively).Secondary outcome measures:AROM:After 6 days of treatment,the AIA group of shoulder abduction were more improved than in the sham AIA group(P<0.05).MMT:The muscle strength of elbow flexion,and elbow extension muscle improved more in the AIA group than in the sham AIA group(P<0.05).Barthel index(BI):After 6 days of treatment,there was a significant improvement in the group compared with before treatment(P<0.05),but no difference compared with the group(P>0.05).Conclusions AIA combined with conventional rehabilitation and acupuncture,can effectively improve the upper limb motor function of patients with post-ischemic stroke flaccid hemiplegia and accelerates the rehabilitation process of upper limb motor function.Clinical Trial Registration The study protocol is registered withhttp://www.chictr.org.cn(accession number:ChiCTR2200058141).

Objective:To investigate the feasibility and effectiveness of robot-assisted surgery in children with cholangiectasis under 3 months of age.Methods:This is a retrospective cohort study. The clinical data of 53 children with cholangiectasis under 3 months admitted to Department of General Surgery of Children′s Hospital Affiliated to Zhejiang University School of Medicine from April 2019 to December 2024 were included retrospectively. According to the surgical method, the patients were divided into robot-assisted surgery(RAS) group(5 males, 24 females, age ( M(IQR)) 49.0(36.0)days (range: 19.0 to 90.0 days), weight 5.00(1.65)kg (range: 3.40 to 7.50 kg)) and laparoscopic-assisted surgery(LAS) group (5 males, 19 females, age 55.5(27.3)days (range: 18.0 to 87.0 days), weight 4.90 (1.62)kg (range: 3.50 to 6.20 kg)). Nineteen cases in each group were prenatally diagnosed. Data were statistically analyzed using the Mann-Whitney U test and the Pearson χ 2 test, respectively. Results:No statistically significant differences were observed between the two groups in age, sex, weight, or preoperative biochemical indices(all P>0.05). All procedures were successfully completed without conversion to open surgery. Postoperative biochemical indices, fasting duration, cyst diameter, operative time, drainage tube retention time, and follow-up duration showed no significant differences between the groups(all P>0.05). Compared to the LAS group, the RAS group demonstrated significantly shorter postoperative hospital stays (9.0(5.0)days (range:7.0 to 18.0 days) vs. 11.5(5.5)days (range:7.0 to 38.0 days), U=236.5, P=0.044) and hepaticojejunostomy time (15.0(3.5)minutes (range:11.0 to 22.0 minutes) vs. 18.0(3.0)minutes (range:13.0 to 25.0 minutes), U=144.5, P=0.001). However, the RAS group incurred higher surgical costs (78 099.9(10 100.1)yuan (range: 72 148.7 to 112 898.6 yuan) vs. 30 158.6(15 283.1)yuan (range: 25 041.7 to 107 673.1 yuan), U=41.0, P<0.01). In the LAS group, 3 patients developed anastomotic leakage requiring reoperation, while the RAS group had 1 case of anastomotic stenosis 2 years postoperatively (received second hepaticojejunostomy) and 1 case of incision infection(received incision debridement and dressing of the abscess). Conclusion:Robot-assisted surgery can be used to treat children with cholangiectasis under 3 months of age and may achieve good results.