Objective:To analyze the neurocognitive abnormalities and related emotional and behavioral problems in 410 adolescent patients with Turner syndrome (TS) managed in Henan Children′s Hospital in the past 5 years, and to explore the relationship between neurocognitive abnormalities and chromosome karyotype, pubertal development, hormone replacement therapy.Methods:A retrospective case series study.A total of 410 adolescent patients who were diagnosed with TS by karyotype or fluorescence in situ hybridization in the outpatient or inpatient Department of Endocrinology, Genetics and Metabolism at Henan Children′s Hospital from June 2018 to June 2023 were selected and divided into 2 groups according to age: < 12 years old and 12-18 years old.Neurocognitive assessments were performed based on the results of the Wechsler Intelligence Scale (4 th edition) for children and behavior scales for children, SPSS 22.0 software was used for data processing and statistical analysis, and chi-square test was used to analyze the correlation between chromosome karyotype, intelligence development level, pubertal development status, hormone therapy status and the occurrence of neuropsychiatric diseases. Results:Among the 410 TS patients, 207 cases had the karyotype of 45, X0/46, XX, accounting for 50.49%, 94 cases had the monosomic karyotype of 45, X0, accounting for 22.93%.Forty-six patients completed the Wechsler intelligence test, with the intelligence quotient (IQ) score ranging from 70 to 105, with high verbal comprehension and perceptual reasoning scores and low processing speed and working memory scores on all assessments.Fifty-two patients completed the hyperactivity scale assessment, and 43 cases had a predisposition to attention deficit hyperactivity disorder (ADHD).There were no significant differences in total IQ, perceptual reasoning and processing speed among the children with karyotype 45, X0, chimeric, and X chromosome structural abnormalities ( H=3.161, 1.955, 5.890, all P>0.05), while there were significant differences in verbal comprehension and working memory among the three groups ( H=7.697, 9.694, all P<0.05).Among TS patients 12-18 years old, 68 cases completed the depression scale self-assessment, of which 23 cases had depressive tendencies.There was no correlation between depressive tendency and chromosome karyotype, pubertal development and hormone replacement therapy ( P>0.05). Conclusions:TS patients generally have low intelligence levels and tend to have ADHD in childhood.TS patients in the pubertal development have a high incidence of depression.Pubertal development status and hormone replacement therapy show no correlation with the occurrence of neuropsychiatric diseases in TS patients.

The correlation between hearing loss (HL) and physical performance in patients receiving maintenance hemodialysis (MHD) remains poorly investigated. This study explored the association between HL and physical performance in patients on MHD. Methods: This multicenter cross-sectional study was conducted between July 2020 and April 2021 in seven hemodialysis centers in Shanghai and Suzhou, China. The hearing assessment was performed using pure-tone average (PTA). Physical performance was assessed using the Timed Up and Go Test (TUGT), handgrip strength, and gait speed. Results: Finally, 838 adult patients (male, 516 [61.6%]; 61.2 ± 2.6 years) were enrolled. Among them, 423 (50.5%) had mild to profound HL (male, 48.6% and female, 53.4%). Patients with HL had poorer physical performance than patients without HL (p < 0.001). TUGT was positively correlated with PTA (r = 0.265, p < 0.001), while handgrip strength and gait speed were negatively correlated with PTA (r = –0.356, p < 0.001 and r = –0.342, p < 0.001, respectively). Physical performance in patients aged <60 years showed significant dose-response relationships with HL. After adjusting for confounders, the odds ratios (95% confidence intervals) for HL across the TUGT quartiles (lowest to highest) were 1.00 (reference), 1.15 (0.73–1.81), 1.69 (1.07–2.70), and 2.87 (1.69–4.88) (p for trend = 0.005). Conclusion: Lower prevalence of HL was associated with a faster TUGT and a stronger handgrip strength in patients on MHD.

Objective:To investigate the RHD genotypes of RhD-negative pregnant women and explore the optimum strategy for fetal RHD screening among this population in the region. Methods:This prospective study recruited 33 cases of RhD-negative singleton pregnancies at ≥12 weeks of gestation in Nanjing Drum Tower Hospital from March to November 2021. On the basis of RHD genotyping, quantitative real-time polymerase chain reaction (PCR) was used to amplify the exons 5 and 10 of RHD gene in the circulating cell-free DNA of RhD-negative pregnant women harboring whole RHD gene deletion and RHD-CE(2-9)- D. High-throughput sequencing was performed to detect chr1:25648453 locus from circulating cell-free DNA in plasma of RhD-negative pregnant women harboring RHD 1227A mutation to screen the fetal RhD blood group. Neonatal umbilical cord blood samples were collected for verifying fetal RHD genotyping. Descriptive statistical analysis was used. Results:Whole RHD gene deletion homozygous genotype ( n=20, 60.6%), RHD-CE(2-9) -D/whole RHD gene deletion heterozygous genotype ( n=5, 21.2%), RHD 1227A/whole RHD gene deletion heterozygous genotype ( n=7, 15.2%) and RHD 711delC/whole RHD gene deletion heterozygous genotype ( n=1) were identified in the 33 RhD-negative pregnant women. In the 25 cases with whole RHD gene deletion homozygous genotype or RHD-CE(2-9)- D/whole RHD gene deletion heterozygous genotype, 22 fetuses were RhD-positive and three were RhD-negative based on prenatal screening, which were confirmed by the neonatal serological test results after birth. In the seven cases carrying RHD 1227A/whole RHD gene deletion heterozygous genotype, all fetuses were RhD-positive, which were consistent with the results of serological detection after delivery. The case harboring RHD 711delC/whole RHD gene deletion heterozygous genotype did not receive fetal RHD screening. Conclusions:This study suggests that whole RHD gene deletion homozygous genotype is the most common allele in RhD-negative population in this area, followed by RHD 1227A/whole RHD gene deletion heterozygous genotype and RHD- CE(2-9)- D/whole RHD gene deletion heterozygous genotype. For women with whole RHD gene deletion homozygous genotype, RHD- CE(2-9)- D, or RHD 1227A mutation, fetal RHD screening with quantitative real-time PCR and high-throughput sequencing are important for the management of RhD-negative pregnant women.

Objective To observe the effect ofintravitreal injection ofconbercept in the treatment of retinopathy of premature (ROP) and to analyze the factors related to the therapy.Methods A retrospective study.A total of 57 patients (57 eyes) with pre-threshold type 1 (30 patients,30 eyes),threshold ROP (21 patients,21 eyes) and acute aggressive posterior ROP (APROP,6 patients,6 eyes)) from premature infants by retinal screening in Henan Provincial People's Hospital during October 2017 and June 2018 were enrolled in this study.All children were received routinely intravitreal injected 10 mg/ml conbercept 0.025 ml (0.25 mg) within 24 hours after diagnosis.Fundus examination was performed 7 days after injection.The interval of examination was 1-3 weeks according to fundus conditions.The mean follow-up was 30.1 ± 4.6 weeks.For patients with relapse or no response to treatment,repeated intravitreal injection of conbercept or laser photocoagulation therapy was given.The retinal blood vessels of the affected eyes were observed.Logistic stepwise regression analysis was used for the correlation test of multiple factors.Results Among 57 eyes,49eyes and 8 eyes were treated with 1 or 2 times of intravitreal injection of conbercept.After 24 weeks of treatment,in 57 eyes,26 eyes were cured (45.6％),22 eyes improved (38.6％),8 eyes relapsed (14.0％),and 1 eye aggravated (1.8％).The recurrence time was 12.9± 4.5 weeks after the first injection,and the corrected gestational age was 49.0±6.7 weeks.There were significant differences in initial injection time,lesion range among the cure,improved and recurrence eyes (F=5.124,7.122;P＜0.01,＜ 0.01).Parameters of ROP condition,including ROP diagnosis (pre-threshold type 1,threshold and APROP),zone (zone 1 and 2),stage (stage 2 and 3) and plus lesions,were significant different among the cure,improved and recurrence eyes (x2=l 1.784,14.100,6.896,9.935;P＜0.01,＜0.01,＜0.05,＜0.01).Logistic stepwise regression analysis showed that the recurrence rate was correlated with ROP zone,more likely recurrence at zone 1 than zone 2 (Wald=9.879,OR=27.333,P=0.002).No injection-related complications such as endophthalmitis,cataract and glaucoma were found during treatment and follow-up period.Conclusions Intravitreal injection ofconbercept is effective in the treatment of ROP without obvious adverse reactions.Lesion zoning is associated with recurrence after treatment.

A "general-special integrated" prevention and treatment model for chronic obstructive pulmonary disease (COPD) patients in the community was preliminarily established with the joint effets of specialists from the terital hospital and general practitioners in the community health service center.During the implementation of the model the general practitioners recieved research training and participanted in the research project of COPD management;and the "general-special integrated" outpatient clinic greatly improved the management for COPD patients.Since the establishment of the model,the number of acute attacks of COPD patients was decreased,and the proportion of standardized medication was increased.The model also improved the research ability and clinical competency of general practitioners.The established model provides experiences for the tiered-management for COPD patients in the community.

Here, we aimed to study the effect of the forkhead box O1-insulin receptor substrate 2 (FOXO1-IRS2) gene interaction and the FOXO1 and IRS2 genes-environment interaction for the risk of type 2 diabetes mellitus (T2DM) in a Chinese Han population. We genotyped 7 polymorphism sites of FOXO1 gene and IRS2 gene in 780 unrelated Chinese Han people (474 cases of T2DM, 306 cases of healthy control). The risk of T2DM in individuals with AA genotype for rs7986407 and CC genotype for rs4581585 in FOXO1 gene was 2.092 and 2.57 times higher than that with GG genotype (odds ratio [OR] = 2.092; 95% confidence interval [CI] = 1.178–3.731; P = 0.011) and TT genotype (OR = 2.571; 95% CI = 1.404–4.695; P = 0.002), respectively. The risk of T2DM in individuals with GG genotype for Gly1057Asp in IRS2 gene was 1.42 times higher than that with AA genotype (OR = 1.422; 95% CI = 1.037–1.949; P = 0.029). The other 4 single nucleotide polymorphisms (SNPs) had no significant association with T2DM (P > 0.05). Multifactor dimensionality reduction (MDR) analysis showed that the interaction between SNPs rs7986407 and rs4325426 in FOXO1 gene and waist was the best model confirmed by interaction analysis, closely associating with T2DM. There was an increased risk for T2DM in the case of non-obesity with genotype combined AA/CC, AA/AC or AG/AA for rs7986407 and rs4325426, and obesity with genotype AA for rs7986407 or AA for rs4325426 (OR = 3.976; 95% CI = 1.156–13.675; P value from sign test [P(sign)] = 0.025; P value from permutation test [P(perm)] = 0.000–0.001). Together, this study indicates an association of FOXO1 and IRS2 gene polymorphisms with T2DM in Chinese Han population, supporting FOXO1-obesity interaction as a key factor for the risk of T2DM.
Asian Continental Ancestry Group* ; Diabetes Mellitus, Type 2* ; Genotype ; Humans ; Multifactor Dimensionality Reduction ; Obesity ; Polymorphism, Single Nucleotide

Objective To investigate the safety of trial of labor after cesarean (TOLAC) and clinical factors associated with successful TOLAC and to compare TOLAC with elective repeat caesarean section (ERCS) in terms of obstetric and neonatal outcomes.Methods A prospective cohort study was conducted among gravidas who had a history of lower segment cesarean section and were hospitalized in the Department of Obstetrics and Gynecology,the Affiliated Drum Tower Hospital of Medical School of Nanjing University from January to December 2014.Exclusion criteria included indications for caesarean section (such as placenta previa,placenta accreta,twin pregnancy,breech presentation and severe preeclampsia),serious maternal complications after cesarean section,lower uterine segment thinner than 3 mm and poor healing of uterine incision.Totally,287 gravidas were enrolled.Among them,142 chose TOLAC and the other 145 requested ERCS.Clinical data of those gravidas were collected and statistically analyzed by t-test,Log-rank test,Chi-square or Fisher's exact test.Results (1) The success rate of TOLAC was 90.8％ (129/142).There was no significant difference in maternal age,gestational age,thickness of lower uterine segment,interval between the two deliveries and neonatal birth weight and asphyxia rate between the successful (n=129) and unsuccessful (n=13) groups (all P＞0.05).Although the two groups had no significant difference in postpartum hemorrhage (PPH) rate,the gravidas who failed in TOLAC lost more blood than those who succeeded [425 (195-675) vs 200 (50-1 400) ml,P＜0.05].Moreover,higher amniotic fluid contamination rate was observed in the unsuccessful group [6/13 vs 17.1％ (22/129),P＜0.05].In the TOLAC group,99.3％ (141/142) were under continuous fetal heart rate monitoring.Incomplete uterine rupture occurred in one women without serious maternal or neonatal outcomes.The reasons for 13 failed TOLAC cases were unbearable pain during labor,abnormal labor,fetal distress and threatened rupture of uterus.(2) Compared with the ERCS group,the TOLAC group showed shorter interval from last cesarean section to the indexed delivery[5 (2-18) vs 6 (2-19) years],younger maternal age [(31±4) vs (33 ±4) years old] and less blood loss [200 (50-1 400) vs 300 (100-1 500) ml] (all P＜0.05).Conclusion Our study shows that,those who preferred TOLAC were younger,or had shorter pregnancy interval from last cesarean section.The success rate of TOLAC is high for women undergoing systematic prenatal assessment and close management during labor with less blood loss and non-serious maternal and neonatal complications compared with ERCS.

As the nerve regeneration has been researched more and more, nerve regeneration related signaling pathways after spinal cord injury (SCI) comes into the view. Inhibiting apoptosis signaling pathways may reduce the apoptosis, inflammation and nerve degenera-tion after SCI. Mitogen activated protein kinase (MAPK) signaling pathway plays an important role in regulation of gene expression, cell proliferation and apoptosis, and there was interaction among the four subordinate pathways. Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway does not only participate in the body cell survival, proliferation, differentiation and apoptosis, but also in the process of inflammatory and oxidative stress in the body. It has been found that blocking the Wnt signaling pathway after inju-ry in the central nervous system would inhibit neural axon regeneration. Exogenous Wnt3a can increase the number of neurons after SCI and promote the axon conduction and nerve function. Inhibiting mammalian target of rapamycin (mTOR) signaling pathway after SCI can signif-icantly reduce neuronal loss, cell death and well promote the functional recovery. When Notch signaling pathways are activated, neural stem cells proliferate actively and differentiation are inhibited, and stem cells enter the stage of differentiation as the pathway inhibited. Activa-tion of Ras homolog gene/Rho associated coiled coil forming protein kinase (Rho/ROCK) signaling pathways leads to the collapse of the growth cone, inhibition of axon regeneration, whereas the selective inhibition of Rho can promote axon regeneration and recovery of motor function after SCI.

Aim Paclitaxel(PTX)has shown an effect against human cancer. However, serious drawbacks hamper PTX clinical use.Overcoming paclitaxel limi-tations is one of the best approaches to enhance water solubility.Methods In this study,water-soluble pa-clitaxel prodrug was prepared,folic acid-polyethylene glycol-glutamic-paclitaxel (FA-PEG-Glu-PTX ) com-posed of folic acid (FA,target),amino acids (Glu, linker),and polyethylene glycol(PEG)in order to im-prove the solubilization and stability. The chemical structure and physicochemical property of prodrug were measured by LC-MS,solubility,drug release rate to e-valuate the antitumor activity and cytotoxicity of FA-PEG-Glu-PTX.MTT assays were conducted on MDA-MB-231,MCF-7,A549 and HELF cell lines.FA-PEG-Glu-PTX prodrugs were labeled with 5 amino flu-orescence visible fluorescent dye (5 AF ) for fluores-cence microscopy.Results The successful conjugation of FA-PEG-Glu-PTX was confirmed by LC-MS,and had better water solubility,release rate curve.In vitro studies indicated that foliate receptor(FR-α)mediated uptake of PTX-conjugated multi-small molecules carri-ers induced highly targeting ability,and antitumor ac-tivity,as well as reduced side toxicity effects of PTX. Conclusion FA-PEG-Glu-PTX has a good antitumor activity.

Objective To explore the effect of Governor Vessel electroacupuncture in different time points on motor function and p75 neurotrophin receptor (p75NTR) after spinal cord injury. Methods A total of 180 adult male Sprague-Dawley rats were randomly divided into three groups (one day, three days and seven days after modeling), and each group was divided into normal control group, normal electroacupuncture group, sham operation group, model group and Governor Vessel electroacupuncture group with 12 cases in each group. The spinal cord injury model was established with the modified Allen's method. The normal electroacupuncture group and the Governor Vessel electroacupuncture group received electroacupuncture on Dazhui (DU14) and Mingmeng (DU04) acupoints. Basso-Beattic-Bresnahan (BBB) Scale was performed to assess the motor function of rats. The expression of p75NTR was detected with Western blotting. Results The BBB score of the model group and the Governor Vessel electroacupuncture group were significantly lower than that of the other three groups. The BBB score was significantly higher in the Governor Vessel electroacupuncture group than in the model group seven days after intervention (t=-4.510, P<0.001). The expression of p75NTR was siginificantly lower in the Governor Vessel electroacupuncture group than in the model group (P<0.01). Conclusion The expression of p75NTR increased after spinal cord injury. Governor Vessel electroacupuncture could improve the motor function, and inhibit the p75NTR expression of damaged spinal cord tissues.