Objective:To explore the clinical application of preimplantation genetic testing for monogenic disorders (PGT-M) in an unique case with Spinal muscular atrophy (SMA) type 2+ 0.Methods:A special SMA family presented at the Third Affiliated Hospital of Guangzhou Medical University on October 19, 2020 was selected as the study subject. Multiple ligation-dependent probe amplification (MLPA) and molecular tagging linkage analysis were carried out to identify the SMN1 genotype of the couple and their fetus. Subsequently, next-generation sequencing (NGS), molecular tagging linkage analysis, and chromosomal microarray analysis were employed to determine the haplotypes and validate the result of PGT-M on the 11 embryos derived for the couple. Results:The female partner was identified as a carrier of the rare SMN1[2+ 0] variant, and prenatal diagnosis confirmed the fetus to be affected by SMA. Ultimately, PGT-M has successfully selected four embryos free from the pathogenic SMN1 variants and X chromosome deletion. Conclusion:PGT-M can effectively prevent the transmission of rare genetic variants such as the SMA 2+ 0 subtype in the families. Above finding has provided guidance for genetic counseling and family planning for the couple.

Objective To explore the difference in left ventricular reverse remodeling(LVRR)between coarctation of aorta(CoA)complicated by bicuspid aortic valve(BAV)and that by tricuspid aortic valve(TAV)after percutaneous intervention.Methods The clinical data on 47 patients undergoing percutaneous balloon dila-tion and stent implantation due to CoA in Fuwai Hospital of Chinese Academy of Medical Sciences from January 2014 to December 2021 were retrospectively analyzed.According to the preoperative imaging data,there were 18 patients with BAVA and 29 with TAV.The results of echocardiography before and one year after the procedure were compared.Results CoA Vmax,CoA PG,LVEDd,LVEDdi,LVM and LVMI were significantly improved in CoA patients one year after percutaneous intervention,and 23.4%of the patients developed left ventricular reverse remodeling.AV Vmax,AV PG and LVEDdi in the patients with BAV were higher than those in the TAV group(P = 0.005 and P = 0.007;P = 0.03),and the rate of left ventricular reverse remodeling in BAV patients was lower than that in TAV patients,but there was no statistical significance.Multivariate analysis did not find any influence factors affecting left ventricular reverse remodeling one year after the procedure.Conclusions Part of the CoA patients develops left ventricular remodeling reversal one year after percutaneous intervention.LVRR in patients with BAV is lower than that in those with TAV,which still needs further clinical research.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

OBJECTIVE: To compare the effectiveness between the posterolateral approach and the posterolateral combined posteromedial approaches in the treatment of Mason type 2B posterior malleolar fracture. METHODS: A retrospective analysis was performed on the clinical data of 79 patients with posterior ankle fracture who met the selection criteria between January 2015 and January 2022. There were 62 cases of Mason 2B Pilon subtype and 17 cases of avulsion subtype. Among Mason 2B Pilon subtype patients, 35 were treated with posterolateral approach (group A), 27 patients were treated with combined approach (group B). There was no significant difference in gender, age, injured side, cause of injury, time from injury to operation, preoperative hospital stay, preoperative visualanalogue scale (VAS) score, and intraoperative internal fixation between the two groups ( P>0.05). All patients with Mason 2B avulsion subtype were treated by posterolateral approach, including 7 males and 10 females, aged from 25 to 68 years, with an average of 46.1 years. The operation time, intraoperative blood loss, postoperative hospital stay, and complications were recorded. The reduction quality was evaluated by Ovadia deals radiographic score, and the ankle function and pain were evaluated by VAS score, American Orthopaedic Foot and Ankle Society (AOFAS) score, and ankle range of motion. RESULTS: Mason 2B Pilon subtype: There was no significant difference in operation time, intraoperative blood loss, postoperative hospital stay, and follow-up time between the two groups ( P>0.05). The radiological evaluation of Ovadia deals in group A was significantly worse than that in group B ( P<0.05). The VAS score in the two groups significantly improved at each time point after operation, and the VAS score and AOFAS score further improved with the extension of time after operation, and the differences were significant ( P<0.05). Except that the AOFAS score of group A was significantly lower than that of group B at last follow-up ( P<0.05), there was no significant difference in VAS score and AOFAS score between the two groups at other time points ( P>0.05). At last follow-up, the ankle range of motion in group A was significantly less than that in group B ( P<0.05). There was no significant difference in the incidence of sural nerve injury, deep tissue infection, limitation of toe movement, and traumatic ankle arthritis between the two groups ( P>0.05). Mason 2B avulsion subtype: The operation time was (119.47±20.61) minutes and the intraoperative blood loss was 50 (35, 55) mL. Seventeen patients were followed up 13-25 months, with an average of 18 months. The Ovadia deals score was excellent in 10 cases, good in 6 cases, and poor in 1 case at 1 week after operation, and the excellent and good rate was 94.1%. All fractures healed in 8-18 weeks with an average of 12.35 weeks. There were 1 case of sural nerve injury and 3 cases of traumatic ankle arthritis after operation. No deep tissue infection or limitation of toe movement occurred. The VAS score decreased significantly and AOFAS score increased significantly with time, and the differences were significant between different time points before and after operation ( P<0.05). The ankle range of motion at last follow-up was (56.71±2.47)°. CONCLUSION Compared with the posterolateral approach, the combined approach is a better choice for the treatment of Mason 2B Pilon subtype. If the posteromedial bone block does not affect the reduction of the medial malleolus, the posterolateral approach can achieve good effectiveness for Mason 2B avulsion subtype.
Female ; Humans ; Male ; Ankle Fractures/surgery* ; Arthritis/etiology* ; Fracture Fixation, Internal/adverse effects* ; Postoperative Hemorrhage ; Retrospective Studies ; Tibial Fractures/surgery* ; Treatment Outcome ; Adult ; Middle Aged ; Aged

Objective To establish a PCR-based capillary electrophoresis(PCR/CE)to detect Survival Motor Neuron 1(SMN1)and Survival Motor Neuron 2(SMN2)genes and to evaluate its performance.Methods PCR/CE and Multiplex Ligation-dependent Probe Amplification(MLPA)for SMA gene diagnosis were used to blindly test the samples in sync.The performance of PCR/CE was assessed using MLPA results as the standard.Results A total of 336 samples were included in this study,consisting of 50 homozygous deletion types(14.9%),65 heterozygous deletion types(19.3%),and 221 non-deletion types(65.8%).The results of PCR/CE for detect-ing SMN1 and SMN2 copy numbers(0,1,2,3,≥4)were in complete agreement with the results of the MLPA.Conclusions PCR/CE for gene testing related to SMA could accurately detect copy numbers of exon 7 and exon 8 of the SMN1 and SMN2 genes(0,1,2,3,≥4).

Long noncoding RNAs (lncRNAs) are expressed in different species and different tissues, and perform different functions, but little is known about their involvement in the synthesis or secretion of follicle-stimulating hormone (FSH). In general, we have revealed lncRNA‍‒‍microRNA (miRNA)‍‒‍‍messenger RNA (mRNA) interactions that may play important roles in rat primary pituitary cells. In this study, a new lncRNA was identified for the first time. First, we analyzed the gene expression of lncRNA-m18as1 in different tissues and different stages by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and observed the localization of lncRNA-m18as1 with fluorescence in situ hybridization, which indicated that this lncRNA was distributed mainly in the cytoplasm. Next, we used RT-qPCR and enzyme-linked immunosorbent assay (ELISA) to analyze the regulation of FSH synthesis and secretion after overexpression or knockdown of lncRNA-m18as1 and found that lncRNA-m18as1 was positively correlated with FSH synthesis and secretion. In addition, mothers against decapentaplegic homolog 2 (Smad2) was highly expressed in our sequencing results. We also screened miR-18a-5p from our sequencing results as a miRNA that may bind to lncRNA-m18as1 and Smad2. We used RNA immunoprecipitation-qPCR (RIP-qPCR) and/or dual luciferase assays to confirm that lncRNA-m18as1 interacted with miR-18a-5p and miR-18a-5p interacted with Smad2. Fluorescence in situ hybridization (FISH) showed that lncRNA-m18as1 and miR-18a-5p were localized mainly in the cytoplasm. Finally, we determined the relationship among lncRNA-m18as1, miR-18a-5p, and the Smad2/3 pathway. Overall, we found that lncRNA-m18as1 acts as a molecular sponge of miR-18a-5p to regulate the synthesis and secretion of FSH through the Smad2/3 pathway.
Animals ; Cell Line, Tumor ; Cell Proliferation ; Follicle Stimulating Hormone/metabolism* ; Gene Expression Regulation, Neoplastic ; In Situ Hybridization, Fluorescence ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Rats

In mammals, the piezoelectric protein, Prestin, endows the outer hair cells (OHCs) with electromotility (eM), which confers the capacity to change cellular length in response to alterations in membrane potential. Together with basilar membrane resonance and possible stereociliary motility, Prestin-based OHC eM lays the foundation for enhancing cochlear sensitivity and frequency selectivity. However, it remains debatable whether Prestin contributes to ultrahigh-frequency hearing due to the intrinsic nature of the cell's low-pass features. The low-pass property of mouse OHC eM is based on the finding that eM magnitude dissipates within the frequency bandwidth of human speech. In this study, we examined the role of Prestin in sensing broad-range frequencies (4-80 kHz) in mice that use ultrasonic hearing and vocalization (to >100 kHz) for social communication. The audiometric measurements in mice showed that ablation of Prestin did not abolish hearing at frequencies >40 kHz. Acoustic associative behavior tests confirmed that Prestin-knockout mice can learn ultrahigh-frequency sound-coupled tasks, similar to control mice. Ex vivo cochlear Ca²⁺ imaging experiments demonstrated that without Prestin, the OHCs still exhibit ultrahigh-frequency transduction, which in contrast, can be abolished by a universal cation channel blocker, Gadolinium. In vivo salicylate treatment disrupts hearing at frequencies <40 kHz but not ultrahigh-frequency hearing. By pharmacogenetic manipulation, we showed that specific ablation of the OHCs largely abolished hearing at frequencies >40 kHz. These findings demonstrate that cochlear OHCs are the target cells that support ultrahigh-frequency transduction, which does not require Prestin.
Animals ; Cochlea/metabolism* ; Hair Cells, Auditory, Outer/metabolism* ; Hearing ; Humans ; Mammals/metabolism* ; Mice ; Mice, Knockout ; Molecular Motor Proteins/metabolism*

Objective:To understand the attitude, practice status and influencing factors of obstetric medical staff on sexual health care during pregnancy, and to provide reference for carrying out sexual education and training during pregnancy.Methods:A self-designed questionnaire on attitude and practice of obstetric medical staff towards sexual health care during pregnancy was used to investigate 462 obstetric medical staff in Guangdong Province from July to August, 2021,and the influencing factors were analyzed.Results:The attitude score of sexual health care during pregnancy among obstetric medical staff was (29.87 ± 5.96) points, and the practice score was (13.61 ± 1.23) points. Profession and hospital level affected obstetric medical staff′s attitude towards sexual health care during pregnancy ( P<0.05); profession, title and hospital level affected obstetric medical staff′s practice in providing pregnancy sexual health care ( P<0.05). Conclusions:Obstetric medical staff have a negative attitude towards sexual health care during pregnancy, and their active sexual health care behaviors need to be improved. Medical schools and work units need to strengthen the training and management of obstetric-related and reproductive health knowledge and skills to promote the effectiveness of pregnancy sexual education implementation and promotion.

In the present experimental study, cecal ligation and puncture significantly increased the myocardial injury assessed in terms of excess release of creative kinase-MB (CK-MB), cardiac troponin I (cTnI), interleukin (IL)-6 and decrease of IL-10 in the blood following 12 h of laparotomy procedure as compared to normal control. Also, a significant increase in protein expression levels of high-mobility group box 1 (HMGB1) and decreased phosphorylation of glycogen synthase kinase-3β (GSK-3β) was observed in the myocardial tissue as compared to normal control. A single independent administration of telmisartan (2 and 4 mg/kg) and AR-A014418 (1 and 2 mg/kg) substantially reduced sepsis-induced myocardial injury in terms of decrease levels of CK-MB, cTnI and IL-6, HMGB1, GSK-3β and increase in IL-10 and p-GSK-3β in the blood in sepsis- subjected rats. The effects of telmisartan at dose 4 mg/kg and AR-A014418 at a dose of 2 mg/kg were significantly higher than the telmisartan at a dose of 2 mg/kg and AR-A014418 1 mg/kg respectively. Further, no significant effects on different parameters were observed in the sham control group in comparison to normal. Therefore it is plausible to suggest that sepsis may increase the levels of angiotensin II to trigger GSK-3β-dependent signaling to activate the HMGB1/receptors for advanced glycation end products, which may promote inflammation and myocardial injury in sepsis-subjected rats.

In the present experimental study, cecal ligation and puncture significantly increased the myocardial injury assessed in terms of excess release of creative kinase-MB (CK-MB), cardiac troponin I (cTnI), interleukin (IL)-6 and decrease of IL-10 in the blood following 12 h of laparotomy procedure as compared to normal control. Also, a significant increase in protein expression levels of high-mobility group box 1 (HMGB1) and decreased phosphorylation of glycogen synthase kinase-3β (GSK-3β) was observed in the myocardial tissue as compared to normal control. A single independent administration of telmisartan (2 and 4 mg/kg) and AR-A014418 (1 and 2 mg/kg) substantially reduced sepsis-induced myocardial injury in terms of decrease levels of CK-MB, cTnI and IL-6, HMGB1, GSK-3β and increase in IL-10 and p-GSK-3β in the blood in sepsis- subjected rats. The effects of telmisartan at dose 4 mg/kg and AR-A014418 at a dose of 2 mg/kg were significantly higher than the telmisartan at a dose of 2 mg/kg and AR-A014418 1 mg/kg respectively. Further, no significant effects on different parameters were observed in the sham control group in comparison to normal. Therefore it is plausible to suggest that sepsis may increase the levels of angiotensin II to trigger GSK-3β-dependent signaling to activate the HMGB1/receptors for advanced glycation end products, which may promote inflammation and myocardial injury in sepsis-subjected rats.