Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

Background Excessive radon exposure is considered the second risk factor for lung cancer. Since the opening of the subway in a city of Zhejiang Province, the exposure level of radioactive gas radon in subway stations and its impact on occupational health have become one of the important issues of public concern. Objective To monitor the radon concentration of subways in a city in Zhejiang Province and explore the effect of radon exposure on chromosome aberration and micronuclei in the working population. Methods A total of 55 vehicle control rooms of 55 stations affiliated to two different subway lines in a city were measured for one year; the 110 ticket offices and 55 security checkpoints from the same 55 stations were measured from 16 March to 14 June. The radon concentrations were compared by job types, subway lines, and seasons referring to Measurement methods for determination of radon in environmental air (HJ 1212-2021). Peripheral blood lymphocyte chromosome aberration and micronucleus analyses were conducted in 165 subway workers from monitoring sites for three different job types, then the influencing factors were analyzed. The detection methods were adopted from the standards of Test and assessment of chromosomal aberrations on occupational health examinations for radiation workers (GBZ/T 248-2014) and Standard for the method of micronucleus detection in lymphocytes on occupational health examination for radiation workers and exposure dose estimation (GBZ/T 328-2023). Results The radon concentration range of the target subways in Zhejiang Province was 10-320 Bq·m⁻³, all lower than the national limit (≤400 Bq·m⁻³). The differences in radon radioactivity levels among different lines, job types, and time segments were statistically significant (P<0.05). The rates of chromosomal aberration and micronucleus formation among the 165 subjects were 0.224% and 0.024%, respectively. There were significant differences in the rates of chromosome aberration and micronuclei among different jobs (vehicle control room, ticket office, security checkpoint) (P<0.05), but the abnormal rates were lower than the limits of the corresponding national standard. No significant correlation was found between jobs and chromosomal aberrations or micronuclei (P>0.05). Chromosome aberration and micronuclei varied by age, subway station seniority, and smoking (P<0.05). No effect of the above factors on chromosome aberration and micronuclei was observed by logistic regression (P>0.05). Conclusion The radon concentration in the target subway system is at a normal level. The rates of chromosomal aberration and micronucleus formation vary by jobs, but both are lower than the corresponding national limits. Therefore, radon exposure has not yet caused outstanding health impact on the subway workers.

Extracellular vesicles (EV), as novel disease biomarkers, have shown broad applicational prospect in the field of laboratory medicine or disease diagnosis. There have been substantial advancements in EV isolation technologies, EV biomarker screening and validation, and EV detection techniques. However, to fully integrate EV into clinical laboratories, ongoing efforts are needed in several areas including multi-omics integration and big data analysis, the development of clinically suitable technologies in isolation and detection, the establishment of standardized and normalization of quality systems, and the execution of clinical trials and administration and approvals of products, so as to promote the application and transformation of EV detection technologies in disease diagnosis, therapeutic evaluation, and prognosis assessment, thereby fostering better service of people's health in the aspect of laboratory medicine.

OBJECTIVE To explore the value of providing pharmaceutical service related to risdiplam in direct-to-patient （DTP） pharmacies. METHODS The follow-up data of spinal muscular atrophy （SMA） patients who purchased and used risdiplam from Shangyao Yunjiankang Yiyao Pharmacy （Shanghai） Co.， Ltd. from May 2021 to January 2023 were collected. The medication information， therapeutic efficacy and the occurrence of adverse events were retrospectively analyzed. RESULTS A total of 42 prescriptions were checked by pharmacists in the DTP pharmacies， and 7 prescriptions were found to be unreasonable （16.7%， 7/42）， which were corrected after the timely intervention. During the follow-up management， pharmacists replied to 4 patients （9.5%， 4/42） regarding medication consultation about medication requirements and adverse events. Two patients with type Ⅰ SMA experienced adverse events： one of them presented with fever and the other presented with skin dryness with darkening. Both of them were grade Ⅰ toxic reactions and generally did not require clinical treatment. Considering that the patient sustained low-grade fever for a long time， the pharmacist suggested symptomatic treatment under the guidance of the doctor. CONCLUSIONS Pharmacists in DTP pharmacies conducting follow-up management of risdiplam use for rare disease SMA patients can help promote rational， standardized medication for patients.

Objective: To investigate the effects of epidural analgesia on puerpera and neonatal. Methods: A total of 150 puerpera were continuously enrolled from May 2017 to May 2018 in Zhoushan Maternal and Child Health Care Hospital, and were divided into analgesia group (102 cases) and non-analgesia group (48 cases) according to their prenatal wishes.The analgesia group was given epidural anesthesia for analgesic delivery, while the control group had no analgesia intervention.Differences in the expression of serum pain and stress hormones were compared between two groups at the time of prenatal, postpartum 1h and 24h.At the same time, differences in neonatal NACS scores were compared between two groups at the time of postpartum 1h, 8h and 24h. Results: No statistically significant differences were found between the two groups in prenatal serum pain and stress hormones, but at the time of postpartum 1h and 24h, serum pain media neuropeptide Y (NPY) (t=5.041, P=0.000; t=4.984, P=0.000), 5-hydroxytryptamine (5-HT) (t=3.083, P=0.002; t=4.203, P=0.000), prostate E2 (PGE2) (t=6.764, P=0.000; t=4.364, P=0.000) and stress hormone angiotensin Ⅱ (AngⅡ) (t=3.670, P=0.000; t=2.911, P=0.004), adrenocorticotropic hormone (ACTH)[(212.54±38.65) ng/mL vs.(231.43±34.82)ng/mL, t=3.510, P=0.001; (163.82±33.21) ng/mL vs.(175.21±32.48) ng/mL, t=2.105, P=0.045)]and cortisol (Cor)[(344.56±57.39) μg/L vs.(381.81±59.23)μg/L, t=3.670, P=0.000; (241.27±43.44) μg/L vs.(262.56±37.97) μg/L, t=2.911, P=0.004)] in the analgesia group were significantly lower than those in the non-analgesia group.There were no statistically significant differences in NACS score, complications and Apgar score between the two groups (all P>0.05). Conclusion The analgesic effect of full-course epidural delivery in analgesic delivery is remarkable, which can effectively reduce maternal stress reaction, and it is safe and has less adverse effect on neonates.

Objective To investigate the expression change of cytokines in peripheral blood and intestinal mucosa in the patients with diarrhea post-infectious irritable bowel syndrome(PI-IBS) and its relation with clinical symptoms scores.Methods Thirty outpatients and inpatients with diarrhea PI-IBS(observation group) and contemporaneous 30 individuals undergoing physical examination(control group) in the Hainan Provincial People's Hospital from January to December 2013 were selected.The peripheral blood mononuclear cells(PBMC) were separated and cultured.Then the levels of IFN-y and IL-10 in peripheral blood and cell culture supernatant fluid were detected by ELISA.The colonic mucosal tissue was taken by coloscopy.Then colonic mucosal IFN-γ and IL-10 protein expression was detected by immunohistochemistry staining.Furthermore,the correlationship between the level change of IFN-γ and IL-10 with clinical symptom score was analyzed by using the Spearman correlation method.Results Peripheral blod IL-10 and IFN-γ levels had no statistical difference between the two groups(P＞0.05).Compared with the control group,in PBMC seperation and cuture,the IFN-γ level in the observation group was increased and IL-10 level was decreased,the difference was statistically signifieant(P＜0.01).The intestinal main symptom score in the observation group had the positive correlation with IFN-γ expression level of PBMC culture supernatant fluid and colonic mucosal IFN-γ expression level(r=0.45,0.94,P＜0.01),and had the negative correlation with IL-10 expression level(r=-0.52,-0.79,P＜0.01).Conclusion The unbalance of IFN-γ and IL-10 level could be involved in the pathogenesis of diarrhea PI-IBS,which can serve as the observation indicators of disease activity.

Objective To observe the expression level and diagnosis performance of serum exosomal miR-21 in lung cancer. Method Sera of 94 lung cancer patients,29 pulmonary tuberculosis patients,and 26 healthy controls from Nan Fang Hospital were collected. Exosomes in serum were purified and characterized ,and miRNA was abstracted from exosomes. Levels of exosomal miR-21 in three groups were compared with relative quantitative RT-PCR. Diagnosis performance of exosomal miR-21 was evaluated by ROC curve. Results Purified serum exosome sample possesses typical exosome features. There were significant difference among exosomal miR-21 levels from lung cancer ,tuberculosis ,and health control group. Exosomal miR-21 obviously increased in lung cancer patients,and decreased in tuberculosis patients. Exosomal miR-21 were increased in early and late stage lung cancer patients. The diagnostic performance of exosomal miR-21 was evaluated by ROC curve. Its area under the curve was 0.702 and specificity was 0.923. Conclusions Serum exosomal miR-21 was increased in many kinds of lung can-cer patients. It possesses excellent diagnosis performance ,which may be developed as new biomarkers to assist lung diagnosis.

Objective: To explore the safety and feasibility of associating diaphragm resection and liver-diaphragmatic metastasis lesions resection for patients with advanced ovarian cancer. Methods: Retrospectively analysis 83 cases(98 times) of advanced ovarian cancer with liver-diaphragmatic metastasis between January 2012 and December 2016 at Department of Liver Surgery, Peking Union Medical College Hospital.The patients were aged from 19 to 75 years.Surgical procedure included metastatic lesions resection(43 times) and stripping(55 times). Operation status, post-operative complications, pathology results and follow-up of the patients were analyzed. Results: Fifteen patients received twice surgical treatment and 68 patients received one time surgical treatment. Postoperative hemorrhage in chest and between liver and diaphragm was not occurred in all cases.Dyspnea and low oxygen saturation were occurred in two cases of stripping patients and 1 case of metastatic lesions resection patients.Results of CT examination indicated that there was medium to large amount of ascites in right chests.The symptoms were relieved after placing thoracic closed drainage.Other patients were recovered smoothly.All patients were diagnosed as ovarian cancer by pathological examination. Conclusion Associating diaphragm resection is safe and feasible for liver-diaphragmatic metastasis lesions from ovarian cancer.

Objective The effect of serum exosome isolation method on obtained exosomal RNA is not yet clear .The aim of this study was to provide evidences to selected exosome isolation methods .Methods This was a method comparison study to assess three methods .Vein blood samples were collected from 3 healthy donors from Nanfang hospital , 4 ℃ 12 h was taken to make blood natural coagulated and the supernatant was taken as the serum . Exosomes extracted by Ultracentrifugation , ExoQuick and Total Exosome Isolation Reagent ( TEI ) kits from serum were assessed by transmission electron microscopy , nanoparticle tracking analysis and protein analysis to identify morphology , protein expression , concentration and size distribution of particles .ExoRNA extracted by Trizol-LS, SeraMir, Total Exosome RNA Isolation ( TER) and exoRNeasy were assessed by Bioanalyzer 2100 and qPCR to ascertain RNA distribution and miRNA expression.Results For exosomes isolation , two commercial kits ( ExoQuick and TEI ) showed higher exosomes recovery and protein concentration than ultracentrifugation , but exosome isolated by ultracentrifugation expressed abundant protein makers mostly .For exo-RNA isolation, the distribution of RNA and expression of miRNAinfluenced by three methods , but there was no effect on the relative expression trend of miRNA.ExoRNeasy resulted in the highest yield and most narrow size distribution pattern of small RNA with higher level of miRNA expression .Results of TEI with TER kits showed no obvious bands of small RNA and moderate miRNA expression among methods .Ultra with Trizol-LS or ExoQuick with SeraMir showed low concentration measurable bands around 100 nt, with changeable miRNA profiling irregularly . Conclusions Extraction of exosomes using traditional ultracentrifugation method is applicable for proteomics research work .Extraction using ExoQuick and TEI kits is suitable for preparing exosomes from scarce samples such as serum.

Exosome is nanoscale vesicles with bilayer membrane structure, is secreted by multiple living cells in vivo, capable of carrying biological materials such as nucleic acids, proteins and lipids etc.Exosome can protect the information material (such as miRNA), which is easy to be inactivated or degraded in the circulatory system, so that they can be safely transferred to the specific target cells to participate in signal regulation, and play an important role in the information transmission between cells.Exosome is widely found in human blood, urine, pleural effusion and other body fluid samples, and can provide rich, stable, sensitive and specific biological information.As a kind of liquid biopsy specimen, exosome has a very high clinical application value in the future.