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

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

To study the correlation between the level of Bordetella pertussis nucleic acid and clinical features of the disease in infants and young children and to investigate the risk factors for the development of severe pertussis. Using retrospective research methods, children aged 1 month-3 years who came to Hunan Children′s Hospital from August 2023 to February 2024 and were diagnosed with pertussis for analysis. According to the logarithmic value of BP-DNA (log 10 copies/ml), 35 cases were divided into the low load group, 78 cases were divided into the medium load group and 94 cases were divided into the high load group; 54 cases were divided into the severe whooping cough group and 153 cases were divided into the general group according to the severity of the disease; the clinical characteristics and laboratory data of the groups were compared, and the risk factors for the occurrence of severe whooping cough were analyzed at the same time. The ROC was used to evaluate the predictive efficacy of BP-DNA and WBC count for the development of severe pertussis. The results showed that in the high-dose group, the WBC count(22.59×10 9/L), L/N ratio(3.31), and hospitalization days(9.0 d) were significantly higher than those in the medium-dose group and low-dose group ( F=6.309, 2.825, 15.149, all P<0.05). The hospitalization rate (100%), combined infection rate (64.96%), incidence of severe whooping cough (31.9%), pyrexia rate (29.8%), and corticosteroid use rate (57.4%) were also significantly higher than the other two groups ( χ2=25.977, 9.163, 9.371, 8.299, 20.332, all P<0.05), and the complete immunity rate (9.6%) was significantly lower than the other two groups ( χ2=11.632, P<0.05). Compared with the group of common whooping cough, the proportion of children under 1 year old (100%, χ2=9.581), the BP-DNA load (6.56 log 10 copies/ml, Z=4.004), the WBC count(31.34×10 9/L, t=7.513), the PCT level(0.07 ng/ml, Z=2.626), the IL-6 level (6.65 ng/ml, Z=4.336), the combined infection rate (88.9%, χ2=36.536), the incidence of wheezing or dyspnea (55.6%, χ2=42.972), the rate of no improvement of symptoms with macrolides prior to the visit (77.8%, χ2=26.266), and the incidence of fever (55.6%, χ2=42.972) were all significantly higher;the complete immunity rate was significantly lower (5.6%, χ2=9.581) in the severe whooping cough group, the differences were all statistically significant(all P<0.05).The result of logistic regression analysis showed severe elevation of BP-DNA, high leukocyte count, co-infection, wheezing or shortness of breath, pyrexia and no improvement of symptoms with macrolides before the treatment were the risk factors for the development of severe pertussis and the logistic regressive model predicts a sensitivity and specificity of 0.83 and 0.90 for severe whooping cough, respectively. The sensitivity of BP-DNA>1.91×10 6 copies/ml, WBC count >19.97×10 9/L and the binominal combined test to predict the occurrence of severe pertussis were 0.87, 0.61 and 0.80, and the specificity were 0.43, 0.86 and 0.73, respectively. In conclusion, nucleic acid load in infants with pertussis correlated with clinical characteristics such as the active immunity status, fever, co-infections and hospitalisation and days in hospital. Children with high nucleic acid load, high white blood cell counts, co-infections, fever and no improvement of symptoms with macrolides prior to seeing a doctor were more likely to develop the severe pertussis. When BP-DNA >1.91×10 6 copies/ml or WBC counts>19.97×10 9/L, they have the highest predictive efficacy for severe pertussis respectively, and combined detection is better.

To study the correlation between the level of Bordetella pertussis nucleic acid and clinical features of the disease in infants and young children and to investigate the risk factors for the development of severe pertussis. Using retrospective research methods, children aged 1 month-3 years who came to Hunan Children′s Hospital from August 2023 to February 2024 and were diagnosed with pertussis for analysis. According to the logarithmic value of BP-DNA (log 10 copies/ml), 35 cases were divided into the low load group, 78 cases were divided into the medium load group and 94 cases were divided into the high load group; 54 cases were divided into the severe whooping cough group and 153 cases were divided into the general group according to the severity of the disease; the clinical characteristics and laboratory data of the groups were compared, and the risk factors for the occurrence of severe whooping cough were analyzed at the same time. The ROC was used to evaluate the predictive efficacy of BP-DNA and WBC count for the development of severe pertussis. The results showed that in the high-dose group, the WBC count(22.59×10 9/L), L/N ratio(3.31), and hospitalization days(9.0 d) were significantly higher than those in the medium-dose group and low-dose group ( F=6.309, 2.825, 15.149, all P<0.05). The hospitalization rate (100%), combined infection rate (64.96%), incidence of severe whooping cough (31.9%), pyrexia rate (29.8%), and corticosteroid use rate (57.4%) were also significantly higher than the other two groups ( χ2=25.977, 9.163, 9.371, 8.299, 20.332, all P<0.05), and the complete immunity rate (9.6%) was significantly lower than the other two groups ( χ2=11.632, P<0.05). Compared with the group of common whooping cough, the proportion of children under 1 year old (100%, χ2=9.581), the BP-DNA load (6.56 log 10 copies/ml, Z=4.004), the WBC count(31.34×10 9/L, t=7.513), the PCT level(0.07 ng/ml, Z=2.626), the IL-6 level (6.65 ng/ml, Z=4.336), the combined infection rate (88.9%, χ2=36.536), the incidence of wheezing or dyspnea (55.6%, χ2=42.972), the rate of no improvement of symptoms with macrolides prior to the visit (77.8%, χ2=26.266), and the incidence of fever (55.6%, χ2=42.972) were all significantly higher;the complete immunity rate was significantly lower (5.6%, χ2=9.581) in the severe whooping cough group, the differences were all statistically significant(all P<0.05).The result of logistic regression analysis showed severe elevation of BP-DNA, high leukocyte count, co-infection, wheezing or shortness of breath, pyrexia and no improvement of symptoms with macrolides before the treatment were the risk factors for the development of severe pertussis and the logistic regressive model predicts a sensitivity and specificity of 0.83 and 0.90 for severe whooping cough, respectively. The sensitivity of BP-DNA>1.91×10 6 copies/ml, WBC count >19.97×10 9/L and the binominal combined test to predict the occurrence of severe pertussis were 0.87, 0.61 and 0.80, and the specificity were 0.43, 0.86 and 0.73, respectively. In conclusion, nucleic acid load in infants with pertussis correlated with clinical characteristics such as the active immunity status, fever, co-infections and hospitalisation and days in hospital. Children with high nucleic acid load, high white blood cell counts, co-infections, fever and no improvement of symptoms with macrolides prior to seeing a doctor were more likely to develop the severe pertussis. When BP-DNA >1.91×10 6 copies/ml or WBC counts>19.97×10 9/L, they have the highest predictive efficacy for severe pertussis respectively, and combined detection is better.

Objective To investigate the value of pancreatitis activity scoring system (PASS) score, Bedside Index for Severity in Acute Pancreatitis (BISAP) score, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE-Ⅱ) score, harmless acute pancreatitis score (HAPS), and Ranson score in evaluating the severity and prognosis of hypertriglyceridemia acute pancreatitis (HTGAP). Methods A retrospective analysis was performed for the clinical data of 300 patients with HTGAP who were admitted to General Hospital of Ningxia Medical University from January 2016 to January 2022, and according to the disease severity, these patients were divided into mild acute pancreatitis (MAP) group, moderate-severe acute pancreatitis (MSAP) group, and severe acute pancreatitis (SAP) group. Clinical data and the above scores were compared between the three groups. The chi-square test was used for comparison of categorical data between groups; an analysis of variance was used for continuous data with homogeneity of variance, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic (ROC) curve was plotted according to disease severity, and related indicators were compared in terms of the area under the ROC curve (AUC). Results There were significant differences between the three groups in PASS score ( F =219.351, P < 0.01), Ranson score ( χ 2 =83.084, P < 0.01), APACHE-Ⅱ score ( χ 2 =43.388, P < 0.01), and BISAP score ( χ 2 = 50.785, P < 0.01). Compared with the other four scoring systems in evaluating and predicting disease severity, PASS score had the highest sensitivity of 0.945 and the largest AUC of 0.963, followed by Ranson score with a sensitivity of 0.655 and an AUC of 0.819. Conclusion For patients with HTGAP, PASS score can more accurately assess the severity and prognosis of HTGAP patients and thus holds promise for clinical application.

Objective:To evaluate the effect of pancreatic duct stenting in the treatment of severe acute pancreatitis (SAP).Methods:The clinical data of 68 patients with SAP admitted to the Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University from January, 2019 to July, 2020 were retrospectively analyzed, including 38 males and 30 females, aged (44.85±8.51) years old. The patients were divided into two groups according to the treatment modality: the conservative group ( n=41) which received the conservative management, and the stent group ( n=27) which underwent pancreatic duct stent implantation and conservative management. The basic information, parenteral nutrition support time, fasting days, and other clinical data of patients were collected. Serum amylase, white blood cell count, acute physiology and chronic health (APACHE) II score and CT score were compared between the two groups at admission and 48 hours after treatment. Results:The serum amylase, white blood cell count, APACHE II score and CT score of the two groups were significantly lower after treatment (all P<0.05). Compared with the conservative group, the APACHE II score [(5.52±2.15) vs. (8.76±2.50)] and CT score [(4.85±1.96) vs. (6.18±1.07)] of patients were lower in the stent group after treatment (both P<0.05). Pancreatic duct stents were successfully implanted in all 27 patients of the stent group. Intubation to the main pancreatic duct failed in one patient, while the accessory pancreatic duct was alternatively intubated through the accessory nipple. No severe complications such as iatrogenic pancreatitis, bleeding, and perforation occurred after endoscopic retrograde cholangiopancreatography. The incidence of postoperative local complications was lower [18.52%(5/27) vs. 41.46%(17/41)], the proportion of antibiotic use>3 types [29.63%(8/27) vs. 56.10%(23/41)] decreased, and the analgesic episodes decreased [2(1, 3) vs. 4(3, 6)] in the stent group. The antibiotic usage duration [8(3, 11) d vs. 13(10, 19) d], the parenteral nutrition time [7(4, 15)d vs. 15(8, 18)d], the fasting time [5(3, 11) d vs. 11(6, 13)d] and the hospital stay [10(5, 16) d vs. 15(13, 23)d] were all shortened (all P<0.05). Conclusion:Both conservative management and pancreatic duct stenting can alleviate the clinical symptoms of SAP, and pancreatic duct stenting could help reduce local complications, relieve symptoms, and shorten hospital stay.

Objective:To investigate the characteristics and clinical significance of distribution of bacteria and fungi in pancreatic fluid and bile in patients with acute biliary pancreatitis (ABP).Methods:The clinical data of patients with ABP who underwent endoscopic retrograde cholangiopancreatography (ERCP) and pancreatic duct stenting with simultaneous bacterial and fungal culture of bile and pancreatic fluid at the Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University from January 1, 2019, to June 30, 2021 were retrospectively analyzed. Of 202 patients, there were 102 males, and 100 females, aged (54±16) years old. Patients were divided into two groups by presence or absence of pancreatic infection: the pancreatic infection group ( n=20) and the non-pancreatic infection group ( n=182). Of the 76 patients with positive bile bacterial cultures, 60 patients with positive pancreatic fluid bacterial cultures were included in the positive pancreatic fluid culture group and 16 patients with negative pancreatic fluid cultures were included in the negative pancreatic fluid culture group. The clinical data including the type and distribution of bacteria cultured, complications, and co-infections of patients were compared. Factors associated with pancreatic infection were analyzed using logistic regression and the value of assessment of the associated factors was analyzed by plotting the receiver operating characteristic (ROC) curve. Results:Of 404 specimens (202 each of pancreatic fluid and bile) were sent for examination, 152 (37.6%) were positive. 174 strains were isolated from the 152 positive specimens, 96 (55.2%) gram-negative, 70 (40.2%) gram-positive and 8 (4.6%) fungal strains. Compared to the pancreatic fluid culture-negative group, patients in the pancreatic fluid culture positive group had a statistically significant ( P<0.05) increased risk of neutrophil to lymphocyte ratio, duration of fever, Balthazar CT score, complication rate, and development of pancreatic necrosis, pancreatic infection and systemic inflammatory response syndrome (SIRS). Compared to patients in the non-pancreatic infection group, patients in the pancreatic infection group had a statistically significant ( P<0.05) increase in duration of fever on admission, duration of fasting, and proportion of patients with combined SIRS, positive bile cultures, positive pancreatic fluid cultures, and diabetes mellitus. Logistic regression analysis showed that positive pancreatic fluid cultures ( OR=6.699, 95% CI: 1.159-38.725) and diabetes mellitus on admission ( OR=4.625, 95% CI: 1.304-16.394) were risk factors for late pancreatic infection ( P<0.05). The area under the ROC curve for the combination of both positive pancreatic fluid culture and diabetes mellitus in predicting late pancreatic infection in patients was 0.788, with a specificity of 59.30% and a sensitivity of 90.00%. Conclusions:Bacterial culture in pancreatic juice and bile of ABP patients showed mainly Gram-negative bacteria. Early culture of pancreatic juice and bile had positive significance in ABP evaluation, infection prediction and anti-infection treatment.

OBJECTIVES: Uterine fluid RNA can be used as a test for endometrial receptivity, but there is still no noninvasive sampling method available. The polyvinyl alcohol (PVA) formaldehyde absorbent sponge, a medical bio-absorbent sponge with good water absorption and biophilic properties, can be used to develop a new noninvasive endometrial fluid sampler. This study aims to investigate the toxicity of PVA acetal absorbent sponges on endometrial epithelial cells and its effect on RNA sequencing (RNA-Seq). METHODS: The experimental group using PVA formaldehyde absorbent sponge was prepared into 0.005%, 0.01% and 0.02% (w/v) suspension, and 0.01%, 0.05% and 0.1% (v/v) extract groups. The control group was only the complete culture medium. Nothing was added to the blank group. In vitro cytotoxicity assay was used to evaluate the survival rate of cells. Eight patients underwent in vitro fertilization treatment in the Reproductive Center of Xiangya Hospital, Central South University from November 2019 to January 2020. The uterine fluid of each patient was aspirated. The experimental group was inhaled with sterile PVA formaldehyde absorbent sponge and then immersed RNA-later solution. The control group was directly injected into the same amount of RNA-later solution. RNA-seq and data analysis was performed later. RESULTS: The vitro cytotoxicity assay showed that in suspension groups, there was no significance difference in cell survival between different co-culture time in 0.005% group (P=0.255). In the 0.01% and 0.02% group, there was no difference at each incubation time within 12 h (all P>0.05), but the cell survival rate was decreased at 24 h compared with 0 h (P<0.01, P<0.05). At the same co-culture time, the cell survival of the 3 concentration gradient groups were significantly lower than that of the control group (all P<0.05). The cell viability of the 0.005% concentration group was decreased less than 30% at 24 h, the 0.01% concentration group decreased more than 30% at 12 h, and the 0.02% concentration group was decreased more than 30% at 0 h. For extract groups, there was no significant difference in the survival rate within 6 h in 0.01% concentration group (all P>0.05), and the survival rate of 12 h and 24 h was lower than that of 0 h group (both P<0.01). In 0.05% group, there was no significant difference at each incubation time within 12 h (all P>0.05), but the survival rate at 24 h was lower than that at 0 h (P<0.05). There was no significant difference in survival rate at different culture time in 0.1% concentration group (P=0.082). At the same culture time, there was no significant difference in survival rate between 0.01% group and control group at 0, 3 and 24 h (all P>0.05). Except for 3 h, the survival rate of 0.05% and 0.1% groups was lower than that of control group (all P<0.05), and the decrease was all less than 30%. Uterine fluid RNA-seq showed that there was no significance difference in exonic rate, the detected genes and transcripts of RNA between the experiment groups and the control group (all P>0.05). CONCLUSIONS The in vitro cytotoxic of PVA formaldehyde absorbent sponge on human endometrial epithelial cell meet the national standard of the cytotoxic of medical materials. Sampling the uterine fluid with this material does not affect the RNA-Seq results. PVA formaldehyde absorbent sponge is safe and feasible when appling to the noninvasive uterine fluid sampling and RNA sequencing.
Humans ; Social Group ; Sequence Analysis, RNA ; RNA

BACKGROUND: Previous studies have suggested that screen time (ST) has a negative effect on children's emotional and behavioral health, but there are few longitudinal studies that have been conducted with infants and toddlers. This study sought to examine the effect of ST in early childhood on emotional and behavioral problems in children aged 4 years, based on a birth cohort study in China. METHODS: A total of 2492 children aged 4 years were enrolled in this study. The parents and guardians of each child completed a questionnaire that included items eliciting information on children's birth information, socio-demographic information at baseline, and ST at each follow-up. Emotional and behavioral problems were assessed using the Strengths and Difficulties Questionnaire (SDQ) at 4 years of age. Multivariate logistic analysis was used to explore the effects of ST on emotional and behavioral problems. RESULTS: The percentages of children with ST > 0 h/day at age 0.5 years, ST > 2 h/day at age 2.5 years, and ST > 2 h/day at age 4 years were 45.7, 55.5, and 34.5% respectively. The prevalence of emotional and behavioral problems was 10.8%. ST at 6 months was a risk factor for emotional symptoms and hyperactivity at the age of 4 years. ST at age 2.5 years was a risk factor for hyperactivity at the age of 4 years. However, ST at age 4 years was a risk factor for total difficulties, conduct problems, peer problems, hyperactivity, and prosocial behavior. CONCLUSIONS Higher ST exposure at early childhood is associated with later emotional and behavioral problems. In particular, sustained high ST exposure is a risk factor for behavioral problems. These findings suggested the importance of controlling ST to prevent the occurrence of emotional and behavioral problems in the early years.
Altruism ; Child, Preschool ; China/epidemiology* ; Cohort Studies ; Emotions ; Female ; Humans ; Male ; Prevalence ; Problem Behavior/psychology* ; Psychomotor Agitation/psychology* ; Screen Time

Objective:To analyze the value of folate receptor-positive circulating tumor cells (FR +-CTC) in the diagnosis and efficacy evaluation of patients with small cell lung cancer (SCLC). Methods:The data of 59 patients with SCLC and 14 patients with benign pulmonary diseases treated in China-Japan Friendship Hospital from May 2017 to October 2019 were retrospectively analyzed. Folate receptor targeted detection was used to detect the level of FR +-CTC in the blood of SCLC patients. The levels of serum progastrin-releasing peptide (Pro-GRP), neuron-specific enolase (NSE), cytokeratin 19 fragment 21-1 (Cyfra21-1) , and carcinoembryonic antigen (CEA) were detected by using chemiluminescence. The median ( P25, P75) was used as all the detection indexes. Mann-Whitney U test was used for pairwise comparison, Spearman correlation test was used to analyze the correlation between two variables, and receiver operator characteristic (ROC) curve was used to evaluate the diagnostic efficacy. Results:The level of FR +-CTC in 59 patients with SCLC was 11.00 FU/3 ml (7.10 FU/3 ml, 14.50 FU/3 ml), and the positive rate of FR +-CTC in patients with SCLC was 66.10% (30/59); the level of FR +-CTC in 14 patients with benign pulmonary diseases was 6.75 FU/3 ml (5.03 FU/3 ml, 7.85 FU/3 ml), and the positive rate of FR +-CTC in 14 patients with benign pulmonary diseases was 14.29% (2/14). The level of FR +-CTC in patients with SCLC was higher than that in patients with benign pulmonary diseases, and the difference was statistically different ( U = 33.50, P < 0.01). The expression level of FR +-CTC was not related to age, gender and smoking history in SCLC patients (all P>0.05). The expression level of FR +-CTC in patients with extensive-stage was higher than that in patients with limited-stage, and the difference was statistically significant ( P < 0.05). Tumor markers Pro-GRP, NSE, Cyfra21-1 and CEA were compared with FR +-CTC, and the ROC curve was drawn; the results showed that FR +-CTC had better sensitivity (71.2%) and specificity (92.90%) in the diagnosis of SCLC. For SCLC patients who received chemotherapy, the decrease range of FR +-CTC in patients with partial remission and stable disease was greater than that in patients with the progression of disease, and the differences were statistically significant (all P < 0.05). Conclusion:FR +-CTC can assist the diagnosis and disease staging of SCLC. For patients receiving chemotherapy, continuous detection of circulating tumor cells can help to evaluate the efficacy of chemotherapy and provide a reference for the choice of clinical treatment.