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 explore the acupoint selection law of acupuncture and moxibustion in treating diabetic gastroparesis (DGP) using data mining technology.Methods:The clinical literature on acupuncture and moxibustion treatment for DGP was retrieved from CNKI, Wanfang Data, VIP, SinoMed, PubMed, the Cochrane Library from the establishment of the databases to July 31, 2023. The acupoint prescriptions were extracted to Excel 2016 to establish a database, and the statistics of acupoint frequency, meridian, distribution site and specific acupoint use were collected. SPSS Modeler 18.0 was used to analyze the association rules among acupoints, and SPSS Statistics 25.0 was used for clustering analysis and factor analysis to summarize the acupoint selection law for acupuncture treatment of DGP.Results:Totally 153 articles were included, involving 59 acupoints, with a total frequency of 802 times. The 5 most frequently used acupoints were "Zusanli" (ST 36), "Zhongwan" (CV 12), "Neiguan" (PC 6), "Sanyinjiao" (SP 6), "Pishu" (BL 20). The commonly used meridians were stomach meridian, Conception Vessel and bladder meridian. The involved acupoints were mostly located in the chest-abdomen and lower limbs, and most of them were Wushu acupoints, Mu acupoints, and Xiahe acupoints. The core acupoints group was "Zusanli (ST 36)-Zhongwan (CV 12)-Neiguan (PC 6)-Pishu (BL 20)-Weishu (BL 21)-Sanyinjiao (SP 6)-Tianshu (ST 25)", 24 groups of association rules, 5 effective clusters and 6 factors were obtained.Conclusion:Acupuncture and moxibustion treatment of DGP focuses on both spleen and stomach, treating both symptoms and root causes, and uses methods of combining acupoints such as distant and near matching, combining Mu acupoints, and Xiahe acupoints, and combining of Wushu acupoints and Mu acupoints, to achieve the therapeutic effect of nourishing yin and tonifying qi, dispelling upper abdominal fullness and resolving turbidity, and harmonizing stomach and strengthening spleen.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Ghrelin is a hormone produced by the stomach that regulates energy metabolism after acting on the central nervous system.Cocaine amphetamine-regulated transcriptional peptide(CART)neurons participate in the regulation of feeding behavior and energy balance.It is known that CART neurons are influenced by hormones to regulate energy homeostasis,but whether ghre-lin exerts its pro-appetite function by influencing CART neurons is unknown.Therefore,this study focuses on the role of VMHCART neurons in the regulation of feeding and relative body weight by ghrelin.Firstly,the whole brain expression of CART was determined by immunofluorescence.Then the effect of intraperitoneal injection of ghrelin on the expression of DMHCART neurons was evalua-ted.Finally,the ghrelin was delivered to DMH and the changes of food intake and relative body weight of mice were measured.CART immunoreactive neurons were detected in medial preoptic nucleus(MPA),arcuate nucleus(ARC),dorsomedial hypothalamic nucleus(DMH),thalamic pa-raventricular nucleus(PVT)and raphe nucleus(ROb).Compared with the control group,periph-eral injection of ghrelin significantly increased the expression of DMHC ART immunoreactive neurons(P=0.037 3).DMH long-term injection of ghrelin resulted in an increase in body weight(P=0.004 0)and feed intake(P=0.023 1).The results provide anatomical evidence for the whole brain distribution of CART,which proves that ghrelin affects feed intake and body weight of mice through CART neurons in DMH,suggesting that specific neuron types and regional specificity are involved in ghrelin regulation of feed intake and energy homeostasis.

Objective To explore the risk factors of antibiotic related diarrhea occurrence in elderly pa-tients with acute exacerbation of chronic obstructive pulmonary disease (COPD) treated by non-invasive vent-ilator.Methods The clinical data of 248 elderly patients with acute exacerbation of COPD treated in this hos-pital from June 2020 to June 2023 were analyzed retrospectively.The univariate and multivariate logistic re-gression were used to analyze the influencing factors for the patients with antibiotic related diarrhea occur-rence.Results Among 248 elderly patients with acute exacerbation of COPD,49 cases (19.76％) developed antibiotic related diarrhea.The results of univariate and multivariate logistic regression analysis showed that the age≥70 years old,non-invasive ventilator treatment time≥7 d,broad-spectrum antibiotics use,antibiotic treatment time≥7 d,hospitalization duration≥10 d and severe illness condition were the risk factors for anti-biotic related diarrhea occurrence in the elderly patients with acute exacerbation of COPD (P<0.05),while the daily disinfection of ventilator tubes and masks was a protective factor (P<0.05).Conclusion The inci-dence rate of antibiotic-related diarrhea in the elderly patients with acute exacerbation of COPD treated by non-invasive ventilator is high,which is closely related to the age of patients,ventilation time,ventilator pipe-line and mask disinfection,antibiotic use time,whether using broad-spectrum antibiotics,hospitalization dura-tion and severity of disease condition.

This paper aims to discuss the ideas and experience about the radiology residency training system of Canada with a presentation of its base accreditation standards for five aspects, competency goals for seven roles, four stages of training arrangement, and two types of final assessment questions. Although the Canada's radiology residency program differs from China's standardized resident and specialist training programs for radiology, there are still several points that are worth referencing, including emphasizing the training priority of competency goals, providing a specific basis for the stratification of training, offering clear guidance for the implementation of training content, and improving assessment methods to focus on competency goals. These points are of great value for improving the standardized radiology resident and specialist training programs in China, so as to provide a reference for the training of excellent radiologists in China.

Objective:To construct a novel dual-specific antibody targeting human CD123 (CD123 DuAb) and study its effects in acute myeloid leukemia (AML) .Methods:Based on the variable region of the CD123 monoclonal antibody independently developed at our institution, the CD123 DuAb expression plasmid was constructed by molecular cloning and transfected into ExpiCHO-S cells to prepare the antibody protein. Through a series of in vitro experiments, its activation and proliferation effect on T cells, as well as the effect of promoting T-cell killing of AML cells, were verified.Results:① A novel CD123 DuAb plasmid targeting CD123 was successfully constructed and expressed in the Expi-CHO eukaryotic system. ②The CD123 DuAb could bind both CD3 on T cells and CD123 on CD123 + tumor cells. ③When T cells were co-cultured with MV4-11 cells with addition of the CD123 DuAb at a concentration of 1 nmol/L, the positive expression rates of CD69 and CD25 on T cells were 68.0% and 44.3%, respectively, which were significantly higher than those of the control group ( P<0.05). ④Co-culture with CD123 DuAb at 1 nmol/L promoted T-cell proliferation, and the absolute T-cell count increased from 5×10 5/ml to 3.2×10 6/ml on day 9, and CFSE fluorescence intensity decreased significantly. ⑤ With the increase in CD123 DuAb concentration in the culture system, T-cell exhaustion and apoptosis increased. When the CD123 DuAb was added at a concentration of 1 nmol/L to the culture system, the proportion of CD8 + PD-1 + LAG-3 + T cells was 10.90%, and the proportion of propidium iodide (PI) - Annexin Ⅴ + T cells and PI + Annexin Ⅴ + T cells was 18.27% and 11.43%, respectively, which were significantly higher than those in the control group ( P<0.05). ⑥ The CD123 DuAb significantly activated T cells, and the activation intensity was positively correlated with its concentration. The expression rate of CD107a on T cells reached 16.05% with 1 nmol/L CD123 DuAb, which was significantly higher than that of the control group ( P<0.05). ⑦The CD123 DuAb promoted cytokine secretion by T cells at a concentration of 1 nmol/L, and the concentration of IFN-γ and TNF-α in the supernatant of the co-culture system reached 193.8 pg/ml and 169.8 pg/ml, respectively, which was significantly higher than that of the control group ( P<0.05). ⑧When CD123 DuAb was added at a concentration of 1 nmol/L to the co-culture system of T cells and CD123 + tumor cells, the killing intensity of T cells significantly increased, and the residual rates of CD123 + MV4-11 cells, CD123 + Molm13 cells, and CD123 + THP-1 cells were 7.4%, 6.7%, and 14.6% on day 3, respectively, which were significantly lower than those in the control group ( P<0.05) . Conclusion:In this study, a novel CD123 DuAb was constructed and expressed. In vitro experiments verified that the DuAb binds to CD123 + tumor cells and T cells simultaneously, promotes T-cell activation and proliferation, and facilitates their anti-leukemia effect, which provides a basis for further clinical research.

Objective To compare the lipid-lowering efficacy and safety of fixed-dose combination and free combination of rosuvastatin and ezetimibe in hypercholesterolemia patients who fail to achieve low-density lipoprotein cholesterol(LDL-C)goal with statin monotherapy.Methods A total of 45 hypercholesterolemia patients who switched from statin monotherapy to fixed-dose combination of rosuvastatin and ezetimibe after failing to achieve target LDL-C goal admitted at cardiological departments of First Affiliated Hospital of Sun Yat-sen University,Nanhai Fourth People's Hospital,Foshan First People's Hospital,and Guangdong Provincial People's Hospital between March and June 2024 were enrolled and served as the study group.Another 120 hyper-cholesterolemia patients who treated with free combination of rosuvastatin and ezetimibe were se-lected from Xiamen Regional Health Medical Big Data Platform with propensity score matching and served as control group.The LDL-C level,LDL-C reduction,and changes in TC,HDL-C and TG levels in 4-6 weeks after the medication switch,as well as the safety indicators(AST,ALT,CK,Cre and eGFR)were compared between the two groups.Results In 4-6 weeks after the medication switch,the patients in the study group exhibited a significant decrease in LDL-C level(1.70±0.44 mmol/L vs 2.12±0.87 mmol/L,P＜0.01),obvious LDL-C reduction[(43.17±16.11)％vs(29.14±29.13)％,P＜0.01]when compared to those of the control group.The LDL-C goal attainment rate was significantly higher in the study group than the control group(71.11％vs 45.00％,P=0.003).In addition,there were no statistical differences in the levels of HDL-C and TG and the reductions of HDL-C and TG between the two groups in 4-6 weeks after treatment(P＞0.05).The study group obtained notably lower TC level and TC reduction than the control group in the time(P＜/0.05,P＜0.01).After treatment,no statistical differences were observed between the two groups in terms of AST,ALT,CK,Cre and eGFR(P＞0.05).Conclusion Com-pared to free combination of rosuvastatin and ezetimibe,fixed-dose combination can further reduce LDL-C level in hypercholesterolemia patients who have not achieved LDL-C goal with statin monotherapy,with higher LDL-C goal attainment rate and good safety.

In atherosclerosis, chronic inflammatory processes in local diseased areas may lead to the accumulation of reactive oxygen species (ROS). In this study, we devised a highly sensitive H₂O₂-scavenging nano-bionic system loaded with probucol (RPP-PU), to treat atherosclerosis more effectively. The RPP material had high sensitivity to H₂O₂, and the response sensitivity could be reduced from 40 to 10 μmol/L which was close to the lowest concentration of H₂O₂ levels of the pathological environment. RPP-PU delayed the release and prolonged the duration of PU in vivo. In Apolipoprotein E deficient (ApoE^‒/‒) mice, RPP-PU effectively eliminated pathological ROS, reduced the level of lipids and related metabolic enzymes, and significantly decreased the area of vascular plaques and fibers. Our study demonstrated that the H₂O₂-scavenging nano-bionic system could scavenge the abundant ROS in the atherosclerosis lesion, thereby reducing the oxidative stress for treating atherosclerosis and thus achieve the therapeutic goals with atherosclerosis more desirably.

ObjectiveTo explore the mental health status and its influencing factors among middle school students in Xide County， Liangshan Yi Autonomous Prefecture， and to provide references for mental health interventions for local middle school students. MethodsUsing a cross-sectional study design， one junior middle school and one senior middle school in Xide County， Liangshan Prefecture， Sichuan Province， were randomly selected on September 16， 2021， and two classes per grade in each school involving 288 students were recruited. Subjects were assessed using Patients' Health Questionnaire Depression Scale-9 item （PHQ-9）， Generalized Anxiety Disorder Scale-7 item （GAD-7）， PTSD Checklist for DSM-5 （PCL-5）， Multidimensional Scale of Perceived Social Support （MSPSS） and UCLA Loneliness Scale （ULS-3）. Then the scores of above scales were compared among middle school students with different demographic characteristics， and binary Logistic regression analysis was conducted to screen the influencing factors of post-traumatic stress disorder (PTSD） symptoms. ResultsAmong the respondents， 17.71% （95% CI： 0.133~0.221）， 8.68% （95% CI： 0.054~0.120）， 2.78% （95% CI： 0.009~0.047） and 45.83% （95% CI： 0.400~0.516） were reported to have symptoms of depression， anxiety， PTSD and loneliness， respectively. Students in senior middle school scored lower on PCL-5 and ULS-3 than those in junior middle school ［（6.46±8.91） vs. （8.87±9.42）， t=2.202， P<0.05； （4.67±1.65） vs. （5.60±1.88）， t=4.431， P<0.01］. Regression analysis denoted that depressive symptoms （OR=7.630， P<0.05） and anxiety symptoms （OR=3.789， P<0.01） were risk factors for PTSD symptoms among middle school students. ConclusionThe middle school students in Xide County， Liangshan Yi Autonomous Prefecture suffer a high prevalence rate of depressive symptoms and loneliness， and those in junior middle school are more likely to feel a sense of strong loneliness， furthermore， depressive symptoms and anxiety symptoms are risk factors for PTSD symptoms.