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:Traditional Chinese medicine compound prescription has a long history in the treatment of primary osteoporosis,and the curative effect is definite,but the medication rule and mechanism are not clear. OBJECTIVE:Using the methodology of data mining and network pharmacology,to explore and verify the law of drug use and molecular mechanism of modern traditional Chinese medicine in the treatment of primary osteoporosis. METHODS:The relevant documents included in CNKI,WanFang,VIP and PubMed were used as data sources,and the relevant data were statistically counted and extracted by Microsoft EXCEL2019,IBMSPSS25.0 and other software.The high-frequency drugs obtained from the data statistics were analyzed by association rules analysis and cluster analysis,and the core drug combination of traditional Chinese medicine compound prescription in the treatment of primary osteoporosis was obtained by combining the two results.The therapeutic mechanism of this combination was explained by network pharmacology and verified by molecular docking. RESULTS AND CONCLUSION:Finally,151 articles were included and 207 prescriptions were selected,involving 285 flavors of Chinese herbs.(1)Ten groups of important drug combinations were obtained through the above two analyses,among which the core drug combination with the highest confidence and improvement was"Drynaria-Eucommia-Angelica."The key components of the combination in the treatment of primary osteoporosis were quercetin,kaempferol,naringenin and so on.The core targets were SRC proto-oncogene,phosphoinositide-3-Kinase regulatory subunit 1 and RELA proto-oncogene.The main pathways were cancer signaling pathway,JAK-STAT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.(2)The key active components were docked with the core targets,and the two showed a good combination.To conclude,Chinese herbal compound therapy in the treatment of primary osteoporosis can use a variety of active components to exert its efficacy through multiple signal pathways and acting on multiple targets,which can provide a theoretical basis for the research and development of new drugs for the follow-up treatment of primary osteoporosis.

Objective: To analyze the developmental trajectories of middle school students loneliness and social support, as well as to explore the interaction between loneliness and social support, so as to provide the evidence based support for the mental health development of adolescents. Methods: A total of 989 first year students from four public middle schools in Xiangxi Tujia and Miao Autonomous Prefecture, Hunan Province were selected for three follow up surveys by a cluster random sampling method (T1:March 2023, T2:June 2023, T3:December 2023). The UCLA Loneliness Scale-20 (ULS-20) and Social Support Scale for University Students (SSSUS) were employed for questionnaire data collection. The growth mixture modeling was utilized to test the developmental trajectories of loneliness and social support among middle school students, while the cross lagged analysis was performed to investigate their mutual influence. Results: The scores for loneliness and social support in T1, T2 and T3 were (43.1±5.8, 42.5± 6.8 , 42.0±6.9; 55.9±12.0, 60.7±15.7, 60.4±16.7), respectively. Correlational analysis revealed a significant negative correlation between loneliness levels (T1, T2, T3) and social support (T1, T2, T3) ( r =-0.47 to -0.36, P <0.01). Growth mixture modeling indicated a linear declining trend of middle school students loneliness, and the developmental trajectory of social support showed a linear increasing trend, with significant individual differences in initial levels and rates of change ( P <0.05). Cross lagged analyses revealed that loneliness levels at T1 negatively predicted social support scores at T2 ( β =-0.16), and loneliness levels at T2 negatively predicted social support scores at T3 ( β =-0.12) ( P <0.05). Additionally, prior loneliness positively predicted its subsequent levels, with path coefficients of 0.58 and 0.47, respectively ( P <0.05). Social support scores at T1 negatively predicted loneliness levels at T2 ( β =-0.10), while scores at T2 negatively predicted loneliness levels at T3 ( β =-0.15) ( P <0.05). Prior loneliness also positively predicted its subsequent levels, with path coefficients of 0.43 and 0.44, respectively ( P <0.05). Conclusion The developmental trajectory of middle school students loneliness demonstrates a decreasing trend, while that of social support exhibits a linear increasing trend, indicating a longitudinal causal relationship between loneliness and social support.

Background: Domestic yaks are the most important livestock species on the Qinghai-Tibetan Plateau. Adult female yaks normally breed in the warm season (July to September) and enter anestrous in the cold season (November to April). Nevertheless, it is unclear how ovarian activity is regulated at the molecular level. Objectives: The peculiarities of yak reproduction were assessed to explore the molecular mechanism of postpartum anestrus ovaries in yaks after pregnancy and parturition. Methods: Sixty female yaks with calves were observed under natural grazing in Haiyan County, Qinghai Province. Three yak ovaries in pregnancy and postpartum anestrus were collected. RNA sequencing and quantitative proteomics were employed to analyze the pregnancy and postpartum ovaries after hypothermia to identify the genes and proteins related to the postpartum ovarian cycle. Results: The results revealed 841 differentially expressed genes during the postpartum hypoestrus cycle; 347 were up-regulated and 494 genes were down-regulated. Fifty-seven differential proteins were screened: 38 were up-regulated and 19 were down-regulated. The differential genes and proteins were related to the yak reproduction process, rhythm process, progesterone-mediated oocyte maturation, PI3K/AKT signaling pathway, and MAPK signaling pathway categories. Conclusions Transcriptome and proteomic sequencing approaches were used to investigate postpartum anestrus and pregnancy ovaries in yaks. The results confirmed that BHLHE40, SF1IX1, FBPX1, HSPCA, LHCGR, BMP15, and ET-1R could affect postpartum hypoestrus and control the state of estrus.

The red doctor’s spirit is an important spiritual guidance for the cultivation of medical talents during the development of medical and health services in China. The teaching reform, which is oriented towards position competence, requires that students majoring in public health management should not only master solid medical knowledge and professional skills, but also possess an ability to handle medical public relations, such as shaping an excellent image of the organization, improving the medical interpersonal communication, and managing public relations crisis. Under the guidance of inheriting the red gene and innovating the medical education, the driving force of learning should be "serving the people to improve their health" led by "political firmness" , the learning goal "striving for perfection" inspired by "excellent technology" , and the working criterion "respecting patients, involving full participation and shouldering public responsibility" embodied in "making selfless dedication and helping the wounded and dying" . The article based on the characteristic culture of red medicine in the Air Force Medical University, applied the teaching method of role-playing case simulations to explore the teaching practice road of "theory-experience-practice-reflection" .

Objective To observe the clinical efficacy of the combination of modification ofChaihu Jia Longgu MuliDecoction with psychological intervention in the treatment of post tumor depression.MethodsTotally 122 cases of post tumor depression were divided into treatment group and control group by simple numeration table random method, with 61 cases in each group. The treatment group was given modification ofChaihu Jia Longgu Muli Decoction orally, at the same time psychological intervention was given. The control group was given escitalopram oxalate tablets for 6 weeks. HAMD scale scores of the two groups were observed before and after treatment to evaluate the clinical efficacy. Changes in life quality of two groups were scored with SF-36 scale. The adverse reactions were also observed.ResultsAfter treatment, the HAMD score of treatment group was lower than control group (P<0.05). The total effective rate was 88.52% (54/61) in the treatment group and 72.13% (44/61) in the control group, with statistical significance (P<0.05). The scores of life quality of treatment group were higher than control group (P<0.05), and the incidence of adverse reactions was lower than control group (P<0.05).Conclusion Combination of modification ofChaihu Jia Longgu MuliDecoction with psychological intervention in the treatment of post tumor depression can significantly improve the depressive state and life quality of the patients with post tumor depression, which is better than the control group, without significant adverse reactions.

Objective:To evaluate the clinical effects of short fiber ribbon combined with resin bonding technology for the treatment of food impaction between posterior teeth. Methods:98 cases of vertical food impaction between posterior teeth( total of 135 vertical food impaction units) were included. 73 units were treated by short quartz fiber ribbon combined with resin bonding technology( SQFRB) and 63 by resin bonding(RB). 12, 24 and 36 months after restoration, clinical effects were evaluated referring to the Modified United States Public Health Service (USPHS) Criteria, data were statistically analyzed. Results:12, 24 and 36 months after treatment the cure rate of SQFRB was 97. 3%, 97. 3% and 95. 9%, inefficacy rate was 0, 0 and 0;the cure rate of RB was 85. 5%, 82. 2% and 82. 2%, the inefficacy rate was 4. 8%, 11. 3% and 12. 9%, respectively(between groups, P<0. 05). Conclusion:Minimally inva-sive restorations using short fiber ribbon combined with resin bonding technology is effective in the treatment of vertical food impaction between posterior teeth.

Objective To investigate the clinical efficacy of nicergoline combined with donepezil hydrochlo-ride in the treatment of mild vascular dementia and its influence on cognitive function.Methods 66 patients with mild vascular dementia from neurology were divided into two groups by random numbers,33 cases in each group.On the based of the routine symptomatic treatment,the control group were given nicergoline,the observation group were treated with nicergoline combined with aricept.Four weeks was a course,both groups were continuously treated for 3 courses.Results The MMSE scores of the observation group after treatment was (36.7 ±5.7)points,which was significantly increased compared with before treatment(t =10.137,P <0.05)and the control group(t =11.236,P <0.05);The ADL score was(35.8 ±16.2)points,which was significantly lower compared with before treatment(t =10.825,P <0.05)and the control group(t =11.415,P <0.05);The total effective rate of the observation group was 78.9%,which was higher than 54.5% of the control group(χ2 =9.24,P <0.05).Conclusion Nicergoline com-bined with donepezil hydrochloride in the treatment of mild vascular dementia can significantly improve cognitive func-tion scores,and it is a significant effect,safe and reliable method.

Objective To investigate the efficacy and influence of motor function and activities of daily living of hexose ganglioside sialic four single(GM1)combined with rehabilitation in treatment of cerebral infarction(ACI). Methods 110 patients with ACI were divided into the two groups in random number table,they were all treated with routine treatment,the patients of the control group(n =55)were given citicoline on the base of those addition,the patients of the observation group(n =55)were given hexose ganglioside sialic four single combined with rehabilitation. The efficacy and influence of motor function and activities of daily living of the two groups were observed and compared.Results The total efficiency of the observation group was 90.91%,which was significantly higher than 76.36% of the control group(χ2 =10.33,P <0.05);The bathel index and the FMA points after treatment of the two groups were significant increased compared with before treatment,the difference was statistically significant(t =7.11, 9.83,8.66,10.27,all P <0.05);The bathel index and the FMA points after treatment of the observation group were (60.79 ±5.64)and(64.34 ±7.83),which were significantly higher than the control group(t =8.89,9.45,all P <0.05).Conclusion Hexose ganglioside sialic four single combined with rehabilitation in treatment of cerebral infarc-tion had significant clinical effect,it can effectively improve motor dysfunction,improve their daily living skills,with a high clinical value and was worth to appliy.

Objective:To investigate the synergistic effect and mechanism of the combined application of recombinant human bone morphogenetic protein-2(rhBMP-2) and basic fibroblast growth factor (bFGF).Methods:24KM male mice were randomly divided into6 groups with4 mice in each group, namely,GroupA(control group),GroupB(only treated with collagen),GroupC(treated with 2 ng bFGF+collagen),GroupD(treated with4 μg rhBMP-2+collagen),GroupE(treated with4 μg rhBMP-2+2 ng bFGF+collagen) andGroupF(treated with4 μg rhBMP-2+4 ng bFGF+collagen). The composites were implanted into the intermuscular septum of hind legs mice; whereas in control group, intermuscular septum of mice was separated and no implantation was performed. General observation, detection of concentration of calcium content, micro computed tomography (Micro-CT), three-dimensional reconstruction scan, measurement of bone mineral density(BMD), bone volume fraction(BVF) and trabecular thickness(Tb.Th), as well as histological observation withHE staining andALP andCD34 immumohistochemical staining were performed.Results:Ectopic osteogenesis was found inGroupsD,E andF mice.The difference in concentration of calcium contentswas statistically significant betweenGroupsD andE(P<0.05), but insignificant betweenGroupsE andF(P>0.05).Micro-CT and three-dimensional reconstruction revealed continuous newborn bone substance in external surface of ectopic bone formation, and the center of bone formation did not show obvious substantial filling by bone substance.The differences in BMD,BVF andTb.Th were statistically significant betweenGroupsD andE orF(P<0.01 or <0.05). HE staining showed that inGroupsD,E andF, newborn bone substance was mainly located at the edge of ectopic bone formation, and the bone formation inGroupsE andF was better than that in GroupD.ALP andCD34 immumohistochemical staining revealed the positive expression mainly at the edge of ectopic bone formation, and area of positiveexpression inGroupsE andF was larger than that inGroupsD.Conclusions:rhBMP-2 possesses the capacity to induce ectopic osteogenesis independently, but bFGF does not have this ability; the combined application of rhBMP-2 and bFGF can enhance the synergetic effect on inducing ectopic osteogenesis.