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

This article has systematically sorted out and verified the name， origin， producing area， quality evaluation， harvesting and processing of Pruni Semen by consulting ancient materia medica， medical books， prescription books and modern literature， in order to provide a basis for the development of famous classical formulas containing Pruni Semen. The results showed that Pruni Semen， as a medicinal material， has been widely used in medical literature of past dynasties since it was collected in Shennong Bencaojing， and also included under the names such as Yuhe， Yuzi and Yuli， and aliases such as Jueli， Queli and Chexiali. The primordial plants mentioned in the past dynasties involve about 12 species of Rosaceae， but with Prunus humilis， P. japonica and P. glandulosa as mainstream varieties used in the past dynasties， while the 2020 edition of Chinese Pharmacopoeia stipulates that the basal plants are P. humilis， P. japonica and P. pedunculata. Most of the ancient records for the origin of Pruni Semen are found everywhere in high mountains， valleys and hills， modern literature records that its origin varies according to its base， for example， P. humilis and P. japonica are mainly produced in Hebei， eastern Inner Mongolia， Liaoning， Shandong and other regions of China， and P. pedunculata is mainly produced in Inner Mongolia. Modern literature summarizes its quality as faint yellow， full and fulfilling， neat and not broken， and non-oiling， and the small Pruni Semen is better than the big Pruni Semen. The ancient processing methods of Pruni Semen mainly include blanching and peeling， blanching and peeling followed by frying， and blanching and peeling followed by pounding， with the common feature of blanching and peeling. The successive editions of Chinese Pharmacopoeia stipulate that it should be pounded when used. Based on the results of the herbal textual research and the writing time of Bianzhenglu， and combined with the market survey of Pruni Semen， it is suggested that P. humilis or P. japonica should be used as the origin of Pruni Semen in Sanpiantang， and it is harvested when the fruits are ripe， the kernels are collected by removing the stones， and processed by blanching， peeling and pounding consulting the decoction method in the current edition of Chinese Pharmacopoeia.

In order to compare the setting of difference coefficients in DRG point payment in different cities in Zhejiang province, the implementation rules of DRG point payment issued by 11 cities in Zhejiang province were comprehensively analyzed. It was found that the difference coefficients in different cities could be divided into three categories, including hospital coefficients alone, hospital coefficients and grade coefficients weighted, and weighted by hospital coefficients, grade coefficients, personal burden levels, case mix indexes, and head-to-time ratio. Its setting differences included four aspects: connotation composition, weight distribution, threshold value, and classification of medical institutions. The authors suggested that the adjustment cycle should be set scientifically to dynamically adjust the difference coefficient, and the scientific setting of the difference coefficient should be promoted through provincial coordination.

The existing doctor-patient communication pattern often falls prey to insufficient informed consent and even medical disputes. In the patient centered perspective, Zhejiang Provincial People′s Hospital explored a new communication mode centering on patients. Based on diagnosis-related groups catalogues and high-frequency surgeries catalogues of the departments, multimedia technology was called into play to produce dubbed PPTs and videos that were easy to understand, standardized and homogeneous, which were embedded into medical records system. Following observation of the PPT or video, patients could directly sign an informed consent on the computer. This practice not only deepens patient′s understanding and achieves homogeneous level of the communication, but also elevates doctor′s work efficiency, contributing to building a harmonious doctor-patient relationship.

The construction of safe hospital is the foundation of high-quality development of the hospital, and innovation provides power for the construction of safe hospital from the perspective of high-quality development. Taking Zhejiang Provincial People′s Hospital as an example, the authors introduced the innovation construction path of safe hospital in detail, and put forward the construction strategy of safe hospital with " two hearts" (patient-centered, employee-centered)and " four wings" (multimedia doctor-patient communication, Wulin aunt medical studio, integrated operation safety inspection, third-party medical liability insurance). Through the combination of basic safety management and innovative practice, the hospital vigorously promoted the culture of " two hearts" , and established an efficient collaborative information management system, so as to form replicable and promotable practical experience and promote the development of safe hospital.

Objective:To determine the difference of curative effects of gamma knife treatment and microsurgery on patients with recurrent trigeminal neuralgia (TN) after microvascular decompression (MVD).Methods:From January 2011 to December 2018, 65 patients with recurrent TN after MVD were enrolled in the study; 40 patients received gamma knife treatment and 25 patients received secondary microsurgical treatment. Barrow Neurological Institute (BNI) proposed pain grading was used to evaluate the efficacies right after treatment and 3 years after follow-up in all patients, and grading I-III was defined as pain relief.Results:Patients received gamma knife treatment had pain relief within 4-10 weeks of treatment and disappeared gradually; patients received secondary microsurgical treatment had disappeared facial pain immediately after waking up from anesthesia or completely alleviated facial pain within one week of treatment. Up to 3 years after surgery, follow-up results showed that 17 patients (68.0%) in the gamma knife treatment group had pain relief, and 16 patients (94.1%) in the microsurgical treatment group had pain relief; the difference in pain relief rate between the two groups was statistically significant ( χ2=4.100, P=0.043). Facial numbness was noted in the gamma knife treatment group, with an incidence of 24.0%; in the microsurgical treatment group, hemiplegia was noted in one patient and facial numbness was noted in the left ones, with complication rate of 29.4%; and the difference in complication rate between the two groups was not statistically significant ( χ2=0.010, P=0.921). Conclusion:For patients with recurrent TN after MVD, secondary microsurgical treatment and gamma knife treatment are safe and effective, among which secondary microsurgical treatment is more effective than gamma knife treatment.

Objective To study the factors influencing prognosis in the patients with recurrent glioblastoma muhiforme (GBM) and to investigate the effect of retreatemt.Methods The retrospective analysis method was adopted to collect the clinical and follow up data in 36 cases of recurrent GBM retreatment in the neurosurgery department of this hospital from March 2008 to March 2013.The prognosis influencing factors were analyzed.Results The univariate analysis results showed that the gender,resection degree,treatment mode and initial scheme had the influence on the progression free survival(P＜0.05).The resection degree had an impact on the overall survival(P＜0.05).The multivariate analysis results showed that KPS score,resection degree and treatment mode had effect on the progression free survival(P＜0.05).The resection degree had an influence on the overall survival (P＜0.05).Conclusion If the patients with recurrent GBM still hasthe chance of operation whole excision,the re-treatment can reach the effect for relieving the symptoms,improving the quality of life and prolonging the survival period.

Objective To investigate the effect of astragalus polysaccharide (AP) on proliferation and apoptosis of human acute myelocytic leukemia cell line KG-1a and the underlying mechanisms.Methods Human acute myelocytic leukemia cell line KG-la was cultured under 37 ℃ and 5 ％ C02,when appropriate cell passage and cryopreservation were performed.After treatment for 48 h with different concentrations of AP,the proliferative activity and apoptosis rate of KG-1a cells were examined by CCK-8 assay and flow cytometry,respectively.The expressions of p-Akt and bcl-2 protein in AP-treated KG-1a cells were evaluated by Western blot.The expression of PTEN mRNA by quantified real-time PCR.Results The proliferative activity of KG-la cell was obviously suppressed by AP treatment,and the inhibition rate increased in a dosedependent manner.The flow cytometry showed that,compared with the control group,the apoptosis rates of KG-1a cells were significantly increased after treatment with AP for 48 h.The early apoptosis rates were (1.98±0.16) ％,(12.60±0.48) ％,(16.31±0.73) ％,the late apoptotic rates were (3.11±0.19) ％,(17.17±1.40) ％,(21.17 ± 0.81)％,the differences were statistically significant (P ＜ 0.05).Western blot showed that the expressions of p-Akt and bcl-2 protein in KG-1a cells decreased significantly after treatment with AP (P ＜ 0.05).In contrast,the mRNA level of PTEN increased (P ＜0.05),which was shown by real-time PCR.Conclusion AP could repress cellular proliferation activity of KG-1a cells,which could be attributed to inhibition of PTEN-PI3K-Akt signaling pathway.

Aim To investigate the neurotoxicity and the changes of nitration in the striatum of rats treated with methamphetamine(MA).Methods The rats were randomly divided into MA group and control group.The stereotyped behavior and body temperature of the rats were recorded.The differences of nitric oxide, nitric oxide synthase(NOS)and nitroprotein were compared between the two groups.Results The score of stereotyped behavior and the body temperature of the rats in MA group were significantly higher than those in the control group(P ＜0.01);Compared with the control group, the content of NO and the activity of NOS of striatum in MA group were significantly increased(P ＜0.01), and nitration of protein was also upregulated(P ＜0.01).Conclusion The increases of NOS activity, NO level and nitroprotein may play an important role in MA-induced neurutoxity in rat striaturn.

Objective To observe the effect of small dosage of perphenazine(2～6 mg)on psychotic symptoms of senile dementia.Methods 31 senile cases with psychotic symptoms after dementia(Alzheimer disease or vascular dementia)accepted small dosage of perphenazine in addition of the conventional therapy.They were assessed with Sadoz Clinical Assessment Geriatric(SCAG)and Treatment Emergent Symptom Scale(TESS).Results The score decreased 50%～75%(markedly improved)in 2 cases,25%～50%(improved)in 22 cases,lower than 25%(no improved)in 7 cases.Some mild emergent symptoms have been observed.Conclusion Small dosage of perphenazine is safe and effective in treating psychotic symptoms of senile dementia.