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 design a mobile personnel radiation protection equipment for operation in environments with high radiation such as spent fuel reprocessing plants, to achieve simultaneous protection against γ radiation, neutron radiation, and radioactive aerosol, to reduce the internal and external exposure dose of radioactive workers, and to meet the requirement of operation for two hours. Methods The core parts of the mobile personnel radiation protection equipment included a shielding chamber and a respiratory maintenance system. An automated chassis was used for the movement and lifting of the shielding chamber. MCNP software was used to simulate and calculate the protective effects of shielding chamber made of different materials and material thicknesses. Experimental verification of the shielding chamber design was conducted. Mathematical models were established to describe the variations in the content of various gases in the chamber with personnel operation time. A respiratory maintenance system, a harmful gas absorption device, and an automated mobile chassis were designed. Results The shielding chamber made of polyethylene with a thickness of 80 mm achieved an 80% neutron shielding rate. The respiratory maintenance system could support workers for 2 hours of operation inside the equipment. The mobile chassis allowed operation of the equipment with one person. Conclusion This mobile personnel radiation protection equipment can solve the problem in simultaneous protection against γ radiation, neutron radiation, and radioactive aerosol. The equipment can provide radiation protection for radioactive workers, reduce exposure dose, and reduce personnel burden. This system provides technical means for the operation and maintenance of equipment in high-radiation sites such as spent fuel reprocessing plants.

Abstract: Hyperuricemia is a metabolic disease caused by elevated uric acid in the body, and is closely related to the increased risk of cardiovascular disease, metabolic disorders, and renal complications. In the development process of uric acid-lowering drugs, activity evaluation is a crucial step. At present, the activity screening methods of uric acid-lowering drugs can be roughly divided into two categories: in vitro and in vivo. In vitro screening is mainly for such targets as xanthine oxidase, urate transporters, and purine nucleoside phosphorylase, etc.; while in vivo screening is achieved by rodent, poultry and organoid models. In this article, the activity evaluation methods for uric acid-lowering compounds are comprehensively summarized both in vitro and in vivo, aiming to provide some insight for the development of uric acid-lowering drugs.

Objective To analyze the clinical outcomes of early invasive fungal disease(IFD)in patients after allogenetic hematopoietic stem cell transplantation(allo-HCST)with metagenomic next-generation sequencing(mNGS).Methods A retrospective analysis was conducted on patients undergoing allo-HCST in our Bone Marrow Transplantation Center between July 2021 and October 2022.These patients experienced one of the following conditions within 100 d after transplantation:① Patients with persistent fever and negative blood culture after empiric antimicrobial therapy for 72 h or longer;② Hyperpyrexia of unknown origin occurred again after effective anti-infection in the past;③ Symptoms in lower respiratory tract associated with lung lesions on CT scan,and empiric anti-infective therapy was ineffective.Peripheral blood or bronchoscopic alveolar lavage fluid were tested with mNGS,and overall survival(OS)and non-relapse mortality(NRM)were analyzed.Results There were 60 patients enrolled in this study.For the peripheral blood samples of 47 cases and bronchoalveolar lavage fluid samples of 13 cases,mNGS found that 19 cases were negative to pathogens,30 cases were non-fungal positive,and 11 case were fungal positive,including 3 cases of aspergillus,5 cases of mucor,2 cases of Candida tropicalis,and 1 case of Trichosporon asahii.Of the 11 patients with fungal positive,8 achieved complete remission after antifungal therapy according to the mNGS results.The 1-year OS and NRM of the 60 patients were 70.0％(95％CI:64.1％～75.9％)and 20.0％(95％CI:11.9％～32.5％),respectively,while those of the fungal infection patients were 54.5％(95％CI:49.5％～69.5％)and 36.4％(95％ CI:15.5％～70.3％),respectively.No significant differences were seen in 1-year OS(P=0.487)and 1-year NRM(P=0.358)among the negative,fungal infection and non-fungal infection patients,neither OS(P=0.238)and NRM(P=0.154)between the fungal infection and the non-fungal infection patients.Conclusion mNGS can rapidly diagnose the early IFD after allo-HSCT,which is helpful for timely and effective treatment and improves the prognosis of patients.

ObjectiveTo observe the effects of electroacupuncture at Zhongwan （CV12） on gastric nociceptive response induced by gastric acid stimulation and explore the underlying mechanisms associated with nuclei of the medullary viscerosensory and visceral motor neurons. MethodsTwenty SD rats were given intragastric administration of 0.5 mol/L diluted hydrochloric acid （0.5 ml/100 g） to induce gastric nociceptive response induction. Eight rats were randomly selected to record the gastric slow wave （GSW） area under the curve， and extracellular discharge frequency of neurons in the nucleus of the solitary tract （NTS） and dorsal motor nucleus of the vagus nerve （DMV） before intragastric administration and at 1， 5， 10， 15， 20， 25， 30， 35， 40， 45， 50， 55， and 60 minutes after intragastric administration. The remaining 12 rats received electroacupuncture intervention at Zhongwan within 5 to 25 minutes after intragastric administration of diluted hydrochloric acid， with a duration of one minute. The GSW area under the curve and extracellular discharge frequency of NTS and DMV neurons were compared between the 1-minute intervals before and after electroacupuncture intervention. ResultsCompared to the baseline before intragastric administration， the area under the curve of GSW significantly increased at 1， 5， 10， 15， 20， and 25 minutes after intragastric administration， and the extracellular discharge frequency of excitatory neurons in the NTS （accounting for 90%， 57/63） significantly increased at 1， 5， 10， 15， 20， 25， 30， 35， and 40 minutes， both reaching peak values at 1 minute after intragastric administration （P＜0.01 or P＜0.05）. The extracellular discharge frequency of inhibitory neurons in the DMV （accounting for 91%， 20/22） showed a non-significant increase at 1 minute after intragastric administration （P＞0.05）， but significantly decreased at other timepoints （P＜0.05）. Compared to the baseline before electroacupuncture intervention， the GSW area under the curve and the extracellular discharge frequency of excitatory neurons in the NTS significantly decreased （P＜0.05）， while the extracellular discharge frequency of inhibitory neurons in the DMV showed no significant difference （P＞0.05）. ConclusionElectroacupuncture at Zhongwan can improve gastric nociceptive response induced by gastric acid stimulation， possibly by reducing the transmission of visceral sensation and decreasing the excitability of NTS neurons in the medulla.

Objective To evaluate the cost-effectiveness of posaconazole compared with voriconazole in the empiric or diagnostic-driven treatment of invasive mould diseases （IMD） in immunocompromised patients from the perspective of Chinese health system. Methods A decision tree model was constructed based on a phase Ⅲ clinical trial and other publicly available data to evaluate the incremental cost-effectiveness ratio （ICER） of posaconazole versus voriconazole. One-way sensitivity analysis, probability sensitivity analysis, and scenario analysis were conducted. Results The results of base-case analysis indicated that, at a willingness-to-pay （WTP） threshold of 3 times Chinese GDP per capita, posaconazole gained 0.0327 quality-adjusted life years （QALYs） with the cost savings of CNY 1 711.24, demonstrating a clear cost-effectiveness advantage. Sensitivity analysis revealed that the cost of voriconazole and posaconazole significantly influenced the ICER. Under different WTP thresholds, posaconazole consistently maintained its economic advantage over voriconazole. Scenario analysis showed that the incidence of mucormycosis did not impact the results, but a price reduction in voriconazole could change result. Conclusion In the empiric or diagnostic-driven treatment of IMD in immunocompromised patients, posaconazole was both an effective and economically viable choice when compared to voriconazole.

Emphasizing symptom efficacy is an important manifestation of the personalized diagnosis and treatment of traditional Chinese medicine （TCM）. However， in current clinical practice of TCM， there are challenges such as diverse symptom expressions， difficulty in standardization， inconsistent evaluation standards for symptom efficacy， lack of universal quantitative methods， and complexity in collecting complete and accurate symptom information. These issues hinder the full and effective utilization of symptom information. Addressing the current research status and existing problems of symptom terminology standardization， quantification and grading of symptom efficacy， and collection of symptom information， this paper proposes methodological strategies for effectively recording and utilizing TCM symptom efficacy information in the era of big data. These strategies include collecting TCM symptom information based on patient reporting， standardizing the evaluation of TCM symptom efficacy from measurement scales and evaluation dimensions， integrating TCM symptom efficacy evaluation into clinical diagnosis and treatment processes， and utilizing artificial intelligence technology to acquire and process TCM symptom efficacy information. TCM symptom efficacy evaluation strategies based on patient perspectives and artificial intelligence technology will help fully explore the value of data elements， promote the objective demonstration of the specific efficacy of TCM， and facilitate the discovery of effective patterns.

Objective To explore the rule of drug use in treating high-risk cervical human papilloma virus(HPV)infection by using data mining method.Methods Medical records and prescriptions of patients with high-risk HPV infection treated at Wang Jin Outpatient Department of Lishui Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University from January 1,2021 to December 1,2022 were collected.SPSS Modeler 18.0 and SPSS 25.0 were used for drug use frequency,association rules,clustering and other data analysis.Results A total of 100 prescriptions were included,involving a total of 162 Chinese materia medicas,with a total of 1445 times of Chinese materia medicas.The drugs with the highest frequency of use were mainly tonic drugs,antipyretic drugs,regulating vital energy drugs and tranquillizing drugs.Complex network analysis showed that there were close correlation among hedyotis,dried tangerine peel,immature tangerine peel,silktree albizia bark and buffalo horn.Three potential new prescriptions were explored.Conclusion The disease was mostly caused by deficiency in origin and excess in pathological products,and the treatment was to treat both symptoms and root causes,and to attack and supplement,with the treatment of clearing heat and removing toxicity,eliminating dampness,benefiting qi for activating blood circulation and nourishing yin,supplemented by nourishing heart for tranquillization.

ObjectiveTo analyze the disciplinary knowledge structure and core competency requirements of exercise rehabilitation and health professionals, based on the World Health Organization (WHO) International Classification of Functioning, Disability, and Health (ICF) and the rehabilitation competency framework (RCF), and to identify the key knowledge, skills, and professional qualities required by professionals in the field of health and rehabilitation, thus providing theoretical foundations for the cultivation of high-quality rehabilitation talent. MethodsBased on the WHO Global Competency Framework for Universal Health Coverage, this study adopted the theories and methods of ICF and RCF to systematically analyze the disciplinary knowledge, skills, five core competency domains, and beliefs and values of exercise rehabilitation and health professionals. This analysis identified the competency framework and content required for these professionals, and provided theoretical support for the development of exercise rehabilitation and health educational programs. ResultsFrom the perspective of health services, this study integrated sports into the four aspects of the health service continuum: prevention, intervention, rehabilitation and health promotion. Exercise rehabilitation and wellness was an applied discipline related to health services, with a focus on prevention, rehabilitation and health promotion. It was a multidisciplinary, interdisciplinary and comprehensive field that encompassed knowledge related to physical education and sports sciences, health sciences, rehabilitation sciences, public health, and health management. The ICF, as a scientific framework for understanding and describing health, functioning and disability, provided an important foundation for the construction of this disciplinary system. Based on the WHO global competency framework and RCF, this study constructed a core competency framework for exercise rehabilitation and health professionals. According to the disciplinary knowledge system and professional competency framework, this study established an educational objective system for undergraduate education program of exercise rehabilitation and health. The overall objective was to cultivate, within the framework of comprehensive health service model, interdisciplinary practitioners who possessed health service knowledge and skills, and were equipped with the competence and professional qualities to engage in physical education, sports and health services. Graduates would be able to provide diverse and high-quality physical education, sports and health services to various populations in a multidisciplinary team. Furthermore, they would possess the potential for professional development and be able to enhance their professional practice, learning and research abilities through further education or continuing education. ConclusionThe establishment of the exercise rehabilitation and health major is a response to the growing demand for interdisciplinary professionals in the sports and health service industry. From the perspective of disciplinary development, this field is a result of the interdisciplinary integration of sports science, health science, rehabilitation science, and health management. Based on the conceptual framework of the ICF, this study has constructed a functioning-based exercise rehabilitation and health disciplinary system, integrating the multidisciplinary achievements of physical education and sports sciences, rehabilitation sciences, health sciences, and health promotion. Based on RCF, it has established a core competency framework for exercise rehabilitation and health professionals, providing competency standards for the development of education program of exercise rehabilitation and health.

To summarize XU Jingshi's clinical experience in treating fever from the perspective of latent pathogen. It is believed that latent pathogen heat accumulation is an important pathogenesis of fever. For latent pathogen in shaoyang and membrane-source， modified Xiaochaihu Decoction （小柴胡汤） plus Qinghao （Artemisiae Annuae Herba） could be used to expel pathogen through membrane and regulate shaoyang； for latent pathogen leading to yin fluids consumption， treatment should clear heat and expel pathogen， and prescribed with Chaihu （Bupleuri Radix）， Huangqin （Scutellaria baicalensis Georgi）， Qinghao （Artemisia carvifolia） combined with Baihu Decoction （白虎汤） or Zhuye Shigao Decoction （竹叶石膏汤） or Qinghao Biejia Powder （青蒿鳖甲散） or Shengmai Decoction （生脉饮） or Siyin Decoction （四阴煎） by syndrome differentiation； for latent pathogen leading to liver wind or reverse transmission to the pericardium， treatment should cool to open pathways， and prescribed with modified Angong Niuhuang Pill （安宫牛黄丸） to clear mind and open the orifices， clear heat and resolve toxins， resolve constraint with aromatics， and expel pathogens to outside； for fever after radiotherapy， chemotherapy or surgery for tumours， prescribed with self-prescribed Fuzheng Anzhong Decoction （扶正安中汤） plus Xiaochaihu Decoction （小柴胡汤） and modified Qinghao Biejia Decoction （青蒿鳖甲汤） to reinforce healthy qi and dispel pathogen， and support the middle jiao.