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

ObjectiveTo investigate the clinical efficacy of Huangqi injection combined with Buzhong Yiqi acupuncture in the treatment of chronic fatigue syndrome （CFS） with Qi deficiency and its effects on TCM syndromes， fatigue symptoms， serum superoxide dismutase （SOD）， malondialdehyde （MDA）， and oxidized low-density lipoprotein （ox-LDL） levels. MethodA total of 200 patients with CFS of Qi deficiency were randomly divided into a control group （100 cases） and an observation group （100 cases）. The control group was treated with vitamin B compounds， and the observation group was treated with Huangqi injection combined with Buzhong Yiqi acupuncture for two weeks. The scores of TCM syndromes， fatigue symptoms， levels of serum SOD， MDA， and ox-LDL and the incidence of adverse reactions were observed and compared before and after treatment in two groups. ResultAfter treatment， the total effective rate of the control group was 54.34% （50/92）， while that of the observation group was 88.54% （85/96）. The total effective rate of the observation group was higher than that of the control group （χ²=27.13，P<0.05）. Compared with those in the two groups before treatment， scores of fatigue self-assessment scale （FSAS）， physical fatigue and mental fatigue， and sleep/rest response scores of fatigue in the two groups after treatment were significantly decreased （P<0.05）. After treatment， scores of FSAS， physical fatigue and mental fatigue， and sleep/rest response scores of fatigue in the observation group were significantly decreased compared with those in the control group （P<0.05）. Compared with those in the two groups before treatment， TCM syndrome scores in the two groups after treatment were significantly decreased （P<0.05）. After treatment， TCM syndrome scores in the observation group were significantly decreased compared with those in the control group （P<0.05）. Compared with those in the two groups before treatment， MDA levels in the two groups were significantly decreased （P<0.05）， ox-LDL levels in the observation group were significantly decreased （P<0.05）， and SOD levels were significantly increased （P<0.05）. After treatment， compared with those in the control group， the serum MDA and ox-LDL levels in the observation group were significantly decreased （P<0.05）， and the serum SOD was significantly increased （P<0.05）. No serious adverse events or adverse reactions occurred during this clinical trial. ConclusionHuangqi injection combined with Buzhong Yiqi acupuncture has a good clinical curative effect in the treatment of CFS with Qi deficiency， which can effectively improve the fatigue symptoms of patients， increase the level of SOD， and reduce the level of serum MDA and ox-LDL. It is related to the production of antioxidants， inhibiting the production of lipid peroxides， and improving the body's ability to resist oxidative stress.

OBJECTIVE：To systematically evaluate clinical efficacy of L-carnitine in the treatment of male infertility ，and to provide evidence-based reference for clinical treatment of male infertility. METHODS ：Retrieved from CNKI ，Wanfang database ， VIP，CBM，PubMed，Embase and the Cochrane library ，randomized controlled trials （RCTs）about L-carnitine and other chemical drugs in the treatment of male infertility were collected during the inception to Apr. 12th，2020. After data extraction of included literatures and quality evaluation with modified Jadad scale ，Meta-analysis was conducted by using RevMan 5.3 software. RESULTS：A total of 8 RCTs were included ，with 520 patients. The results of Meta-analysis showed that compared with other chemical drugs ，L-carnitine could significantly enhance the semen volume [MD＝0.55，95％CI（0.20，0.91），P＝0.002] and sperm mortality rate [MD＝1.60，95％CI（0.50，2.69），P＝0.004] of male infertility patients ，with statistical significance. There was no statistical significance in sperm count [MD＝4.00，95％ CI（－3.15，11.15），P＝0.27]，the percentage of forward motile sperm [MD＝12.58，95％CI（－3.87，29.03），P＝0.13]，and the percentage of inducing pregnancy rate [OR＝0.85，95％CI（0.47，1.52），P＝ 0.58] of male infertility patients. CONCLUSIONS ：L-carnitine can significantly improve the semen volume and sperm mortality of male infertility patients ，and has the same effects as other drugs on improving sperm count ，percentage of forward motile sperm and percentage of inducing pregnancy rate.

Objective: To explore the method of relieving intestinal obstruction in patients with recurrent cervical cancer accompanied with intestinal obstruction after radical radiotherapy. Methods: The data of 10 recurrent cervical cancer patients accompanied with high risk weak constitution and intestinal obstruction after radical radiotherapy from May 2012 to May 2018 were retrospectively analyzed, including preoperative radiotherapy dose, physique and obstruction status, operation time, operation blood loss, postoperative digestive tract patency and diet. All of the 10 patients with cervical cancer recurrence accompanied with intestinal obstruction and disturbance of independent walking after radical radiotherapy. Results: The median fasting time of the 10 patients was 21 days, the median weight was 35.5 kg, the median body mass index (BMI) was 13.3 kg/m^2, the median value of hemoglobin was 67 g/L, and the median value of platelet was 44×10⁹ /L. All of the patients underwent enterostomy. the median operation time was 6.0 min and the median amount of bleeding was 5.0 ml. All of the patients defecated after operation, fed on the first day after operation, and were able to walk on their own 5 days after operation. Conclusions Although the cervical cancer patients with recurrent intestinal obstruction after radical radiotherapy are extremely weak, some patients still have the opportunity to relieve intestinal obstruction if the treatment strategy and surgical method are appropriate.

Objective To explore the impact of family education methods and parental rearing or not on the psychological problem tendency of primary school students.Methods The mental health test (MHT) was used on getting mental health data of the 2 838 primary school students from Dongguan city.Results (1) The results of MHT showed that 94.28％ of primary school students had no psychological problems,the tendency rate of psychological problems was 4.29％,and 1.43％ of them were suffering from serious psychological problems.Learning anxiety,physical symptoms and allergy tendency were more prominent.(2) The total MHT scores of primary school students with authoritarian,democratic,permissive and neglected family education methods were (34.84±14.58),(31.04±13.60),(35.19±12.82) and (41.19±13.10)respectively.There was no statistically significant difference in the terrorist tendency dimension scores of primary school students with different education methods (F=2.33,P=0.054),and the differences in the MHT total score and other dimensions were statistically significant (F=4.35-16.88,P＜0.01).(3) There were statistically significant differences in the scores of the total score of psychological problem tendency,dimensions of learning anxiety,anxiety to people,allergy tendency and impulse tendency of primary school students who were parental rearing or not (t=2.09-3.67,P＜0.05).However,there was no statistically significant difference in the dimensions of loneliness tendency,self-accusation tendency,physical symptoms and terrorist tendency (P＞0.05).Conclusion Family education methods and parenting styles has a impact on the mental health of primary school students.

Cardiogenic shock is caused by dysfunction of the cardiac pump,resulting in multiple or-gan failure and metabolic disturbances. Because of its rapid onset,various manifestations,rapid progress and high mortality rate,it becomes one of the critical diseases in pediatrics. Early diagnosis and active treatment is the key to improve prognosis. The application of hemodynamic monitoring and mechanical circulatory assist devices play an increasingly important role in the treatment of cardiogenic shock in children.

Objective To investigate the clinical efficacy of Dahuang Xiaozhi Suppository combined with tetracycline in treating type Ⅲ prostatitis infected with nano-bacteria. Methods Totally 120 patients of type Ⅲprostatitis infected with nano-bacteria were randomly divided into treatment group and control group, with 60 cases in each group. Both groups were disabled anti-infective drugs and other preparations for diet and life intervention. Both groups received tetracycline, once a tablet, twice a day, orally. The treatment group received Dahuang Xiaozhi Suppository, once a capsule, once a day, placing in the anus 3-4 cm. 10 d was a treatment course, for 3 courses. The clinical efficacy, major symptoms improving time, NIH-CPSI, leukocyte count and ecithin corpuscles in expressed prostatic secretion (EPS), urinary flow rate, and cytokine content of TNF-α, IL-6, IL-8, were evaluated. Results The total effective rate was 100.0% (60/60) in treatment group and 83.3% (50/60) in the control group, and treatment group was higher than the control group (P<0.05). Pelvic pain, urinary symptom, and scrotum wet improvement time of treatment group were lower than the control group (P<0.05). Compared with before the treatment, the NIH-CPSI pain scores, urinary symptom scores, life quality score, leukocyte count and TNF-α, IL-6, IL-8 content of EPS in both groups were significantly lower after treatment (P<0.05), and the cases with lecithin corpuscles +++ - ++++ in both groups significantly increased after treatment (P<0.05). The urinary peak flow rate and mean flow rate in both groups were higher after treatment (P<0.05). There was statistical significance in the scores of NIH-CPSI pain, urinary symptom and life quality, leukocyte count and TNF-α, IL-6, IL-8 content of EPS, and the cases with lecithin corpuscles ++++ between the two groups (P<0.05). Conclusion Dahuang Xiaozhi Suppository can improve the efficacy of treating type Ⅲ prostatitis infected with nano-bacteria. Combining Dahuang Xiaozhi Suppository with tetracycline can reduce prostate inflammation, with obvious efficacy.

OBJECTIVE: To compare the changes in muscle enzyme between children with myocarditis and Duchene/Becker muscular dystrophy (DMD/BMD), and to seek the explanations for variation.
 METHODS: The retrospective analysis for 83 myocarditis children (myocarditis group) and 69 DMD/BMD children (DMD/BMD group), who were collected from Department of Pediatric of Shengjing Hospital affiliated to China Medical University since January 2008 to May 2015, was carried out. At the same time, 24 healthy children from the Department of Pediatric Development served as a control group. The examination indexes included creatine kinase (CK), creatine kinase-isoenzyme MB (CK-MB), creatine kinase isoenzyme MB mass (CK-MB mass), cardiac troponin I (cTnI) and high-sensitive-cTnT (hs-cTnT).
 RESULTS: 1) In the myocarditis group, the CK increased from 100 to 1 000 U/L, reached a peak after 5 days, which lasted for a week and then dropped to the normal; the CK-MB reached a peak after 5 to 7 days and dropped to the normal a month later; the CK-MB mass reached a peak on the first day and dropped to the normal after 3 weeks; the cTn reached to a peak after 5 days and dropped to the normal after about 17 days; hs-cTnT reached to a peak on the first day and dropped to the normal after about 19 days. 2) In the DMD/BMD group, the CK increased significantly and 27 cases had a CK value of more than 10 000 U/L. After the treatment for 1 to 2 weeks, their enzyme rose again after a slight drop. In terms of cTnI, 6 cases showed a moderate increase, 5 of them couldn't drop to the normal level until more than 3 weeks later; the hs-cTnT increased in the 45 cases, which lasted for more than 3 weeks in the 31 cases of them and showed a tendency of persisting increase.
 CONCLUSION The cTnI and hs-cTnT rise significantly and possess wider observation window than CK and CK-MB mass in myocarditis children, with more sensitive and specific changes. The myocardial damage can occur before myasthenia and keep this trend for a long time in the DMD/BMD children. The trend of cTnI change in myocarditis children is similar to hs-cTnT, while hs-cTnT in DMD/BMD children is more sensitive than cTnI.
Biomarkers ; Child ; China ; Creatine Kinase ; blood ; metabolism ; Creatine Kinase, MB Form ; blood ; metabolism ; Female ; Humans ; Male ; Muscle Weakness ; enzymology ; Muscular Dystrophy, Duchenne ; enzymology ; therapy ; Myocarditis ; enzymology ; therapy ; Retrospective Studies ; Time Factors ; Troponin I ; blood ; metabolism ; Troponin T ; blood ; metabolism

Objective To investigate the effects of heme oxygenase-1 (HO-1) protein transduction mediated by cell penetrating peptide PEP-1 on intestinal injury in a rat model of sepsis induced by cecal ligation and puncture (CLP).Methods Twenty-four healthy male Sprague-Dawley rats,aged 7-9 weeks,weighing 210-260 g,were randomly divided into 4 groups (n =6 each) using a random number table:sham operation group (group S),group CLP,low-dose fusion protein PEP-1-HO-1 + CLP group (group P1) and high-dose fusion protein PEP-1-HO-1 + CLP group (group P2).Fusion protein PEP-1-HO-1 0.3 mg was administrated via the left iliac vein at 1 h before CLP and 5 h after CLP in group P1.Fusion protein PEP-1-HO-1 0.6 mg was administrated via the left iliac vein at 1 h before CLP and 5 h after CLP in group P2.The equal volume of normal saline was given instead of PEP-1-HO-1 in the other groups.The animals underwent laparotomy,but the caecum was not ligated or punctured in group S.Blood samples were collected at 12 h after CLP from the right common carotid artery for measurement of serum TNF-α and IL-6 levels.The rats were then sacrificed and intestines were removed for microscopic examination and for determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in intestinal tissues.Results Compared with group S,the serum TNF-α and IL-6 levels,and MDA content in intestinal tissues were significantly increased,while SOD activity in intestinal tissues was decreased in CLP,P1 and P2 groups.Compared with group CLP,the serum TNF-α and IL-6 levels,and MDA content in intestinal were significantly decreased,while SOD activity in intestinal tissues was increased in P1 and P2 groups.Compared with group P1,the serum TNF-α and IL-6 levels,and MDA content in intestinal tissues were significantly decreased,while SOD activity in intestinal tissues was increased in group P2.The pathological changes of intestines were significantly mitigated in P1 and P2 groups as compared with group CLP.Conclusion HO-1 protein transduction attenuates intestinal injury induced by sepsis in rats,and the mechanism is related to inhibition of systemic inflammatory responses and lipid peroxidation in intestinal tissues.

BACKGROUND:At present, the development of reprogramming technology provides a wide prospect for stem cellresearch. Through the ectopic co-expression of reprogramming factors, the somatic cells can be reprogrammed to a pluripotent state, termed as induced pluripotent stem cells, which can avoid the ethical controversy faced in the research and application of embryonic stem cells. Also, we can generate patient-specific and disease-specific induced pluripotent stem cells, which significantly decrease immuno-rejection. However, reprogramming technology faces some chal enges, such as low efficiency and safety.
OBJECTIVE:Based on the characteristics of induced pluripotent stem cells and the principles of reprogramming, to detail the progress in reprogramming technology from five aspects, including cellresources, carriers, transcription factors, microRNA and signal transduction pathway. 
METHODS:A computer-based online retrieval was performed to search papers published form January 1990 to April 2013 in VIP periodical ful-text database, Wanfang periodical ful-text database, CNKI periodical ful-text database, PubMed database and Springer database with key words of“reprogramming, induced pluripotent stem cell, signal transduction pathway, epigenetics, microRNA, transcription factor, vector, somatic cell, smal molecule compound, safety”both in Chinese and English. After excluding objective-independent papers, 67 papers were included for further analysis.
RESULTS AND CONCLUSION:By exploring different cellresources, different carriers, various combination of transcription factors, microRNAs or inhibition of the signal transduction pathways, the reprogramming efficiency and safety have been improved greatly. However, currently, induced pluripotent stem cells stil could not meet the requirement of clinical application. To achieve the clinical application of induced pluripotent stem cells, it is urgent to explore the mechanism of reprogramming, and to optimize the programming strategy.