Intellectual disability (ID) is a kind of neurodevelopmental disorder with high clinical and genetic heterogeneity, which seriously endangers the physical and mental health of children. Its etiology is complex, many genetic and environmental factors can participate in the pathogenesis, and metabolic disorders are one of the important etiology. Targeted assays such as plasma amino acids and acylcarnitine and urinary organic acids are of limited use in helping to diagnose and manage these patients. Non-targeted metabolomics has become a tool to explore changes in the metabolites of organisms and a means to study possible biomarkers of such diseases. In recent years, metabolomics technology has made some progress in the etiology and mechanism of ID, providing new ideas and methods for its early recognition, treatment and improvement of prognosis. This paper reviews the progress of non-targeted metabolomics in ID.

Intellectual disability (ID) is a kind of neurodevelopmental disorder with high clinical and genetic heterogeneity, which seriously endangers the physical and mental health of children. Its etiology is complex, many genetic and environmental factors can participate in the pathogenesis, and metabolic disorders are one of the important etiology. Targeted assays such as plasma amino acids and acylcarnitine and urinary organic acids are of limited use in helping to diagnose and manage these patients. Non-targeted metabolomics has become a tool to explore changes in the metabolites of organisms and a means to study possible biomarkers of such diseases. In recent years, metabolomics technology has made some progress in the etiology and mechanism of ID, providing new ideas and methods for its early recognition, treatment and improvement of prognosis. This paper reviews the progress of non-targeted metabolomics in ID.

Börjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked intellectual disability. The main features of the patients include intellectual disability/global developmental delay, characteristic face, anomalies of fingers and toes, hypogonadism, linear skin hyperpigmentation, and tooth abnormalities in female patients, and obesity in male patients. A case of BFLS caused by a novel mutation of PHF6 gene who was treated in the Department of Pediatrics, Xiangya Hospital, Central South University was reported. The 11 months old girl presented the following symptons: Global developmental delay, characteristic face, sparse hair, ocular hypertelorism, flat nasal bridge, hairy anterior to the tragus, thin upper lip, dental anomalies, ankyloglossia, simian line, tapering fingers, camptodactylia, and linear skin hyperpigmentation. The gene results of the second-generation sequencing technology showed that there was a novel heterozygous mutation site c.346C>T (p.Arg116*) of the PHF6 (NM032458.3), variation rating as pathogenic variation. During the follow-up, the patient developed astigmatism, strabismus, awake bruxism, and stereotyped behavior, and the linear skin hyperpigmentation became gradually more evident. The disease is lack of effective therapy so far.
Humans ; Male ; Female ; Child ; Infant ; Intellectual Disability/genetics* ; Mental Retardation, X-Linked/pathology* ; Obesity/complications* ; Hypogonadism/pathology*

More than 100 genes located on the X chromosome have been found to be associated with X-linked intellectual disability (XLID) to date, and NEXMIF is a pathogenic gene for XLID. In addition to intellectual disability, patients with NEXMIF gene mutation can also have other neurological symptoms, such as epilepsy, abnormal behavior, and hypotonia, as well as abnormalities of other systems. Two children with intellectual disability and epilepsy caused by NEXMIF gene mutation were treated in the Department of Pediatrics, Xiangya Hospital, Central South University from March 8, 2017 to June 20, 2020. Patient 1, a 7 years and 8 months old girl, visited our department because of the delayed psychomotor development. Physical examination revealed strabismus (right eye), hyperactivity, and loss of concentration. Intelligence test showed a developmental quotient of 43.6. Electroencephalogram showed abnormal discharge, and cranial imaging appeared normal. Whole exome sequencing revealed a de novo heterozygous mutation, c.2189delC (p.S730Lfs*17) in the NEXMIF gene (NM_001008537). During the follow-up period, the patient developed epileptic seizures, mainly manifested as generalized and absent seizures. She took the medicine of levetiracetam and lamotrigine, and the seizures were under control. Patient 2, a 6-months old boy, visited our department due to developmental regression and seizures. He showed poor reactions to light and sound, and was not able to raise head without aid. Hypotonia was also noticed. The electroencephalogram showed intermittent hyperarrhythmia, and spasms were monitored. He was given topiramate and adrenocorticotrophic hormone (ACTH). Whole exome sequencing detected a de novo c.592C>T (Q198X) mutation in NEXMIF gene. During the follow-up period, the seizures were reduced with vigabatrin. He had no obvious progress in the psychomotor development, and presented strabismus. There were 91 cases reported abroad, 1 case reported in China, and 2 patients were included in this study. A total of 85 variants in NEXMIF gene were found, involving 83 variants reported in PubMed and HGMD, and the 2 new variants presented in our patients. The patients with variants in NEXMIF gene all had mild to severe intellectual disability. Behavioral abnormalities, epilepsy, hypotonia, and other neurological symptoms are frequently presented. The phenotype of male partially overlaps with that of female. Male patients often have more severe intellectual disability, impaired language, and autistic features, while female patients often have refractory epilepsy. Most of the variants reported so far were loss-of-function resulted in the reduced protein expression of NEXMIF. The degree of NEXMIF loss appears to correlate with the severity of the phenotype.
Child ; Epilepsy/genetics* ; Female ; Humans ; Intellectual Disability/genetics* ; Male ; Muscle Hypotonia/complications* ; Mutation ; Phenotype ; Seizures/genetics* ; Strabismus/complications*

Cardio-facio-cutaneous (CFC) syndrome is an extremely rare autosomal dominant genetic disease due to BRAF and other gene mutations. The main characteristics of the patients are craniofacial deformities, cardiac malformations, skin abnormalities, delay of language and motor development, gastrointestinal dysfunction, intellectual disability, and epilepsy. In this case, the child has a typical CFC syndrome face and developmental delay. The gene results of the second-generation sequencing technology showed that there was a mutation site c.1741A>G (p. Asn581Asp) (heterozygous) in exon 14 of the BRAF (NM_004333.5) gene. The mutation was not observed in the child's parents. The above-mentioned mutation may be a de novo mutation. There is no effective therapy for this disease so far.
Abnormalities, Multiple ; Child ; Ectodermal Dysplasia/genetics* ; Facies ; Failure to Thrive ; Heart Defects, Congenital/genetics* ; Humans ; Mutation ; Proto-Oncogene Proteins B-raf/genetics*

Strengthening the performance appraisal of tertiary public hospitals is key to advancing the healthcare system reform in China. Based on the practical experience of performance appraisal of tertiary public hospitals in one city, the authors named the bottlenecks and causes impeding effective implementation of performance appraisal from the aspects of data quality, index orientation, index determination and index calculation. On such basis, they put forward corresponding countermeasures and suggestions, such as effective control of the data quality, dialectical view of the index orientation, scientific allocation of performance indicator weight, and formulation fair and reasonable index scoring methods, aiming to provide references for performance appraisal in the future.

Aurora kinases constitute a highly evolutionarily conserved family of serine/threonine kinases, which includes Aurora A, Aurora B, and Aurora C. These kinases are dynamically distributed throughout the cell cycle, and ensure the normal completion of the cell cycle by regulating centrosome maturation and separation, bipolar spindle assembly and stabilization, accurate separation of chromosomes, and efficient division of cytoplasm during mitosis. In recent years, it has been shown that Aurora kinases are overexpressed in a variety of solid tumors in the human body. The overexpression of Aurora kinases leads to abnormal mitosis, causes genetic instability, and is closely related to the occurrence, proliferation, and poor prognosis of tumors, which indicates that these kinases could be novel anti- tumor targets. Currently, Aurora kinase inhibitors are considered as novel candidates for molecular targeted therapies. Some of these inhibitors with strong anti-tumor activity have even entered clinical trials. In this article, we have reviewed the relationship between the biological characteristics of Aurora kinases, Aurora kinase inhibitors, and the occurrence and development of gastrointestinal tumors.

Objective To explore the clinical efficacy of Da Vinci robot-assisted radical gastrectomy for gastric cancer.Methods The retrospective cohort study was conducted.The clinicopathological data of 472 patients who underwent radical gastrectomy for gastric cancer in the 940 Hospital of the People's Liberation Joint Service from June 2016 to June 2018 were collected.There were 372 males and 100 females,aged (57± 11) years,with a range from 17 to 85 years.Patients underwent gastrointestinal angiography,magnetic resonance imaging,computed tomography or gastrointestinal endoscopy before surgery,and were diagnosed with gastric cancer by biopsy.Of the 472 patients,241 underwent Da Vinci robot-assisted radical gastrectomy for gastric cancer were allocated into robotic group and 231 underwent laparoscopy-assisted radical gastrectomy were allocated into laparoscopic group.Observation indicators:(1) surgical situations;(2) postoperative situations;(3) follow-up and survival.Follow-up using outpatient examination and telephone interview was performed to detect the tumor recurrence and metastasis and survival of patients up to January 30,2019.Measurement data with normal distribution were expressed as Mean±SD,and comparison between groups was done using the t test.Measurement data with skewed distribution were described as M (range).Count data were described as absolute number or percentage,and the chi-square test was used for comparison between groups.Comparison of ordinal data was done using the rank-sum test.The accumulative survival rate,tumor-bearing survival rate and mortality of tumor recurrence were calculated by the Kaplan-Meier method,and Log-rank test was used for survival analysis.Results (1) Surgical situations:472 patients underwent successful operation,with R0 margin.Cases with total gastrectomy + D2 lymph node dissection + Roux-en-Y anastomosis,cases with distal subtotal gastrectomy + D2 lymph node dissection + Billroth Ⅱ anastomosis,operation time,upper margin distance,lower margin distance,tumor diameter,cases with shallow muscular invasion,deep muscular invasion,subserosal invasion and serosal invasion (depth of tumor invasion)were 107,134,(234±44)minutes,(4±3)cm,(6±4)cm,(5 ±3)cm,8,17,32,184 in the robotic group,and 94,137,(239±46)minutes,(4±3)cm,(6±4) cm,(5±3)cm,7,19,30,175 in the laparoscopic group,respectively;there was no significant difference in above indicators between the two groups (x2 =0.200,2.459,t =-1.212,-1.074,-0.420,-1.236,Z =0.171,P＞ 0.05).The volume of i ntraoperative blood loss,number of lymph nodes dissected in total gastrectomy,number of lymph nodes dissected in distal subtotal gastrectomy were (126±113)mL,45±14,and 36±18 in the robotic group,and (149±132) mL,39±14,30± 16 in the laparoscopic group,showing statistically significant differences between the two groups (t=-2.093,3.275,2.195,P＜0.05).(2) Postoperative situations:the time to recovery of gastrointestinal function,time of postoperative abdominal drainage tube removal,and hospitalization cost in the robotic group were (2.6 ± 0.6)days,(5.7± 1.2) days,and (100 157±44 888) yuan,respectively.The above indices of the laparoscopic group were (3.1±0.7)days,(7.0±3.0)days,and (82 220± 18 941)yuan,respectively.There were statistically significant differences between the two groups (t =-5.371,-3.212,5.603,P ＜ 0.05).The duration of postoperative hospital stay was (12±6)days in the robotic group and (12±6)days in the laparoscopic group,with no significant difference between the two groups (t =0.755,P＞ 0.05).Eighteen out of 472 patients had complications.There were 3 cases of anastomotic leakage in the robotic group,2 cases of gastroplegia,1 case of duodenal stump,and 1 case of pulmonary infection,with a incidence of postoperative complication as 2.90％ (7/241).There were 4 cases of anastomotic leakage in the laparoscopic group,1 case of gastroplegia,1 case of duodenal stump,and 3 cases of pulmonary infection,with a incidence of postoperative complication as 3.90％ (9/231).There was no statistically significant difference in the incidence of postoperative complication between the two groups (x2 =1.503,P ＞ 0.05).Patients with digestive tract fistula were re-explored and performed continuous flushing-negative pressure aspiration and nutritional support treatment,and then discharged after improvement.Patients with gastroplegia and lung infection were discharged after corresponding conservative treatment.(3) Follow-up and survival:404 out of 472 patients were followed up for 7-31 months,with a median follow-up time of 19 months,including 212 in the robotic group and 192 in the laparoscopic group.The 3-year survival rates were 96.70％ and 91.67％ in the robotic group and laparoscopic group,with no statistically significant difference between the two groups (x2=1.037,P＞0.05).During the follow-up,the tumor-beating survival rate and mortality of tumor recurrence of the robotic group were 0.47％ and 2.36％,respectively,versus 1.04％ and 6.77％ of the laparoscopic group,with statistically significant differences between the two groups (x2 =3.198,4.208,P＜0.05).Conclusion The Da Vinci robot-assisted radical gastrectomy for gastric cancer is safe and effective,which can reduce volume of intraoperative blood loss,shorten the postoperative recovery time,increase the number of lymph node dissection,however,it will increase the treatment expense.

To investigate the effects of ventricular shunt placement in children with post-infective hydrocephalus.
 Methods: A total of 24 cases of post-infectious hydrocephalus, who received ventricular shunt, were enrolled. Age, gender, disease progression, clinical manifestation, laboratory data, treatment, prognosis, complication, and sequela for each patient were retrospectively reviewed.
 Results: Of the 24 cases, 8 had a full recovery, 11 had slight sequela, 2 had severe sequela, 1 was in vegetative state, and 2 died because of bacterial meningitis and tubercular meningitis. Epilepsy, mental impairment, visual and hearing damage were the main sequelae.
 Conclusion: Ventricular shunt is the preferred treatment in children with post-infective hydrocephalus, which shows positive clinical efficacy and can improve the long-term prognosis of such patients.
Child ; Humans ; Hydrocephalus ; Retrospective Studies ; Treatment Outcome ; Tuberculosis, Meningeal ; Ventriculoperitoneal Shunt

Objective: To summarize the clinical features and gene variation characteristics of a child with Okur-Chung syndrome caused by CSNK2A1 gene variation. Methods: The medical records of one patient who was diagnosed with Okur-Chung syndrome in Department of Pediatrics, Xiangya Hospital of Central South University in July 2018 were analyzed. Using "CSNK2A1" gene as the keyword, relevant information about CSNK2A1 gene was searched at CNKI, Wangfang Data, OMIM, PubMed, ClinVar, Decipher (until August 2018). The characteristics of CSNK2A1 gene variation and the clinical phenotype of children with Okur-Chung syndrome were summarized. Results: The boy, 1 year and 8 months old, was sent to hospital at the age of 1 year and 6 months because of delayed growth for more than 1 year. He was susceptible to cough while eating or drinking. He was also suffering from constipation and poor sleep. Physical examination showed that his body weight was 10.2 kg, microcephalus, broad nasal bridge, micrognathia and hypotonia were observed. Whole exome-sequencing test identified a de novo heterozygous variation c.524A>G (p.D175G) in CSNK2A1 gene. This was the first case report of CSNK2A1 gene variation in the mainland of China. So far, a total of 52 cases were reported worldwide (52 single nucleotide variants), including 35 cases in 7 articles, 9 cases in Decipher database and 14 cases in ClinVar database, 6 of which were also reported in PubMed. In previously reported 52 cases, there were 48 missense variants, whereas, splice and frameshift variations were found in 3 cases and 1 case, respectively. Among the variation sites, p.K198R was the most common sites (12 cases), followed by p.R47 (6 cases), p.R80H (4 cases) and p.S51 (4 cases). Among these 52 cases, only 27 cases have been elaborately described in other studies, so the clinical characteristics were summarized in 28 cases eventually (including 27 cases in the articles and this patient), 27 of whom presented severe intellectual disability or global development delay, 1 case with mild language development delay, and 19 had hypotonia; 8 had autism spectrum disorders, 5 had attention deficit hyperactivity disorder, and 9 had sleep problems. 20 had dysmorphic facial features, 10 of them had microcephalus. 16 had failure to thrive or short stature, 12 had gastrointestinal or oromotor problem, 5 had immunological problem, and 4 had skin abnormalities. Conclusions The main clinical feature of patients with CSNK2A1 gene variations is intellectual disability with multiple systems involved, such as microcephalus, abnormal facial shape and hypotonia. The variation of CSNK2A1 gene is the cause of Okur-Chung syndrome. Missense variation is the main cause, and P. K198R is the hotspot variation.