Correlation of early neurodevelopmental features of children with SYNGAP1 variants and their genotypes / 中华医学遗传学杂志

OBJECTIVE@#To explore the early neurodevelopmental features of young children with SYNGAP1 variants and their genotype-phenotype correlation.@*METHODS@#Young children with neurodevelopmental disorders (NDDs) (< 5 years old) who were referred to the Children's Hospital Affiliated to the Capital Institute of Pediatrics between January 2019 and July 2022 were selected as the study subjects. All children had undergone whole-exome sequencing, comprehensive pediatric neuropsychological assessment, familial segregation analysis, and pathogenicity classification. Meanwhile, young Chinese NDD children (< 5 years old) with pathogenic/likely pathogenic SYNGAP1 variants were retrieved from the literature, with information including detailed clinical and genetic testing, neurodevelopmental quotient (DQ) of the Children Neuropsychological and Behavior Scale-Revision 2016 (CNBS-R2016). Children who did not have a detailed DQ but had their developmental status assessed by a medical professional were also included. The correlation between neurodevelopmental severity, comorbidity and SYNGAP1 variants were summarized.@*RESULTS@#Four young NDD children carrying SYNGAP1 variants were recruited (1 male and 3 females, with a mean age of 34.0 ± 18.2 months), among whom one harboring a novel variant (c.437C>G, p.S146*). Combined with 19 similar cases retrieved from the literature, 23 Chinese NDD young children were included in our study (8 males and 10 females, 5 with unknown sex, with a mean age of 37.1 ± 14.2 months). A loss of function (LOF) variant was found in 19 (82.6%) children. All of the children had presented global developmental delay (GDD) before the age of two. In addition, 16 (69.6%) had seizure/epilepsy at the age of 27.0 ± 12.1 months, among whom 15 had occurred independent of the global developmental delay. Myoclonic and absence were common types of seizures. Compared with those with variants of exons 8 to 15, the severity of developmental delay was milder among children with variants in exons 1 to 5.@*CONCLUSION@#The early neurodevelopment features of the SYNGAP1 variants for young children (< 5 years old) have included global developmental delay and seizure/epilepsy. All of the children may present GDD before the age of two. The severity of developmental delay may be related to the type and location of the SYNGAP1 variants.

Clinical, genetic characteristics and follow-up in 14 patients with transthyretin familial amyloid polyneuropathy / 中华神经科杂志

Objective:To summarize the clinical and genetic characteristics in patients with transthyretin familial amyloid polyneuropathy (TTR-FAP).Methods:Fourteen unrelated TTR-FAP patients diagnosed at Xuanwu Hospital, Capital Medical University from September 2014 to February 2022 were retrospectively reviewed. The clinical manifestation, electrophysiology, cardiac function, biopsy and gene mutation were analyzed.Results:In the 14 patients (13 males, 1 female) diagnosed as TTR-FAP, the mean age at onset was 53.9 years (range: 33.0-71.0 years), with a mean course from symptom-onset to diagnosis of 4.1 years. The late-onset type occurred in 9 cases. Seven patients had a family history of TTR-FAP. Distal paresthesia of lower limbs was the commonest initial symptom (8 cases), with sensorimotor neuropathy and autonomic dysfunction seen initially in 4 and 2 cases, respectively. Cardiac involvement occurred in 6/8 of the patients. Nerve conduction studies indicated extremely axonal impairment with demyelinating features. Sural nerve biopsies showed moderate to severe axonal loss of myelinated fibers and the positive rate of Congo red staining was 8/14. Of 8 different TTR mutations detected, V50M was the most common (appearing in 5 cases). No obvious neuropathy progression was seen in the 5 patients who received tafamidis and 2 patients died of dyscrasia. Conclusions:TTR-FAP is more common in males, with sensorimotor axonal polyneuropathy, autonomic dysfunction and cardiac subclinical damage as the predominant symptoms. V50M is the commonest mutation. Tafamidis can delay the progression of disability.

Construction of Lung Adenocarcinoma Prognosis Model and Drug Sensitivity Analysis Based on Cuproptosis Related Genes / 中国肺癌杂志

BACKGROUND@#Lung cancer is one of the most common malignant tumors in the world, and the current lung cancer screening and treatment strategies are constantly improving, but its 5-year survival rate is still very low, which seriously endangers human health. Therefore, it is critical to explore new biomarkers to provide personalized treatment and improve the prognosis. Cuproptosis is a newly discovered type of cell death, which is due to the accumulation of excess copper ions in the cell, eventually leading to cell death, which has been suggested by studies to be closely related to the occurrence and development of lung adenocarcinoma (LUAD). Based on The Cancer Genome Atlas (TCGA) database, this study explored the association between cuproptosis-related genes (CRGs) and LUAD prognosis, established a prognostic risk model, and analyzed the interaction between CRGs and LUAD immune cell infiltration.@*METHODS@#The RNA-seq data of LUAD tissue and paracancerous or normal lung tissue were downloaded from the TCGA database; the RNA-seq data of normal lung tissue was downloaded from the Genotype-tissue Expression (GTEx) database, and the data of 462 lung adenocarcinoma cases were downloaded from the Gene Expression Omnibus repository (GEO) as verification. T the risk score model to assess prognosis was constructed by univariate Cox and Lasso-Cox regression analysis, and the predictive ability of the model was evaluated by receiver operating characteristic (ROC) curve and calibration curve. Immune-related and drug susceptibility analysis was further performed on high- and low-risk groups.@*RESULTS@#A total of 1656 CRGs and 1356 differentially expressed CRGs were obtained, and 13 CRGs were screened out based on univariate Cox and Lasso-Cox regression analysis to construct a prognostic risk model, and the area under the curves (AUCs) of ROC curves 1-, 3- and 5- year were 0.749, 0.740 and 0.689, respectively. Further study of immune-related functions and immune checkpoint differential analysis between high- and low-risk groups was done. High-risk groups were more sensitive to drugs such as Savolitinib, Palbociclib, and Cytarabine and were more likely to benefit from immunotherapy.@*CONCLUSIONS@#The risk model constructed based on 13 CRGs has good prognostic value, which can assist LUAD patients in individualized treatment, and provides an important theoretical basis for the treatment and prognosis of LUAD.

Recent Advances in Post-operatively New Onset Myasthenia Gravis in Thymoma Patients / 肿瘤防治研究

Patients with thymoma without preoperative myasthenia gravis may develop symptoms of myasthenia gravis after tumor resection. A comprehensive understanding toward this rare clinical phenomenon is lacking. Recent studies indicate that post-operatively new onset myasthenia gravis (ponoMG) is the result of multiple mechanisms and their interactions, which may be related to the thymoma-mediated production, release and long-term presence of abnormal T cells and autoimmune antibodies in the periphery, as well as the presence of ectopic thymus and late recurrence of thymoma. Preoperative antibody titer is the main predictor. The treatment strategy is based on anticholinesterase drugs and hormonal therapy. In this study, we review the incidence, pathogenesis, predictors, and prevention and treatment strategies of ponoMG.

Influencing factors for endoscopic retrograde cholangiopancreatography-related adverse events in novice trainees and establishment of its prediction model: a prospective study / 中华消化外科杂志

Objective:To investigate the influencing factors for endoscopic retrograde cholangiopancreatography (ERCP)-related adverse events in novice trainees and establishment of its prediction model.Methods:The prospective study was conducted. The clinical data of 12 novice trainees of ERCP in the First Hospital of Lanzhou University from July 2016 to July 2019 were selected. The operation was performed by 12 novice trainees of ERCP under the guidance of the endoscopic experts. Observation indicators: (1) ERCP-related adverse events in novice trainees; (2) analysis of influencing factors for ERCP-related adverse events in novice trainees; (3) establishment of a prediction model for ERCP-related adverse events in novice trainees. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed by the t test. Measurement data with skewed distribution were represented as M(range), and com-parison between groups was analyzed by the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed by the chi-square test. The Logistic regression model was used for univariate and multivariate analyses. The regression coefficients were used to construct a prediction model. The receiver operating characteristic curve was drawn, and the area under curve was used to evaluate the predictive ability. Results:(1) ERCP-related adverse events in novice trainees. Of the 300 patients with ERCP operated by 12 novice trainees, 52 cases had ERCP-related adverse events and 248 cases had no ERCP-related adverse events. Cases in grade 1?2 or grade 3?4 of ERCP difficulty classification, score for intubation time, score for cannulation time, cases with or without completion of the cannulation, cases with or with-out basket stone removal, cases with or without stenosis expansion, score for contrast-enhanced interpretation, score for implementation of reasonable treatment and score for expected purpose reached were 22, 30, 8(range, 5?10), 20(rang, 9?20), 24, 28, 11, 41, 0, 52, 39±17, 39±19 and 44±23 for novice trainees with ERCP-related adverse events, versus 146, 102, 6(range, 4?9), 12(range, 8?20), 163, 85, 94, 154, 20, 228, 52±22, 80±20, 52±23 for novice trainees without ERCP-related adverse events, showing significant differences in the above indicators between them ( χ2=4.79, Z=?2.46, ?2.72, χ2=7.01, 5.30, 4.49, t=?4.00, ?2.97, ?2.29, P<0.05). (2) Analysis of influencing factors for ERCP-related adverse events in novice trainees. Results of univariate analysis showed that the diffi-culty classification of ERCP, intubation time, cannulation time, completion of cannulation, basket stone extraction, contrast-enhanced interpretation, implementation of reasonable treatment and expected purpose reached were related factors for ERCP-related adverse events in novice trainees ( odds ratio=1.95, 1.11, 1.08, 0.45, 0.44, 0.97, 0.98, 0.98, 95% confidence intervals as 1.07?3.58, 1.02?1.22, 1.02?1.14, 0.24?0.82, 0.22?0.90, 0.96?0.99, 0.96?0.99, 0.97?1.00, P<0.05). Results of multi-variate analysis showed that difficulty classification of ERCP and contrast-enhanced interpretation were independent influencing factors for ERCP-related adverse events in novice trainees ( odds ratio=2.08, 0.95, 95% confidence intervals as 1.10?3.96, 0.92?0.99, P<0.05). (3) Establishment of a predic-tion model for ERCP-related adverse events in novice trainees. According to the important outcome indicators of clinical training and results of multivariate analysis, 4 indicators including difficulty classification of ERCP, intubation time, cannulation time and contrast-enhanced interpretation were included to establish a prediction model for ERCP-related adverse events in novice trainees, which indicated that trainees with the predicted score >0.4 were in high risk of ERCP-related adverse events. The area under receiver operating characteristic curve of the prediction model was 0.72(95% confidence interval as 0.65?0.79, P<0.05), with the best cut-off value as 0.40, the sensitivity as 76.9% and the specificity as 63.3%. Conclusion:The difficulty classification of ERCP and contrast-enhanced interpretation are independent influencing factors for ERCP-related adverse events in novice trainees. Novice trainees with a predicted score >0.4 are high-risk groups of ERCP-related adverse events.

Effects of anxiety and depression on Internet gaming disorder in medical students： the moderating role of gender / 四川精神卫生

ObjectiveTo explore the effects of anxiety and depression on Internet gaming disorder in medical students， and to evaluate the moderating effect of gender， so as to provide references for the prevention and intervention of Internet gaming disorder in medical students. MethodsIn November 2021， a total of 11 771 medical students from a medical college in Sichuan province participated in an online survey through Wenjuanxing platform. Participants completed the Self-rating Anxiety Scale （SAS）， Self-rating Depression Scale （SDS） and the nine-item Internet Gaming Disorder Scale-Short Form （IGDS9-SF）. Then a hierarchical multiple regression analysis was conducted to discuss the moderating role of gender in the relationships between anxiety， depression and Internet gaming disorder in medical students. Results①Males scored lower on SDS （t=-8.302， P<0.01）， and higher on IGDS9-SF than females （t=33.384， P<0.01）. ②SAS score of medical students was positively correlated with SDS score （r=0.735， P<0.01）， SAS and SDS scores were positively correlated with IGDS9-SF score in medical students （r=0.288， 0.238， P<0.01）. ③Anxiety and depression could positively predict Internet gaming disorder （β=0.245， 0.058， t=18.864， 4.444， P<0.01）. ④Gender played a moderating effect between anxiety and Internet gaming disorder （β=-0.194， t=-4.518， P<0.01）. ConclusionAnxiety and depression have a positive predictive effect on Internet gaming disorder in medical students. Furthermore， the effects of anxiety on Internet gaming disorder are moderated by gender， and the anxiety of male students exhibits a markedly stronger impact on Internet gaming disorder than that of female students.

Standards for the interpretation of constitutional copy number gain: Recommendation from the American College of Medical Genetics and Genomics (ACMG) and Clinical Genome Resource (ClinGen) / 中华医学遗传学杂志

Copy number variants (CNVs) are common causes of human genetic diseases. CNVs detection has become a routine component of genetic testing, especially for pediatric neurodevelopmental disorders, multiple congenital abnormalities, prenatal evaluation of fetuses with structural anomalies detected by ultrasound. Although the technologies for CNVs detection are continuously improving, the interpretation is still challenging, with significant discordance across different laboratories. In 2020, the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) developed a guideline for the interpreting and reporting of constitutional copy number variants, which introduced a quantitative, evidence-based scoring framework. Here, we detailed the key points of interpreting the copy number gain based on the guideline, used six examples of different categories to illuminate the scoring process and principles. We encourage a professional understanding and application of this guideline for the detected copy number gains in China in order to further improve the clinical evaluation accuracy and consistency across different laboratories.

Total saponins of Cornus officinalis Sieb.ameliorates the endothelium dependent relaxation of mesenteric artery by regulating nitric oxide release in streptozotocin-induced diabetic rats / 中南大学学报(医学版)

Objective:To explore the effects of total saponins of Cornus offlcinalis Sieb.(TSCO) on the contractility and relaxation of mesenteric artery in streptozotocin (STZ)-induced diabetic rats.Methods:Sprague Dawley rats were administrated STZ intra-peritoneally at a dosage of 60 mg/kg to induce diabetes.TSCO was administrated at a dosage of 60 mg/kg or 120 mg/kg (per os) to the diabetic rats for 28 days.Glucose and insulin in the serum as well as the responsiveness ofmesenteric artery rings were determined.Results:TSCO decreased the contractile responsiveness to phenylephrine of mesenteric artery rings from diabetic rats,but increased the reactivity to acethylcholine.TSCO (120 mg/kg) ameliorated the baseline release of nitric oxide of mesenteric artery,but had little effect on the induced release of nitric oxide.Rosiglitazone had less effect on the mesenteric artery function than that of TSCO,though it was more effective on lowering blood glucose.Conclusion:The effects of TSCO on mesenteric artery of diabetic rats are dose dependent,and are possibly exerted by lowering blood glucose and ameliorating the release of nitric oxide in the endothelium.

The effects of therapeutic exercise on the expression of Bcl-2 and Bax in neuronal cells after cerebral hemorrhage / 中华物理医学与康复杂志

Objective To investigate the effects of therapeutic exercise(cage running)on the expression of Bel-2 and Bax in neuronal cells after cerebral hemorrhage(ICH)in rats. Methods A total of 120 male Sprague-Dawley rats weighing 270 to 300 g were divided into a trial group(ICH and exercise group,n=40),a control group (ICH only,n=40)and a sham-operated group(sham ICH operation and no exercise,n=40).The brains were removed at 7,14,21 and 28 days after ICH.The activation of Bcl-2 and Bax WaS measured by immunohistochemical techniques,Western blotting and reverse transcriptase polymerase chain reaction(RT-PCR).Results (1)Bel-2-positive and Bax-positive cells appeared in tissues surrounding the hematoma in the cortex.The number of Bcl-2-posotive and Bax-positive cells was nearly zero in the sham-operated group.In the trim group.the number of Bcl-2-positive cells increased significantly from the 21 st to the 28th day.Bax.positive cells decreased from the 7th to the 28th day after ICH when compared with the control group and the sham-operated group.(2)The expression of Bcl-2mRNA and Bax-mRNA as shown by Western blotting and RT-PCR methods was synchronous with the immunohistochemistry results.The peaks of Bcl-2mRNA and BaxmRNA expression were a little earlier than those of Bcl-2 and Bax proteins. Conclusion Exercise can mitigate neuronal cell apoptosis by upregulating the expression of Bcl-2 and Bcl-2 mRNA,and downregulating the expression of Bax and Bax mRNA.

Effect of three extracts of Fufang Dihuang decoction on relaxation of mesentery artery in streptozotocin -induced diabetic rats / 中国临床药理学与治疗学

AIM: To investigate the effects of three extracts of Fufang Dihuang decoction on the relaxation of mesentery artery in streptozotocin(STZ)-induced diabetic rats. METHODS: Diabetic rat model was induced by i.p injection STZ at a dosage of 60 mg?kg~ -1 . 30 d later, 95% ethanol, 70% ethanol or water extract of Radix Rehmanniae was p.o administrated for 30 d at the dosage of 107.8 , 154.7 and 56.8 mg?kg~ -1 , respectively. On the 60th day, the responses of mesentery artery were determined in the absence or presence of L-argine (L-Arg), N-Nitro-L-argine (NLA) and Indomethacin (Ind). RESULTS: The relaxation of mesentery artery of diabetic rat was diminished compared with the normal control. The basal release of NO and the L-argine-induced release of NO decreased 64.6 %, 77.6 % respectively in diabetic group compared with the normal control, with the decreased proportion of NO in the endothelium dependent relaxation. 95% and 70% ethanol extract of Fufang Dihuang decoction ameliorated the impaired release of NO in rat's mesentery artery. CONCLUSION: Abnormal relaxation of mesentery artery in diabetic rat may be due to the decreased releasing of NO. The extracts of Fufang Dihuang decoction can protect the endothelium cells and improve the relaxation of mesentery artery, among them 70% ethanol extract exert the best potency, followed by 95% ethanol extract. And the water extract has a poor effect.