OBJECTIVE: To delineate the clinical and genetic features of a Chinese girl harboring a rare de novo variant of SYNGAP1 associated with Mental retardation, autosomal dominant 5 (MRD5), and to conduct a comprehensive genotype-phenotype correlation analysis within the Chinese population through an extensive literature review. METHODS: A 5-year-old girl presenting with seizures without an obvious cause was enrolled in September 2020. Genomic DNA was extracted from the patient and her parents. Whole exome sequencing (WES) was performed on the proband to identify suspected pathogenic variants based on her clinical phenotype. Sanger sequencing was used for validation, followed by bioinformatic analysis of the variant. Additionally, data from 54 previously reported Chinese cases with SYNGAP1 variants were integrated to summarize the distribution of variant types and clinical characteristics. Ethical approval was obtained from the Ethics Committee of Kunming Children's Hospital (Ethics No.: 2021-03-055-K01). RESULTS: WES identified a heterozygous nonsense variant, SYNGAP1 c.725G>A (p.Trp242*), in the proband. Sanger sequencing confirmed it was a de novo variant. According to the ACMG guidelines, this variant was classified as pathogenic (PVS1+PS2). Based on the clinical manifestations, the patient was diagnosed with MRD5. Bioinformatic analysis suggested that this variant introduces a premature stop codon at tryptophan 242, disrupting the PH domain and leading to the loss of the C2, Ras-GAP, and C-terminal domains. The pooled analysis of Chinese cases revealed that nonsense (38.2%) and frameshift (36.4%) variants were the predominant types. Intellectual disability/developmental delay was present in 100.0% of patients, epilepsy in 83.6%, and autism spectrum disorder in 41.3%. The incidence of epilepsy differed significantly among variant types (P = 0.045). Exons 8 and 15 were identified as mutation hotspots. CONCLUSION This study has identified a SYNGAP1 c.725G>A variant in the Chinese population and confirmed it as a potential cause of MRD5, which expanded the mutational spectrum of this disorder.
Humans ; Female ; Child, Preschool ; Intellectual Disability/genetics* ; ras GTPase-Activating Proteins/genetics* ; Phenotype ; Exome Sequencing ; Genetic Association Studies

ObjectiveTo explore the typical syndromes and their characteristic of symptoms and signs with high diagnostic value in patients with metabolic syndrome （MS）. MethodsTraditional Chinese medicine （TCM） diagnostic information was collected from 135 MS patients. Syndrome element differentiation and latent class analysis （LCA） were applied to identify the major TCM syndromes in MS patients. Symptoms were analyzed based on the differentiated syndromes， and a binary logistic regression model was constructed to determine symptoms and signs with high diagnostic value. ResultsA total of 135 MS patients were included， involving 163 symptoms and signs with a total frequency of 1749； twenty-three syndrome elements were extracted， 367 times frequency in total， among which 8 syndrome elements occurred ≥10 times with 323 frequencies （88.01% of the total）. These included location-related elements such as kidney （48 times）， spleen （14 times）， and stomach （14 times）， and nature-related elements such as phlegm （71 times）， yin deficiency （64 times）， dampness （57 times）， heat （42 times）， and qi deficiency （13 times）. Based on LCA， the 135 patients were categorized into two groups distinguished by the syndrome elements of dampness and phlegm， forming the "phlegm-dampness syndrome" as the major syndrome type. Nine high-frequency symptoms and signs associated with the phlegm-dampness syndrome were identified，i.e. obesity （39 times）， greasy coating （38 times）， slippery pulse （33 times）， white coating （31 times）， preference for fatty and heavy foods （30 times）， excessive urination （30 times）， fatigue and lack of strength （29 times）， wiry pulse （25 times）， and dark red tongue （25 times）. A binary logistic regression model was constructed combining these nine symptoms and signs with the LCA classification results， ultimately identifying obesity， greasy coating， fatigue and lack of strength， and white coating as independent factors associated with the phlegm-dampness syndrome in MS patients （P＜0.05）. ConclusionThe major TCM syndrome in MS patients is phlegm-dampness syndrome， and obesity， greasy coating， fatigue and lack of strength， and white coating are the typical symptoms and signs for diagnosing phlegm-dampness syndrome in MS patients.

Objective To investigate whether interleukin-37(IL-37)affects macrophage M1 polarization via nu-cleotide oligomerization of structural domain receptor protein 1(NOD1)/nuclear factor κB(NF-κB)in plasma cell mastitis.Methods A total of 15 patients with plasma cell mastitis were recruited according to the collection standard as inflammatory breast tissue and normal breast tissue with a distance of ≥ 3 cm from the edge of the in-flammatory breast tissue.QPCR was performed to detect NOD1 and IL-3.Phorbol ester(PE)was used to induce THP-1 cells to differentiate into resting macrophages(M0).Lipopolysaccharide(LPS)combined with interferon(IFN-γ)was used to induce the polarization of M0 macrophages towards the M1 phenotype.NOD1 lentiviral RNA interference or over-expression vectors were constructed to regulate the expression of NOD1 in M1 macrophages.M0 macrophages were pretreated with IL-37 recombinant protein and then incubated with LPS and IFN-γ for induction.The expression of NOD1,IL-37,M1 markers(IL-6 and iNOS)and M2 markers(IL-10 and Arg-1)was quantified by qPCR.Western blot was employed to assess the protein level of NOD1,NF-κB p65,and p-NF-κB p65.Co-immunoprecipitation was used to detect the interaction between NOD1 and IL-37.Results Up-regulation of NOD1 and down-regulation of IL-37 as were found in inflammatory breast tissues(P＜0.05).Compared to M0 cells,M1 cells showed up-regulated NOD1 and M1 markers and the elevated phosphorylated NF-κB p65 but the down-regulated IL-37(P＜0.05).In M1 macrophages,both NF-κB inhibitor and NOD1 knockdown led to the down-regulation of NOD1 and M1 markers and caused a decrease in the phosphorylated NF-κB p65(P＜0.05).IL-37 recombinant protein decreased phosphorylation of NOD1,M1 marker and NF-κB p65,which was reversed by over-expression of NOD1.IL-37 may interact with NOD1(P＜0.05).Conclusions IL-37 may inhibit M1 polarization in macrophages by down-regulating NOD1/NF-κB pathway thereby preventing plasma cell mastitis progression.

Objective To investigate the correlations of serum stromal cell-derived factor-1(SDF-1),chemokine receptor 7(CXCR7)and vascular density in the optic disc area with clinical stages in patients with normal-tension glaucoma(NTG).Methods A total of 157 patients with NTG were included in the NTG group and divided into stage Ⅰ group(n=29),stage Ⅱ group(n=88),and stage Ⅲ group(n=40)based on different clinical stages;additionally,56 healthy individuals with physical examinations in the same period were selected as control group.Serum SDF-1 and CXCR7 levels were compared between the NTG group and the control group;changes in vascular den-sity in the optic disc area among patients with different clinical stages were analyzed;the multivariate Logistic regression analysis was conducted to explore the risk factors for NTG.Results Compared with the control group,the NTG group had significantly increased serum levels of SDF-1 and CXCR7(P＜0.05).Compared with the control group,patients in the NTG group showed significantly decreased densities of large vessels,capillaries,and the entire area,as well as significantly increased density of avascular areas(P＜0.05).The densities of capillaries and the entire area were significantly lower in the stage Ⅱ group and stage Ⅲ group than the stage Ⅰ group,while the density of avascu-lar areas was significantly higher(P＜0.05).The densities of large vessels(r=-0.503,P=0.006),capillaries(r=-0.546,P＜0.001),and the entire area(r=-0.553,P＜0.001)were negatively significantly correlated with clinical stages,while the density of avascular area was positively significantly correlated with clinical stages(r=0.521,P=0.002).The proportions of patients with hypertension,history of alcohol consumption,family history of glaucoma,and high ser-um levels of SDF-1 and CXCR7 in the NTG group were significantly higher than those in the control group(P＜0.05).Multivariate Logistic regression analysis revealed that hypertension,family histo-ry of glaucoma,history of alcohol consumption,and high serum levels of SDF-1 and CXCR7 were risk factors for NTG(P＜0.05).Conclusion Patients with NTG have significantly increased ser-um levels of SDF-1 and CXCR7.The densities of large vessels,capillaries,and the entire area are negatively correlated with clinical stages,while the density of avascular areas is positively correlated with clinical stages.Serum levels of SDF-1 and CXCR7 can serve as effective reference indicators for the diagnosis and clinical staging of NTG.

The signaling pathways involved in acupuncture intervention in post-stroke depression (PSD) mainly include cAMP signaling pathway, MAPK signaling pathway, PI3K/Akt/mTOR signaling pathway, NF-κB signaling pathway, CREB signaling pathway, and CaMK signaling pathway. A variety of regulatory networks are formed between these signaling pathways, which play a key role in reducing inflammation, inhibiting apoptosis, improving neuroplasticity, promoting angiogenesis, and protecting neurons.

Acupuncture has a certain effect for the patients with post-stroke depression. In clinics, acupuncture treat this disease from the brain, liver and kidney, heart and spleen, and phlegm and blood stasis. Acupuncture plays a role in nourishing the bone of marrow, regulating the liver and kidney, nourishing the heart and mind, and invigorating the spleen and stomach. Acupuncture plays an antidepressant role by regulating neurotransmitters and receptors, promoting nerve function repair, inhibiting the secretion of inflammatory factors, reducing inflammatory response, inhibiting the hyperfunction of hypothalamic-pituitary-adrenal axis, and regulating the brain-gut axis.

Objective To explore the regulation of DIRAS2 gene expression by acetylated STAT3 and its involvement in the proliferation of triple-negative breast cancer(TNBC)cells.Methods The expression levels of DIRAS2 and acetylated STAT3 in TNBC tissues and cells were analyzed by database query,Western blotting,and qRT-PCR.TNBC cell lines MDA-MB-231 and SUM159 were selected,and lentivirus or plasmid was used to construct DIRAS2 overexpression and STAT3 wild or Lys685 mutation cell lines.The CCK-8 assay was used to evaluate the effect of DIRAS2 and STAT3 acetylation on the proliferation of TNBC cells.Western blotting,pyrosequencing,ChIP and IP were employed to investigate the regulatory effect and mechanism of acetylated STAT3 on DIRAS2 expression.Results The expression of DIRAS2 was decreased in TNBC tissues and cells.Pyrosequencing analysis found that the methylation level of CpG islands in the DIRAS2 promoter was increased in TNBC cells compared with normal breast epithelial cells,which promoted the growth of cancer cells.Furthermore,TNBC cells showed an increase in STAT3 acetylation,which was accompanied by a shift in the methylation status of the DIRAS2 promoter.ChIP and IP experiments showed that acetylated STAT3 could bind to the DIRAS2 promoter,and the STAT3 Lys685 mutation disrupted the interaction between STAT3 and DNMT1.Conclusion Acetylated STAT3 induces DIRAS2 promoter methylation by recruiting DNMT1,leading to loss of DIRAS2 expression and cancer cell proliferation in TNBC.

AIM: To analyze and compare the efficacy of binocular visual perception training and suspended vision trainer in postoperative rehabilitation of strabismus.METHODS: A total of 96 children who received surgical treatment from July 2022 to September 2023 were included in the study subjects, and they were group A(n=32), group B(n=32)and group C(n=32). After operation, binocular visual training, visual perception training and suspension vision trainer were used to compare the efficacy among groups.RESULTS: The changes of simultaneous visual function, fusion visual function, stereoscopic visual function, perceptual eye position(horizontal and vertical)and CIXTQ of the three groups of children were observed before training and at 3 mo after training, and the study found that the simultaneous visual function recovered differently at 3 mo after training, with the best recovery in the group B(all P<0.05); there were no significant differences in fusion visual function of the groups A and B(P>0.05), but there were statistical significance in fusion visual function among the three groups(all P<0.05); and there were no significant differences in recovery rate of stereoscopic visual function among the three groups(P>0.05). The improvement of perceptual eye position of the group B, either horizontally or vertically, was better than that of both the group A and group C(all P<0.05).CONCLUSION: Visual perception training has a higher value in the simultaneous visual function, fusion function, stereoscopic visual function, perceptual eye position and quality of life in children with strabismus.

OBJECTIVE To explore the surgical approach and method for treating giant sternal goiter through the neck. METHODS A retrospective analysis was conducted on the clinical data of 31 patients with massive retrosternal goiter admitted to the Department of Otolaryngology Head and Neck Surgery at Southeast University Affiliated Zhongda Hospital from January 2016 to December 2022. RESULTS All patients underwent complete tumor resection through a low neck neck incision,with an average surgical time of 131.64 minutes and an average blood loss of 80 ml. Surgical methods:Total thyroidectomy in 18 cases,left lobe and isthmus resection in 9 cases,and right lobe and isthmus resection in 4 cases. Two cases were transferred to the intensive care unit for transition after surgery,and the remaining 29 cases were all returned to the general ward;No deaths have occurred;Postoperative pathology:The postoperative pathological types were nodular goiter in 21 cases,papillary thyroid carcinoma in 4 cases,follicular thyroid tumors in 2 cases,follicular thyroid carcinoma in 2 cases,large B-cell lymphoma in 1 case,and thyroid borderline tumor in 1 case. Follow up for 6 months to 3 years,with no recurrence cases. CONCLUSION The surgical treatment of huge thyroid nodules behind the sternum through the cervical approach requires thorough preoperative evaluation,understanding of surgical indications,and the use of a low neck incision. During the operation,the main blood vessels supplying the thyroid gland are gradually ligated,separated,and the huge thyroid nodules are pulled out from behind the sternum,successfully and completely removed from the neck,avoiding open chest surgery,reducing the occurrence of related complications,and shortening the patient's course of illness.

OBJECTIVE To explore the clinical characteristics,diagnosis and treatment of primary hyperparathyroidism(PHPT),and to improve the diagnosis and treatment ability of this disease.METHODS The clinical data of 27 patients with PHPT admitted to Southeast University Affiliated Zhongda Hospital from January 2016 to June 2023 were retrospectively analyzed,and the clinical characteristics,preoperative diagnosis,surgical treatment and postoperative follow-up were summarized.RESULTS All patients had elevated serum calcium and parathyroid hormone before operation,and were diagnosed before operation.All patients underwent parathyroidectomy with low neck incision,19 underwent unilateral parathyroidectomy and 8 underwent bilateral parathyroidectomy.PTH was rapidly detected 10 min after resection of the diseased gland,all 27 cases terminated surgery after PTH decreased by more than 50%.All patients experienced no postoperative complications such as hoarseness and coughing due to diet.There were 20 cases diagnosed pathologically as parathyroid adenoma and 7 cases diagnosed as parathyroid hyperplasia after operation.After operation,15 patients had short-term hypocalcemia,the hypocalcemia patients were treated with calcitriol and calcium for 2-4 weeks and their blood calcium returned to normal.and one patient was slightly higher than normal value,the hypercalcemia returned to normal about one week after operation.The remaining patients had normal serum calcium after operation.The parathyroid hormone returned to normal in 27 patients within 6 months.All patients were followed up for 6 months to 6 years,and no one recurred.CONCLUSION Parathyroidectomy is the best treatment for PHPT.Preoperative imaging location and intraoperative PTH measurement are helpful to narrow the exploration range,shorten the operation time and reduce the complications.