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

Ten-eleven translocation 2 （TET2）， as a core enzyme in epigenetic regulation， dynamically regulates the differentiation and function of CD4⁺ T cells by mediating DNA demethylation. Recent studies have shown that TET2 deficiency can promote the progression of autoimmune hepatitis （AIH） by disrupting the Th17/Treg balance and activating inflammatory signals along the gut-liver axis. This article systematically reviews the bridging role of TET2 between CD4⁺ T cells and gut microbiota， explores the molecular mechanisms by which it drives AIH through the gut microbiota-epigenetics-immunity network， and discusses the potential intervention strategies targeting the TET2-microbiota axis.

ObjectiveTo investigate the current status of HIV-related health service uptake among cross-border couples (Chinese husbands and Myanmar wives) in Dehong Dai and Jingpo Autonomous Prefecture (hereinafter referred to as Dehong Prefecture), and to provide evidence for optimizing HIV prevention and control strategies in border areas. MethodsA cross-sectional survey was conducted from September 2022 to September 2023 among 14 662 cross-border couples (Chinese husbands and Myanmar wives) in Dehong Prefecture. Data on sociodemographic characteristics, HIV/AIDS knowledge awareness, and utilization of HIV-related health services within the past year were collected. Multivariable logistic regression was used to analyze factors associated with HIV testing uptake among husbands and wives. ResultsA total of 29 324 individuals (14 662 couples) were included. The overall awareness rate of HIV/AIDS was 82.09%, with the rate among husbands significantly higher than that among wives (85.17% vs. 79.01%, P<0.001). Overall, 94.98% of participants had received at least one HIV-related health service, and the HIV testing rate in the past year was 65.52%. Multivariable logistic regression analysis showed that, compared with participants married for 0‒3 years, those married for 4‒10 years and ≥11 years were more likely to have received HIV testing. The corresponding ORs were 1.344 (95%CI: 1.187‒1.521) and 1.381 (95%CI: 1.211‒1.574) among husbands, and 1.308 (95%CI: 1.155‒1.481) and 1.344 (95%CI: 1.178‒1.533) among wives, respectively. Compared with those holding a marriage certificate, those possessing a border marriage registration certificate were positively associated with HIV testing uptake, with ORs of 1.710 (95%CI: 1.575‒1.857) among husbands and 1.700 (95%CI: 1.565‒1.847) among wives. Compared with illiterate participants, those with primary school education showed lower testing rates, with ORs of 0.738 (95%CI: 0.650‒0.837) among husbands and 0.827 (95%CI: 0.766‒0.891) among wives. Additionally, a history of sexually transmitted diseases (OR=3.656, 95%CI: 1.243‒15.589) and participation in the New Rural Cooperative Medical Scheme (OR=1.51, 95%CI: 1.179‒1.935) were independently associated with higher testing rates among husbands. ConclusionThe overall utilization of HIV-related health services among cross-border couples in Dehong Prefecture is satisfactory, but significant gender disparities exist, with foreign wives showing lower rates of knowledge awareness and lower proportions obtaining such knowledge through certain channels compared with their Chinese husbands. Couples with shorter marriage duration, those with primary school education, and those not included in the border marriage registration system are vulnerable groups with lower HIV testing uptake. Future interventions should prioritize cross-border marriage families at the early stage of entry and in the newly married period. Based on the border marriage registration management system and primary healthcare networks, health education and HIV testing services targeting foreign spouses should be strengthened to improve service accessibility and equity.

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.

Objective To compare the efficacy of endoscopic parotidectomy through postauricular incision with conventional incision parotidectomy.Methods A total of 60 parotid tumor patients admitted to Zhejiang Cancer Hospital from March 2023 to March 2024 were selected as the study subjects.Thirty patients had the requirement for small scar cosmetic surgery,and the endoscopic parotid tumor resection of the posterior ear were in endoscopic group,and remaining 30 patients underwent traditional open surgery at the same period in open group.Two groups were compared in terms of operation time,intraoperative blood loss,postoperative drainage volume,length of hospital stay,postoperative complications,nursing satisfaction,and incision satisfaction at one month postoperatively.Results Endoscopic group had significantly lower drainage volume,hospital stay,and postoperative complications than open group,there were significant difference between two groups(P＜0.05).The nursing satisfaction and incision satisfaction in endoscopic group were significantly higher than those in open group(P＜0.05).Conclusion Efficacy of endoscopic parotidectomy through postauricular incision postoperative recovery was faster,the hospitalization time was shorter,and the postoperative complications were less.Perioperative optimization nursing in the endoscopic group improved patient satisfaction,which is worth promoting clinically.

Objective To summarize the effect of standardized perioperative nursing management in the treatment of early hypopharyngeal carcinoma and precancerous lesions with endoscopic submucosal dissection(ESD).Methods A total of 43 patients who underwent ESD treatment for hypopharyngeal mucosal lesions in Zhejiang Cancer Hospital from June 1,2018 to June 1,2023 were selected as the study objects,and 12 patients who underwent ESD treatment from June 1,2018 to November 30,2020 were divided into control group,and 31 patients who underwent ESD treatment from December 1,2020 to June 1,2023 were divided into observation group,the control group received routine perioperative nursing management,and the observation group received standardized perioperative nursing management.Observation indicators were compared between two groups.Results Intubation method,operation time,postoperative exposure satisfaction,postoperative pain score,and hospital length were significant between two groups(P＜0.05).Conclusion ESD treatment of early hypopharyngeal cancer and precancerous lesions with standardized perioperative nursing management effect is good,can increase the surgical area exposure satisfaction,shorten the operation time and hospital stay,reduce patients'postoperative pain and discomfort,help patients to recover.

Objective:To explore the CT and MRI features of Rosai-Dorfman disease (RDD) in nasal cavity and paranasal sinus.Methods:The study was a cross-sectional study. From July 2007 to August 2023, the imaging findings of 23 patients with pathologically confirmed sinonasal RDD were retrospectively analyzed in the Eye & ENT Hospital of Fudan University. Among 23 patients, there were nine males and 14 females with 44±16 years old. Imaging features including tumor location, the extent, density, signal, enhancement pattern of tumors, bone change, abnormal lesions in peripheral lymph nodes and other regions were recorded. The apparent diffusion coefficient (ADC) value of lesions in patients performed diffusion weighted imaging (DWI) were measured.Results:For the 23 cases, totally 20 patients showed bilateral sinonasal involvement and three patients had unilateral lesions. Totally nine patients had lesions confined to the nasal cavity and paranasal sinuses, and 14 patients had lesions with extrasinonasal invasion, including orbit (6 cases), nasolacrimal duct (9 cases), anterior skull base (3 cases), nasal dorsum subcutaneous tissue (2 cases) and hard palate (1 case). Soft tissue lesions on the posterior wall of the subglottic trachea were found in 2 cases and intracranial lesions were found in 1 case. Totally 10 patients were accompanied by lymph nodes enlargement. The lesions showed isodense on all 20 non-contrast enhanced CT images, and mild enhancement in three cases, moderate enhancement in seven cases and significant enhancement in seven cases on CT enhancement images. Bone changes were found in 19 of 20 patients on CT, showing mild bone destruction in five cases and bone destruction with hyperplasia in 14 cases. The lesions showed isointense on T 1WI in all 14 cases. The lesions were graded as isointense in nine cases, hypointense in four cases and hyperintense in one case on T 2WI. The lesions displayed moderate to obvious homogeneous enhancement on enhanced MRI. The lesions showed significant diffusion limitation and ADC value was (0.66±0.08)×10 -3 mm 2/s in 11 cases on DWI. Conclusions:The CT and MRI imaging characteristics of sinonasal RDD are diffuse masses on both sides of nasal cavity and paranasal sinuses, accompanied by bone hyperplasia. The lesions show isointense or hypointense on T 2WI, and may involve adjacent tissues and may be accompanied by lymph nodes enlargement in the retropharyngeal and neck.

Objective To analyze the clinical and pathogenic characteristics,as well as influencing factors for the prognosis of patients with Candida bloodstream infection(CBSI).Methods Clinical data of 47 CBSI patients in a hospital from January 2015 to September 2024 were collected.Distribution of departments and infection strains,an-timicrobial resistance,and influencing factors for the poor prognosis of patients were analyzed.Results A total of 51 strains of Candida were detected from 47 CBSI patients,mainly from the intensive care unit(ICU;n=25,53.2％),department of intestinal fistula surgery(n=8,17.0％),and department of respiratory medicine(n=4,8.6％),et al.The main detected pathogens were Candida albicans(n=29,56.9％),Candida tropicalis(n=7,13.7％),Candida glabrata(n=6,11.8％),and Candida parapsilosis(n=6,11.8％).Resistance rate of Candida albi-cans to fluconazole was 11.5％(3/26).According to the prognosis results,patients were divided into a good prog-nosis group(n=26,55.3％)and a poor prognosis group(n=21,44.7％).Univariate analysis showed statistically significant differences between patients in the good prognosis group and the poor prognosis group in terms of abso-lute neutrophil count,ICU admission,mechanical ventilation,tracheal intubation,gastrointestinal hemorrhage/per-foration,and surgical treatment(lesion clearance,drainage or unblocking for obstruction)(all P＜0.05).Prelimi-nary multivariate logistic regression analysis showed that gastrointestinal hemorrhage/perforation was a potential risk factor for the poor prognosis in CBSI patients(OR=11.156,95％CI:1.434-86.809,P=0.021).Conclusion The detected CBSI strains are mainly Candida albicans,and gastrointestinal hemorrhage/perforation may be one of the potential risk factors affecting the prognosis of CBSI patients.These patients are generally in critical condition and should be detected and treated as early as possible to improve their prognosis.Due to the small amount of speci-mens,further research is still needed for confirmation.