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

BackgroundMonitoring the blood concentrations of antipsychotic drugs and their metabolites can guide the adjustment of clinical treatment plans， improving therapeutic efficacy while reducing adverse effects. However， there is currently a lack of a method that can accurately and efficiently quantitatively detect multiple antipsychotic drugs and their metabolites. ObjectiveTo establish a ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） method for the simultaneous identification and quantitation of 12 antipsychotic drugs and their main metabolites in human serum. MethodsUsing UPLC-MS/MS technology， protein precipitation method was employed for sample pretreatment. An Agela Technologies Durashell C₈ chromatographic column （50 mm×3.0 mm， 5 μm） was selected for chromatographic separation with gradient elution. The flow rate was 0.4 mL/min， and the total analysis time was 5 minutes. The column temperature was 40℃. The mass spectrometry detection was carried out in the multiple reaction monitoring （MRM） mode， and the isotope internal standard method was used for quantification. ResultsThe relative standard deviation （RSD） of the internal standard normalization matrix effect factor for 12 antipsychotic drugs and their main metabolites at low and high quality concentrations was all less than 15%. The extraction recovery rate was 85% to 115%. They showed good linear relationships within their respective standard curve ranges （r>0.995）. At low， medium， and high quality concentrations， the accuracy was 85.24% to 114.71%， and the RSD of intra-batch and inter-batch precision was all ≤14.15%， with good stability. ConclusionAll the analytical performance indicators of this method meet the verification requirements， providing an analytical means for the quantitative detection of antipsychotic drugs and their main metabolites in human serum. ［Funded by The Third Batch of Science and Technology Projects in Chaozhou City in 2023 （number， 202303GY02）］

Objective To explore the value of coronary fat attenuation index(FAI)combined with laboratory indicators in predicting the risk of acute coronary syndrome(ACS)in patients with coronary heart disease(CHD).Methods A retrospective analysis was conducted on 454 patients who were diagnosed with CHD in Guangdong Provincial People's Hospital SCAD group(n=233)and an ACS group(n=221).Univariate and multivariate Logistic regression analyses were performed on the FAI values of the main coronary branches[right coronary artery(RCA),left anterior descending branch(LAD),left circumflex branch(LCX)],laboratory indicators,and clinical data,to identify independent risk factors for ACS in CHD patients.Receiver operating characteristic curves were constructed,and area under the curve(AUC)was calculated to evaluate the predictive performance of the independent risk factors and their combinations.Results LAD-FAI,RCA-FAI,and high-sensitivity C-reactive protein(hs-CRP)were independent influencing factors for ACS in CHD patients.The AUC for the prediction of ACS occurrence in CHD patients based on LAD-FAI,RCA-FAI,and elevated hs-CRP values alone were 0.568,0.703,and 0.749,respectively.When these three factors were analyzed in combination,the AUC was 0.815.Conclusion The combined analysis of LAD-FAI,RCA-FAI,and hs-CRP has good predictive performance for assessing the risk of ACS in CHD patients.

OBJECTIVE: To explore the clinical application value of mineralized collagen (MC) bone scaffolds in repairing various types of skull defects, and to assess the suitability and repair effectiveness of porous MC (pMC) scaffolds, compact MC (cMC) scaffolds, and biphasic MC composite (bMC) scaffolds. METHODS: A retrospective analysis was conducted on the clinical data of 105 patients who underwent skull defect repair with pMC, cMC, or bMC between October 2014 and April 2022. The cohort included 63 males and 42 females, ranging in age from 3 months to 55 years, with a median age of 22.7 years. Causes of defects included craniectomy after traumatic surgery in 37 cases, craniotomy in 58 cases, tumor recurrence or intracranial hemorrhage surgery in 10 cases. Appropriate MC scaffolds were selected based on the patient's skull defect size and age: 58 patients with defects <3 cm² underwent skull repair with pMC (pMC group), 45 patients with defects ≥3 cm² and aged ≥5 years underwent skull repair with cMC (cMC group), and 2 patients with defects ≥3 cm² and aged <5 years underwent skull repair with bMC (bMC group). Postoperative clinical follow-up and imaging examinations were conducted to evaluate bone regeneration, the biocompatibility of the repair materials, and the occurrence of complications. RESULTS: All 105 patients were followed up 3-24 months, with an average of 13 months. No material-related complication occurred in any patient, including skin and subcutaneous tissue infection, excessive ossification, and rejection. CT scans at 6 months postoperatively showed bone growth in all patients, and CT scans at 12 months postoperatively showed complete or near-complete resolution of bone defects in all patients, with 58 cases repaired in the pMC group. The CT values of the defect site and the contralateral normal skull bone in the pMC group at 12 months postoperatively were (1 123.74±93.64) HU and (1 128.14±92.57) HU, respectively, with no significant difference ( t=0.261, P=0.795). CONCLUSION MC exhibits good biocompatibility and osteogenic induction ability in skull defect repair. pMC is suitable for repairing small defects, cMC is suitable for repairing large defects, and bMC is suitable for repairing pediatric skull defects.
Humans ; Tissue Scaffolds ; Male ; Female ; Collagen ; Retrospective Studies ; Adult ; Child ; Adolescent ; Middle Aged ; Child, Preschool ; Skull/surgery* ; Young Adult ; Infant ; Plastic Surgery Procedures/methods* ; Tissue Engineering/methods* ; Craniotomy/methods* ; Bone Regeneration ; Treatment Outcome ; Porosity ; Biocompatible Materials

Objective To investigate the effects of comprehensive nutrition management on glycolipid metabolism and pregnancy outcomes in patients with gestational diabetes mellitus(GDM).Methods A total of 121 pregnant women with GDM at 24-28 weeks gestation who were registered in the obstetrics department of 6 sub-central hospi-tals in China from May 2021 to July 2021 were included in this study and were randomly divided into intervention group(n=74)and control group(n=47).The intervention group received intensive comprehensive nutrition man-agement,including at least 6 outpatient interventions,individualized nutrition management and a half-day standard-ized outpatient education on gestational diabetes mellitus,continuous dynamic blood glucose monitoring and micro-blood glucose monitoring,and routine check of glycated albumin and urine every 4 weeks.Body weight,body com-position and diet and exercise implementation procedures and fetal development as well as complications were recor-ded.The control group received conventional nutritional guidance.The two groups were compared for difference in blood glucose related indicators at 37 weeks of gestation,weight gain before delivery,some lipid metabolism indica-tors,pregnancy outcomes,and oral glucose tolerance test(OGTT)at 42 days postpartum.Results Compared with the control group,the level of prenatal fasting blood glucose(P=0.006),intravenous plasma glucose(P=0.009)and blood ketone(P = 0.044)in the intervention group was significantly reduced.There was no significant difference in weight gain and weight attainment rate between the two groups.The 2-hour postpartum OGTTs of preg-nant women in the intervention group(P=0.006)were significantly lower than those in the control group,and the incidence of preeclampsia and postpartum blood loss were lower than those in the control group but no statistical difference was found.For newborns,the incidence of macrosomia(P=0.042)and planation(P=0.048)in the in-tervention group was slightly lower than that in the control group,and the results were statistically different.Other adverse pregnancy outcomes were not statistically different between the two groups.Conclusions Intensive compre-hensive nutrition management has a positive impact on the control of the blood glucose in pregnant women and im-proves the maternal and neonatal outcomes of women with GDM.

Objective To explore the post-traumatic growth course for women with termination of pregnancy due to fetal abnormalities and analyze the promoting factors,in order to provide a basis for nursing and intervention tactics.Methods The purposive sampling and theoretical sampling methods were used to select 16 women who were diagnosed with fetal abnormalities and decided to terminate pregnancy in the obstetrics department of a tertiary care maternity hospital in Beijing from May 2021 to February 2022.Women were interviewed by semi-structured interviews,and the data was analyzed by Charmaz's constructing grounded theory paradigm.Results Women with termination of pregnancy due to fetal abnormalities underwent 4 stages of post-traumatic growth:traumatic stress period,rumination and seeking of help period,and acceptance internalization period,and post-traumatic growth period.The behavior of each period was influenced by the psychological experience of the corresponding period and influenced the experience of the next period.Extroverted personality,previous normal pregnancy and delivery experience,positive perception of events,positive self-identification,good social support,appropriate hospitalization environment and regulations,open mindedness towards death and religious belief,affected women's post-traumatic growth.Conclusion The post-traumatic growth course of women with termination of pregnancy due to fetal anomaly is a complex continuously sublimated process.Medical staff should pay attention to psychological and behavioral changes in women's post-traumatic growth,combine the factors that promote post-traumatic growth,and provide targeted guidance to help them successfully go through this difficult period and achieve personal growth.

Objective:To investigate the efficacy of Peritoneal interposition flap (PIF) technique in preventing postoperative pelvic lymphocele formation during laparoscopic radical prostatectomy with extended pelvic lymph node dissection (LRP+ ePLND).Methods:A retrospective analysis was conducted on clinical data of 113 patients with locally high-risk or locally advanced prostate cancer who underwent LRP+ ePLND at Shanghai East Hospital, from January 2020 to November 2023. Among them, 27 patients received PIF technique and 86 received traditional LRP+ ePLND. ePLND was carried out as the clearance of external iliac vessels, medial side of the internal iliac artery, and pararectal lymph nodes. The PIF technique was the suturing the peritoneal flap after freeing the bladder to the lateral side of the bladder, pulling the peritoneal edge that follows the bladder's free edge posteriorly to the pubis, curling it onto the lateral surface of the bladder. This could expose the lymph node clearance bed, establishing a pathway from the lymph node clearance bed to the abdominal cavity space, allowing exuded lymphatic fluid to flow into the abdominal cavity for absorption by the peritoneum. There were no statistically significant differences in age [(68.37±6.92)years vs.(70.47±5.72)years], body mass index [(25.47±2.49)kg/m 2vs.(24.46±2.80)kg/m 2], and preoperative PSA [(23.28±13.94)ng/ml vs.(24.81±13.99)ng/ml] between the PIF group and the control group ( P>0.05). Biopsy Gleason score in PIF group: 6 in 2 cases, 7 in 9 cases, 8 in 9 cases, 9-10 in 2 cases. Biopsy Gleason score in control group: 6 in 4 cases, 7 in 35 cases, 8 in 27 cases, 9-10 in 20 cases. Clinic stage in PIF group: T 2 in 18 cases, T 3 in 6 cases, T 4 in 3 cases. Clinic stage in control group: T 2 in 51cases, T 3 in 27 cases, T 4 in 8 cases. The preoperative Gleason scores and TNM staging comparisons between the PIF group and the control group showed no statistically significant differences ( P>0.05). Surgical duration, intraoperative blood loss, lymph node positivity rate, incidence of postoperative lymphocele, and recovery of urinary control were compared between the two groups. Results:All surgeries were completed successfully without intraoperative complications in both groups. There were no statistically significant differences between the PIF group and the control group in terms of surgical duration [(202.96±24.15)min vs.(201.1±29.85)min], intraoperative blood loss [(85.56±32.27)ml vs.(90.7±49.25)ml], and lymph node positivity rate [(4 in PIF group, 14.8%)vs.(25 in control group, 29.1%)]( P>0.05). Urinary catheters were retained for 10-14 days postoperatively. Following catheter removal, there were no statistically significant differences in urinary control rates at 1 month [51.85%(14/27)vs. 48.83%(42/86)]and 2 months[74.07%(20/27) vs. 72.09%(62/86)] between the PIF group and the control group ( P>0.05). At the 2 to 6-month follow-up CT scan, none of the 27 patients in the PIF group developed pelvic lymphocele, whereas 9 patients in the control group did (6 cases bilateral, 3 cases unilateral), showing a statistically significant difference between the two groups ( P=0.002). Postoperatively, 3 patients in the control group experienced symptoms, with 1 case of lymphocele infection causing fever 1 month after surgery. Lymphocysts were found in 2 patients with ipsilateral lower extremity swelling 2 weeks after surgery. Conclusions:The application of PIF technique during laparoscopic radical prostatectomy with extended pelvic lymph node dissection via the abdominal approach could be safe and feasible. It may prevent postoperative pelvic lymphocele formation.

Japanese encephalitis is an acute central nervous system infectious disease caused by Japanese encephalitis virus (JEV) with brain parenchyma inflammation, characterized by high fever, headache, positive meningeal irritation, impaired consciousness, convulsion, and respiratory failure, with mortality rate as high as 20%-30%, and with neurological sequelae in 30%-50% of survivors. The mechanism of brain damage caused by JEV infection is still unclear, and some studies imply its close relation with immune-inflammatory response. This article reviews the research progress on immune-inflammatory response mechanism of Japanese encephalitis to help to understand its pathogenesis.

Objective:To observe the effect of taping on the kinematic characteristics of the ankle joint during forward and lateral jumps by male basketball players with chronic ankle instability (CAI).Methods:A Vicon 3D motion capture system and a Kistler 3D ergometer were used to collect data describing the landing data with or without taping from forward and lateral jumps of 29 male basketball players with CAI. The landing data included the dorsiflexion and plantarflexion angles, valgus and inversion angles and external and internal rotation angles. Dorsiflexion or plantarflexion angular velocity was also recorded along with valgus or inversion angular velocity and external or internal rotation angular velocity 200ms, 150ms, 100ms and 50ms before and after touchdown. The data obtained were modeled using three-dimensional motion analysis software, and then analyzed.Results:Taping reduced the ankle plantarflexion in landing from a forward jump by 3.27° 50ms before landing and by 2.70° at touchdown. The ankle inversion angle was reduced 2.13° 50ms before touchdown, while the angle of external rotation decreased by 2.59° 200ms before touchdown and 2.17° 150ms before. Moreover, the angle of external rotation 100ms after landing was reduced by a significant 1.59° compared with that without taping. In lateral jumps taping reduced the average ankle plantarflexion angle by 1.94° 50ms before landing and 3.23° at touchdown compared with no taping. Ankle inversion was reduced significantly by 2.86° 50ms before landing and by 2.87° at touchdown. External rotation was a significant 0.93° less 200ms before landing and 2.36° smaller 150ms before touchdown. In the forward jump landing, taping reduced the average angular velocity of ankle dorsiflexion on landing by a significant 58.5°/s and by 28.39°/s 100ms later. In the lateral jump landings the average ankle dorsiflexion velocity decreased by significant 20.5°/s with taping, but the valgus velocity increased by 49.7°/s compared with no taping. However, 50ms after touchdown the speed of external rotation with taping was 30.3°/s slower than without taping.Conclusions:Ankle taping can modify ankle rotation angles and angular velocities during landing from jumps. This is particularly helpful for basketball players with CAI.

It is discovered that activated caspase-3 tends to induce apoptosis in gasdermin E (GSDME)-deficient cells, but pyroptosis in GSDME-sufficient cells. The high GSDME expression and apoptosis resistance of pancreatic ductal adenocarcinoma (PDAC) cells shed light on another attractive strategy for PDAC treatment by promoting pyroptosis. Here we report a hGLuc-hGSDME-PCA system for high-throughput screening of potential GSDME activators against PDAC. This screening system neatly quantifies the oligomerization of GSDME-N to characterize whether pyroptosis occurs under the stimulation of chemotherapy drugs. Based on this system, ponatinib and perifosine are screened out from the FDA-approved anti-cancer drug library containing 106 compounds. Concretely, they exhibit the most potent luminescent activity and cause drastic pyroptosis in PDAC cells. Further, we demonstrate that perifosine suppresses pancreatic cancer by promoting pyroptosis via caspase-3/GSDME pathway both in vitro and in vivo. Collectively, this study reveals the great significance of hGLuc-hGSDME-PCA in identifying compounds triggering GSDME-dependent pyroptosis and developing promising therapeutic agents for PDAC.