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

Obesity and its related metabolic diseases have become a major global public health threat, and its rising incidence significantly increases the risk of cardiovascular and cerebrovascular diseases, diabetes and other complications. Pancreatic lipase is a key enzyme that converts food-borne lipids into triglycerides and fatty acids, and the effective inhibition of its activity has become an important strategy for the treatment of obesity. This paper discusses the screening methods of pancreatic lipase inhibitors, and summarizes and reviews the basic principles, advantages and disadvantages and application status of traditional screening methods, modern new screening methods and virtual screening methods. In view of the problems faced by the screening methods of pancreatic lipase inhibitors, future research urgently needs to move towards a collaborative innovation path of multi-technology integration, intelligent screening and complex systematization of traditional Chinese medicine, so as to open up new research paradigms.

Objective To investigate the clinical relevance and diagnostic or prognostic value of ST3β-galactoside α-2, 3-sialyltransferase 1 (ST3GAL1) in glioma and to confirm its role in promoting malignant phenotypes. Methods Using data from The Cancer Genome Atlas (TCGA) database, we analyzed the correlation between ST3GAL1 expression levels in glioma and clinical parameters to evaluate its diagnostic and prognostic value. The impact of ST3GAL1 on malignant phenotypes of glioma cells-including proliferation, cell cycle progression, apoptosis, and invasion was further validated through ST3GAL1 knockdown experiments. Results The expression level of ST3GAL1 was significantly higher in glioma tissues compared to healthy brain tissues and showed a strong correlation with clinical characteristics of glioma patients. Survival analysis and receiver operating characteristic (ROC) curve demonstrated that ST3GAL1 could serve as a potential diagnostic and prognostic biomarker for glioma. Knockdown of ST3GAL1 suppressed proliferation, invasion, and migration capabilities of glioma cell lines, and induced G1-phase cell cycle arrest. Conclusion ST3GAL1 promotes malignant phenotypes in glioma and plays a critical role in its malignant progression, suggesting its potential as a biomarker for glioma diagnosis and prognosis.
Humans ; Sialyltransferases/metabolism* ; Glioma/diagnosis* ; Cell Proliferation/genetics* ; Cell Line, Tumor ; Brain Neoplasms/enzymology* ; beta-Galactoside alpha-2,3-Sialyltransferase ; Disease Progression ; Prognosis ; Cell Movement/genetics* ; Apoptosis/genetics* ; Male ; Female ; Gene Expression Regulation, Neoplastic ; Biomarkers, Tumor/metabolism* ; Middle Aged

OBJECTIVES: To evaluate the correlation of mean arterial oxygen tension (PaO₂) during the first 24 h following intensive care unit (ICU) admission with mortality in critically ill patients with acute kidney injury (AKI) and determine the optimal PaO₂ threshold for devising oxygen therapy strategies for these patients. METHODS: We collected the clinical data of ICU patients with AKI from the MIMIC-IV database. Based on the optimal first 24-h PaO₂ threshold determined by receiver operating characteristic (ROC) curve analysis and the Youden index maximization principle, we classified the patients into hyperoxia group (with PaO₂ ≥137.029 mmHg) and hypoxemia group (PaO₂<137.029 mm Hg). Multivariable logistic regression and propensity score matching were used to evaluate the correlation of first 24-h PaO₂ levels with in-hospital mortality of the patients. RESULTS: Among the 18 335 patients, 46.7% were in the hyperoxia group, who had an overall mortality rate of 16.9%. The optimal PaO₂ threshold (137.029 mm Hg) had a sensitivity of 78.3%, a specificity of 63.7%, and an AUC of 0.76 (95% CI: 0.74=0.78). Hyperoxia within the first 24 h after ICU admission was associated with a significantly lower in-hospital mortality (OR=0.78) and 90-day mortality (OR=0.77), particularly in stage 1 AKI patients. A non-linear relationship was identified between PaO₂ and mortality of the patients (P<0.001). Kaplan-Meier survival curves indicated a significantly increased 90-day survival rate in the patients in hyperoxia group (P<0.001), who also had shorter durations of mechanical ventilation, less vasopressor use, and shorter lengths of hospital/ICU stay. CONCLUSIONS Maintenance of a PaO₂ level ≥137.029 mmHg within 24 h after ICU admission may improve clinical outcomes of critically ill AKI patients, which underscores the importance of targeted oxygen delivery in ICU care.
Humans ; Acute Kidney Injury/blood* ; Male ; Female ; Middle Aged ; Intensive Care Units ; Aged ; Oxygen/blood* ; Hospital Mortality ; Partial Pressure ; Adult ; Databases, Factual

Objective To observe the difference of iron deposition in brain deep nuclei of systemic lupus erythematosus(SLE)patients with different disease activity levels using quantitative susceptibility mapping(QSM).Methods Fifty-four SLE patients were retrospectively enrolled and divided into moderate to severe activity group(score＞9,n=25)and mild activity group(score≤9,n=29)according to SLE disease activity index(SLEDAI)score.Patients' general clinical data,as well as the mean QSM of bilateral head of caudate nuclei,putamina,globi pallidi,red nuclei,substantiae nigrae,dentate nuclei and thalami were compared between groups.Pearson or Spearman coefficients were performed to analyze correlations of the mean QSM of nuclei being significant different between groups and conventional clinical indicators.Then receiver operating characteristic(ROC)curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of the mean QSM for distinguishing moderate to severe and mild activity SLE.Results Compared with mild activity group,moderate to severe activity group had higher serum ferritin,erythrocyte sedimentation rate(ESR),C reactive protein(CRP),anti-double stranded DNA(anti-dsDNA)antibody levels,also higher proportion of positive anti-ribosomal P protein(anti-P)antibodies,but lower complement C3 and C4 levels(all P＜0.05).The mean QSM of bilateral putamina and thalami were significantly higher in moderate to severe activity group than in mild activity group(both P＜0.05).The mean QSM of bilateral putamina was positively correlated with SLEDAI scores,ferritin levels and positivity of anti-P antibodies in SLE patients(with r or rs of 0.447,0.526 and 0.473,respectively,and all P＜0.05).The AUC for distinguishing moderate to severe SLE and mild activity SLE based on the mean bilateral putamina QSM was 0.810.Conclusion There were significant differences of iron deposition in deep brain nuclei of SLE patients with moderate to severe and mild activity.The mean QSM of bilateral putamina could be used to distinguish SLE with moderate to severe activity and mild activity.

Objective:To compare the efficacy and safety of extended-field versus reduced-field radiotherapy in upper tract urothelial carcinoma (UTUC) patients after radical operation.Methods:A retrospective analysis was conducted on the data of 210 UTUC patients who underwent full-length nephrectomy and received postoperative adjuvant radiotherapy in Peking University First Hospital from January 2013 to November 2023, and follow-up continued until June 2024. According to the target area of postoperative radiotherapy, patients were divided into the extended-field radiotherapy group (127 cases) and the reduced-field radiotherapy group (83 cases). The overall survival (OS), distant metastasis free survival (DMFS), local recurrence free survival (LRFS) and adverse reactions were compared. In the same period, 114 patients with recurrent abdominal and pelvic lymph nodes who did not receive adjuvant therapy after surgery for UTUC in our center were prospectively collected, and the coverage of the reduced-field target area was analyzed. Chi square test was used to compare the clinical characteristics, Kaplan-Meier method was used to analyze survival outcomes, log-rank test was used to compare the survival rate, and Cox multivariate regression analysis was performed on the influencing factors of survival.Results:The median follow-up was 24.5 (range: 3-74) months. There were no significant differences between the extended-field and reduced-field radiotherapy groups in terms of 2-year LRFS (93.3% vs. 98.1%, P=0.156), 2-year DMFS (84.8% vs. 91.2%, P=0.176), and 2-year OS (90.4% vs. 90.7%, P=0.707). The most common toxicities of adjuvant radiotherapy were nausea and leukopenia, with significantly higher grade 1-2 incidence in the extended-field group compared to the reduced-field group ( P<0.05). According to the analysis of patients with retroperitoneal lymph node recurrence after surgery, the reduced-field target designed according to the location of the primary tumor can cover more than 90% of the postoperative metastatic lymph node area Multivariate analysis revealed that variant histology ( HR=2.180,95% CI: 1.021-4.658, P=0.044) was an independent predictor of worse DMFS, while variant histology ( HR=3.825,95% CI: 1.514-9.662, P=0.005) and T 3-4 stage ( HR=4.452,95% CI: 1.025-19.339, P=0.046) were independent predictors of poorer OS. Conclusions:Compared with extended-field radiotherapy, reduced-field radiotherapy designed based on primary tumor location significantly reduced treatment-related toxicities without compromising postoperative therapeutic efficacy, and the reduced-field can cover more than 90% of local recurrent lesions.

Objective:To compare the clinical outcomes between all-inside and conventional transtibial tunnel reconstructions for posterior cruciate ligament (PCL) injuries.Methods:A retrospective study was conducted to analyze the clinical data of the 108 patients who had been treated for PCL injuries at Department of Arthrosis Surgery, Xuzhou Renci Hospital, from March 2021 to March 2023. There were 48 females and 60 males, with an age of (30.3±10.8) years and an injury-to-surgery interval of (25.7±6.4) days. Of them, 49 left and 59 right knees were affected. By the difference in the tunnel reconstruction, the patients were divided into 2 groups: an all-inside group ( n=52) in which the PCL was reconstructed using the all-inside techniques and a conventional group in which the PCL was reconstructed using the conventional techniques. The following were observed and compared: operation time and postoperative hospital stay; visual analogue scale (VAS) pain scores, The International Knee Documentation Committee (IKDC) subjective scores and Lysholm knee function scores at preoperation, postoperative 3 months and the last follow-up; posterior drawer test, posterior sag sign, reverse Lachman test and the diameter and morphology of the PCL shown by the knee joint MRI at the last follow-up. Results:The baseline characteristics were comparable between the 2 groups ( P>0.05). All patients were followed up for (12.3±1.2) months. The all-inside group incurred significantly longer operation time [(128.3±7.6) min] than the conventional group [(103.5±6.9) min] ( P<0.05), but no significant difference was observed in postoperative hospital stay between the 2 groups ( P> 0.05). There was no significant difference in VAS pain score, IKDC subjective score, or Lysholm score between the 2 groups at preoperation, postoperative 3 months or the last follow-up ( P>0.05). In both groups, the VAS pain scores, IKDC subjective scores and Lysholm scores at postoperative 3 months and the last follow-up were significantly improved compared with those at preoperation ( P<0.05). At the last follow-up, the posterior drawer test, posterior sag sign, reverse Lachman test were negative in both groups, and the knee joint MRI showed good diameter and morphology of the PCL reconstructed. Conclusions:Both conventional and all-inside reconstructions yield satisfactory clinical outcomes for PCL injuries, demonstrating comparable functional recovery and complication incidence. However, the all-inside technique requires longer operation time than the conventional approach.

Objective:To summarize the surgical strategies and to evaluate the clinical outcomes of up-per urinary tract reconstruction in patients with stone-related ureteral strictures.Methods:This retro-spective study included 71 patients diagnosed with ureteral strictures secondary to urinary stones who un-derwent upper urinary tract reconstructive surgery at Peking University First Hospital between March 2014 and November 2023.Patient data were collected,including demographic characteristics,clinical presen-tation,laboratory results,imaging findings,surgical procedures,and follow-up outcomes.Ureteral stric-tures were classified according to anatomical location into upper,middle,lower,or multiple segments.Surgical procedures were carried out depending on the stricture characteristics.Surgical success was de-fined as resolution or improvement of clinical symptoms,radiographic improvement or stabilization of hy-dronephrosis,and maintenance of normal and stable renal function.Results:Among the 71 patients,36(50.7％)had strictures in the upper ureter,9(12.7％)in the middle ureter,15(21.1％)in the lower ureter,and 11(15.5％)had multifocal ureteral strictures.The median stricture length was 5.0 cm(interquartile range:3.0-15.0 cm).Surgical approach selection was individualized based on the location and extent of the stricture.For upper ureteral strictures,the most frequently employed techniques were oral mucosal graft ureteroplasty(13/36,36.1％)and appendiceal flap ureteroplasty(8/36,22.2％).Other options included ureteroureterostomy and ileal ureter replacement for longer or more complex strictures.In middle ureteral strictures,treatment was stratified by length:balloon dilation(1/9,11.1％)and ureteroureterostomy(1/9,11.1％)were applied in shorter strictures,while oral mucosal graft ureteroplasty(3/9,33.3％)and ileal ureter replacement(4/9,44.4％)were reserved for longer segments.For lower ureteral strictures,ureteral reimplantation into the bladder was the most common approach(10/15,66.7％),often combined with a psoas hitch or Boari flap when necessary.All the patients with multiple segmental strictures underwent ileal ureter replacement due to the extensive nature of the disease.The median follow-up period was 14.2 months(range:6.1-107.1 months).During follow-up,69 of 71 patients(97.2％)achieved surgical success.Conclusion:Stone-related ure-teral strictures present with considerable heterogeneity in terms of anatomical location,length,and com-plexity.Careful preoperative evaluation and individualized surgical planning are critical to successful re-construction.With appropriate selection of surgical methods,favorable long-term clinical outcomes can be achieved in the majority of patients.

Objective:To summarize the surgical strategies and to evaluate the clinical outcomes of up-per urinary tract reconstruction in patients with stone-related ureteral strictures.Methods:This retro-spective study included 71 patients diagnosed with ureteral strictures secondary to urinary stones who un-derwent upper urinary tract reconstructive surgery at Peking University First Hospital between March 2014 and November 2023.Patient data were collected,including demographic characteristics,clinical presen-tation,laboratory results,imaging findings,surgical procedures,and follow-up outcomes.Ureteral stric-tures were classified according to anatomical location into upper,middle,lower,or multiple segments.Surgical procedures were carried out depending on the stricture characteristics.Surgical success was de-fined as resolution or improvement of clinical symptoms,radiographic improvement or stabilization of hy-dronephrosis,and maintenance of normal and stable renal function.Results:Among the 71 patients,36(50.7％)had strictures in the upper ureter,9(12.7％)in the middle ureter,15(21.1％)in the lower ureter,and 11(15.5％)had multifocal ureteral strictures.The median stricture length was 5.0 cm(interquartile range:3.0-15.0 cm).Surgical approach selection was individualized based on the location and extent of the stricture.For upper ureteral strictures,the most frequently employed techniques were oral mucosal graft ureteroplasty(13/36,36.1％)and appendiceal flap ureteroplasty(8/36,22.2％).Other options included ureteroureterostomy and ileal ureter replacement for longer or more complex strictures.In middle ureteral strictures,treatment was stratified by length:balloon dilation(1/9,11.1％)and ureteroureterostomy(1/9,11.1％)were applied in shorter strictures,while oral mucosal graft ureteroplasty(3/9,33.3％)and ileal ureter replacement(4/9,44.4％)were reserved for longer segments.For lower ureteral strictures,ureteral reimplantation into the bladder was the most common approach(10/15,66.7％),often combined with a psoas hitch or Boari flap when necessary.All the patients with multiple segmental strictures underwent ileal ureter replacement due to the extensive nature of the disease.The median follow-up period was 14.2 months(range:6.1-107.1 months).During follow-up,69 of 71 patients(97.2％)achieved surgical success.Conclusion:Stone-related ure-teral strictures present with considerable heterogeneity in terms of anatomical location,length,and com-plexity.Careful preoperative evaluation and individualized surgical planning are critical to successful re-construction.With appropriate selection of surgical methods,favorable long-term clinical outcomes can be achieved in the majority of patients.

Objective To observe the difference of iron deposition in brain deep nuclei of systemic lupus erythematosus(SLE)patients with different disease activity levels using quantitative susceptibility mapping(QSM).Methods Fifty-four SLE patients were retrospectively enrolled and divided into moderate to severe activity group(score＞9,n=25)and mild activity group(score≤9,n=29)according to SLE disease activity index(SLEDAI)score.Patients' general clinical data,as well as the mean QSM of bilateral head of caudate nuclei,putamina,globi pallidi,red nuclei,substantiae nigrae,dentate nuclei and thalami were compared between groups.Pearson or Spearman coefficients were performed to analyze correlations of the mean QSM of nuclei being significant different between groups and conventional clinical indicators.Then receiver operating characteristic(ROC)curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of the mean QSM for distinguishing moderate to severe and mild activity SLE.Results Compared with mild activity group,moderate to severe activity group had higher serum ferritin,erythrocyte sedimentation rate(ESR),C reactive protein(CRP),anti-double stranded DNA(anti-dsDNA)antibody levels,also higher proportion of positive anti-ribosomal P protein(anti-P)antibodies,but lower complement C3 and C4 levels(all P＜0.05).The mean QSM of bilateral putamina and thalami were significantly higher in moderate to severe activity group than in mild activity group(both P＜0.05).The mean QSM of bilateral putamina was positively correlated with SLEDAI scores,ferritin levels and positivity of anti-P antibodies in SLE patients(with r or rs of 0.447,0.526 and 0.473,respectively,and all P＜0.05).The AUC for distinguishing moderate to severe SLE and mild activity SLE based on the mean bilateral putamina QSM was 0.810.Conclusion There were significant differences of iron deposition in deep brain nuclei of SLE patients with moderate to severe and mild activity.The mean QSM of bilateral putamina could be used to distinguish SLE with moderate to severe activity and mild activity.