Objective:To summarize the clinical phenotypes, genotypes, and treatment outcomes of NPRL2-related epilepsy. Methods:This was a case summary.Clinical data of patients with NRPL2 variants admitted to the Department of Pediatrics, Peking University People′s Hospital between October 1, 2013 and October 31, 2023 were retrospectively analyzed.Previous reports of patients with the same disease were reviewed. Results:Six cases of NPRL2-related epilepsy were collected, and 37 cases were reported in the previous literatures.The age of onset ranged from 3 days to 18 years with the median age of 24 months.There were 15 patients with onset in infancy.Among the 41 patients diagnosed with epilepsy, 73.1% (30/41) had focal seizures, 34.1% (14/41) had frontal lobe epilepsy, and 17.1% (7/41) had epileptic spasms.Among the patients with known cranial imaging, 58.6% (17/29) had cortical malformations. NPRL2 variants involved 11 nonsense mutations, 10 splice site mutations, 7 frameshift mutations, 1 large fragment deletion, and 14 missense mutations; among them, 39 mutations were pathogenic or likely pathogenic, while the rest 4 mutations had unclear pathogenicity.Among the 27 patients with known outcomes, 11 (40.7%) had no seizures after administration of 1 or 2 types of drugs, and 16 (59.2%) had drug-resistant epilepsy.Among the 16 patients, 1 had no seizures after treatment with 3 types of anti seizure medications, and 7 had no seizures after surgery.Most patients had varying degrees of delay in intellectual and motor development. Conclusions:Patients with NPRL2 variants usually present with frequent focal seizures and epileptic spasms, and the age of onset varies greatly.About half of the patients have drug-resistant epilepsy, half of whom have cortical malformations.For those with drug-resistant epilepsy and abnormal cranial imaging, surgery may be considered.

Objective:To summarize the phenotype and genotype of leukoencephalopathy with calcifications and cysts(LCC).Methods:A case summary.Clinical, imaging, and genetic data of 2 patients with early-onset LCC admitted to the Department of Pediatrics, Peking University People′s Hospital between December 2023 and August 2024 were retrospectively summarized.A review of the literature was also conducted.Results:Case 1: a 19-month-old female infant presented with febrile seizures in infancy and mild developmental delay.Trio whole-exome sequencing (trio-WES) identified compound heterozygous pathogenic variants in the SNORD118 gene: n.92C>T (paternally inherited) and n. 72A>G (maternally inherited). Case 2: an 11-year-and-4-month-old girl had non-specific encephalopathy in the neonatal period, developmental delay with regression, and seizures since early childhood.Trio-WES revealed compound heterozygous pathogenic variants in SNORD118: n.3C>T (paternally inherited) and n. 57G>C (maternally inherited). Both cases showed typical imaging findings of leukoencephalopathy, intracranial calcifications, and cysts.Case 2 has been treated with Bevacizumab for 3 months and remains under follow-up.Combining this 2 cases with previously reported genetically confirmed cases, a total of 97 LCC patients with identified SNORD118 variants were analyzed.The median age of onset was 5 years.Seventy-one cases had childhood onset, including 31 cases with onset at ≤1 year.The inaugural symptoms were: seizures in 40 patients (41.2%), motor disorders in 25 patients (25.8%), developmental delay or cognitive impairment in 19 patients (19.6%) and headaches or increased intracranial pressure in 13 patients (13.4%). Neurological dysfunctions progress during the course.All patients had typical leukoencephalopathy, intracranial calcifications and cysts, with varied imaging progress.A total of 61 variants of SNORD118 were reported and most were compound heterozygous variants.Treatment is primarily symptomatic.Three out of the 4 patients treated with Bevacizumab showed improvement. Conclusions:LCC is a rare autosomal recessive inherited cerebral microangiopathy, characterized by progressive neurological dysfunction and radiological triad of diffuse and asymmetric leukoencephalopathy, intracranial calcifications and cysts.Patients with pathogenic SNORD118 variants should definitely be diagnosed.Symptomatic treatment is the mainstay therapy and Bevacizumab may slow down the progression.

Objective:To summarize the clinical phenotypes, genotypes, and treatment outcomes of NPRL2-related epilepsy. Methods:This was a case summary.Clinical data of patients with NRPL2 variants admitted to the Department of Pediatrics, Peking University People′s Hospital between October 1, 2013 and October 31, 2023 were retrospectively analyzed.Previous reports of patients with the same disease were reviewed. Results:Six cases of NPRL2-related epilepsy were collected, and 37 cases were reported in the previous literatures.The age of onset ranged from 3 days to 18 years with the median age of 24 months.There were 15 patients with onset in infancy.Among the 41 patients diagnosed with epilepsy, 73.1% (30/41) had focal seizures, 34.1% (14/41) had frontal lobe epilepsy, and 17.1% (7/41) had epileptic spasms.Among the patients with known cranial imaging, 58.6% (17/29) had cortical malformations. NPRL2 variants involved 11 nonsense mutations, 10 splice site mutations, 7 frameshift mutations, 1 large fragment deletion, and 14 missense mutations; among them, 39 mutations were pathogenic or likely pathogenic, while the rest 4 mutations had unclear pathogenicity.Among the 27 patients with known outcomes, 11 (40.7%) had no seizures after administration of 1 or 2 types of drugs, and 16 (59.2%) had drug-resistant epilepsy.Among the 16 patients, 1 had no seizures after treatment with 3 types of anti seizure medications, and 7 had no seizures after surgery.Most patients had varying degrees of delay in intellectual and motor development. Conclusions:Patients with NPRL2 variants usually present with frequent focal seizures and epileptic spasms, and the age of onset varies greatly.About half of the patients have drug-resistant epilepsy, half of whom have cortical malformations.For those with drug-resistant epilepsy and abnormal cranial imaging, surgery may be considered.

Objective:To summarize the phenotype and genotype of leukoencephalopathy with calcifications and cysts(LCC).Methods:A case summary.Clinical, imaging, and genetic data of 2 patients with early-onset LCC admitted to the Department of Pediatrics, Peking University People′s Hospital between December 2023 and August 2024 were retrospectively summarized.A review of the literature was also conducted.Results:Case 1: a 19-month-old female infant presented with febrile seizures in infancy and mild developmental delay.Trio whole-exome sequencing (trio-WES) identified compound heterozygous pathogenic variants in the SNORD118 gene: n.92C>T (paternally inherited) and n. 72A>G (maternally inherited). Case 2: an 11-year-and-4-month-old girl had non-specific encephalopathy in the neonatal period, developmental delay with regression, and seizures since early childhood.Trio-WES revealed compound heterozygous pathogenic variants in SNORD118: n.3C>T (paternally inherited) and n. 57G>C (maternally inherited). Both cases showed typical imaging findings of leukoencephalopathy, intracranial calcifications, and cysts.Case 2 has been treated with Bevacizumab for 3 months and remains under follow-up.Combining this 2 cases with previously reported genetically confirmed cases, a total of 97 LCC patients with identified SNORD118 variants were analyzed.The median age of onset was 5 years.Seventy-one cases had childhood onset, including 31 cases with onset at ≤1 year.The inaugural symptoms were: seizures in 40 patients (41.2%), motor disorders in 25 patients (25.8%), developmental delay or cognitive impairment in 19 patients (19.6%) and headaches or increased intracranial pressure in 13 patients (13.4%). Neurological dysfunctions progress during the course.All patients had typical leukoencephalopathy, intracranial calcifications and cysts, with varied imaging progress.A total of 61 variants of SNORD118 were reported and most were compound heterozygous variants.Treatment is primarily symptomatic.Three out of the 4 patients treated with Bevacizumab showed improvement. Conclusions:LCC is a rare autosomal recessive inherited cerebral microangiopathy, characterized by progressive neurological dysfunction and radiological triad of diffuse and asymmetric leukoencephalopathy, intracranial calcifications and cysts.Patients with pathogenic SNORD118 variants should definitely be diagnosed.Symptomatic treatment is the mainstay therapy and Bevacizumab may slow down the progression.

The reprogramming of lipid metabolism is a significant factor influencing various aspects of head and neck squamous cell carcinoma,including its occurrence,development,metastasis,and resistance to radio-chemotherapy.There is a considerable elevation in the expression levels of enzymes and genes related to lipid metabolism in tumor tissues compared to normal tissues.This up-regulation is associated with both treatment resistance and a poor prognosis.This review focuses mainly on alterations in lipid metabolism in head and neck squamous cell carcinoma.It systematically explores the atypical expression and clinical significance of lipid metabolism-related enzymes,evaluates their influence on treatment resistance,elucidates the underlying mechanisms of this resistance,and discus-ses current and potential targeted therapeutic approaches.The comprehensive analysis comprises four pivotal aspects:de novo lipogene-sis,fatty acid oxidation,glycerophospholipids metabolism,and mevalonate and cholesterol synthesis pathways.Feasible strategies,such as the adjustment of dietary structure,the administration of multi-target drugs,and the utilization of combination treatment thera-pies,are deliberated as potential interventions to modulate lipid metabolism,reverse treatment resistance,and enhance the efficacy of anti-cancer treatments.

Objective: To investigate the impact of molecular classification and key oncogenes on the oncologic outcomes in patients with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) receiving fertility-preserving treatment. Methods: Patients with EC and AEH undergoing progestin-based fertility-preserving treatment and receiving molecular classification as well as key oncogenes test at Obstetrics and Gynecology Hospital, Fudan University from January 2021 to March 2023 were reviewed. Hysteroscopic lesion resection and endometrial biopsy were performed before initiating hormone therapy and every 3 months during the treatment to evaluate the efficacy. The risk factors which had impact on the treatment outcomes in EC and AEH patients were further analyzed. Results: Of the 171 patients analyzed, the median age was 32 years, including 86 patients with EC and 85 patients with AEH. The distribution of molecular classification was as follows: 157 cases (91.8%) were classified as having no specific molecular profile (NSMP); 9 cases (5.3%), mismatch repair deficient (MMR-d); 3 cases (1.8%), POLE-mutated; 2 cases (1.2%), p53 abnormal. No difference was found in the cumulative 40-week complete response (CR) rate between the patients having NSMP or MMR-d (61.6% vs 60.0%; P=0.593), while the patients having MMR-d had increased risk than those having NSMP to have recurrence after CR (50.0% vs 14.4%; P=0.005). Multi-variant analysis showed PTEN gene multi-loci mutation (HR=0.413, 95%CI: 0.259-0.658; P<0.001) and PIK3CA gene mutation (HR=0.499, 95%CI: 0.310-0.804; P=0.004) were associated with a lower cumulative 40-week CR rate, and progestin-insensitivity (HR=3.825, 95%CI: 1.570-9.317; P=0.003) and MMR-d (HR=9.014, 95%CI: 1.734-46.873; P=0.009) were independent risk factors of recurrence in EC and AEH patients. Conclusions: No difference in cumulative 40-week CR rate is found in the patients having NSMP or MMR-d who received progestin-based fertility-preserving treatment, where the use of hysteroscopy during the treatment might be the reason, while those having MMR-d have a higher risk of recurrence after CR. Oncogene mutation of PTEN or PIK3CA gene might be associated with a lower response to progestin treatment. The molecular profiles help predict the fertility-preserving treatment outcomes in EC and AEH patients.
Pregnancy ; Female ; Humans ; Adult ; Hyperplasia ; Progestins ; Fertility Preservation ; Endometrial Neoplasms/pathology* ; Endometrial Hyperplasia/surgery* ; Treatment Outcome ; Precancerous Conditions ; Fertility ; Class I Phosphatidylinositol 3-Kinases ; Retrospective Studies

Objective: To investigate the effects of application of citrate anticoagulation in bedside continuous blood purification (CBP) of severe burn patients with sepsis, so as to provide reference for choosing anticoagulants in CBP of these patients. Methods: Thirty severe burn patients with sepsis, conforming to the study criteria, were admitted to our burn intensive care unit from January 2014 to July 2017. Patients were divided into heparin group and citrate group according to computer randomization method, with 15 cases in each group. Patients in two groups all received bedside CBP treatment. Patients in heparin group used local heparin anticoagulation, while patients in citrate group used local citrate anticoagulation. Time of predicted single-time CBP treatment, time of single-time CBP treatment, time of accumulative CBP treatment, and rate of reaching the standard of CBP treatment time were counted. Changes of prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen, serum procalcitonin, and C-reactive protein (CRP) of patients before and after treatment were monitored. Hemorrhage in wounds, incision on trachea, and arteriovenous intubation point, and other complications during and after CBP treatment were observed. Data were processed with independent sample t test and chi-square test. Results: (1) Time of predicted single-time CBP treatment of patients in the two groups was equal. Time of single-time CBP treatment and time of accumulative CBP treatment of patients in citrate group were longer than those in heparin group. Rate of reaching the standard of CBP treatment time of patients in citrate group was significantly higher than that in heparin group (χ²=16.655, P<0.01). (2) There was no statistically significant difference in PT, APTT, INR, fibrinogen, serum procalcitonin, and CRP of patients in the two groups before CBP treatment (t=0.203, -1.006, 0.203, 0.039, -1.591, -0.824, P>0.05). PT and APTT of patients in citrate group after CBP treatment were (14.2±1.6) and (45±7) s, respectively, significantly shorter than (15.5±1.4) and (53±6) s in heparin group (t=2.395, 3.321, P<0.05 or P<0.01). INR of patients in citrate group after CBP treatment was 1.13±0.12, significantly lower than 1.24±0.12 in heparin group (t=2.395, P<0.05). Fibrinogen of patients in citrate group after CBP treatment was (3.5±0.6) g/L, significantly higher than (3.0±0.6) g/L in heparin group (t=-2.427, P<0.05). Serum procalcitonin and CRP of patients in citrate group after CBP treatment were significantly lower than those in heparin group (t=2.520, 2.710, P<0.05). Decreased degree of serum procalcitonin and CRP of patients in citrate group after CBP treatment were (1.8±0.6) ng/mL and (143±69) mg/L, respectively, significantly higher than (0.9±0.6) ng/mL and (95±50) mg/L in heparin group (t=-4.033, -2.170, P<0.05 or P<0.01). (3) During CBP treatment, patients in heparin group experienced 21 times of exacerbation of wound hemorrhage and 10 times of new hemorrhage, including 2 times of hemorrhage at incision on trachea and 8 times of hemorrhage at arteriovenous intubation point. No exacerbation of hemorrhage or new hemorrhage happened in patients of citrate group. After CBP treatment, no electrolyte disturbance happened in patients of heparin group, but 1 patient in citrate group experienced hypocalcemia. Conclusions Application of citrate anticoagulation in bedside CBP of severe burn patients with sepsis shows light impact on systematic coagulation status, and can effectively decrease inflammation reaction of burn sepsis with low rate of hemorrhage.

Objective To assess the value of free-hand transperineal multiparametric nagnetic resonance imaging/transrectal ultrasound (mpMRI/TRUS) fusion-guided targeted biopsy (TB) for the diagnosis of prostate cancer(PCa).Methods Patients with elevated PSA level and/or an abnormal DRE finding were recruited prospectively between January 2015 and September 2016.Patients were classified to various scores from 2 to 5 according to prebiopsy mpMRI PI-RADS.Based on free-hand transperineal mpMRI/TRUS fusion-guiding,a 2-cores TB for each cancer-suspicious lesion were carried out and followed 12-cores systematic biopsy (SB) protocol.Pathological findings of biopsy and radical prostatectomy (RP) specimens were analyzed.Results A total of 397 patients were enrolled in this study.The median age of the patients was (68.2 ± 7.4) years old,ranging 42-78 years.The median PSA level was (15.0 ±12.4)ng/ml,ranging 3.0-88.3 ng/ml.DRE showed abnormality in 28 patients(7.1％).The median prostate volume was (41.6 ± 16.4)cm3,ranging 24.6-89.8 cm3.The PCa detection rate of TB was significantly increased compared with SB (44.8 ％ vs.34.8％) (P =0.003),especially in clinically significant PCa (P ＜ 0.001) and intermediate/high-risk PCa (P =0.003),respectively.Of the all 588 mpMRI targeted lesions,277 lesions were positive.A total of 105 index tumors were identified in RP specimens,the locations of TB-proven cancer showed 96.6％ (85/88) in correspondence with the location of the index lesion in RP specimens.Conclusions Free-hand transperineal mpMRI/TRUS fusion-guided TB providing greater detection of intermediate-high risk PCa while limits over detection of low risk PCa.Moreover,TB can reliably predict the location of an index tumor.

Objective To explore the effect of " hospital informationized blood glucose management" on perioperative diabetic patients. Methods Three hundred patients with type 2 diabetes mellitus, who underwent selective operations from orthopedics, general surgery, urological surgery, and thoracic surgery were divided into two groups: 150 cases of blood glucose information management group and 150 cases of traditional blood glucose monitoring and management group. The blood glucose on target rate, percent of hypoglycemic events, percent of hyperglycemic events, the blood glucose level on the first postoperative day, the average hospitalization day, perioperative infection rate were evaluated for efficacy. Results The blood glucose on target rate in informationized blood glucose management group was significantly higher than that of the control group [(52.52 ± 18.31)%vs (14.88 ± 8.39)%, P＜0.01]. The frequency of hyperglycemia, the average daily blood glucose, the average blood glucose on fasting, after three meals and at night, the fasting and postprandial blood glucose level on the first postoperative day in informationized blood glucose management group were significantly lower than that of the control group [( 45. 31 ± 18.87)%vs (84.41±8.86)%, (8.59±1.34 vs 12.47±2.37) mmol/L, (7.33±1.41 vs 10.01±1.99)mmol/L, (8.89 ±2.34vs13.61±3.47)mmol/L,(9.47±1.94vs13.46±2.77)mmol/L,(9.40±2.72vs13.28±2.94)mmol/L, (8.28±2.11vs11.31±2.89)mmol/L,(8.29±2.51vs11.58±3.52)mmol/L,(8.25±3.67vs17.65±19.68) mmol/L, all P＜0.01]. In addition, the average hospitalization day of the informationized blood glucose management group was significantly shorter than that of the control group [(16±7 vs 21±15)d, P＜0.05]. The infection rate of the management group and the control group were 41. 2% and 58. 8% respectively. There was no significant difference between two groups (P＞0.05). Conclusion The " hospital informationized blood glucose management" is simple and practical, which may significantly improve the rate of blood glucose control in each period, reduce the average hospitalization day, and decrease perioperative infection tendency.

Objective To investigate the effect of lumboperitoneal (L-P) shunt and ventriculoperitoneal(V-P) shunt for trea-ting the patients with communicating hydrocephalus .Methods The databases of PubMed ,Web of Science ,Scopuss ,Karge , EBSCO+MEDLINE ,OVID ,EMBASE ,CNKI ,CBM disc databases ,Wanfang databases ,Weipu databases were retrieved by com-puter .The relevant literatures about L-P shunt and V-P shunt for treating communicating hydrocephalus included in these databases during 1990-2016 were collected and performed the meta analysis by using the STATA 12 .0 software .Results The success rate of L-P shunt in treating communicating hydrocephalus was apparently higher than that of V-P shunt(P<0 .05) .Moreover ,postopera-tive infection rate ,obstruction rate of shunt system and total postoperative complications rate in L-P shunt were apparently lower than those of V-P shunt(P<0 .05) ,However ,there was no statistical difference in shunt poor rate between L-P shunt and V-P shunt(P>0 .05) .Conclusion L-P shunt is worth recommending .But due to lower quality of the evidences ,it is needed more high quality primary studies to remedy the insufficiency of the study .