OBJECTIVES: To summarize the clinical and genetic characteristics of epilepsy with intellectual disability caused by SETD1B gene variants in children. METHODS: A retrospective analysis was conducted on the clinical data of three children with SETD1B gene variants diagnosed and treated at the Department of Pediatric Neurology of Xiangya Hospital of Central South University. Relevant literature was reviewed to summarize the clinical characteristics of this condition. RESULTS: All three children presented with symptoms during infancy or early childhood, including mild intellectual disability and myoclonic seizures, with two cases exhibiting eyelid myoclonia. After treatment with three or more antiepileptic drugs, two cases achieved seizure control or partial control, while one case remained refractory. Each of the three children was found to have a heterozygous variant in the SETD1B gene (one deletion, one frameshift, and one missense variant). To date, 54 cases with SETD1B gene variants have been reported, involving a total of 56 variants, predominantly missense variants (64%, 36/56). The main clinical manifestations included varying degrees of developmental delay (96%, 52/54) and seizures (81%, 44/54). Among the 44 patients with seizures, myoclonic (20%, 9/44) and absence seizures (34%, 15/44) were common, with eyelid myoclonia reported in six cases. Approximately one-fifth of these patients had poorly controlled seizures. CONCLUSIONS The primary phenotypes associated with SETD1B gene variants are intellectual disability and seizures, and seizures exhibit distinct characteristics. Eyelid myoclonia is not uncommon.
Humans ; Intellectual Disability/complications* ; Epilepsy/complications* ; Male ; Female ; Histone-Lysine N-Methyltransferase/genetics* ; Child, Preschool ; Child ; Retrospective Studies

Objective: To investigate the Alzheimer's disease (AD) influencing factors among the elderly, so as to provide a basis for early prevention and intervention. Methods: From March to June 2024, participants aged 60 years and above from a sub-district in Haishu District, Ningbo City, Zhejiang Province were selected using a convenience sampling method. Data on demographics, lifestyle, and health status were collected through questionnaire surveys. Depressive symptoms were evaluated using the short-form Geriatric Depression Scale. The Chinese Mini-Mental State Examination (MMSE) was used for the initial screening of AD, and individuals who screened positive were further diagnosed by psychiatrists. Factors affecting AD among the elderly were analyzed using a multivariable logistic regression model. Results: A total of 3 644 individuals were surveyed, comprising 1 526 males (41.88%) and 2 118 females (58.12%). The mean age was (71.85±7.44) years. AD was detected in 200 cases, with a detection rate of 5.49%. Multivariable logistic regression analysis showed that individuals aged ≥65 years (65-<70 years, OR=3.012, 95%CI: 1.007-9.012; 70-<75 years, OR=3.131, 95%CI: 1.059-9.260; 75-<80 years, OR=5.779, 95%CI: 1.989-16.784; ≥80 years, OR=16.810, 95%CI: 5.926-47.685), those who were unmarried, divorced, or widowed (OR=1.973, 95%CI: 1.383-2.815), those with hearing loss (OR=1.573, 95%CI: 1.128-2.193), those with diabetes mellitus (OR=1.958, 95%CI: 1.362-2.814), and those with depressive symptoms (OR=4.143, 95%CI: 2.997-5.728) had a higher risk of AD. Conversely, individuals with an educational level of primary school or above (primary school, OR=0.579, 95%CI: 0.401-0.835; junior high school or above, OR=0.438, 95%CI: 0.259-0.741), and those who engaged in regular physical exercise (OR=0.414, 95%CI: 0.264-0.649) had a lower risk of AD. Conclusions The detection rate of AD was relatively high among the elderly in Haishu District. AD among the elderly was related to age, educational level, marital status, physical exercise, hearing loss, diabetes mellitus, and depressive symptoms.

Purpose To investigate the expression of thioredoxin-interacting protein(TXNIP)in placental tissues of gestational diabetes mellitus(GDM)and its role in lipid deposition in the placental trophoblast.Methods The pla-centa tissues of 16 GDM pregnant women and 25 women with normal glucose tolerance(NGT)were collected.Mean-while,in vitro models of high-glucose induced human chorionic trophoblast cells(HTR-8/SVneo)were established,which were divided into normal glucose control group(NG),high glucose group(HG),high glucose+si nonsense in-terference group(HG+siNC)and high glucose+TXNIP siRNA group(HG+siTXNIP).The pathological structure and morphological changes of placenta were observed by HE staining.Lipid droplet formation was detected by oil red O staining.The expression and localization of TXNIP in cells were detected by immunocytochemical EnVision method.The mRNA and protein expression levels of TXNIP and lipogenic protein SREBP1 were detected by real-time fluorescent quantitative PCR and Western blot.The relationships between TXNIP expression and lipid droplet accumulation in-duced by high glucose was analyzed.Results High glucose results in abnormal placental structure of GDM.The area of human chorionic intervillous tissue in placenta of GDM group was decreased,the size of fetal capillaries was different and the lumen was dilated.Compared with those NGT group,the accumulation of lipid droplets and the expression of TXNIP mRNA and protein in placental tissue of GDM were increased(P＜0.05).The TXNIP and SREBP1 were up-regulated and the formation of droplets increased in high glucose induced HTR-8/SVneo cells(P＜0.05).On the con-trary,TXNIP siRNA transfection reversed the gene expression level and lipid deposition in high glucose induced cells(P＜0.05).Conclusion TXNIP is involved in abnormal lipid deposition in the placental trophoblast of GDM.

Objective:To evaluate the impact of roxadustat on thyroid function and to identify the associated factors in patients undergoing maintenance peritoneal dialysis (PD).Methods:This study was a single-center retrospective study. PD patients who received roxadustat or recombinant human erythropoietin (rHuEPO) treatment at Nanjing Drum Tower Hospital between January 2020 and June 2024 were included. The general and clinical information as well as laboratory indexes were collected. Serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were compared before and after treatment initiation. Hemoglobin (Hb) responses were also observed between the two groups. Logistic regression analysis was performed to explore the factors associated with thyroid function changes.Results:A total of 120 patients were enrolled, with an age of (55.17±16.42) years, including 66 males (55.0%). There were 81 patients received roxadustat (roxadustat group) and 39 patiens received rHuEPO (rHuEPO group). Compared to the rHuEPO group, the roxadustat group had a higher proportion of patients with diabetes ( χ 2= 4.172, P=0.041), a shorter PD vintage ( Z=-3.406, P=0.002), a lower serum level of total cholesterol ( Z=-2.082, P=0.037) and a lower level of fasting blood glucose ( Z=-2.589, P=0.010). Following treatment with roxadustat, the levels of FT4 ( Z=-5.349, P<0.01) and TSH ( Z=-3.720, P<0.01) decreased significantly. In contrast, no significant changes in FT4 or TSH levels were observed in the rHuEPO group (both P>0.05). For both roxadustat and rHuEPO groups, there were no significant changes in FT3 levels after treatment (both P>0.05). Multivariate analysis identified that higher baseline TSH (TSH≥2.27 μIU/ml, OR=1.581, 95% CI 1.196-2.089, P=0.001) and roxadustat exposure ( OR=3.432, 95% CI 1.410-8.355, P=0.007) as independent associated factors of subsequent TSH decline, and identified that higher baseline FT4 (FT4≥14.9 pmol/L, OR=1.390, 95% CI 1.162-1.662, P=0.001) and roxadustat exposure ( OR=5.798, 95% CI 2.225-15.113, P=0.001) as independent associated factors of subsequent FT4 decline. The degrees of hemoglobin changes after roxadustat or rHuEPO treatment did not differ significantly between roxadustat group and rHuEPO group ( t=-1.062, P=0.290). Of the 31 patients who underwent a second thyroid function test during roxadustat treatment, 24 continued with the original regimen, while 7 discontinued roxadustat. Among 24 patients who maintained roxadustat treatment, TSH ( Z=-0.400, P=0.689) and FT4 ( t=0.143, P=0.888) remained stable between the second and third tests. All 7 patients who discontinued roxadustat treatment showed TSH rebound and the changes of TSH levels were more significant than that in continuers ( Z=-2.505, P=0.012). FT4 recovery occurred in only 3 of them, with no significant difference in FT4 change between discontinuers and continuers ( Z=-0.685, P=0.493). Conclusions:Roxadustat commonly suppresses TSH and FT4, but not FT3, in PD patients. Baseline levels of TSH and FT4 are key associated factors of the inhibitory effect of roxadustat on thyroid function. This suppression does not intensify with prolonged exposure and is reversible after discontinuation, with TSH levels normalizing more quickly than FT4. Roxadustat-induced thyroid suppression does not compromise its efficacy in treating renal anemia.

Objective:To investigate the clinical effect of transposition of gracilis muscle flap in repairing urethral perineal fis-tula after Miles operation.Methods:The clinical data of 3 patients with urethral perineal fistula treated in the Second Affiliated Hos-pital of Zhejiang University from September 2023 to November 2024 were analyzed retrospectively.All patients were male,aged from 59 to 68 years(mean 63 years).All patients underwent Miles operation because of low rectal cancer.Urethral perineal fistula occurred after 2 months to 13 years of the operation.The underlying comorbidities included diabetes(2/3),preoperative chemoradiotherapy(1/3),and chemotherapy alone(1/3).The endourethral fistula was located in the apical and membranous part of the prostate,with a diameter of 1.5-2.0 cm and a mean of 1.7 cm.Suprapubic cystostomy was performed one month before operation.In all 3 cases,perineal inverted"Y"incision was taken under general anesthesia to expose urethral fistula,cut off necrotic tissue and suture urethral fistula.The gracilis muscle of the right thigh was taken and turned through the perineal subcutaneous tunnel.and 6 stitches were suture at the urethral fistula.Results:The operations of all 3 patients were completed successfully.The follow-up period ranged from 2 months to 12 months,with an average of 8 months.There was no case of urinary incontinence after removal of catheter 3 weeks after operation.In two patients,urethrography was reviewed 1 month after surgery to show no fistula residue and urethral stenosis,and the fistula was removed.In one patient with a history of radiotherapy,urethrography was reviewed 1 month after surgery to show a small amount of contrast overflow around the urethra,and urethrography was reviewed again 3 months after surgery to show no contrast over-flow around the urethra.All the 3 patients had no disturbance of movement of the right lower limb,and the pain of different degrees of thigh incision was acceptable and basically relieved half a month after operation.Conclusion:Gracilis muscle flap is one of the ef-fective methods for repairing urethral perineal fistula after Miles operation,which has a precise surgical result and few complications.

Purpose To investigate the expression of thioredoxin-interacting protein(TXNIP)in placental tissues of gestational diabetes mellitus(GDM)and its role in lipid deposition in the placental trophoblast.Methods The pla-centa tissues of 16 GDM pregnant women and 25 women with normal glucose tolerance(NGT)were collected.Mean-while,in vitro models of high-glucose induced human chorionic trophoblast cells(HTR-8/SVneo)were established,which were divided into normal glucose control group(NG),high glucose group(HG),high glucose+si nonsense in-terference group(HG+siNC)and high glucose+TXNIP siRNA group(HG+siTXNIP).The pathological structure and morphological changes of placenta were observed by HE staining.Lipid droplet formation was detected by oil red O staining.The expression and localization of TXNIP in cells were detected by immunocytochemical EnVision method.The mRNA and protein expression levels of TXNIP and lipogenic protein SREBP1 were detected by real-time fluorescent quantitative PCR and Western blot.The relationships between TXNIP expression and lipid droplet accumulation in-duced by high glucose was analyzed.Results High glucose results in abnormal placental structure of GDM.The area of human chorionic intervillous tissue in placenta of GDM group was decreased,the size of fetal capillaries was different and the lumen was dilated.Compared with those NGT group,the accumulation of lipid droplets and the expression of TXNIP mRNA and protein in placental tissue of GDM were increased(P＜0.05).The TXNIP and SREBP1 were up-regulated and the formation of droplets increased in high glucose induced HTR-8/SVneo cells(P＜0.05).On the con-trary,TXNIP siRNA transfection reversed the gene expression level and lipid deposition in high glucose induced cells(P＜0.05).Conclusion TXNIP is involved in abnormal lipid deposition in the placental trophoblast of GDM.

Objective:To evaluate the impact of roxadustat on thyroid function and to identify the associated factors in patients undergoing maintenance peritoneal dialysis (PD).Methods:This study was a single-center retrospective study. PD patients who received roxadustat or recombinant human erythropoietin (rHuEPO) treatment at Nanjing Drum Tower Hospital between January 2020 and June 2024 were included. The general and clinical information as well as laboratory indexes were collected. Serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were compared before and after treatment initiation. Hemoglobin (Hb) responses were also observed between the two groups. Logistic regression analysis was performed to explore the factors associated with thyroid function changes.Results:A total of 120 patients were enrolled, with an age of (55.17±16.42) years, including 66 males (55.0%). There were 81 patients received roxadustat (roxadustat group) and 39 patiens received rHuEPO (rHuEPO group). Compared to the rHuEPO group, the roxadustat group had a higher proportion of patients with diabetes ( χ 2= 4.172, P=0.041), a shorter PD vintage ( Z=-3.406, P=0.002), a lower serum level of total cholesterol ( Z=-2.082, P=0.037) and a lower level of fasting blood glucose ( Z=-2.589, P=0.010). Following treatment with roxadustat, the levels of FT4 ( Z=-5.349, P<0.01) and TSH ( Z=-3.720, P<0.01) decreased significantly. In contrast, no significant changes in FT4 or TSH levels were observed in the rHuEPO group (both P>0.05). For both roxadustat and rHuEPO groups, there were no significant changes in FT3 levels after treatment (both P>0.05). Multivariate analysis identified that higher baseline TSH (TSH≥2.27 μIU/ml, OR=1.581, 95% CI 1.196-2.089, P=0.001) and roxadustat exposure ( OR=3.432, 95% CI 1.410-8.355, P=0.007) as independent associated factors of subsequent TSH decline, and identified that higher baseline FT4 (FT4≥14.9 pmol/L, OR=1.390, 95% CI 1.162-1.662, P=0.001) and roxadustat exposure ( OR=5.798, 95% CI 2.225-15.113, P=0.001) as independent associated factors of subsequent FT4 decline. The degrees of hemoglobin changes after roxadustat or rHuEPO treatment did not differ significantly between roxadustat group and rHuEPO group ( t=-1.062, P=0.290). Of the 31 patients who underwent a second thyroid function test during roxadustat treatment, 24 continued with the original regimen, while 7 discontinued roxadustat. Among 24 patients who maintained roxadustat treatment, TSH ( Z=-0.400, P=0.689) and FT4 ( t=0.143, P=0.888) remained stable between the second and third tests. All 7 patients who discontinued roxadustat treatment showed TSH rebound and the changes of TSH levels were more significant than that in continuers ( Z=-2.505, P=0.012). FT4 recovery occurred in only 3 of them, with no significant difference in FT4 change between discontinuers and continuers ( Z=-0.685, P=0.493). Conclusions:Roxadustat commonly suppresses TSH and FT4, but not FT3, in PD patients. Baseline levels of TSH and FT4 are key associated factors of the inhibitory effect of roxadustat on thyroid function. This suppression does not intensify with prolonged exposure and is reversible after discontinuation, with TSH levels normalizing more quickly than FT4. Roxadustat-induced thyroid suppression does not compromise its efficacy in treating renal anemia.

【Objective】 To explore the learning curve of single-surgeon robot-assisted laparoscopic radical prostatectomy (RARP), which provides a reference for physicians who intend to carry out RARP. 【Methods】 The clinical data of 65 prostate cancer patients who underwent RARP in our hospital during Sep.2022 and Dec.2023 were retrospectively analyzed.The patients’ median age was 67.5(58.1-82.4) years, median total prostate-specific antigen (PSA) was 15.6 (6.7-98.4) ng/mL, median body mass index (BMI) was 20.8(17.4-27.3) and preoperative clinical stage of tumor was T2aN0M0-T3bN1M0.The cumulative sum (CUSUM) method was used to fit the learning curves of machine installation time and operation time.According to the inflection points, the learning curves were divided into different learning stages, and the clinical data of patients at different learning stages were compared. 【Results】 The learning curve of RARP was 12 cases.The 65 cases were divided into three stages: 1st-12th cases in the learning stage, 13rd-43rd cases in the mastery stage, and 44th-65th cases in the proficiency stage.With the increase of the number of surgical cases, the median operation time [191(100-360) min vs. 116(83-165) min vs. 90(75-105) min] and median intraoperative blood loss [403(180-900) mL vs. 236(180-305) mL vs. 94(30-200) mL] in the three stages showed a gradual downward trend (P<0.05).The median machines installation time of the learning stage was significantly longer than that in the mastery stage and the proficiency stage [25(21-28) min vs. 12(11-15) min vs. 12(11-14) min] (P<0.05).The positive surgical marginrate (PSM) in the learning stage was significantly higher than that in the mastery stage and proficiency stage (41.7% vs.22.6% vs.22.7%) (P<0.05). 【Conclusion】 For surgeons with rich experience in traditional laparoscopic surgery, the learning curve of RARP is about 12 cases, and after 43 cases, the operation time and intraoperative blood loss can be further reduced.

Objective:To develop and validate a model to predict the risk of malnutrition in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy. Methods:From April 2022 to August 2023, 430 patients with nasopharyngeal carcinoma who were admitted to the department of radiotherapy of the first affiliated hospital of Guangxi medical university in Nanning were conveniently selected as the study subjects, and they were divided into the modelling group (300 cases) and the internal validation group (130 cases) in the internal validation group in the ratio of 7:3, and 61 patients with nasopharyngeal carcinoma admitted to the affiliated cancer hospital of Guangxi medical university in Nanning City were selected as the external validation group. Logistic regression was used to establish the risk prediction model and draw nomograms,Hosmer-Lemeshow, calibration curve and ROC were used to verify the goodness of fit and predictive power of the model, and clinical decision curve was used to assess the clinical utility. Results:Logistic regression analysis showed that skeletal muscle mass index, self-rated anxiety scale score, Pittsburgh sleep quality questionnaire score, Chinese diet pagoda score, regular exercise, and digestive symptom groups were the influencing factors for malnutrition in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy. In the modelling group, the area under the ROC curve was 0.853 (95％CI:0.81 ～ 0.89), the maximum Youden was 0.600, and the corresponding specificity was 0.764 and the sensitivity was 0.836. The Hosmer-Lemeshow test=4.040 and P=0.853 indicated that the model had good predictive ability. Calibration curve of the calibration showed that the predictive effect of the model matched actual probability well, with an average absolute error was 0.024. When the threshold probability of the clinical decision curve is 0.05 ～ 0.85, the clinical response rate is higher. The area under the operating curve of the subjects in the internal validation group was 0.891, the sensitivity was 77.36％, the specificity was 89.61％, and the practical application accuracy was 84.62％. The area under the operating curve of the subjects in the external validation group was 0.886, the sensitivity was 76.00％, the specificity was 83.33％, and the overall accuracy was 80.33％. Conclusion:The risk prediction model constructed in this study has a good effect, which can effectively predict the incidence of malnutrition in patients receiving concurrent radiotherapy and chemotherapy for nasopharyngeal carcinoma, and provide a reference for clinical staff to formulate and implement nutritional interventions.

AIM:To explore the influence factors of the treatment zone diameter(TZD)and its correlation with axial length growth(ALG)after Paragon CRT orthokeratology.METHODS: Retrospective clinical study. The data of 226 myopic patients(226 eyes)wearing Paragon CRT orthokeratology from April 2020 to September 2022 were collect. The correlated factors of TZD after wearing lens for 1mo, and the relationship between the overlapping treatment zone/ pupil area ratio and the ALG after wearing lens for 1a were analyzed.RESULTS: After wearing lens for 1mo, the TZD was negatively correlated with central corneal thickness(CCT)and positively correlated with the flat corneal eccentricity. After wearing lens for 1a, the ALG of the small TZD group(0.25±0.18mm)was significantly smaller than that of the large TZD group(0.34±0.24mm, P=0.002), and the ALG of the small area ratio group(0.24±0.19mm)was significantly smaller than that of the large area ratio group(0.35±0.23mm,P<0.001). Age and overlapping treatment zone area/pupil area ratio were significantly associated with the ALG in multivariate linear regression(all P<0.05).CONCLUSION: The wearers with thicker CCT and smaller flat corneal eccentricity usually had smaller TZD, and both the TZD and the overlapping treatment zone area/pupil area ratio were correlated with the ALG.