OBJECTIVE: To explore the genetic variants and phenotypic characteristics of patients with Neurofibromatosis type I (NF1). METHODS: Twenty two NF1 patients who presented at Enze Medical (Center) Group in Taizhou between 2018 and 2024 were selected as the study subjects. Clinical phenotype and family history were collected for the patients. Whole exome sequencing (WES) was carried out for the 22 probands to screen the variants of NF1 gene. Candidate variants were verified by Sanger sequencing of their family members. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K20230902). RESULTS: The 22 probands were diagnosed between the age of 5 months to 47 years old, and have all shown cafe au lait spots on their skin. Seventeen patients exhibited the phenotype at birth, and 11 had various degrees of neurofibromatosis. Among them, probands 1 and 13 underwent surgical resection of the tumor but had recurred, while proband 12 had amputation due to the huge size and serious impact of the neurofibroma and had no recurrence. Five patients had various degrees of scoliosis. In total 22 germline mutations and one somatic mutation were identified among the 22 families, with 5 variants unreported previously, including 1 nonsense mutation c.1603C>T (Q535*), 3 frameshift mutations [c.7268_7269delCA (Thr2423fs), c.2293del (Arg765Alafs*26), and c.5433_5438delinsGC (Phe1812ArgfsTer50)], and 1 deletion involving exons 41-44 of the NF1 gene and adjacent introns. Proband 13 was found to harbor germline mutation c.6796C>T (Gln2266Ter) and somatic mutation c.1019_1020del (Ser340Cysfs Ter12) in the peripheral blood and tumor tissue, respectively. Among the 22 NF1 probands, 6 had received treatment due to severe illness. Proband 1 had tumor resection in the right upper limb, but was found to have malignant lung tumor and died during follow-up. Proband 12 had multiple recurrence of neurofibroma in the left ring finger. Proband 4 underwent spinal correction surgery due to severe scoliosis. Proband 11 had died due to a central nervous system disease. Among the 22 germline mutations, 6 had led to the occurrence of truncated proteins, which may have a more severe impact on the phenotype. CONCLUSION This study investigated the genetic variants and clinical phenotypes of 22 NF1 families and identified 5 novel variants of the NF1 gene, which has expanded the genotypic and phenotypic spectra of the NF1. Preliminary studies have identified an association between truncated mutations, young age, and severe phenotypes, which may provide important clues for prognosis evaluation. For the clinical diagnosis and treatment of NF1, it is necessary to consider the phenotypic characteristics and genetic testing in combination with genetic counseling and long-term follow-up.
Humans ; Neurofibromatosis 1/pathology* ; Male ; Female ; Pedigree ; Adult ; Child ; Child, Preschool ; Middle Aged ; Adolescent ; Infant ; Young Adult ; Neurofibromin 1/genetics* ; Phenotype ; Asian People/genetics* ; Mutation ; Exome Sequencing ; East Asian People

OBJECTIVE To conduct a rapid and comprehensive evaluation of commonly used oral dihydropyridine calcium channel blockers （DHP CCBs） in Guangxi， and provide scientific basis for clinical medication and drug selection in medical institutions. METHODS Based on the actual drug use data of public medical institutions at the second level and above in Guangxi Zhuang Autonomous Region， and based on the national centralized collection catalog， commonly used oral DHP CCBs were selected. The Professional Committee of Evidence-based Pharmacy of the Guangxi Pharmaceutical Association organized relevant experts from multiple medical institutions in the region to conduct a quantitative scoring of the selected oral DHP CCBs from five key dimensions of pharmaceutical characteristics， effectiveness， safety， economy， and other attributes， by referring to the Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions （the Second Edition）， combined with the latest evidence-based medical research results， and widely soliciting suggestions from clinical and pharmaceutical experts. Finally， the Guangxi Expert Consensus on Rapid Comprehensive Evaluation of Oral Dihydropyridine Calcium Channel Blockers in the Treatment of Cardiovascular Disease was formulated. RESULTS A total of 30 commonly used oral DHP CCBs were selected. Among them， Amlodipine besylate tablets （Huizhi） demonstrated superior comprehensive performance （81.79 points）， excelling particularly in pharmaceutical properties， effectiveness and other attributes. The compound scores of Amlodipine besylate tablets （Chongqing Yaoyou） and Amlodipine besylate tablets （Suzhou Dongrui） ranked second and third respectively， with scores of 81.66 and 81.60 points. CONCLUSIONS This consensus can provide guidance and decision-making support for the rational clinical application of oral DHP CCBs in Guangxi Region and the selection of drug directories in medical institutions.

Objective:To explore the value of applying stone burden in evaluating the treatment efficacy of patients with upper ureteral stones undergoing extracorporeal shock wave lithotripsy.Methods:A retrospective selection was conducted on 328 patients with upper ureteral stones admitted to Beijing Friendship Hospital, Capital Medical University from October 2018 to August 2024. The maximum diameter of the stones was 1.0-2.0 cm, and the patients were divided into successful lithotripsy group ( n=306) and failed lithotripsy group ( n=22) based on the success or failure of lithotripsy. Using multi-slice spiral CT scanning to collect the longest diameter, maximum CT value, volume, and average CT value of the stones in the enrolled patients, evaluate the predictive value of stone burden on the effectiveness of extracorporeal shock wave lithotripsy in patients with upper ureteral stones. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used for comparison between groups; count data were expressed as the cases and percentage, and Chi-square test was used for comparison between groups. Univariate and multivariate Logistic regression analysis were used to evaluate the factors affecting the efficacy of extracorporeal shock wave lithotripsy in patients with upper ureteral stones. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was used to evaluate the predictive value of each influencing factor for the therapeutic effect. Results:The results of univariate analysis showed that there were no statistically significant differences in age, gender, disease duration, and stone side between the successful and failed lithotripsy groups ( P>0.05). However, there were statistically significant differences in the longest diameter, maximum CT value, volume, average CT value of the stones and stone burden ( P<0.05). The results of multivariate Logistic regression analysis showed that the longest diameter, maximum CT value, volume, average CT value of the stones and the stone burden were all risk factors affecting the therapeutic effect of extracorporeal shock wave lithotripsy for upper ureteral stones ( P<0.05). The results of ROC curve analysis showed that the AUC of the longest diameter, maximum CT value, volume, average CT value of the stones and the stone burden, burden 1, burden 2, and burden 3 were 0.844, 0.827, 0.948, 0.873, 0.889, 0.835, 0.911 and 0.865, respectively. Conclusion:The stone burden has good predictive value for the therapeutic effect of extracorporeal shock wave lithotripsy in the treatment of upper ureteral stones, and is worthy of promotion and application.

OBJECTIVE: To determine the types of genetic variants in six Chinese pedigrees affected with Marfan syndrome (MFS) and analyze their clinical characteristics and molecular pathogenesis. METHODS: Six MFS pedigrees presented at the Taizhou Enze Medical Center (Group) between 2017 and 2022 were selected as the study subjects. Clinical data of pedigrees were retrospectively analyzed. Peripheral blood samples were collected from the probands and their family members for the extraction of genomic DNA. Whole exome sequencing (WES) was carried out. Candidate variants of the FBN1 gene were verified by Sanger sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), pathogenicity of the candidate variants was assessed. AlphaFold3 and PyMOL software were used for homology modeling of the FBN1 protein and analysis of its three-dimensional structure and amino acid sequence conservation. This study was approved by the Medical Ethics Committee of Taizhou Enze Medical Center (Group) (Ethics No. 20231002). RESULTS: Cardiovascular system abnormalities were noted in all pedigrees, ocular abnormalities were present in pedigrees 2 and 5, skeletal system abnormalities were presented in pedigrees 1, and 4 to 6. FBN1 gene mutations were identified in all pedigrees, including c.1957_1958dupGT (p.Asp654fs), c.5014T>A (p.Cys1672Ser), c.8135delC (p.Pro2712fs), c.2302G>T (p.Glu768*), c.3473A>G (p.Glu1158Gly) and c.6169C>T (p.Arg2057*), with each involving a different exon. Four variants were rated as pathogenic, one as likely pathogenic, and one as variant of uncertain significance. Among these, c.5014T>A (p.Cys1672Ser), c.1957_1958dupGT (p.Asp654fs), c.8135delC (p.Pro2712fs), and c.2302G>T (p.Glu768*) were unreported previously. Bioinformatic analysis with SIFT and PolyPhen-2 predicted that the c.5014T>A (p.Cys1672Ser) and c.3473A>G (p.Glu1158Gly) variants were deleterious. Protein homologous sequence alignment analysis revealed that the four novel mutation sites are highly conserved across various species. Homology modeling of the FBN1 protein three-dimensional structure indicated that the six variant sites in the amino acid sequence are all close to hydrogen bonds and may alter the secondary and tertiary structures to varying degrees, thereby confirmed the relationship between the variants and MFS. CONCLUSION Four novel variants of the FBN1 gene have been discovered in this study, which has enriched the mutational and phenotypic spectrum of MFS and provided a basis for disease diagnosis and genetic counseling.
Adolescent ; Adult ; Child ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; China ; East Asian People/genetics* ; Exome Sequencing ; Fibrillin-1/genetics* ; Marfan Syndrome/genetics* ; Mutation ; Pedigree ; Retrospective Studies ; Adipokines

Objective:To investigate the efficacy and safety of en-bloc Holmium laser enucleation of the prostate (HoLEP) with an early apical mucosa dissection technique for the treatment of benign prostate hyperplasia (BPH).Methods:The clinical data of 215 patients treated with HoLEP for BPH from January 2020 to January 2023 in the Department of Urology, Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. According to different treatment methods, the patients were divided into study group ( n=112) and control group ( n=103). Patients in the study group were treated by the en-bloc HoLEP with an early apical mucosa dissection technique, while patients in the control group were treated by the classical two or three-lobes HoLEP. The primary endpoints included the rates of urinary incontinence at 1-month, 3-month, and 6-month after surgery in two groups of patients. The secondary endpoints included operative time, hemoglobin decrease, dissected prostate weight, postoperative indwelling catheter time, postoperative hospital stay, and international prostate symptom score (IPSS), quality of life (QoL), Qmax, and postvoid residual urine (PVR) at 3-month and 6-month after surgery. The measurement data were tested by Shapiro-Wilk normality test. The normal distribution of the measurement data were expressed as mean ± standard deviation ( ± s), and independent sample t-test was used for comparison between two groups. Measurement data of skewness distribution were expressed as median (interquartile distance) [ M( Q1, Q3)], and Wilcoxon or Mann-Whitney U test were used for comparison between two groups. The count data in the two groups were compared by the Chi-square test. Results:The incidence of urinary incontinence in the study group was 9.0% (10/112) and 3.6% (4/112) at 1-month and 3-month after surgery, which was significantly lower than those in the control group [18.5% (19/103) and 11.7% (12/103)], and the differences were statistically significant ( P< 0.05). Urinary incontinence in two groups recovered completely 6-month after surgery. The operation time of the study group was (68.74±23.71) min, which was lower than that of the control group [(88.04±25.43) min], and the difference was statistically significant ( P<0.05). There were no significant differences in hemoglobin decrease, dissected prostate weight, postoperative indwelling catheter time, postoperative hospital stay in the two groups ( P> 0.05). The IPSS, QoL, Qmax and PVR of the two groups were significantly improved at 3-month and 6-month after surgery ( P< 0.05), but there was no significant difference between the two groups ( P> 0.05). Conclusion:En-bloc HoLEP with an early apical mucosa dissection technique is safe and reliable in treating BPH, and has advantages over classic HoLEP in terms of short-term urinary continence rates, shortening operation time.

Objective:To evaluate the consistency between bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA) in the measurement of body composition in children aged 6-17 years in China.Methods:Fat-free mass, fat mass and fat mass percentage were measured by both BIA and DXA in 1 161 children. t-test or Wilcoxon paired test was used to evaluate the different outcome of the two methods. The correlation and consistency between the methods were evaluated by Spearman correlation coefficients ( r) and Bland-Altman analysis. Results:Body compositions measured by BIA was positively correlated with those measured by DXA (fat mass r=0.95, fat-free mass r=0.98, fat mass percentage r=0.86, all P<0.05). Comparing with DXA, BIA underestimate children's fat mass [the mean difference is -3.15 kg, and the SD is 2.35 kg, 95% limits of agreement (LoA): -7.74-1.45 kg] and fat mass percentage (the mean difference is -8.45%, and the SD is 4.63%, 95% LoA: -17.53%-0.64%). Conclusions:Body compositions measured by BIA was highly positively correlated with those measured by DXA. BIA has certain application value in the measurement of body fat mass and fat-free mass of children aged 6-17 years.

Objective:To investigate the clinical efficacy and safety of transurethral flexible ureteroscopy combined with single channel minimally invasive percutaneous nephroscopy in the treatment of complex renal calculi.Methods:A total of 72 patients with complex renal calculi admitted to Beijing Friendship Hospital, Capital Medical University from November 2019 to April 2022 were prospective selected, which were randomly divided into study group and control group by the random number table method, with 36 cases in each group. The control group underwent single channel minimally invasive percutaneous nephrolithotomy, while the study group underwent transurethral flexible ureteroscopy combined with single channel minimally invasive percutaneous nephrolithotomy. The perioperative indexes (operation time, postoperative hospital stay, intraoperative blood loss), stone removal effect, renal function indicators [blood urea nitrogen (BUN), serum creatinine (SCr)] and complication rate were compared between the two groups. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used for inter-group comparison. The Chi-square test or Fisher exact probability method were used to compare the count data of two groups. Results:The operation time [(101.05±11.34) min vs (107.84±10.28) min] and postoperative hospital stay [(8.54±3.15) d vs (12.36±4.08) d] in the study group were significantly shorter than those in the control group, and the difference were statistically significant ( P<0.05). The amount of intraoperative bleeding was close to that in the control group, but the difference was not statistically significant ( P>0.05). The primary stone clearance rate and summary stone clearance rate in the study group were 91.67% (33/36) and 100.0% (36/36), respectively, which were significantly higher than 69.44% (25/36) and 83.33% (30/36) in the control group, and the differences were statistically significant ( P<0.05). The postoperative BUN and SCr levels in the study group were (5.24±0.31) mmol/L and (90.65±25.57) μmol/L, respectively, the control group was (7.69±0.78) mmol/L and (131.96±37.80) μmol/L, respectively. BUN and SCr levels in the study group were significantly lower than those in the control group, and the differences were statistically significant ( P<0.05). The total incidence of postoperative complications in the study group was significantly lower than that in the control group (5.56% vs 16.67%), and the difference was statistically significant ( P<0.05). Conclusion:Transurethral flexible ureteroscopy combined with single channel minimally invasive percutaneous nephroscopy is an ideal method for the treatment of complex renal calculi, which has good removal effect, less complications and helps to improve renal function.

Objective:To investigate the efficacy and safety of en-bloc low-power (22.5 W) holmium laser for enucleation of prostate (LP-HoLEP) in the treatment of benign prostatic hyperplasia (BPH).Methods:The clinical data of 98 patients with BPH who underwent surgical treatment in the Department of Urology, Beijing Friendship Hospital, Capital Medical University from January 2020 to October 2022 were retrospectively analyzed. They were divided into LP-HoLEP group ( n=53) and TURP group ( n=45) according to different treatment methods. Patients in the LP-HoLEP group were treated with en-bloc holmium laser enucleation of prostate, and patients in the TURP group were treated with transurethral resection of prostate (TURP). Perioperative indexes of the two groups were compared, including operation time, postoperative hemoglobin changes, tissue resection amount, postoperative catheter indentation time, postoperative hospital stay, complications, and international prostate symptom score (IPSS), quality of life (Qol) score, maximum urine flow rate (Qmax), postvoid residual volume (PVR) and other indicators were obtained at 3 and 6 months after surgery. The measurement data were tested by Shapiro-Wilk normality test. The measurement data conforming to normal distribution were expressed as mean ± standard deviation ( ± s), independent sample t-test was used for comparison between groups, measurement data of skewness distribution were expressed as median (interquartile distance)[ M( Q1, Q3)], and Mann-Whitney U test was used for comparison between groups. The Chi-square test was used to compare the count data between groups. Results:In the LP-HoLEP group, the operative time was (65.74±22.82) min, the hemoglobin decreased 5.71(3.97, 9.01) g/L, the tissue resection volume was (60.59±24.40) g, and the catheter indinduration time was (3.03±0.91) d. The length of postoperative hospitalization was (4.14±1.05) d. TURP group was (77.04±27.33) min, 11.02(8.89, 16.51) g/L, (39.49±11.32) g, (4.80±0.91) d, (5.98±1.03) d, respectively. All the indexes of LP-HoLEP group were better than TURP group. The differences were statistically significant ( P<0.05). Compared with preoperative, IPSS, Qol score, Qmax and PVR of two groups were significantly improved at 3 months after surgery, but there were no statistical significance between groups ( P>0.05). Conclusion:En-bloc LP-HoLEP is safe and reliable in the treatment of BPH, and has advantages over TURP in terms of tissue resection volume, shortening hospitalization and indwelling catheter time, and reducing intraoperative bleeding.

OBJECTIVE To optimize the extraction process of volatile oil components in “Three-Six-Nine” ointment to prepare the “Three-Six-Nine” sustained-release gel paste. METHODS The Box-Behnken response surface method was used to optimize the extraction process of the volatile oil of the “Three-Six-Nine” ointment. The receiving rate of the volatile oil was taken as the evaluation indicator, and the particle size of raw material, extraction temperature and extraction time were taken as the investigation factors. The binomial equation was used to fit the experimental results to verify the optimal extraction conditions. The nano-lipid drug delivery system based on β-cyclodextrin was prepared by emulsification ultrasound-rotary evaporation method. The quality evaluation criteria were sensory evaluation, formativity measurement, skin followability, cold resistance evaluation and heat resistance evaluation. RESULTS The best extraction process of the volatile oil of “Three-Six-Nine” ointment was as follows: raw material particle size over 40 mesh screen, with extraction time of 3 h and extraction temperature of 50 ℃. The amount of volatile oil extracted was (0.469±0.021)mL, the yield of volatile oil was (1.78±0.08)mL·g-1. The results implied “Three-Six-Nine” ointment shown stable formability, heat and cold resistance, and had good adhesion and skin adhesion. CONCLUSION Box-Behnken response surface optimization method is simple and predictable, the prepared “Three-Six-Nine” gel paste has good quality.

Objective:To retrospectively compare the clinical efficacy of two PDE3 inhibitors, oplinone and Milrinone, in order to evaluate which drug has better effects on the improvement of cardiac function, protection of renal function and adverse effects of arrhythmia.Methods:A total of 41 neonates with congenital heart disease after biventricular treatment under cardiopulmonary bypass in the Department of Cardiothoracic Surgery at Soochow University Children's Hospital during 2018-2022 were collected. The experimental group was divided into two groups: Oprilinone(25 cases) and Milinone(16 cases). A retrospective study was conducted on the incidence of renal function, cardiac function improvement and arrhythmia in the children.Results:On the first day after operation, EF in both groups decreased significantly compared with that before operation( P<0.01); On day 4 after surgery, EF in the oprilinone group was significantly higher than that on day 1 after surgery( P<0.01), Milrinone group was slightly higher than that on day 1 after surgery( P<0.05), and EF in oprilinone group was significantly higher than that in Milinone group during the same period( P<0.01); EF in Milinone group continued to increase on day 7 compared with day 4( P<0.01), but there was no significant difference between the two groups. Long-term follow-up showed that there was no significant difference in EF value in the oprilinone intervention group on day 7 after surgery( P<0.05), and the long-term EF in Milinone group was higher than that at 7 days after surgery( P<0.05). The creatinine level in the oprinone intervention group continued to decrease on the 4th and 7th day after surgery( P<0.01; P<0.05); The creatinine level of Milinone group on day 4 after surgery was significantly lower than that on day 1 after surgery( P<0.01), the decrease was not significant on the 7th day after surgery compared with the 4th day after surgery; The creatinine level in the oprilinone group was lower than that in the Milrinone group on day 7 after surgery( P<0.05). The rate of arrhythmia in children was slightly decreased in the intervention group of olplinone. There was no change in the Milinone group. Conclusion:Oplinone improved cardiac function better than Milrinone, and the recovery time to normal cardiac function was shorter. In terms of renal function protection, oplinone was stronger than Milrinone, and the protective effect of oplinone on kidney lasted longer. No significant abnormalities were found with respect to adverse reactions, such as the incidence of arrhythmia.