Objective:To investigate the safety and effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis and treatment of pediatric pancreaticobiliary maljunction (PBM).Methods:Data of 40 pediatric patients under 14 with PBM diagnosed and treated by ERCP at Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from November 2012 to September 2022 were collected. PBM types, ERCP-related diagnosis and treatment, adverse events and prognosis were retrospectively analyzed.Results:Nineteen cases were P-B type (joining of common bile duct with pancreatic duct), 17 were B-P type (joining of pancreatic duct with common bile duct), and 4 were complex type. Forty children with PBM underwent 50 ERCP-related operations, among which 48 procedures succeeded. One case failed during cannulation of ERCP, replaced by rendezvous-assisted endoscopic retrograde pancreatography (RV-ERP) afterwards. There were no serious postoperative adverse events such as bleeding, perforation or death. Thirty-four patients (85%) were followed up successfully, among which 14 underwent further surgery and 20 continued conservative treatment.Conclusion:ERCP is the golden standard to diagnose pediatric PBM, and it is also safe and effective treatment for PBM.

Objective To screen and verify the genes that play key role in the occurrence and development of esophageal cancer by u-sing bioinformatics and real-time fluorescence quantitative PCR(qRT-PCR)methods to find new markers for diagnosis of esophageal cancer(ESCA).Methods Using the TCGA database and Wayne plot analysis,the cross genes between the differentially expressed genes of ESCA and the genes which have the most significant impacts on disease-free survival(DFS)rate in esophageal cancer patients were preliminarily identified.Following conducting protein-protein interaction(PPI)network analysis on the overlapping genes,GO and KEGG functional analysis was performed to screen the potential key genes as the diagnostic markers of esophageal cancer.qRT-PCR was used to quantitatively analyze the expression of mRNA of the key gene in peripheral blood.Statistical analysis was con-ducted based on the clinico-pathological characteristics of the patients to determine its potential value as a new diagnostic marker for e-sophageal cancer.Results After overlapping of differentially expressed genes of ESCA and disease-free survival genes in the TCGA database,39 upregulated genes and 20 downregulated genes were found to be differentially expressed,all of which affected disease-free survival rate.After conducting PPI network analysis,15 upregulated genes with core interactions were identified,and the downregulat-ed genes did not form any interaction network.Further enrichment analysis of these 15 core interacting genes through GO and KEGG,revealed that fibronectin 1(FN1)may be a potential biomarker for ESCA diagnosis.The qRT-PCR results showed that compared with the healthy control group,the mRNA expression level of FN1 in the peripheral blood of esophageal cancer patients was significantly ele-vated.After analyzing the clinical characteristics of patients,it was found that the patients with poor differentiation and high clinico-pathological staging had significantly increased peripheral blood FN1 mRNA levels.The model with FN1 mRNA expression levels can distinguish esophageal cancer patients from healthy individuals.Conclusion FN1 mRNA may be a potential non-invasive diagnostic biomarker for esophageal cancer.

Objective:To investigate the application value of a multi-dimensional digital moni-toring platform for perioperative period in gastric cancer patients.Methods:The retrospective cohort study was conducted. The clinical data of 50 patients who underwent laparoscopic radical gastrec-tomy in The Affiliated Hospital of Nanjing University of Chinese Medicine from July 2022 to January 2024 were collected. There were 35 males and 15 females, aged (64±12)years. All patients followed the concept of enhanced recovery after surgery, and the multi-dimensional digital monitoring platform based on wearable monitoring equipment was used to implement perioperative management measures. Observation indicators: (1) results of heart rate variability (HRV) monitoring; (2) results of blood glucose and blood oxygen monitoring; (3) results of exercise and sleep monitoring; (4) results of body composition monitoring. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(IQR). Repeated measurement data were analyzed using the repeated ANOVA. Measurement data with skewed distri-bution were transformed to normal distribution by SPSS transformation function before testing. For comparison between pre- and postoperation, paired sample t test was used for measurement data with normal distribution, and nonparametric Wilcoxon signed rank sum test was used for measure-ment data with skewed distribution. Results:(1) Results of HRV monitoring. From preoperation to the third day after surgery, the standard deviation normal to normal heart beat of 50 patients was changed from(103±26)ms to(101±36)ms, the mean of the standard deviations of normal to normal heart beat calculated per 5 min segment was changed from (45±16)ms to(33±12)ms, the number of pairs of adjacent NN intervals differing by more than 50 ms in the entire recording was changed from 6.02%(4.96%) to 5.79%(4.20%), the low frequency power was changed from 376.78(468.96)ms 2 to 742.79(525.20)ms 2, the high frequency power was changed from 273.61(273.58)ms 2 to 397.48(164.87)ms 2, the ratio of low frequency power to high frequency power was changed from 1.6±0.5 to 1.6±0.6, showing significant differences in above indicators before and after operation ( F=34.43, 26.15, 24.58, 5.51, 6.11, 6.02, P<0.05). (2) Results of blood glucose and blood oxygen monitoring. From preoperation to the third day after surgery, the blood glucose of 50 patients was changed from 6.75(2.05)mmol/L to 6.90(2.63)mmol/L, showng a significant difference before and after operation ( F=45.84, P<0.05). The blood oxygen was changed from 97.00%(5.00%) to 97.50%(3.00%), showing no significant difference before and after operation ( F=2.25, P>0.05). (3) Results of exercise and sleep monitoring. From preoperation to the third day after surgery, the number of steps fo 50 pati-ents was changed from 3 043(1 224) to 1 473(767), sleep duration was changed from(8.2±1.1)hours to(7.3±0.8)hours, sleep score was changed from 80±10 to 78±5,showing significant differences in above indicators before and after operation ( F=716.46, 29.02, 47.32, P<0.05).(4) Results of body composition monitoring. The body weight of 50 patients was changed from (63±8)kg to(61±8)kg before and after operation, body fat rate was changed from 24%±8% to 22%±9%, muscle mass was changed from 43 (12)kg to 41(17)kg, body mass index was changed from (23.0±2.6)kg/m 2 to(22.1±2.5)kg/m 2, showing significant differences in above indicators before and after operation ( t=8.19, 3.00, Z=-2.78, t=7.34, P<0.05), while there was no significant difference in basal metabolic indicators from (1 390±134)kcal to (1 379±139)kcal before and after operation ( t=1.02, P>0.05). Conclusion:The multi-dimensional digital monitoring platform for preoperative period can accurately monitor the perioperative stress level and evaluate the postoperative recovery of gastric cancer patients, which can present the visual results.

Objective To establish a stable rat model of non-obese polycystic ovary syndrome(PCOS)with clinical characteristics.Methods Dehydroepiandrosterone(DHEA)was used to establish a PCOS rat model by subcutaneous injection.Three-week-old female SD rats were divided into a normal group,6 mg/kg DHEA model group,and 60 mg/kg DHEA model group.The model groups were subcutaneously injected with the corresponding dose of DHEA daily,while the normal group was subcutaneously injected with glycerol daily for 21 consecutive days.The model was evaluated with ovarian histopathology as the gold standard to determine the optimal dosage of DHEA to induce a PCOS rat model.On this basis,the optimal DHEA modeling dose was selected,and stop and continue modeling groups were set up to observe the model for 28 days and evaluate its maintenance.The stop modeling group was no longer given DHEA,and the continued modeling group was subcutaneously injected with 60 mg/kg DHEA every 48 h.The evaluation indicators included body mass,estrous cycle,fasting blood glucose,serum insulin,histopathologic morphology of the ovaries,and serum sex hormone levels.Results(1)Compared with the normal group,the 6 mg/kg and 60 mg/kg DHEA model groups showed no significant difference in body mass,and their estrous cycles were irregular.There were more cystically dilated large follicles in the ovaries;fewer mature follicles;reduced layers of granulosa cells,which were arranged in a sparse and disorganized manner;and fewer lutea in the 6 mg/kg and 60 mg/kg DHEA model groups than the normal group.Furthermore,serum T and E2 levels were significantly higher in the 60 mg/kg DHEA model group(P＜0.05)than the normal group.(2)The stop modeling group(A2 group)resumed regular estrous cycles after 2 weeks,various growth follicles and corpora lutea were observed in the ovarian tissues,the number of cystic follicles was reduced,the number of granulosa cell layers increased,mature follicles were visible,oocyte morphology was locally intact,and the levels of E2 and AMH were reduced compared with the normal group(A1 group)(P＜0.05).(3)The continue model group(B2 group)was in the late stage of estrous cycle for a long period,and there were more large follicles with cystic dilatation,fewer mature follicles,fewer layers of granulosa cells with a sparse and disordered arrangement,and significantly fewer corpus lutea in the ovaries compared with the normal group(B1 group).The levels of serum LH,LH/FSH,and T were elevated(P＜0.05).Conclusions Subcutaneous injection of 60 mg/kg DHEA for 21 consecutive days can be used to successfully construct a non-obese PCOS rat model that possesses clinical characteristics.Subcutaneous injection of 60 mg/kg DHEA every 48 hours maintains the stability of the model.

Objective:To investigate the effect of single nucleotide polymorphism (SNP) of FCN gene on the susceptibility of pre-eclampsia (PE) in Han nationality pregnant women.Methods:A total of 274 PE pregnant women (PE group) and 154 healthy pregnant women (control group) admitted to Boai Hospital of Zhongshan, Affiliated Hospital to Southern Medical University from October 2020 to October 2022 were collected. The general information, medical history, reproductive history, blood pressure, body mass index and blood biochemical indicators before delivery were compared between the two groups. Twenty-three SNP loci of FCN gene family were genotyped by time-of-flight mass spectrometry, and the serum levels of ficolins (ficolin-1, -2 and -3) were detected by enzyme-linked immunosorbent assay.Results:(1) Compared with the control group, the body mass index, mean arterial pressure, gestational age at delivery, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, direct bilirubin, albumin, and C-reactive protein in the PE group were significantly higher than those in the control group (all P<0.05). The levels of N-terminal pro-B type natriuretic peptide (NT-proBNP), placental growth factor (PlGF) and human soluble vascular endothelial growth factor receptor-1 (sFlt-1) were significantly different between the two groups (all P<0.05). (2) Among the 23 SNP loci in FCN gene family, 18 loci were in Hardy-Weinberg genetic equilibrium, including 5 loci in FCN1 gene, 10 loci in FCN2 gene, and 3 loci in FCN3 gene. Five loci that did not conform to Hardy-Weinberg genetic equilibrium were not included in the subsequent analysis. Compared with the control group, the genotype distribution of 3 loci of FCN2 gene (rs7872508, rs11103563, rs73664188) and 1 locus of FCN3 gene (rs3813800) in the PE group were significantly different (all P<0.05). After Bonferroni correction, only the genotype distribution of rs7872508 and rs73664188 in FCN2 gene were statistically different between the PE group and the control group (all P<0.05). Further analysis showed that for the rs7872508 locus of FCN2 gene, compared with GG genotype, genotype GT ( OR=3.025, 95% CI: 1.080-8.471) and TT ( OR=4.777, 95% CI: 1.758-12.979) both significantly increased the risk of PE (both P<0.05). For rs73664188 locus of FCN2 gene, compared with TT genotype, genotype TC ( OR=0.510, 95% CI: 0.334-0.778) significantly reduced the risk of PE ( P<0.05). (3) Compared with the control group, the serum levels of ficolin-1 and ficolin-2 in pregnant women in the PE group were significantly reduced (both P<0.05), while the level of ficolin-3 showed no significant change ( P=0.271). Correlation analysis showed that the serum levels of ficolin-2 in pregnant women in the PE group were significantly positively correlated with PlGF level ( r=0.321, P<0.001), and significantly negatively correlated with sFlt-1 level ( r=-0.187, P=0.002) and NT-proBNP level ( r=-0.392, P<0.001). Further analysis revealed that the serum levels of ficolin-2 in pregnant women of the PE group with GT and TT genotypes at rs7872508 locus of FCN2 gene were significantly reduced (both P<0.05), while the serum level of ficolin-2 in pregnant women of the PE group with TC genotype at the rs73664188 locus were significantly increased ( P<0.05). Conclusion:The SNP of FCN2 gene in FCN gene family might be related to the susceptibility to PE and have an effect on serum ficolin-2 level in PE pregnant women.

RBM46 is a germ cell-specific RNA-binding protein required for gametogenesis, but the targets and molecular functions of RBM46 remain unknown. Here, we demonstrate that RBM46 binds at specific motifs in the 3'UTRs of mRNAs encoding multiple meiotic cohesin subunits and show that RBM46 is required for normal synaptonemal complex formation during meiosis initiation. Using a recently reported, high-resolution technique known as LACE-seq and working with low-input cells, we profiled the targets of RBM46 at single-nucleotide resolution in leptotene and zygotene stage gametes. We found that RBM46 preferentially binds target mRNAs containing GCCUAU/GUUCGA motifs in their 3'UTRs regions. In Rbm46 knockout mice, the RBM46-target cohesin subunits displayed unaltered mRNA levels but had reduced translation, resulting in the failed assembly of axial elements, synapsis disruption, and meiotic arrest. Our study thus provides mechanistic insights into the molecular functions of RBM46 in gametogenesis and illustrates the power of LACE-seq for investigations of RNA-binding protein functions when working with low-abundance input materials.
Animals ; Mice ; 3' Untranslated Regions/genetics* ; Cell Cycle Proteins/metabolism* ; Gametogenesis/genetics* ; Meiosis/genetics* ; Nuclear Proteins/genetics* ; RNA-Binding Proteins/genetics*

Humans ; Asthma/drug therapy* ; Biological Therapy

15q11-q13 Duplication syndrome is a rare genetic disease of the nervous system, characterized by developmental retardation, intellectual impairments, hypotonia, autism, epilepsy and so on. This article reports a 33-year-old male patient, with the clinical manifestation of early-onset intractable epilepsy and mental retardation. The high-throughout whole exome sequencing showed a 10.53 Mb repeat sequence in the 15q11.2-q13.3 region, further confirming the diagnosis of 15q11-q13 duplication syndrome. The literature reports of the pathogenic mechanism, classification, typical clinical manifestation, seizure features,accessory examination and therapy of the 15q11-q13 duplication syndrome are summarized and reviewed, so as to enhance the understanding of the disease, as well as to improve the diagnosis and treatment level of the clinicians.

OBJECTIVE To establish the fingerprint of Gegenqinlian tablets and determine the content of eleven components(3’-hydroxy puerarin, puerarin, 3’-methoxy puerarin, daidzin, baicalin, palmatine hydrochloride, berberine hydrochloride, scutellarin, baicalein, ammonium glycyrrhizinate and wogonin) by quantitative analysis of multi-components by single-marker(QAMS).METHODS Ten batches of Gegenqinlian tablets were determined by HPLC and a common fingerprint was established. Baicalin was selected as internal reference. The relative correction factors of the component with 3’-hydroxy puerarin, puerarin, 3’-methoxy puerarin, daidzin, palmatine hydrochloride, berberine hydrochloride, scutellarin, baicalein, ammonium glycyrrhizinate and wogonin were calculated and their contents were calculated. The feasibility and scientificity of QAMS was evaluated by comparison on the results between the measured value and calculation value by external standard method and QAMS. The chromatographic separation was performed on ananalytical column of Waters Xbridge-C18(250 mm× 4.6 mm, 5 μm) with gradient elution, the mobile phase was acetonitrile 0.1% phosphoric acid aqueous solution, at a flow rate of 1.0 mL·min-1. The column temperature was 30 ℃ and the detection wavelength was 260 nm.RESULTS There were 20 peaks in 10 batches of Gegenqinlian tablets and 11 chemical constituents were identified. The similarity of 10 batches of Gegenqinlian tablets was >0.97. The linear range of 3’-hydroxy puerarin, puerarin, 3’-methoxy puerarin, daidzin, baicalin, palmatine hydrochloride, berberine hydrochloride, scutellarin, baicalein, ammonium glycyrrhizinate and wogonin were 0.056 6-2.830 2, 0.241 2-12.058 6, 0.128 0-6.401 0, 0.059 7-2.983 5, 0.242 7-12.134 9, 0.045 7-2.285 7, 0.192 8-9.641 0, 0.043 3-2.167 0, 0.018 0-0.900 2, 0.021 0-1.048 4, 0.011 5-0.575 4 μg (r2= 0.999 6-1.000) respectively. The average recovery were 100.23%, 102.01%, 101.66%, 102.73%, 100.17%, 98.45%, 98.41%, 100.95%, 101.85%, 97.97%, 100.09%(RSD=1.24%-2.57%, n=6) respectively. The relative correction factors of 3’-hydroxy puerarin, puerarin, 3’-methoxy puerarin, daidzin, palmatine hydrochloride, berberine hydrochloride, scutellarin, baicalein, ammonium glycyrrhizinate and wogonin were 0.860 4, 0.605 3, 0.850 9, 0.582 8, 0.557 1, 0.498 6, 0.767 2, 0.652 1, 2.608 1, 0.545 2 respectively. RAD between QAMS method and external standard method were 0.03%-2.12%. CONCLUSION The combination of QAMS and fingerprint can provide reference for the quantitative determination and quality control of Gegenqinlian tablets.

Objective:To investigate the efficacy and safety of a new China-made direct visualization system of peroral cholangiopancreatography in the diagnosis and treatment of biliopancreatic diseases.Methods:Clinical data of 37 patients who underwent endoscopic examination through the direct visualization system of peroral cholangiopancreatography at Digestive Endoscopy Center of Nanjing Drum Tower Hospital from April 2020 to June 2021 were retrospectively analyzed. Technical success rate and complications were analyzed.Results:The examination was completed in 37 patients through the system. The technical success rate was 100.0%. The nature of biliary stricture was confirmed in 24 cases, presenece or absence of bleeding or residual stones in the bile duct was confirmed in 6 cases, neoplasm or residual stones in the pancreatic duct was determined in 2 cases, biliary stricture was passed assisted with visualized guidewire in 2 cases, and lithotripsy was performed assisted with biliary laser in 3 cases. Nine patients were pathologically diagnosed as having malignant biliary stricture, and 8 of them were confirmed malignant by the system. Drainage was performed in 34 cases after the examination. There were 3 cases of cholangitis, 4 cases of bacteremia and 2 cases of postoperative pancreatitis after the operation, which were relieved in a short time after conservative treatment. Bleeding occurred in 1 case which was improved after two times of endoscopic hemostasis.Conclusion:The new direct visualization system of peroral cholangiopancreatography is safe and effective in the diagnosis and treatment of biliopancreatic diseases.