Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Objective:To investigate the application of sentinel lymph node biopsy (SLNB) in early-staged cervical cancer by laparoscopy.Methods:It was a prospective, single-arm, single-center clinical study. Seventy-eight cases of cervical cancer patients were collected from July 2015 to December 2018 at the Fourth Hospital of Hebei Medical University. All the patients were injected with tracer into the disease-free block of cervical tissue after anesthesia by the same surgeon who learned sentinel lymph node (SLN) mapping technique in Memorial Sloan-Kettering Cancer Center, and underwent SLN mapping followed by complete pelvic lymphadenectomy. Moreover, all the dissected lymph nodes were stained with hematoxylin eosin staining (HE) pathological examination. Besides, the negative SLN on hematoxylin-eosin staining were detected by immunohistochemistry cytokeratin staining micro-metastasis. To analyze the distribution, detection rate, false negative rate the sensitivity and negative predictive value of the SLN in early-staged cervical cancer by laparoscopy, and explore the value of SLN mapping in predicting the lymph nodes metastasis in early-staged cervical cancer.Results:The overall detection rate of SLN in cervical cancer was 99% (77/78), bilateral detection rate was 87% (68/78). The average of 12.4 lymph node (LN) and 3.6 SLN were dissected for each patients each side. SLN of cervical cancer were mainly distributed in the obturator space (61.5%, 343/558), followed by external iliac (23.5%, 131/558), common iliac (7.3%, 41/558), para-uterine (3.8%, 21/558), internal iliac (2.2%, 12/558), para abdominal aorta (1.1%, 6/558), and anterior sacral lymphatic drainage area (0.7%, 4/558). Fourteen cases of LN metastasis were found among all 78 cases. There were a total of 38 positive LN, including 26 SLN metastasis and 12 none sentinel LN metastasis. Through immunohistochemical staining and pathological ultra-staging, 1 SLN was found to be isolated tumor cells (ITC), and 5 SLNs were found to be micro-metastases (MIC), accounting for 23% (6/26) of positive SLN. SLN mapping with pathological ultra-staging improved the prediction of LN metastasis in cervical cancer (2/14). Metastatic SLN mainly distributed in the obturator space (65%, 17/26), peri-uterine region (12%, 3/26), common iliac region (15%, 4/26), and external iliac region (8%, 2/26). The consistency of the diagnosis of lymph node metastasis by SLN biopsy and postoperative retroperitoneal lymph node metastasis showed that the Kappa value was 1.000 ( P<0.001), indicated that the metastasis status of SLN and retroperitoneal lymph node were completely consistent. The sensitivity, specificity, accuracy, false-negative rate, and negative predictive value of SLN biopsy in the diagnosis of lymph node metastasis were 100%, 100%, 100%, 0, and 100%, respectively. Conclusions:SLN in early-staged cervical cancer patients were mainly distributed in the obturator and external iliac space, pathalogical ultra-staging of SLN could improve the prediction of LN metastasis. Intraoperative SLN mapping is safe, feasible and could predict the state of retroperitoneal LN metastasis in early-staged cervical cancer. SLNB may replace systemic pelvic lymphadenectomy.

OBJECTIVE: To study the influence of maternal sex chromosomal abnormalities on the prediction of fetal sex chromosome abnormalities (SCAs) by non-invasive prenatal testing (NIPT). METHODS: Thirty-six pregnant women with a prediction for fetal SCAs by NIPT were verified as false positive after prenatal diagnosis using amniotic fluid samples. With informed consent, these women were subjected to chromosomal karyotyping or copy number variations (CNVs) analysis through high-throughput sequencing. RESULTS: Sex chromosomal abnormalities were found in 8 women, which yielded an abnormal rate of 22.22% (8/36). Among these, 3 had sex chromosome aneuploidies (47, XXX), 4 had sex chromosome mosaicisms, and 1 carried structural chromosomal abnormalities. Reanalysis of the results of NIPT were consistent with the maternal CNVs by large. With the ratio of cffDNA (ChrX)/cffDNA was more than 2, 6 of the eight women were found to harbor sex chromosome abnormalities, and the fetal karyotype was normal. However, with a ratio of less than 2, only 2 of the 38 pregnant women had sex chromosome abnormalities, and 10 of the fetuses were confirmed as positive. CONCLUSION The presence of maternal sex chromosomal abnormalities can greatly influence the result of NIPT, which may also be an important reason for false prediction for fetal SCAs by NIPT. When NIPT indicates abnormal SCAs, it is necessary to analyze maternal sex chromosomes. The ratio of cffDNA(ChrX)/cffDNA may help to determine the source of abnormal signals.

OBJECTIVETo explore the cause of failure of non-invasive prenatal testing (NIPT) using cell-free fetal DNA from peripheral maternal blood.

METHODSA total of 31 832 cases of NIPT were retrospectively analyzed. The clinical data of pregnant women were analyzed and the outcome of pregnancy was followed up.

RESULTSAmong the 31 832 cases, 200 patients have failed for the first NIPT test. Second test has succeeded in 171 (85.9%) of 199 cases, while 28 cases (14.1%) still yielded no effective results. This gave rise for a total failure rate of 0.088%. Of the 28 cases, 11 (39.2%) were due to high content of total free DNA and could not be sequenced, 17 (60.7%) were found to have the fetal DNA content of less than 4%. Among the 171 cases which have obtained a valid result, NIPT showed that there were 4 patients with high risk of trisomy 21, 18 cases with high risk of 18 trisomy and 1 case with high risk of 13 trisomy. Karyotyping analysis of the amniocytic chromosomes has identified 3 cases with 47,XN,+21, 1 case with 46,XN,rob(21;21), 1 case with 47,XN,+18, while the 13 trisomy case was found to be false positive. For the 28 cases with failed NIPT retest, 14 had normal delivery, with no anomaly noticed in the neonates. Nine patients had opted for artificial abortion during middle or late pregnancy due to maternal factors (4 cases) or fetal factors (5 cases). Four patients developed complications of pregnancy. One case was in good condition upon follow-up. Four cases were lost during follow-up. Of the 11 pregnant women who had failed the NIPT test due to high content of total free DNA, 6 (54.5%) had opted for artificial abortion during midterm pregnancy, which was significantly higher than that of pregnant women with low free DNA content (17.6%).

CONCLUSIONFailure of NIPT testing should attract attention from researchers. Failure of single NIPT test should not be regarded as a high risk signal for fetal chromosomal aneuploidies. For those where the test has failed again, genetic counseling and strengthened perinatal care should be provided for the pregnant women.

Objective To assess the mortality and risk factors for stroke among dialysis patients with different dialysis modality. Methods 590 patients who underwent hemodialysis (HD) or peritoneal dialysis (PD) from January 2008 to December 2012 were recruited in our study, and categorized according to dialysis modality. The prognostic risks of stroke were hazard ratio of risk was calculated by Cox regression analysis in HD and PD patients respectively. by the Kaplan?Meier curves or the Cox proportional hazards model. Results A total of 590 patients is under a median follow?up of 32.5 months. The stroke incidence rate of 49.2/1, 000 patient?years in total patients, and 74.1/1, 000 patient?years in HD patients, which was significantly higher compared with that of 31.8/1,000 patient?years in PD patients. On multivariate analysis, independent predictors of stroke occurrence were age(HR=1.05;95%CI:1.02~1.09;P=0.003)、diabete(HR=1.98;95%CI:1.31~3.46;P=0.001)、CVD(HR=2.06;95%CI:1.62-3.05;P < 0.001)、Total triglycerides(HR = 1.20; 95% CI:1.08-1.58; P = 0.034) and hemodialysis (HR = 2.03; 95% CI:1.46-3.89; P = 0.005). Conclusions Age, diabete, CVD, total triglycerides and hemodialysis are independently associated with increased stroke risks in dialysis patients, which suggest that these patients should pay attention to weight control and glucose control.

Objective To discuss the expression level of CUEDC2 protein and its connection with 24 h urinary albumin and serum creatinine iu db/db mice with diabetic nephropathy.Methods db/db mice were selected as experimental groups (n =10),and db/m mice as control (n =10).All mice were fed in barrier facilities under the same conditions.At week 24,all were sacrificed and the samples were collected for analyses.The histological changes were assessed by Hematoxylin-Eosin(HE) staining,periodic acid-Schiff (PAS) staining and Masson's trichrome (Masson) staining.The location and expression of CUEDC2 were measured by immunohistochemistry assays.24 h urinary albumin and serum creatinine were quantified by clinic lab in our hospital.Results Immunohistochemistry demonstrated that CUEDC2 was mainly located in the medulla tubules plasma cells.The results of HE staining revealed that there appeared glomerular number decreased,atrophy and inflammatory cell infiltration in the mice kidney of diabetic nephropathy group at the 24th week.The mesangial matrix expansion and renal tissue collagen deposition were significantly up-regulated in db/db mice compared with the normal control.As compared with the control group,the CUEDC2 protein expression and mRNA expression in db/db mice were significantly decreased than that in db/m mice (both P ＜ 0.05),and 24 h urinary albumin and serum creatinine were significantly increased.The correlation analysis showed CUEDC2 was negatively correlated with 24 h urinary albumin and serum creatinine (both P ＜ 0.05).Conclusion The expression of CUEDC2 in diabetic nephropathy mice kidney is significantly decreased and negatively correlated with the levels of 24 h urinary albumin and serum creatinine.

OBJECTIVETo assess the association of single nucleotide polymorphisms (SNPs) of NLRP3 gene with metabolic syndrome (MetS).

METHODSA total of 885 subjects including 410 MetS patients and 475 healthy controls were recruited. MetS was defined based on the National Cholesterol Education Program in Adult Treatment Panel III criteria. Two common SNPs of the NLRP3 gene, rs10754558 and rs4612666, were detected using polymerase chain reaction-restriction fragment length polymorphism method.

RESULTSThe frequencies of G allele and GG genotype of the NLRP3 rs10754558 in the MetS group were significantly higher than those of the control group. Logistic regression analysis showed that the GG genotype (OR=2.223, 95%CI: 1.296-6.924, P=0.00034) and G allele (OR=1.440, 95%CI: 1.189-4.063, P=0.00028) were associated with increased risk of MetS. NLRP3 rs10754558 GG genotype was associated with higher level of insulin resistance and visceral adiposity index. No association of NLRP3 rs4612666 SNPs with susceptibility to MetS was identified in this population.

CONCLUSIONNLRP3 gene rs10754558 polymorphisms are associated with increased risk of MetS. The G allele and genotype GG are risk factors for MetS.

Adult ; Aged ; Carrier Proteins ; genetics ; Female ; Genotype ; Humans ; Insulin Resistance ; Logistic Models ; Male ; Metabolic Syndrome ; etiology ; genetics ; Middle Aged ; NLR Family, Pyrin Domain-Containing 3 Protein ; Polymorphism, Single Nucleotide

Objective To study the effects of CUEDC2 on renal interstitial fibrosis and inflammation response in rats with unilateral ureteral obstruction (UUO). Methods 30 Balb/c rats were randomly distributed into sham operation group(sham-vector),uuo operation group(uuo-vector) and CUEDC2 treatment group after uuo (uuo-cuedc2). Hematoxylin-eosin and Masson staining were used to measure renal pathology; Inflammation factors were quantified by ELISA; Immunohistochemistry was performed to measure the expression of CUEDC2;Protein expression of CUEDC2, Fibronectin, E-cadherin, Collagen I were detected by Western Blot. Results At 7 and 14d after operation, the area of interstitial fibrosis and expression of ICAM1,MCP1,IL1,IL8, Fibronectin and Collagen I in uuo-cuedc2 showed a marked decrease when compared to uuo-vector (p?0.05),the level of E-cadherin was significantly increased (P < 0.05). Conclusion CUEDC2 can inhibit renal interstitial fibrosis and decrease the expression of inflammation factors and Collagen deposition.

Objective To explore the correlations of lung resistance protein (LRP) and glutathione S transferase π (GST-π) to chemotherapy resistance and prognosis of epithelial ovarian cancer.Methods The expressions of LRP and GST-π in epithelial ovarian cancer were examined with immunohistochemistry.Correlations of LRP and GST-π to chemotherapy efficacy and survival time after operation were analyzed.Results The short-term efficacy rates of ovarian cancer were lower in patients with positive expressions of LRP and GST-π than those with negative expressions [61.2％,61.7％ vs 94.1％,89.5％,x2 =6.47,4.94,P =0.011,P =0.026].The positive rates of LRP and GST-π were significant higher in patients with chemotherapy resistance than in those sensitive to chemotherapy [91.3％,87.0％ vs 65.1％,62.8％,P ＜ 0.05].Log-rank test showed that patients with positive LRP and GST-π had shorter survival time than those negative,and patients with both positive LRP and GST-π had shorter survival time than those both negative (P ＜ 0.05).Conclusions The expressions of LRP and GST-π in epithelial ovarian cancer could be used to predict chemotherapy resistance and prognosis of patients.

Portal vein thrombosis (PVT) develops in some patients with liver cirrhosis and may aggravate portal hypertension. The risk factors for PVT have not yet been completely clarified. Splenectomy might increase the risk of developing PVT, which may progress to a life-threatening complication after splenectomy if not diagnosed promptly and treated properly. In this review, we discuss the recent findings concerning the risk factors for PVT after splenectomy. It is pointed out that splenectomy is the major cause of PVT developed in patients with liver cirrhosis.