Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive disease caused by SLC25A13 gene mutations, and is characterized by delayed jaundice clearance, liver dysfunction, and elevated aminoacidemia. The confirmed diagnosis depends on gene analysis. Citrin deficiency is one of the important causes of neonatal intrahepatic cholestasis in China. Recently more and more researches about NICCD were reported. The paper summarized the epidemiology, pathogenesis, clinical characteristics, and progresses in diagnosis and treatment of NICCD.

2', 3', 5'-Tri-O-acetyl-N6-(3-hydroxylaniline)adenosine (WS070117) is a derivative compound of natural product cordycepin. It has significant lipids regulating activity and low toxicity which has been proved by in vitro and in vivo experiments. In this study, 1H NMR-based metabolomics was used to investigate the dose-related effects of WS070117 on hyperlipidemia of high-fat-fed hamsters. The hyperlipidemic hamsters were administrated with six different doses of WS070117, including 3, 12, 50, 100, 200 and 400 mg x kg(-1) x d(-1). 1H NMR spectra of hamster serum were visually and statistically analyzed using two multivariate analyses: principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). As a result, WS070117-treated groups showed dose-related regulation of metabolites associated with lipid metabolism, choline metabolism and glucose metabolism. The dose of 3 mg x kg(-1) x d(-1) of WS070117 only exhibited a little lipids regulating activity. However, the doses of 12 and 50 mg x kg(-1) x d(-1) of WS070117 both regulated the contents of metabolites to reverse significantly toward normal levels. When the dose of WS070117 reached 100 mg x kg(-1) x d(-1), it was more effective than positive control drugs. The work suggested that NMR-based metabolomics might be a valuable approach to evaluate dose-related effects of lipids regulating compounds.
Adenosine ; analogs & derivatives ; pharmacology ; Animals ; Cricetinae ; Hyperlipidemias ; metabolism ; Least-Squares Analysis ; Lipid Metabolism ; drug effects ; Magnetic Resonance Spectroscopy ; Metabolomics ; Multivariate Analysis ; Principal Component Analysis

OBJECTIVETo investigate the protective effect of hypothermia combined with dexamethasone on spermatogenesis and the expression of intercellular adhesion molecule 1 (ICAM1) after testicular torsion-detorsion.

METHODSWe made unilateral testicular torsion models in 100 pubertal male Sprague-Dawley rats by 720 degree torsion of the left testis and then randomly divided them into four groups of equal number to be treated with normal temperature + physiological saline (group A), hypothermia + physiological saline (group B), normal temperature + dexamethasone (group C), and hypothermia + dexamethasone (group D). After 48 hours, we collected the testes, observed pathological changes of the testicular tissue by HE staining under the light microscope, detected the apoptosis of spermatogenic cells by TUNEL, and determined the expression of ICAM1 by Western blot.

RESULTSHE staining showed different degrees of testicular tissue injury in the four groups of rats, most obvious in group A, but mild in the other three. The ICAM1 protein expression was significantly higher in group A (0.68 +/-0. 03) than in B (0. 49 +/- 0. 06, P <0. 05) , C (0. 46 +/- 0. 09, P < 0.05) , and D (0.17 +/- 0.08, P <0.01). The nuclei were deep brown or brown. Lots of apoptotic spermatogenic cells were seen in the torsion testis of group A, with a significantly higher apoptosis index ( [33. 13 +/- 3.21 ]%) than in B ( [ 17. 12 +/-5.23 ]%, P < 0.05), C ([14.13 +/- 2.03]%, P <0.05), and D ([9.05 +/- 1.03]%, P <0.01).

CONCLUSIONHypothermia combined with dexamethasone can protect the testis from injury as well as the reproductive function of the testis after testicular torsion-detorsion and reduce the expression of ICAM1.

Animals ; Dexamethasone ; pharmacology ; Disease Models, Animal ; Hypothermia, Induced ; Intercellular Adhesion Molecule-1 ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Spermatic Cord Torsion ; metabolism ; physiopathology ; Spermatogenesis ; drug effects

The main treatment strategies for chronic pancreatitis in young patients include therapeutic endoscopic retrograde cholangio-pancreatography (ERCP) intervention and surgical intervention. Therapeutic ERCP intervention is performed much more extensively for its minimally invasive nature, but a part of patients are referred to surgery at last. Historical and follow-up data of 21 young patients with chronic pancreatitis undergoing duodenum-preserving total pancreatic head resection were analyzed to evaluate the outcomes of therapeutic ERCP intervention and surgical intervention in this study. The surgical complications of repeated therapeutic ERCP intervention and surgical intervention were 38% and 19% respectively. During the first therapeutic ERCP intervention to surgical intervention, 2 patients developed diabetes, 5 patients developed steatorrhea, and 5 patients developed pancreatic type B pain. During the follow-up of surgical intervention, 1 new case of diabetes occurred, 1 case of steatorrhea recovered, and 4 cases of pancreatic type B pain were completely relieved. In a part of young patients with chronic pancreatitis, surgical intervention was more effective than therapeutic ERCP intervention on delaying the progression of the disease and relieving the symptoms.

Many studies indicated that with the rise of cardiac function class in patients with heart failure (HF), serum CA125 concentration gradually rose, and it's significant positively correlated with BNP level and NYHA class. It 's reported that in HF patients with pleural effusion, serum CA125 level significantly increases, and rehospitalization rate and mortality of HF patients rise along with CA125 level. Therefore, the present article made a discussion on relationship between serum CA125 level and HF.

Oxidative stress is a redox imbalance in the body, which is one of the important factors leading to tissue damage and diseases. The nuclear factor E2-related factor 2 (Nrf2)-Kelch like ECH-associated protein 1 (Keap1) signaling pathway is not only an important defense system against oxidative damage, but also one of the key signaling pathways of the antioxidant capacity. Numerous studies have shown that targeting the Keap1-Nrf2 signaling pathway to activate Nrf2 has become an effective strategy for the treatment of oxidative stress and related diseases. Using small molecules to directly block the Keap1-Nrf2 protein-protein interaction (PPI) is one of the important directions for activating Nrf2 and exerting the cytoprotective effect, which can avoid the potential side effects of covalent modification of Nrf2. On the other hand, the Keap1 is an efficient E3 ubiquitin ligase that has been used in the design of proteolysis targeting chimeras (PROTACs). This review summarizes the research progresses of Keap1-Nrf2 protein interaction inhibitors and degraders based on the Keap1 E3 ubiquitination system in recent years.

OBJECTIVE: To study the types and characteristics of TUBB1 mutation in children with congenital hypothyroidism (CH) and thyroid dysgenesis (TD) in Shandong, China. METHODS: Mutations of the whole coding region of the TUBB1 gene were analyzed for 289 children with CH and TD in Shandong. Whole-genome DNA was extracted from peripheral blood leukocytes. PCR multiplication was performed for the whole coding region of the TUBB1 gene. Sanger sequencing was performed for the PCR products, and a biological information analysis was performed. RESULTS: Among the 289 children with CH and TD, 4 (1.4%) were found to have a c.952C>T(p.R318W) heterozygous mutation in the TUBB1 gene, resulting in the change of tryptophan into arginine at codon 318 of TUBB1 protein. This mutation was evaluated as "potentially pathogenic" based on the classification criteria and guidelines for genetic variation by American College of Medical Genetics and Genomics. CONCLUSIONS A novel mutation is detected in the exon of the TUBB1 gene in children with CH and TD in Shandong, suggesting that the TUBB1 gene may be a candidate pathogenic gene for CH children with TD.
Child ; China ; Congenital Hypothyroidism ; genetics ; DNA Mutational Analysis ; Humans ; Mutation ; Thyroid Dysgenesis ; genetics ; Tubulin ; genetics

Objective To investigate the expression level of lipoprotein lipase (LPL) mRNA in chronic lymphocytic leukemia (CLL) patients and evaluate the prognostic value of LPL in CLL Methods Quantitative real-time RT-PCR (qRT-PCR) was performed in 62 CLL patients, 10 normal controls using Taqman probe system. Association between LPL and other known prognostic factors, such as IgVH mutation status, ZAP-70 and CD38 expression, was determined using the Spearman correlation analysis. ROC curve was used to determine the cut-off value of LPL expression level, the positive and negative predictive value of IgVH mutation status. Results The correlation coefficients of the standard curves in qRT-PCR were not less than 0.990. The coefficients of variation (CV) of interrun assay and intramn assay were < 5%, and the sensitivity can reached 102 copies/μg RNA. The median LPL mRNA expression level was 0.006 0 (0-0.737 0) in 62 CLL patients, whereas in 10 normal controls LPL mRNA expression level was extremely low with the median level of 0 (0-0.000 4). The expression levels of LPL in three CLL samples after miniMACS-sorted CD19 positive B cells were 0.036 0, 0.075 0 and 0.197 0, which were similar to the levels before miniMACS-sorted (0.024 0, 0.074 0 and 0.225 0). LFL expression was significantly associated with IgVH mutation status (r=0.45, P<0.05) . LPL expression level in IgVH unmutated patients [0.006 0 (0.000 7-0.110 0)] was significantly higher than the level in IgVH mutated patients [0.002 0(0.000 2-0.027 0)] (U=96.5, P<0.05). LPL expression was also significantly associated with ZAP-70 (r=0.38, P<0.05), CD38 expressions (r=0.43, P<0.05). According to ROC curve, the cut-off of LPL mRNA expression level was 0.036, with a 66.7% specificity, a 72.4% sensitivity, a 51.8% positive predictive value (IgVH unmutated), and a 83.3% negative predictive value (IgVH mutated) for IgVH mutation status. Conclusions The qRT-PCR assay is reliable and sensitive. LPL mRNA expression significantly correlates with IgVH mutation status, ZAP-70 and CD38 expression, and could be a predictive marker of IgVH mutation status. Our data confirms a role for LPL as a novel prognostic indicator in CLL.

OBJECTIVETo investigate the effects of crypotanshinone (CPT) on the proliferation and apoptosis of DU145 prostate cancer cells as well as on the metadherin expression and the downstream PI3K/AKT signaling pathway in the DU145 cells.

METHODSWe treated DU145 prostate cancer cells with different concentrations of CPT for 24, 48, and 72 hours followed by evaluation of the proliferation and apoptosis of the cells by MTT assay and TUNEL, respectively. We determined the expressions of metadherin protein and mRNA in the DU145 cells by Western blot and RT-PCR respectively at different time points after CPT treatment. We also detected the expressions of the proteins metadherin, AKT, p-AKT, and Bcl-2 in the CPT-treated DU145 cells at 48 hours.

RESULTSCPT significantly inhibited the proliferation of the DU145 cells in a dose- and time-dependent manner (P < 0.05). After treatment with 10 µmol/L CPT for 24, 48, and 72 hours, the apoptosis rates of the DU145 cells were (29.42 ± 4.51), (55.07 ± 5.67) and (70.84 ± 4.66)%, respectively, significantly higher than (3.1 ± 2.48)% in the control group (P < 0.05). The expression of metadherin was remarkably downregulated at the transcription and translation levels (P < 0.05) and the expressions of the AKT signaling pathway and the Bcl-2 protein were markedly inhibited in the DU145 cells after treated with 10 µmol/L CPT for 48 hours (P < 0.05).

CONCLUSIONCPT can inhibit the proliferation and induce the apoptosis of DU145 prostate cancer cells, which may be associated with its suppression of the downstream PI3K/AKT signaling pathway by reducing the expression of metadherin in the DU145 cells.

Apoptosis ; drug effects ; Cell Adhesion Molecules ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Diterpenes, Abietane ; pharmacology ; Down-Regulation ; Drugs, Chinese Herbal ; pharmacology ; Humans ; In Situ Nick-End Labeling ; Male ; Neoplasm Proteins ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Prostatic Neoplasms ; metabolism ; pathology ; Proto-Oncogene Proteins c-akt ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RNA, Messenger ; metabolism ; Signal Transduction ; drug effects ; Time Factors

Objective:To explore the predictive value of regional leptomeningeal collateral circulation scale (rLMC) based on multimodal CT in recanalization of blood vessels in patients with acute ischemic stroke after thrombectomy.Methods:A retrospective analysis was conducted on clinical data of patients with acute ischemic stroke within 6 h of first onset, admitted to our hospital from October 2017 to December 2019. Before operation, the conditions of their vessels were evaluated by rLMC based on multimodal CT. Two areas, anterior cerebral artery (ACA)-middle cerebral artery (MCA) area and posterior cerebral artery (PCA)-MCA area, were divided. The total rLMC scores of two areas (0-10) were calculated: scores of 0-3, scores of 4-7, scores of 8-10. After admission, the recanalization of the blood vessels after thrombectomy was evaluated immediately according to grading of thrombolysis in cerebral infarction (TICI) after completion of thrombectomy within the time window; TICI grading≥II was defined as succeed recanalization. The correlation between rLMC scores and vascular recanalization in patients with acute ischemic stroke was evaluated.Results:Among the 80 patients, 17 were in the rLMC scores of 0-3 group, 25 in the group of rLMC scores of 4-7, and 38 in the group of rLMC scores of 8-10; 68 patients (85.00%) had vascular recanalization, and the success rate of vascular recanalization in patients from the group of rLMC scores of 8-10 was significantly higher than that in the group of rLMC scores of 0-3 (97.36% vs. 58.82%, P<0.05). Correlation analysis results showed that the rLMC score was positively correlated with success rate of vascular recanalization ( r s=0.625, P=0.000); whose sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 89.5%, 90.9%, 94.45%, 83.3% and 90.0%, respectively. Conclusion:The rLMC is closely related to the recanalization rate in patients with acute ischemic stroke after thrombectomy; the success rate of recanalization after intravascular treatment is relatively high in patients with rLMC scores of 8-10.