Recent insights collectively suggest the important roles of lysyl oxidase (LysOX) in the pathological processes of several acute and chronic neurological diseases, but the molecular regulatory mechanisms remain elusive. Herein, we explore the regulatory role of LysOX in the seizure-induced ferroptotic cell death of neurons. Mechanistically, LysOX promotes ferroptosis-associated lipid peroxidation in neurons via activating extracellular regulated protein kinase (ERK)-dependent 5-lipoxygenase (Alox5) signaling. In addition, overexpression of LysOX via adeno-associated viral vector (AAV)-based gene transfer enhances ferroptosis sensitivity and aggravates seizure-induced hippocampal damage. Our studies show that pharmacological inhibition of LysOX with β-aminopropionitrile (BAPN) significantly blocks seizure-induced ferroptosis and thereby alleviates neuronal damage, while the BAPN-associated cardiotoxicity and neurotoxicity could further be reduced through encapsulation with bioresponsive amorphous calcium carbonate-based nanocarriers. These findings unveil a previously unrecognized LysOX-ERK-Alox5 pathway for ferroptosis regulation during seizure-induced neuronal damage. Suppressing this pathway may yield therapeutic implications for restoring seizure-induced neuronal injury.

Preoperative biliary drainage (PBD) has become an essential part of perioperative management for perihilar cholangiocarcinoma. However, it is controversial about the indication of PBD. There are three main PBD methods, including percutaneous transhepatic biliary drainage, endoscopic nasobiliary drainage and endoscopic biliary stenting. At present, different centers have different preferences on PBD, and the controversies mainly focus on the followings: the relationship between percutaneous transhepatic biliary drainage and seeding metastasis; the success rate, tolerance and pancreatitis risk of endoscopic nasobiliary drainage; as an internal drainage, the merits and demerits of endoscopic biliary stenting. Additionally, whether PBD could increase the incidence of postoperative infections is still ambiguous. This review summarizes the recent scenario about the above-mentioned controversies to provide references for clinical decision-making.

Objective:To study the risk factors and microbial spectrum for infectious complications for patients with biliary tract cancer after major hepatectomy with cholangiojejunostomy.Methods:Enrolled into this study were 78 consecutive patients (57 patients with perihilar cholangiocarcinoma, 17 with intrahepatic cholangiocarcinoma and 4 with gallbladder cancer), who underwent major hepatectomy with cholangiojejunostomy at Nanjing Drum Tower Hospital between September 2010 and March 2019. The clinical data were reviewed using multivariate analysis to find independent risk factors for postoperative infectious complications. Microorganisms isolated from bile and infected sites were determined to study the microbial spectrum.Results:A total of 45(57.7%) patients suffered from postoperative infectious complications. Male sex ( OR=7.765, 95% CI=1.895-31.815, P<0.05) was the independent risk factor, whereas increased preope-rative red blood cell (RBC) ( OR=0.151, 95% CI=0.038-0.592, optimal cut-off value=3.7×10 12/L) and increased total cholesterol (TC) on postoperative day (POD) 1 ( OR=0.227, 95% CI=0.083-0.626, optimal cut-off value=3.5 mmol/L) were protective factors (both P<0.05). The area under the receiver operating characteristic (ROC) curve was 0.805 (95% CI=0.707-0.902, P<0.05). 205 and 230 microorganisms were cultured respectively from 286 and 681 specimens which were collected from pre-/intraoperative bile and potentially infected sites. Staphylococcus, enterococcus, acinetobacter, klebsiella and pseudomonas were the most common pathogens on bile culture. The first 5 most frequently isolated microorganisms from the infected sites were enterococcus, staphylococcus, klebsiella, candida and xanthomonas. Sixteen (61.5%) of 26 patients had at least one pathogen being isolated from the infected sites with the pathogen being previously isolated in bile culture. Conclusions:Male sex were independent risk factors of infectious complications. Increased preoperative RBC and inreased TC on POD were proteetive factors. For patients without a positive bile culture, a third-generation cephalosporin can be considered as a prophylactic antibiotic. It is important to identify high-risk patients and monitor perioperative pathogens actively to prevent and to cure postoperative infectious complications.

Background and Objectives: The application of adipose derived stem cells (ADSCs) in skin repair has attracted much attention nowadays. Epidermal growth factor (EGF) participates in the progress of skin proliferation, differentiation and so forth. We aimed to explore the role of EGF in the proliferation, invasion, migration and transdifferentiation into epidermal cell phenotypes of ADSCs. Methods: and Results: ADSCs were extracted from adipose tissues from patient. Immunophenotyping was determined by flow cytometry. Overexpressed EGF or siEGF was transfected by lentiviruses. EGF was determined by enzyme linked immunosorbent assay (ELISA) or western blot. ADSCs and HaCaT cells were co-cultured by Transwell chambers. Conditioned medium (CM) was obtained from cultured HaCaT cells and used for the culturing of ADSCs. Cell viability was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Invasion rate was measured by Transwell invasion assay and migration rate by wound healing test. mRNA and protein levels were measured by qPCR and western blot respectively. The extracted cells from adipose tissues were identified as ADSCs by morphology and immunophenotyping. The expression of EGF was up or down regulated constantly in HaCaT cell line after transfection. EGF overexpression upregulated the proliferation, migration and invasion rates of ADSCs, and EGF expression regulated the expression of cytokeratin-19 (CK19) and integrin-β as well. Conclusions EGF could be served as a stimulus to promote the proliferation, migration, and invasion as well as the transdifferentiation into epidermal stem cell immunophenotyping of ADSCs. The results showed that EGF had a promising effect on the repair of skin wound.

Antipsychotic-induced weight gain (AIWG) is a common adverse effect of this treatment, particularly with second-generation antipsychotics, and it is a major health problem around the world. We aimed to review the progress of pharmacogenetic studies on AIWG in the Chinese population to compare the results for Chinese with other ethnic populations, identify the limitations and problems of current studies, and provide future research directions in China. Both English and Chinese electronic databases were searched to identify eligible studies. We determined that > 25 single-nucleotide polymorphisms in 19 genes have been investigated in association with AIWG in Chinese patients over the past few decades. HTR2C rs3813929 is the most frequently studied single-nucleotide polymorphism, and it seems to be the most strongly associated with AIWG in the Chinese population. However, many genes that have been reported to be associated with AIWG in other ethnic populations have not been included in Chinese studies. To explain the pharmacogenetic reasons for AIWG in the Chinese population, genome-wide association studies and multiple-center, standard, unified, and large samples are needed.
Antipsychotic Agents ; adverse effects ; Asian Continental Ancestry Group ; genetics ; China ; Genome-Wide Association Study ; Genotype ; Humans ; Lipid Metabolism ; genetics ; Neurosecretory Systems ; drug effects ; Pharmacogenomic Testing ; Polymorphism, Single Nucleotide ; Receptors, Adrenergic ; genetics ; Receptors, Dopamine ; genetics ; Receptors, Histamine ; genetics ; Receptors, Serotonin ; genetics ; Weight Gain ; drug effects ; genetics

Objective To compare the clinical outcomes of endoscopic nasobiliary drainage (ENBD) versus percutaneous transhepatic biliary drainage (PTBD) in patients with perihilar cholangiocarcinoma.Methods This retrospective case-control study was conducted on 55 patients with perihilar cholangiocarcinoma who were treated by of hepatobiliary and pancreatic surgeons at the Nanjing Drum Tower Hospital between December 2010 and August 2017.Results There was no significant difference in the effectiveness of the two drainage methods (P＞0.05).Morbidity after drainage was significantly higher in the ENBD group than the PTBD group (86.7％ vs 28.0％,P＜0.05).24 patients in the ENBD group developed postERCP pancreatic complications which included hyperamylasemia (n =20) and pancreatitis (n =4).All these patients responded well to conservative treatment.A patient in the PTBD group developed catheter tract tumor implantation.There were no significant differences in the surgical outcomes and in the different Clavien-Dindo grades of complications (P＞0.05).Abdominal infection after surgery was more common in the PTBD group than the ENBD group (64.3％ vs 26.3％,P＜0.05).Conclusion As PTBD caused catheter tract tumor implantation and increased the incidence of abdominal infection after surgery,ENBD was recommended for patients with perihilar cholangiocarcinoma treated in a tertiary medical center.

Objective To explore the efficacy and safety of glucocorticoids+cyclophosphamide+tacrolimus capsules (GC+CTX+FK506) in the treatment of patients with type Ⅲ+V and Ⅳ+Vlupus nephritis. Methods The 31 cases with first diagnosis as systemic lupus erythematosus (SLE) with type Ⅲ+V and Ⅳ+Vlupus nephritis (LN) were selected, then divided into group A (CTX+GC) with 16 cases and group B (FK506+CTX+GC) with 15 cases. The group A received CTX+GC during treatment, group B received GC+CTX+FK506 for the first three months, and received FK506+GC for the last three months. The patients were followed up once monthly to observe the efficacy and safety,the efficacy was analysed after 6 months. Results After treatment, the total efficacy in group B was significantly higher than group A (86.7%vs.50.0%, P<0.05). The 24 h urine protein of group B was lower than group A(P<0.05). The plasma albumin of group B was higher than group A (P<0.05). After treatment, the systemic lupus erythematosus disease activity index (SLEDAI) in two groups were lower and C3 level was higher than those pre-treatment(P<0.05), but there was no significant difference in above indicators between two groups. There was one case menelipsis in group A, and one case with transient increasing of creatinine. Conclusion The FK506+CTX+GC could reduce urine protein sifnificantly compared with CTX+GC without serious adverse reaction.

Aim To assess the protective role of chry-sophanol in rats with diabetes-associated cognitive de-cline (DACD) and explore the potential molecular mechanisms.Methods The learning and memory performance was assessed by Morris water maze test;the activities of AChE,ChAT,iNOS and oxidative stress markers including CAT,SOD and GSH-PX in the hippocampus were detected using respective com-mercial kits.The level of BDNF was also measured with commercial ELISA kit.Results Chrysophanol significantly improved learning and memory functions in the diabetic groups.Additionally,the activities of AChE,BDNF also found to be evidently increased, while decreased activities of ChAT,iNOS,CAT,SOD and GSH-PX were observed in the hippocampus of dia-betic rats.Conclusions Collectively,chrysophanol has a protective role against DACD and this neuropro-tection is associated with increasing BDNF level.Chry-sophanol can also suppress the activities of iNOS, CAT,SOD and GSH-PX in diabetic rats.It is likely to be a novel therapeutic drug for the treatment of diabetic patients with cognitive deficits in clinical practice.

OBJECTIVE: To investigate the neuroprotective effects of osthole (OST) on glutamate-induced toxicity in hippocampal HT22 cells and to explore the correlation between the protection and phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling pathway.
 METHODS: The cell injury model of HT22 was induced by glutamate and the cell viability was detected by MTS assay. The lactate dehydrogenase (LDH) release and the caspase-3 activity were determined by commercial kits. Western blot analysis was utilized to detect the protein levels of PI3K, Akt, p-PI3K and p-Akt. 
 RESULTS: OST markedly improved the cell survival and decreased the LDH release in glutamate-treated HT22 cells in a dose-dependent manner. Furthermore, the levels of p-PI3K and p-Akt proteins were significantly increased in glutamate and OST-co-treated HT22 cells. The effect of OST on p-Akt phosphorylation in HT22 cells was attenuated in the presence of PI3K specific inhibitor (LY294002).
 CONCLUSION OST protects HT22 cells from glutamate excitotoxicity through a mechanism involving the activation of PI3K/Akt signaling pathway.
Animals ; Caspase 3 ; metabolism ; Cell Line ; Cell Survival ; Chromones ; pharmacology ; Coumarins ; pharmacology ; Glutamic Acid ; adverse effects ; Hippocampus ; cytology ; Mice ; Morpholines ; pharmacology ; Neuroprotective Agents ; pharmacology ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction

OBJECTIVETo study the methylation changes in promoter CpG islands induced by low-dose X-ray radiation (LDR).

METHODSTwenty male BALB/c mice were randomly divided into control and fractionated radiation group exposed to 6 MV X-ray for 10 days (0.05 Gy/day). All the mice were sacrificed 2 h after the last radiation on day 10, and blood samples were collected for detecting DNA methylation changes using Roche-NimbleGen mouse DNA methylation 3×720K Promoter Plus CpG Island Array. MeDIP-qPCR was used to further validate the methylation status of specific genes.

RESULTSA total of 811 genes were found to show specific hypermethylation in fractional radiation group as compared with the control group, involving almost all the main biological processes by GO analysis. Eight candidate genes (Rad23b, Tdg, Ccnd1, Ddit3, Llgl1, Rasl11a, Tbx2, and Slc6a15) were confirmed to be hypermethylated in LDR samples by MeDIP-qPCR, consistent with the results of the methylation chip study.

CONCLUSIONLDR induces promoter hypermethylation on specific genes, which may contribute to radiation-induced pathogenesis.

Animals ; CpG Islands ; radiation effects ; DNA Methylation ; Dose-Response Relationship, Radiation ; Genome ; Male ; Mice ; Mice, Inbred BALB C ; X-Rays