Objective To observe prospectively the role of endoscopic diagnosis and treatment of biliary leakages in patients with liver transplantation, and the incidence of bile duct stricture after healing of the leakage. Methods Six eases of T-tube leakage and seven cases of anastomosis leakage complicating liver transplantation were enrolled in this prospective study. Six patients treated by endoscopic plastic stent placement , 2 by naso-biliary catheter drainage, 2 by papillosphincterotomy and 3 by naso-biliary catheter drainage combined with plastic stent placement. Some patients received growth hormone treatment. Results The bile leak resolution time was between 10-35 days in 10 patients with complete document. The median time of leak resolution was 15. 3 days. Four cases of anastomosis stricture, three cases of common hepatic duct and one ease of multiple bile duct stenosis were observed by followed-up nasobiliary catheter cholangiography or ER-CP. Conclusion Endoscopic nasobiliary catheter or plastic stent placement is a safe and effective treatment for bile duct stricture occurred after bile leak resolution in most of liver transplantation patients. Naso-biliary catheter combined with plastic stent placement maybe the best choice for treating bile leak, because, theoretically, it may prevent serious condition happened at accidental nasobiliary catheter dislocation, and it may have prophylactic effect on upcoming bile duct stricture and should be further confirmed.

Objective To investigate the effect of raloxifene on ERα, ERβ and MT-1a expression in renal tubular epithelial cells contaminated with cadmium chloride,for exploring the protective effect and action mechanism of raloxifene in renal injury induced by cadmium. Methods Renal tubule cells were isolated from kidneys of new born SD rats and purified by Percoll. The cells of the second generation were selected for experiment. The cells were divided into 3 groups:blank control group,cadmium chloride group and raloxifene group. After 4 h,cell viability was detected by MTT,and after 24 h,mRNA and protein expression levels of ERα, ERβ and MT-1a in renal tissues were determined by RT-PCR and immunohistochemistry technology,respectively. Results Compared with the blank control group,morphology of plenty cells were changed in cadmium chloride group,a number of cells were dead,and the survival rate was only 55.3%;at the same time,mRNA and protein expression levels of ERβ and MT-1a significantly increased (P<0.05). Compared with cadmium chloride group,only a small part of cells underwent morphological changes,and the survival rate was 88.6% in raloxifene group,and the mRNA and protein expression levels of ERβand MT-1a were significantly decreased ( P<0.05) . The expression of ERαshowed no significant difference among the three groups ( P>0.05) . Conclusion Raloxifene can bond with ERβcompetively,down-regulate MT-1a and decrease Cd-MT synthesis,so as to reduce cadmium-induced damage of renal tubular epithelial cells.

Objective:To investigate the predictive value of C-reactive protein to lymphocyte ratio (CLR) for stroke-associated pneumonia (SAP).Methods:Consecutive patients with acute ischemic stroke admitted to the Department of Neurology, Guangming Ophthalmic Hospital from September 2018 to December 2020 were enrolled retrospectively. Fasting venous blood was taken the next morning after admission to detect the levels of C-reactive protein and lymphocytes. The baseline clinical data of the patients in the SAP group and the non-SAP group were compared. Multivariate logistic regression analysis was used to identify the independent predictors of SAP. The predictive value of CLR for SAP was evaluated by receiver operator characteristic (ROC) curve analysis. Results:A total of 479 patients with acute ischemic stroke were included. The median CLR was 3.69×10 -9, 81 patients (16.9%) had SAP. The incidence of SAP in the high CLR group was significantly higher than that in the low CLR group (26.7% vs. 7.1%; P=0.001). Univariate analysis showed that there were significant differences in age, atrial fibrillation, dysphagia, baseline National Institutes of Health Stroke Scale score, stroke etiology type, leukocyte count, fasting blood glucose, total cholesterol and CLR between the SAP group and the non-SAP group (all P<0.05). Multivariate logistic regression analysis showed that after adjusting for confounding factors, CLR was an independent predictor of SAP (odds ratio 3.472, 95% confidence interval 1.431-14.706; P=0.013). ROC curve analysis showed that the area under the curve of CLR predicting SAP was 0.735 (95% confidence interval 0.693-0.774; P<0.001). The optimal cut-off value was 6.14 ×10 -9. The sensitivity and specificity were 69.1% and 72.6% respectively. Conclusion:Higher baseline CLR can predict SAP risk in patients with acute ischemic stroke.

OBJECTIVETo investigate the effect of microRNA-140 (miR-140) on the migration and invasion of colorectal cancer (CRC) cells and the possible mechanism.

METHODSmiR-140 mimics, miR-140 specific inhibitor or small interfering RNA (siRNA) against Smad3 were transfected into human CRC cell line RKO cells respectively, using Oligofectamine or Lipofectamine2000. Quantitative real-time PCR (real-time PCR) was used to measure the expression levels of miR-140 and Smad3 mRNA. Smad3 protein was analyzed by Western blot. The in vitro cell migrating and invasive abilities were determined by wound-healing and Transwell chamber assay after up-regulating or down-regulating miR-140 or knocking down Smad3.

RESULTSThe Western blot assays showed that the Smad3 protein level was significantly reduced after up-regulating miR-140 (0.04 ± 0.01), compared with that of (0.47 ± 0.02, P < 0.05) in the control group and that of (0.52 ± 0.06) in the negative control group (P < 0.05 for both). The results of real-time PCR indicated that no significant difference was found in the levels of Smad3 mRNA between miR-140 transfection and NC groups (1.11 ± 0.13 vs. 1.00 ± 0.06, P > 0.05). The wound-healing assay showed that the migrating ability was dramatically attenuated by miR-140 compared with that in the control and NC groups, whereas no significance was found when compared with that of the Smad3 siRNA transfected cells. The number of cells migrating through Transwell chamber without matrigel in the miR-140 group was (76.2 ± 4.4), remarkably lowered than that in the control (267.1 ± 4.9) and NC (336.1 ± 5.7) groups (P < 0.05 for both), but no significant difference between the miR-140 (76.2 ± 4.4) and Smad3 siRNA (83.5 ± 7.3) groups. Transwell chamber with matrigel assay showed that number of cells penetrating through the membrane was (109.5 ± 7.4) in the miR-140 group, significantly lower than that in the control (403.1 ± 5.1) and NC (392.6 ± 8.4) groups (P < 0.05 for both), while Smad3 siRNA transfection had a similar effect (138.8 ± 3.6)(P > 0.05). Down-regulation of miR-140 increased the level of smad3 protein expression, and partially reversed the inhibition of the cell migration and invasion mediated by miR-140. Co-transfection of miR-140 inhibitor and Smad3 siRNA had no significant effect on the Smad3 protein expression and the abilities of cell migration and invasion.

CONCLUSIONSmiR-140 regulates the Smad3 expression at the post-transcriptional level. miR-140 suppresses the migrating and invasive abilities of CRC cells, possibly through down-regulation of Smad3. The findings of this study suggest that miR-140 may have a unique potential as a possible biomarker candidate for diagnosis and therapy of tumor metastasis.

Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Colorectal Neoplasms ; metabolism ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; genetics ; Humans ; MicroRNAs ; Neoplasm Invasiveness ; RNA, Messenger ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Smad3 Protein ; genetics ; metabolism ; Transfection ; Up-Regulation

Novel coronavirus Omicron variant infection can cause severe illness and even death in certain populations. Omicron variant infection may lead to systemic inflammatory response, coagulation disorder, multi-organ dysfunction and other pathophysiological changes, which are different from other Novel coronavirus variants to a certain extent, so therapeutic strategies should not be the same. The National Medical Center for Major Public Health Events invited experts in fields of infectious diseases, respiratory medicine, intensive care, pediatrics and fever clinic to develop this quick guideline based on the current best evidence and extensive clinical practices. This quick guideline aims to standardize the diagnosis and treatment of novel coronavirus Omicron infection, and to improve the disease management abilities of clinicians.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems