Case report: Severe cholestatic jaundice associated with hyperthyroidism treated with methimazole.

RATIONALE: We present a case of a 43-year-old female patient diagnosed with hyperthyroidism. This study aims to demonstrate the rare association between hyperthyroidism and severe cholestatic jaundice, and the effectiveness of methimazole treatment. PATIENT CONCERNS: The patient developed severe jaundice, a typically mild symptom in most hyperthyroidism cases. DIAGNOSIS: The severe jaundice was suspected to be a result of cholestasis induced by hyperthyroidism, with other potential causes such as drug-induced or autoimmune liver dysfunction being ruled out. OUTCOMES: The patient was effectively treated with methimazole. Outcomes: Treatment with methimazole alleviated the severe cholestatic jaundice and restored normal thyroid function. LESSONS: The specific mechanism of cholestasis as a secondary complication of hyperthyroidism remains unclear, and there are no specific biochemical markers for cholestasis caused by this hormonal disease. This case underscores the possibility of severe jaundice as a clinical manifestation of hyperthyroidism, and highlights antithyroid drug treatment as an effective strategy for managing severe cholestatic jaundice.

Cascaded Deep Video Deblurring Using Temporal Sharpness Prior and Non-Local Spatial-Temporal Similarity.

We present compact and effective deep convolutional neural networks (CNNs) by exploring properties of videos for video deblurring. Motivated by the non-uniform blur property that not all the pixels of the frames are blurry, we develop a CNN to integrate a temporal sharpness prior (TSP) for removing blur in videos. The TSP exploits sharp pixels from adjacent frames to facilitate the CNN for better frame restoration. Observing that the motion field is related to latent frames instead of blurry ones in the image formation model, we develop an effective cascaded training approach to solve the proposed CNN in an end-to-end manner. As videos usually contain similar contents within and across frames, we propose a non-local similarity mining approach based on a self-attention method with the propagation of global features to constrain CNNs for frame restoration. We show that exploring the domain knowledge of videos can make CNNs more compact and efficient, where the CNN with the non-local spatial-temporal similarity is 3× smaller than the state-of-the-art methods in terms of model parameters while its performance gains are at least 1 dB higher in terms of PSNRs. Extensive experimental results show that our method performs favorably against state-of-the-art approaches on benchmarks and real-world videos.

Long noncoding-RNA component of mitochondrial RNA processing endoribonuclease is involved in the progression of cholangiocarcinoma by regulating microRNA-217.

Cholangiocarcinoma (CCA) is a malignant tumor originating from bile duct epithelium and its incidence is increasing year by year. In recent years, long noncoding RNAs (lncRNAs) have been found to play an important role in the occurrence and progression of malignant tumors. In the present study, for the first time, abnormal expression of lnc-RNA component of mitochondrial RNA processing endoribonuclease (RMRP) and its possible role in CCA were found. We explored the effects of RMRP on various behaviors of CCA cells in vitro and in vivo. In addition, by second-generation sequencing, we explored the microRNA expression profiles that RMRP may affect in the HCCC-9810 cell line. We also validated and explored the role of microRNA-217 (miR-217) with high differential expression by in vitro experiments. Our findings indicated that RMRP can play a part in promoting cancer by regulating the expression of miR-217. RMRP is involved in the progression of CCA and can be a novel indicator of poor prognosis in patients with CCA.

SP/NK-1R promotes gallbladder cancer cell proliferation and migration.

Aberrant substance P/neurokinin-1 receptor (SP/NK-1R) system activation plays a critical role in various disorders, however, little is known about the expression and the detailed molecular mechanism of the SP and NK-1R in gallbladder cancer (GBC). In this study, we firstly analyzed the expression and clinical significance of them in patients with GBC. Then, cellular assays were performed to clarify their biological role in GBC cells. Moreover, we investigated the molecular mechanisms regulated by SP/NK-1R. Meanwhile, mice xenografted with human GBC cells were analyzed regarding the effects of SP/NK1R complex in vivo. Finally, patient samples were utilized to investigate the effect of SP/NK-1R. The results showed that SP and NK-1R were highly expressed in GBC. We found that SP strongly induced GBC cell proliferation, clone formation, migration and invasion, whereas antagonizing NK-1R resulted in the opposite effects. Moreover, SP significantly enhanced the expression of NF-κB p65 and the tumor-associated cytokines, while, Akt inhibitor could reverse these effects. Further studies indicated that decreasing activation of NF-κB or Akt diminished GBC cell proliferation and migration. In consistent with results, immunohistochemical staining showed high levels of Akt, NF-κB and cytokines in tumor tissues. Most importantly, the similar conclusion was obtained in xenograft mouse model. Our findings demonstrate that NK-1R, after binding with the endogenous agonist SP, could induce GBC cell migration and spreading via modulation of Akt/NF-κB pathway.

Pivotal prognostic and diagnostic role of the long non­coding RNA colon cancer­associated transcript 1 expression in human cancer (Review).

Long non­coding RNAs (lncRNAs) have been classically defined as regulatory RNA members >200 nucleotides in length, without detectable open­reading frames to encode proteins. Previous studies have demonstrated that lncRNAs serve critical roles in multiple cancer types. Colon cancer­associated transcript 1 (CCAT1), a novel cancer­associated lncRNA, is significantly overexpressed in a number of malignancies. Functionally, as an oncogenic lncRNA, CCAT1 is involved in proliferation, migration, cell cycle progression, apoptosis, chemoresistance and other biological processes of cancer cells through complex regulation mechanisms in the cytoplasm or nucleus. In clinical applications, CCAT1 is additionally positively associated with histological differentiation, tumour node metastasis stage, vascular invasion, overall survival and recurrence­free survival, which demonstrates its important role as a diagnostic and prognostic marker in cancer. The present review summarises the current research progress of the oncogenic potential and clinical uses of CCAT1 in various human cancer types.

Long Non-coding RNA PVT1 Promotes Cell Proliferation and Migration by Silencing ANGPTL4 Expression in Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is the most common biliary tract malignancy, with a low survival rate and limited treatment options. Long non-coding RNAs (lncRNAs) have recently been verified to have significant regulatory functions in many kinds of human cancers. It was discovered in this study that the lncRNA PVT1, whose expression is significantly elevated in CCA, could be a molecular marker of CCA. Experiments indicated that PVT1 knockdown greatly inhibited cell migration and proliferation in vitro and in vivo. According to RNA sequencing (RNA-seq) analysis, PVT1 knockdown dramatically influenced target genes associated with cell angiogenesis, cell proliferation, and the apoptotic process. RNA immunoprecipitation (RIP) analysis demonstrated that, by binding to epigenetic modification complexes (PRC2), PVT1 could adjust the histone methylation of the promoter of ANGPTL4 (angiopoietin-like 4) and, thus, promote cell growth, migration, and apoptosis progression. The data verified the significant functions of PVT1 in CCA oncogenesis, and they suggested that PVT1 could be a target for CCA intervention.

TRPC3 overexpression and intervention in airway smooth muscle of ovalbumin-induced hyperresponsiveness and remodeling.

Transient receptor potential canonical channel 3 (TRPC3) proteins function as non-voltage-gated Ca2+ -permeable channels and play divergent roles in many processes of pathophysiology. The purpose of this study was to determine the relationship between TRPC3 expression and airway hyperresponsiveness and remodeling in ovalbumin-induced asthmatic Kunming mice. Mice were sensitized and challenged by ovalbumin to establish asthmatic model. Hematoxylin-eosin staining, hydroxyproline assay, and isometric tracheal ring force measurement were used to evaluate airway remodeling and hyperresponsiveness in asthmatic mice. Western blot was performed to detect the expression of TRPC3 proteins. MTT assay was used to measure the proliferation of airway smooth muscle cells. TRPC3 protein expression increased in airway smooth muscle of asthmatic mice. GdCl3 , a nonspecific TRPC blocker, attenuated the contractile force of airway smooth muscle. Fetal bovine serum stimulated airway smooth muscle cells proliferation and augmented TRPC3 protein expression. Both TRPC3 blockade by GdCl3 or specific TRPC3 antibodies and gene silencing by siRNA inhibited the proliferation of airway smooth muscle cells. In contrast, the current drugs treatment for asthma such as Dexamethasone and Aminophylline had no effects on TRPC3 protein overexpression. Therefore, TRPC3 protein overexpression may be involved in airway smooth muscle hyperresponsiveness and remodeling in asthmatic mice, providing evidence for a new direction of asthma pathogenesis research and a new target for drug intervention.

The diagnostic/prognostic potential and molecular functions of long non-coding RNAs in the exosomes derived from the bile of human cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive malignancy associated with unfavorable prognosis, and it's difficult to diagnose and no effective treatments are available. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and metastasis. Intact lncRNAs from exosomes have sparked much interest as potential biomarker for the non-invasive analysis of disease. Here, via exosome sequencing on lncRNAs, GO analysis, KEGG pathway and co-expression analysis, receiver operating characteristic curve and survival analyses, we found that, compared with control group, lncRNAs of ENST00000588480.1 and ENST00000517758.1 showed significantly increased expressions in CCA group. Moreover, area under the curve (AUC) was increased to 0.709 when combined the two lncRNAs, they had a sensitivity and specificity of 82.9% and 58.9% respectively. Further, the higher levels of the two lncRNAs showed a significantly increasing trend with the advancement of cancer TNM stages, and prognosticated a poor survival. In addition, KEGG pathway analysis showed that the most significant difference term was "p53 signaling pathway" (KEGG ID: hsa04115, p: 0.001). The altered lncRNAs and their target genes were included to reconstruct a co-expression network. These altered lncRNAs were mainly related to cellular processes, environmental information processing and organismal systems, etc. Collectively, our findings provided the potential roles of lncRNAs of ENST00000588480.1 and ENST00000517758.1 in CCA, and implicated these lncRNAs as potential diagnostic and therapeutic targets for CCA.

LINC00152: A pivotal oncogenic long non-coding RNA in human cancers.

In recent years, increasing evidence has shown the potential role of long non-coding RNAs (lncRNAs) in multiple cancers. Deregulation of lncRNAs was detected being closely associated with many kinds of tumours where they can act as a tumour suppressor or accelerator. LINC00152 was identified as an oncogene involved in many kinds of cancers, such as gastric cancer, hepatocellular carcinoma, colon cancer, gallbladder cancer and renal cell carcinoma. Moreover, inhibition of LINC00152 can suppress proliferation, migration and invasion of the cancer cells. Increasing evidence has showed that LINC00152 may act as a diagnostic and prognostic biomarker for the above-mentioned cancers. In our review, we summarize the recent research progress of the expression and role of LINC00152 in various kinds of cancers.

Endoscopic retrograde cholangiopancreatography in patients with surgically altered anatomy: One single center's experience.

Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy is challenging. Results of ERCP in those patients varied.The aim of our study was to evaluate the safety and effectiveness of various endoscopes-assisted ERCP in patients with surgically altered anatomy.Fifty-two patients with Billroth II reconstruction (group A), 20 patients with subtotal or total gastrectomy with Roux-en-Y anastomosis (group B), 25 patients with pancreatoduodenectomy or Roux-en-Y hepaticojejunostomy reconstruction (group C) were included. Gastroscope, duodenoscope, colonoscope, and double-balloon enteroscope were used.The endoscope insertion success rate of groups A, B, C was 96.2% (50/52), 85.0% (17/20), 80% (20/25), respectively. χ test showed that there was no significant difference between the 3 groups (P = 0.068). The mean insertion time was 36.7, 68.4, and 84.0 minutes, respectively. One-way ANOVA showed that the insertion time of group C was significantly longer than that of groups B and C (both P <0.001). The endoscopic cannulation success rates of groups A, B, C were 90%, 82.4%, and 100%, respectively. χ test showed that there was no significant difference between the 3 groups (P = 0.144). The mean cannulation time was 19.4, 28.1, and 20.4 minutes, respectively. One-way ANOVA showed that the cannulation time of group B was longer than that of groups A and C (P <0.001, P = 0.001, respectively). In total, 74 patients with successful biliary cannulation achieved the therapeutic goal; thus, the clinical success rate was 76.3% (74/97).Our study showed that ERCP in patients with surgically altered anatomy was safe and feasible.

ERCP-induced duodenal perforation successfully treated with endoscopic purse-string suture: a case report.

Duodenal perforation is one of the most serious complications of endoscopic retrograde cholangiopancreatography (ERCP) and is difficult to manage. Recently, endoscopic purse-string suture, using endoloops with endoclips, is a relatively new technology and has provided good clinical results. However, the study and use of endoscopic purse-string suture on duodenal perforation is less and its feasibility and safety are unknown. Here, we report a case of ERCP-induced duodenal perforation successfully treated with endoscopic purse-string suture. During ERCP, fluoroscopy revealed abnormal perinephric gas shadowing after breaking and extracting the stones with a stone-removal basket. Then duodenal endoscopy showed an approximately 2.0 cm × 1.5 cm perforation on the lateral duodenal wall, with visible retroperitoneal loose connective tissue. Titanium clips were used to attempt closure of the perforation but failed because of the long diameter of the injury. Therefore, an endoscopic purse-string suture, using endoloops with endoclips, was employed with an Olympus double-lumen endoscope. The perforation was successfully closed. At the 2-month follow-up visit, the patient had no complaints or symptoms. Our case once again proved its feasibility and safety and provided a new perspective for surgeons.

Upregulation of TRPC1 contributes to contractile function in isoproterenol-induced hypertrophic myocardium of rat.

AIMS: The transient receptor potential canonical channel 1 (TRPC1) is a crucial component of the stretch-activated ion channels (SACs). The objective of this research was to demonstrate the contribution of TRPC1 in maintaining cardiac contractile function in the hypertrophic myocardium. METHODS: Hypertrophic rat hearts were induced by injecting isoproterenol intraperitoneally, and the expressions of TRPC1/3/6 and Na(+)/Ca(2+) exchanger 1 (NCX1) proteins were analyzed by Western blot. The intracellular calcium images, the action potential of myocardium, the length-dependent contractile force of ventricle muscle and the cardiac output of isolated heart were investigated. RESULTS: The expression of TRPC1 was increased in the hypertrophic myocardium. After being stretched, the ascendant amplitude of the increase in the intracellular calcium ion concentration ([Ca(2+)]i) in the hypertrophic myocardium was higher than that in the normal myocardium. The increase of the APD50 and the amplitude of the membrane potential depolarization were more significant in the hypertrophic myocardium after the activation of SACs. When the heart preparations were perfused with Tyrode's solution, there was no difference in the cardiac systolic function between the cardiac hypertrophy group and the control group. Gadolinium, a SACs blocker, reduced the length-dependent contractile force and suppressed the ascending limb of the Frank-Starling curves in the hypertrophic heart. CONCLUSIONS: The upregulation of TRPC1 contributes to the contractile function in the hypertrophic myocardium by increasing [Ca(2+)]i through the SACs.