Intrahepatic cholangiocarcinoma is a malignant tumor with an extremely poor prognosis， and its pathogenesis is complex and remains unclear. In recent years， more and more studies have focused on the role of bile-gut axis in the development and progression of intrahepatic cholangiocarcinoma. Bile-gut axis refers to the complex interaction between bile and gut microbiota， including bile salt metabolism， dynamic changes of microbiota， inflammatory response， and immune system regulation. This article elaborates on the potential mechanisms of bile-gut axis in intrahepatic cholangiocarcinoma， especially gut microbiota dysbiosis， abnormal bile salt metabolism， chronic inflammatory response， and immune system interaction， this article aims to provide new perspectives and possible therapeutic targets for future research and promote the early diagnosis and effective treatment of intrahepatic cholangiocarcinoma.

Humans ; Coronary Aneurysm/etiology* ; Mucocutaneous Lymph Node Syndrome/complications* ; Hemodynamics ; Coronary Angiography ; Thrombosis ; Risk Assessment

Type 2 diabetes (T2D) is characterized by the malfunction of pancreatic β cells. Susceptibility and pathogenesis of T2D can be affected by multiple factors, including sex differences. However, the mechanisms underlying sex differences in T2D susceptibility and pathogenesis remain unclear. Using single-cell RNA sequencing (scRNA-seq), we demonstrate the presence of sexually dimorphic transcriptomes in mouse β cells. Using a high-fat diet-induced T2D mouse model, we identified sex-dependent T2D altered genes, suggesting sex-based differences in the pathological mechanisms of T2D. Furthermore, based on islet transplantation experiments, we found that compared to mice with sex-matched islet transplants, sex-mismatched islet transplants in healthy mice showed down-regulation of genes involved in the longevity regulating pathway of β cells. Moreover, the diabetic mice with sex-mismatched islet transplants showed impaired glucose tolerance. These data suggest sexual dimorphism in T2D pathogenicity, indicating that sex should be considered when treating T2D. We hope that our findings could provide new insights for the development of precision medicine in T2D.

Objective:To investigate the clinical treatment of large segmental humeral defects with unilateral external fixation and bone transport.Methods:A retrospective study was conducted of the 9 patients who had been treated at Department of Orthopedics, Shenzhen People's Hospital for large segmental humeral defects from September 2017 to June 2019. They were 5 males and 4 females with an average age of 29 years (from 21 to 41 years). Their defects were caused by trauma in 2 cases, by chronic osteomyelitis in 6 cases and by bone tumor in one case. The length of bone defect ranged from 4.2 to 9.0 cm, with an average of 5.9 cm. A unilateral external fixator was placed in operation, and adjusted regularly 7 to 10 days after operation for bone transport and bone lengthening to restore the length of humerus gradually. The external fixation bracket was removed after 3 to 4 layers of cortex were observed on X-ray films. Recorded were length and rate of humeral lengthening, fracture healing time, time for carrying external fixator and complications; the Disabilities of the Arm, Shoulder and Hand (DASH) scores were compared between preoperation and 15 months postoperation.Results:All the patients were followed up for 15 to 36 months (mean, 19 months). The length of lengthening averaged 5.9 cm (from 4.2 to 9.0 cm) with an average lengthening rate of 26%, the healing index 31 d/cm, the bone healing time 8.3 months, and the time for carrying external fixator 10.8 months(from 8.0 to 13.5 months). Their average DASH scores improved significantly from 25.0 ± 2.4 preoperation to 12.0 ± 1.8 at 15 months postoperation ( P<0.05). Good correction of large humeral defects was achieved in all but one case who reported temporary radial nerve paralysis. There were no such complications as neurovascular injury. The shoulder and elbow functions were basically normal after operation. Conclusions:In the treatment of large segmental humeral defects, unilateral external fixation plus bone transport can quickly repair the defects and recover the upper limb function of the patients.

This paper aims to explore the feasibility of building a finite element model of left atrial diverticulum (LAD) using reverse engineering software based on computed tomography (CT) images. The study was based on a three-dimensional cardiac CT images of a atrial fibrillation patient with LAD. The left atrium and LAD anatomical features were accurately reproduced by using Geomagic Studio 12 and Mimics 15 reverse engineering software. In addition, one left atrial model with LAD and one without LAD were created with ANSYS finite element analysis software, and the validity of the two models were verified. The results show that it is feasible to establish the LAD finite element model based on cardiac three-dimensional CT images using reverse engineering software. The results of this paper will lay a theoretical foundation for further hemodynamic analysis of LAD.

Objective:To investigate the therapeutic effect of continuous blood purification (CBP) on acute pancreatitis (AP) and its influence on prognosis.Methods:200 patients with AP in our hospital from January 2010 to December 2016 were selected as the subjects,and they were divided into conventional treatment group and CBP treatment group according to the random number table method,600 cases in each group.The conventional treatment group was received conventional drug therapy,and the CBP treatment group was treated with CBP on the basis of commonly used drugs.The disappeared time of clinical symptoms after treatment and the changes of inflammatory factors and the changes of intestinal function before and 72 h after treatment were compared between the two groups,the mortality rate was compared between the two groups at 7 d after treatment.Results:Abdominal pain disappeared time,abdominal distension disappeared time and abdominal tenderness disappeared time in CBP treatment group after treatment were lower than the conventional treatment group (P＜0.05).There was no significant difference in the levels of endotoxin,C reactive protein (CRP),amylase (AMS),two amine oxidase and malondialdehyde before treatment in the two groups (P＞0.05).At 72 h after treatment,endotoxin,CRP,AMS,two amine oxidase and malondialdehyde levels were lower than those before treatment,and the CBP treatment group was lower than the conventional treatment group (P＜0.05).The mortality rate of CBP treatment group was lower than that of conventional treatment group at 7 d after treatment,the difference was statistically significant (P＜0.05).Conclusion:CBP can effectively improve the clinical therapeutic effect of AP,and improve the clinical prognosis of patients.

OBJECTIVETo evaluate the feasibility of integrating cancer gene therapy with therapeutic effect evaluation using siRNA-loaded nano-scale microbubbles (siRNA-NBs).

METHODSsiRNA-NBs were prepared by hetero-assembly of polymeric siRNA micelles and liposomal microbubbles, and the particle sizes and surface potentials were examined with dynamic light scattering. The distributions of cy3-labled siRNA in the tumor tissues were evaluated using confocal laser scanning microscopy. A siRNA targeting the anti-apoptosis gene SIRT2 was designed and its gene silencing effects was tested in vivo using siRNA-NBs with ultrasound exposure. The therapeutic effect of the loaded siRNA-NBs was evaluated by contrast-enhanced ultrasonography.

RESULTSThe siRNA-NBs had a mean diameter of 400.7 ± 30.5 nm with a weak positive charge of +8.8 ± 0.8 mV. With ultrasound exposure, siRNA-NBs effectively delivered cy3-siRNA into the cytoplasm of cancer cells and caused SIRT2 suppression and cell apoptosis in tumor tissues, resulting in significantly suppressed tumor growth. In addition, contrast-enhanced ultrasonography of siRNA-NBs provided good imaging quality to allow real-time observation of blood supply during gene therapy.

CONCLUSIONSAs a novel ultrasound contrast agent, siRNA-NBs make possible the integration of tumor gene therapy and therapeutic effect evaluation for cancer.

Apoptosis ; Contrast Media ; Gene Silencing ; Genetic Therapy ; Humans ; Liposomes ; Micelles ; Microbubbles ; Neoplasms ; therapy ; Particle Size ; Polymers ; RNA, Small Interfering ; Sirtuin 2 ; genetics ; Ultrasonics

PURPOSE: Protein phosphatase 4 regulatory subunit 1 (PP4R1), as an interaction partner of the catalytic serine/threonine-protein phosphatase 4 catalytic subunit has been shown to involve in cellular processes and nuclear factor kappaB signaling. However, the functions of PP4R1 in human breast cancers remain unclear. This study is designed to explore the effect of PP4R1 knockdown on the biological characteristics of breast cancer cells. METHODS: A lentivirus-mediated short hairpin RNA (shRNA) was designed to knockdown the expression of PP4R1 in ZR-75-30 breast cancer cells. The efficiency of lentivirus-mediated shRNA infection was determined using fluorescence microscopy to observe lentivirus-mediated green fluorescent protein expression and confirmed to be over 80%. PP4R1 expression in infected ZR-75-30 cells was detected by quantitative real-time polymerase chain reaction and western blot analysis. Cell proliferation and colony formation ability were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and colony formation assay, respectively. Flow cytometry was used to measure cell cycle progression and cell apoptosis. In addition, apoptosis makers, including poly-ADP-ribose polymerase (PARP) and caspase-3, were investigated in PP4R1-silenced ZR-75-30 cells by western blot assay. RESULTS: We successfully constructed lentivirus-mediated shRNA to target PP4R1 in ZR-75-30 cells. MTT assay and colony formation assay showed the loss of PP4R1 suppressed the proliferation of ZR-75-30 cells. Flow cytometry analysis indicated cell cycle arrest and increased cell apoptosis in PP4R1 knockdown cells. Further, the apoptosis response in cells depleted of PP4R1 was illustrated by downregulation of PARP and upregulation of caspase-3. CONCLUSION: Our results suggest that PP4R1 could promote breast cancer cell proliferation and might play a vital role in breast cancer occurrence.
Apoptosis ; Blotting, Western ; Breast Neoplasms* ; Breast* ; Caspase 3 ; Catalytic Domain ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Proliferation ; Down-Regulation ; Flow Cytometry ; Humans ; Microscopy, Fluorescence ; Population Characteristics ; Real-Time Polymerase Chain Reaction ; RNA* ; RNA, Small Interfering ; Up-Regulation

Objective To evaluate the feasibility of integrating cancer gene therapy with therapeutic effect evaluation using siRNA-loaded nano-scale microbubbles (siRNA-NBs). Methods siRNA-NBs were prepared by hetero-assembly of polymeric siRNA micelles and liposomal microbubbles, and the particle sizes and surface potentials were examined with dynamic light scattering. The distributions of cy3- labled siRNA in the tumor tissues were evaluated using confocal laser scanning microscopy. A siRNA targeting the anti-apoptosis gene SIRT2 was designed and its gene silencing effects was tested in vivo using siRNA-NBs with ultrasound exposure. The therapeutic effect of the loaded siRNA-NBs was evaluated by contrast-enhanced ultrasonography. Results The siRNA-NBs had a mean diameter of 400.7 ± 30.5 nm with a weak positive charge of+8.8 ± 0.8 mV. With ultrasound exposure, siRNA-NBs effectively delivered cy3-siRNA into the cytoplasm of cancer cells and caused SIRT2 suppression and cell apoptosis in tumor tissues, resulting in significantly suppressed tumor growth. In addition, contrast-enhanced ultrasonography of siRNA-NBs provided good imaging quality to allow real-time observation of blood supply during gene therapy. Conclusions As a novel ultrasound contrast agent, siRNA-NBs make possible the integration of tumor gene therapy and therapeutic effect evaluation for cancer.

Objective To evaluate the feasibility of integrating cancer gene therapy with therapeutic effect evaluation using siRNA-loaded nano-scale microbubbles (siRNA-NBs). Methods siRNA-NBs were prepared by hetero-assembly of polymeric siRNA micelles and liposomal microbubbles, and the particle sizes and surface potentials were examined with dynamic light scattering. The distributions of cy3- labled siRNA in the tumor tissues were evaluated using confocal laser scanning microscopy. A siRNA targeting the anti-apoptosis gene SIRT2 was designed and its gene silencing effects was tested in vivo using siRNA-NBs with ultrasound exposure. The therapeutic effect of the loaded siRNA-NBs was evaluated by contrast-enhanced ultrasonography. Results The siRNA-NBs had a mean diameter of 400.7 ± 30.5 nm with a weak positive charge of+8.8 ± 0.8 mV. With ultrasound exposure, siRNA-NBs effectively delivered cy3-siRNA into the cytoplasm of cancer cells and caused SIRT2 suppression and cell apoptosis in tumor tissues, resulting in significantly suppressed tumor growth. In addition, contrast-enhanced ultrasonography of siRNA-NBs provided good imaging quality to allow real-time observation of blood supply during gene therapy. Conclusions As a novel ultrasound contrast agent, siRNA-NBs make possible the integration of tumor gene therapy and therapeutic effect evaluation for cancer.