Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Although previous studies have demonstrated that exercise independently reduces hepatic steatosis measured by imaging modalities in NAFLD, the effect of exercise on histological endpoints remains unclear. We aimed to conduct a systematic review of the independent effect of exercise on hepatic steatosis, steatohepatitis, and liver fibrosis as measured by histological assessment or non-invasive tests (NITs) in biopsy-proven NAFLD. A systematic literature search of PubMed, Embase, and Web of Science databases was performed using keywords related to exercise, NAFLD, and biopsy. Articles were selected based on the following inclusion criteria: (1) involved human subjects with biopsy-proven NAFLD, (2) analyzed the independent effect of exercise, (3) assessed changes in hepatic steatosis, steatohepatitis, or liver fibrosis via either histological evaluation or NITs, and (4) were original research studies. We identified a total of six studies that analyzed the independent effect of exercise on histological endpoints in biopsy-proven NAFLD. Two randomized controlled trials (RCTs) did not detect significant histological improvement following exercise interventions, while other non-randomized interventional studies showed that exercise reduces hepatocyte ballooning and liver fibrosis. In addition, five studies assessed NIT outcomes, collectively demonstrating that exercise improves hepatic steatosis measured by magnetic resonance imaging-based techniques but not serum biomarkers for steatohepatitis and liver fibrosis. Additional large RCTs and meta-analyses are warranted to investigate the independent effect of exercise on histological and clinical outcome endpoints in NAFLD.

The Hippo pathway plays a crucial role in controlling organ size by inhibiting cell proliferation and promoting cell death. Recent findings implicate that this pathway is involved in the process of intestinal regeneration and tumorigenesis. Here we summarize current studies for the function of the Hippo signaling pathway in intestinal homeostasis, regeneration and tumorigenesis, and the crosstalk between the Hippo signaling pathway and other major signaling pathways, i.e. Wnt, Notch and Jak/Stat signaling pathways in intestinal compartment.
Animals ; Cell Transformation, Neoplastic ; Drosophila ; Drosophila Proteins ; metabolism ; Homeostasis ; Intestinal Mucosa ; metabolism ; Intracellular Signaling Peptides and Proteins ; metabolism ; Nuclear Proteins ; metabolism ; Protein-Serine-Threonine Kinases ; metabolism ; Regeneration ; Signal Transduction

OBJECTIVETo investigate the levels of cardiovascular disease risk factors and their relations to clinical phenotype associated with coronary artery disease (CAD).

METHODSThe subjects were recruited from five independent cardiovascular centers. Coronary angiography was employed to define the CAD with stenosis in each major vessel > or = 70% and control with stenosis < 10% in every lesion. The classic risk factors including family history, body mass index, smoking habits, hypertension, diabetes mellitus, and serum lipid levels were surveyed according to established criteria. Associations between risk levels and clinical phenotypes were assessed by case control and correlation analysis.

RESULTSA total of 762 individuals were collected, including 481 men and 281 women, aged from 17 to 81 (mean 60 +/- 10) years. The patients with CAD accounted for 55.5% of all participants, and controls 44.5%, respectively. Compared with the pattern in published data, our study showed that mean serum high density lipoprotein cholesterol (HDL-C) level was significantly lower (P < 0.001) and triglycerides was significantly higher (P < 0.001), while total cholesterol (TC) and low density lipoprotein cholesterol levels were comparative (both P > 0.05). The prevalence of low HDL-C (< 40 g/L) and hypertriglyceridemia (> 150 g/L) were 27.2% and 41.4%, respectively. Mean serum levels of HDL-C and apolipoprotein A1 were significantly higher in female subjects than in male (P < 0.001). Lower HDL-C functioned as an independent risk factor for CAD only in men (RR = 2.8, 95% CI: 1.5-4. 2, P < 0.001), yet increased non-HDL cholesterol combined with diabetes mellitus and obesity seemed to play a key role in the development of CAD in women. Similarity in risk association with CAD was found for hypertension and TC/HDL ratio in male and female subjects, while family history had no relationship with the presence of CAD.

CONCLUSIONIt is remarkable that emphasis of intervention in future should be given on the prevalent low serum HDL-C and its strong risk correlation with the presence of CAD in male subjects of Chinese Han population.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; China ; epidemiology ; Coronary Artery Disease ; epidemiology ; Ethnic Groups ; Female ; Humans ; Male ; Middle Aged ; Risk Factors

Methods: Patients presenting with a spine fracture were diagnosed with AS or DISH at a single tertiary care center between 2010 and 2019. We excluded those who lacked cross-sectional imaging or fractures occurring at spinal segments affected by ankylosis, as well as polytraumatized patients. Patient demographics, injury mechanism, fracture level, neurologic status, treatment, and 1-year mortality were recorded. Computed tomography imaging was reviewed by two independent readers and graded according to the indicated AO Spine Injury Classification System. Differences in fracture severity, treatment method, and mortality were examined using Student t -tests, chi-square tests, and two-proportion Z-tests with significance set to p <0.05. Results: We identified 167 patients with spine fracture diagnosed with AS or DISH. Patients with AS had more severe fractures and more commonly had surgery than patients with DISH (p <0.001). Despite these differences, 1-year mortality did not significantly differ between AS and DISH patients (p =0.14). Conclusions Although patients with AS suffered more severe fractures compared to DISH and more frequently underwent surgery for these injuries, outcomes and 1-year mortality did not differ significantly between the two groups. For patients with ASDs and fractures, outcomes appear similar regardless of treatment modality. Consequently, there may be an opportunity for critical reappraisal of operative indications in ASD and a larger role for nonoperative management in these challenging patients.

BACKGROUNDGlucose regulated protein 78 (GRP78), an endoplasmic reticulum (ER) chaperone, plays a critical role in chemotherapy resistance in a variety of cancers. In this study, we investigated the up-regulation of GRP78 induced by A23187 and its association with the chemotherapeutical sensibility to cisplatin in human lung cancer cell line SPCA1.

METHODSSPCA1 cells were pretreated with A23187 at different concentrations. The expression of GRP78 at the mRNA level was analyzed by RT-PCR; the expression of GRP78 at the protein level was determined by Western blotting and immunofluorescence assay. Cell survival was determined by MTT assay. Cell apoptosis was analyzed by flow cytometry.

RESULTSThe expression of GRP78 at both the mRNA and protein levels was obviously induced by A23187 in SPCA1 cells, with an elevation of GRP78 by 2.1-fold at the mRNA level and by 3.8-fold at the protein level compared to the control. There was a dose-dependent response. Survival curve analysis demonstrated that A23187 induction caused a significant reduction of survival for the cells subjected to cisplatin treatment (P < 0.05). After treatment by cisplatin, the percentage of apoptotic cells in the A23187 pretreated group increased about three fold compared with the control group ((27.53 ± 4.32)% vs. (9.25 ± 3.64)%, P < 0.05).

CONCLUSIONSA23187 treatment was fairly effective for the induction of GRP78 in SPCA1 cells at both the mRNA and protein levels. To a certain extent, GRP78 up-regulation by A23187 was associated with the enhancement of drug sensitivity to cisplatin in human lung cancer cell line SPCA1.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Blotting, Western ; Calcimycin ; pharmacology ; Cell Line, Tumor ; Cisplatin ; pharmacology ; Flow Cytometry ; Heat-Shock Proteins ; genetics ; metabolism ; Humans ; Lung Neoplasms ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

Objective: To investigate the feasibility and the accuracy of the coronary CT angiography (CCTA)-derived Registry of Crossboss and Hybrid procedures in France, the Netherlands, Belgium and United Kingdom (RECHARGE) score (RECHARGE CCTA) for the prediction of procedural success and 30-minutes guidewire crossing in percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). Materials and Methods: One hundred and twenty-four consecutive patients (mean age, 54 years; 79% male) with 131 CTO lesions who underwent CCTA before catheter angiography (CA) with CTO-PCI were retrospectively enrolled in this study. The RECHARGE CCTA scores were calculated and compared with RECHARGECA and other CTA-based prediction scores, including Multicenter CTO Registry of Japan (J-CTO), CT Registry of CTO Revascularisation (CT-RECTOR), and Korean Multicenter CTO CT Registry (KCCT) scores. Results: The procedural success rate of the CTO-PCI procedures was 72%, and 61% of cases achieved the 30-minutes wire crossing. No significant difference was observed between the RECHARGE CCTA score and the RECHARGECA score for procedural success (median 2 vs. median 2, p = 0.084). However, the RECHARGE CCTA score was higher than the RECHARGE CA score for the 30-minutes wire crossing (median 2 vs. median 1.5, p = 0.001). The areas under the curve (AUCs) of the RECHARGE CCTA and RECHARGE CA scores for predicting procedural success showed no statistical significance (0.718 vs. 0.757, p = 0.655). The sensitivity, specificity, positive predictive value, and the negative predictive value of the RECHARGE CCTA scores of ≤ 2 for predictive procedural success were 78%, 60%, 43%, and 87%, respectively. The RECHARGE CCTA score showed a discriminative performance that was comparable to those of the other CTA-based prediction scores (AUC = 0.718 vs. 0.665–0.717, all p > 0.05). Conclusion The non-invasive RECHARGE CCTA score performs better than the invasive determination for the prediction of the 30-minutes wire crossing of CTO-PCI. However, the RECHARGECCTA score may not replace other CTA-based prediction scores for predicting CTO-PCI success.

Objective: To investigate the feasibility and the accuracy of the coronary CT angiography (CCTA)-derived Registry of Crossboss and Hybrid procedures in France, the Netherlands, Belgium and United Kingdom (RECHARGE) score (RECHARGE CCTA) for the prediction of procedural success and 30-minutes guidewire crossing in percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). Materials and Methods: One hundred and twenty-four consecutive patients (mean age, 54 years; 79% male) with 131 CTO lesions who underwent CCTA before catheter angiography (CA) with CTO-PCI were retrospectively enrolled in this study. The RECHARGE CCTA scores were calculated and compared with RECHARGECA and other CTA-based prediction scores, including Multicenter CTO Registry of Japan (J-CTO), CT Registry of CTO Revascularisation (CT-RECTOR), and Korean Multicenter CTO CT Registry (KCCT) scores. Results: The procedural success rate of the CTO-PCI procedures was 72%, and 61% of cases achieved the 30-minutes wire crossing. No significant difference was observed between the RECHARGE CCTA score and the RECHARGECA score for procedural success (median 2 vs. median 2, p = 0.084). However, the RECHARGE CCTA score was higher than the RECHARGE CA score for the 30-minutes wire crossing (median 2 vs. median 1.5, p = 0.001). The areas under the curve (AUCs) of the RECHARGE CCTA and RECHARGE CA scores for predicting procedural success showed no statistical significance (0.718 vs. 0.757, p = 0.655). The sensitivity, specificity, positive predictive value, and the negative predictive value of the RECHARGE CCTA scores of ≤ 2 for predictive procedural success were 78%, 60%, 43%, and 87%, respectively. The RECHARGE CCTA score showed a discriminative performance that was comparable to those of the other CTA-based prediction scores (AUC = 0.718 vs. 0.665–0.717, all p > 0.05). Conclusion The non-invasive RECHARGE CCTA score performs better than the invasive determination for the prediction of the 30-minutes wire crossing of CTO-PCI. However, the RECHARGECCTA score may not replace other CTA-based prediction scores for predicting CTO-PCI success.

Humans ; HIV Infections/prevention & control* ; Pre-Exposure Prophylaxis

Purpose: The optimal treatment for gastroesophageal junction adenocarcinoma (GEJA) remains controversial. We evaluated the treatment patterns and outcomes of patients with locally advanced GEJA according to the histological type. Materials and Methods: We conducted a single-institution retrospective cohort study of patients with locally advanced GEJA who underwent curative-intent surgical resection between 2010 and 2020. Perioperative therapies as well as clinicopathologic, surgical, and survival data were collected. The results of endoscopy and histopathological examinations were assessed for Siewert and Lauren classifications. Results: Among the 58 patients included in this study, 44 (76%) were clinical stage III, and all received neoadjuvant therapy (72% chemoradiation, 41% chemotherapy, 14% both chemoradiation and chemotherapy). Tumor locations were evenly distributed by Siewert Classification (33% Siewert-I, 40% Siewert-II, and 28% Siewert-III). Esophagogastrectomy (EG) was performed for 47 (81%) patients and total gastrectomy (TG) for 11 (19%) patients.All TG patients received D2 lymphadenectomy compared to 10 (21%) EG patients.Histopathological examination showed the presence of 64% intestinal-type and 36% diffuse-type histology. The frequencies of diffuse-type histology were similar among Siewert groups (37% Siewert-I, 36% Siewert-II, and 33% Siewert-III). Regardless of Siewert type and compared to intestinal-type, diffuse histology was associated with increased intraabdominal recurrence rates (P=0.03) and decreased overall survival (hazard ratio, 2.33; P=0.02). With a median follow-up of 31.2 months, 29 (50%) patients had a recurrence, and the median overall survival was 50.5 months. Conclusions Present in equal proportions among Siewert types of esophageal and gastric cancer, a diffuse-type histology was associated with high intraabdominal recurrence rates and poor survival. Histopathological evaluation should be considered in addition to anatomic location in the determination of multimodal GEJA treatment strategies.

Purpose: The optimal treatment for gastroesophageal junction adenocarcinoma (GEJA) remains controversial. We evaluated the treatment patterns and outcomes of patients with locally advanced GEJA according to the histological type. Materials and Methods: We conducted a single-institution retrospective cohort study of patients with locally advanced GEJA who underwent curative-intent surgical resection between 2010 and 2020. Perioperative therapies as well as clinicopathologic, surgical, and survival data were collected. The results of endoscopy and histopathological examinations were assessed for Siewert and Lauren classifications. Results: Among the 58 patients included in this study, 44 (76%) were clinical stage III, and all received neoadjuvant therapy (72% chemoradiation, 41% chemotherapy, 14% both chemoradiation and chemotherapy). Tumor locations were evenly distributed by Siewert Classification (33% Siewert-I, 40% Siewert-II, and 28% Siewert-III). Esophagogastrectomy (EG) was performed for 47 (81%) patients and total gastrectomy (TG) for 11 (19%) patients.All TG patients received D2 lymphadenectomy compared to 10 (21%) EG patients.Histopathological examination showed the presence of 64% intestinal-type and 36% diffuse-type histology. The frequencies of diffuse-type histology were similar among Siewert groups (37% Siewert-I, 36% Siewert-II, and 33% Siewert-III). Regardless of Siewert type and compared to intestinal-type, diffuse histology was associated with increased intraabdominal recurrence rates (P=0.03) and decreased overall survival (hazard ratio, 2.33; P=0.02). With a median follow-up of 31.2 months, 29 (50%) patients had a recurrence, and the median overall survival was 50.5 months. Conclusions Present in equal proportions among Siewert types of esophageal and gastric cancer, a diffuse-type histology was associated with high intraabdominal recurrence rates and poor survival. Histopathological evaluation should be considered in addition to anatomic location in the determination of multimodal GEJA treatment strategies.