Search

Objective: The study aimed to investigate the efficacy and safety of semaglutide in weight loss in non-diabetic people., Methods: In this study, 84 non-diabetic people who used semaglutide to lose weight in the outpatient department of our hospital from January 1, 2022, to June 30, 2022, were enrolled and compared for changes in body weight, waist circumference, Body Mass Index (BMI), fasting blood glucose, blood pressure, pulse, and body composition (body fat ratio, visceral fat area, and skeletal muscle) before treatment and 12 weeks after the treatment to analyze the weight loss efficacy and safety., Results: After administering semaglutide 0.25 mg, 0.5 mg, 0.75 mg, or 1 mg subcutaneously once a week for 12 weeks, 84 participants in this study obtained an average weight loss of 5.91 ± 3.37 kg, equivalent to 6.15 ± 4.28% of baseline body weight, and there was also a significant reduction in visceral fat area and a slight reduction in blood pressure. The most common adverse reactions included gastrointestinal reactions (nausea, vomiting, and diarrhea), which were mild and subsided within 1-2 days. No severe adverse reaction, such as hypoglycemia and hypotension, was observed., Conclusion: Low-dose semaglutide has been found to be effective and safe for short-term weight loss in non-diabetic people., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To compare the effects of laparoscopic hepatectomy (LH) on the short-term and long-term outcomes in hepatocellular carcinoma (HCC) patients with and without clinically significant portal hypertension (CSPH)., Methods: A systematic literature search of the PubMed, EMBASE, and Cochrane databases was performed for articles published from inception to March 1, 2023. Meta-analysis of surgical and oncological outcomes was performed using a random effects model. Data were summarized as mean difference and risk ratio with 95% confidence intervals., Results: Five cohort studies with a total of 310 HCC patients were included (CSPH 143; Non-CSPH 167). In terms of surgical outcomes, estimated blood loss and the length of hospital stay were significantly lower in the Non-CSPH group than in the CSPH group. There were no significant differences between the two groups regarding other surgical outcomes, including the operative time, ratio of conversion to open surgery, and overall complication rate. In addition, there were also no significant differences between the two groups regarding the oncological outcomes, such as 1-, 3-, and 5-year overall survival., Conclusions: HCC patients with and without CSPH who underwent LH had comparable surgical and oncological outcomes. LH is a safe and effective treatment for HCC patients with CSPH under the premise of rational screening of patients., (© 2023. The Author(s).)

Objective: How different surgical procedures, including the robotic-assisted liver resection (RLR) and laparoscopic liver resection (LLR), can affect the prognosis of patients with liver malignancies is unclear. Thus, in this study, we compared the effects of RLR and LLR on the surgical and oncological outcomes in patients with liver malignancies through propensity score-matched cohort studies., Methods: The PubMed, Embase, and Cochrane databases were searched using Medical Subject Headings terms and keywords from inception until May 31, 2023. The quality of the included studies was assessed using the Newcastle-Ottawa quality assessment scale. The mean difference with 95% confidence interval (95% CI) was used for analysis of continuous variables; the risk ratio with 95% CI was used for dichotomous variables; and the hazard ratio with 95% CI was used for survival-related variables. Meta-analysis was performed using a random-effects model., Results: Five high-quality cohort studies with 986 patients were included (370 and 616 cases for RLR and LLR, respectively). In terms of surgical outcomes, there were no significant differences in the operation time, conversion rate to open surgery, overall complication rate, major complication rate, and length of hospital stay between the RLR and LLR groups. In terms of oncological outcomes, there were no significant differences in the 5-year overall survival and disease-free survival between the two groups., Conclusion: Surgical and oncological outcomes are comparable between RLR and LLR on patients with liver malignancies. Therefore, the benefits of applying RLR in patients with liver malignancies need to be further explored., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

As a ubiquitous RNA-binding protein, heterogeneous nuclear ribonucleoprotein K (hnRNPK) interacts with numerous nucleic acids and proteins and is involved in various cellular functions. Available literature indicates that it can regulate dendritic spine density through the extracellular signal-regulating kinase (ERK) - brain-derived neurotrophic factor (BDNF) pathway, which is crucial to retain the synaptic plasticity in patients with major depressive disorder (MDD) and mouse depression models. However, ERK upstream regulatory kinase has not been fully elucidated. Furthermore, it remains unexplored whether hnRNPK may impact the depressive condition via the ERK pathway. The present study addressed this issue by integrating approaches of genetics, molecular biology, behavioral testing. We found that hnRNPK in the brain was mainly distributed in the hippocampal neurons; that it was significantly downregulated in mice that displayed stress-induced depression-like behaviors; and that the level of hnRNPK markedly decreased in MDD patients from the GEO database. Further in vivo and in vitro analyses revealed that the changes in the expressions of BDNF and PSD95 and in the phosphorylation of ERK (Thr202/Tyr204) paralleled the variation of hnRNPK levels in the ventral hippocampal neurons in mice with depression-like behaviors. Finally, esketamine treatment significantly increased the level of hnRNPK in mice. These findings evidence that hnRNPK involved in the pathogenesis of depression via the ERK-BDNF pathway, pinpointing hnRNPK as a potential therapeutic target in treating MDD patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

The role of lncRNAs in the regeneration of fibrotic liver is unclear. To address this issue, we established a 70% hepatectomy model of liver fibrosis in mice, used high-throughput sequencing technology to obtain the expression profiles of lncRNAs, miRNAs, and mRNAs, and constructed a lncRNA-miRNA-mRNA regulatory network. A total of 1329 lncRNAs, 167 miRNAs, and 6458 mRNAs were differentially expressed. On this basis, a lncRNA-miRNA-mRNA ceRNA regulatory network consisting of 38 DE lncRNAs, 24 DE miRNAs, and 299 DE mRNAs was constructed, and a transcription factor (TF) - mRNA regulatory network composed of 20 TFs and 98 DE mRNAs was built. Through the protein network analysis, a core protein interaction network composed of 20 hub genes was derived. Furthermore, Xist/miR-144-3p/Cdc14b and Snhg3/miR-365-3p/Map3k14 axes in the ceRNA regulatory network were verified by Real-Time quantitative PCR. Therefore, we concluded that these new insights may further our understanding of liver regeneration., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Programmed cell death 1 receptor (PD-1) and its ligands constitute an inhibitory pathway to mediate the mechanism of immune tolerance and provide immune homeostasis. Significantly, the binding partners of PD-1 and its associated ligands are diverse, which facilitates immunosuppression in cooperation with other immune checkpoint proteins. Accumulating evidence has demonstrated the important immunosuppressive role of the PD-1 axis in the tumor microenvironment and in autoimmune diseases. In addition, PD-1 blockades have been approved to treat various cancers, including solid tumors and hematological malignancies. Here, we provide a comprehensive review of the PD-1 pathway, focusing on the structure and expression of PD-1, programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2); the diverse biological functions of PD-1 signaling in health and immune-related diseases (including tumor immunity, autoimmunity, infectious immunity, transplantation immunity, allergy and immune privilege); and immune-related adverse events related to PD-1 and PD-L1 inhibitors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Zhu, Shen, Xu, Tang, Cui, Jiang, Dai, Chen, Lin and Li.)

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for hematologic malignancies and non-malignant disorders, such as aplastic anemia, fanconi anemia, and certain immune deficiencies. Post-transplantation kidney injury is a common complication and involves a wide spectrum of structural abnormalities, including glomerular (MSPGN, mesangial proliferative glomerulonephritis; FSGS, focal segmental glomerulosclerosis; MPGN, membranoproliferative glomerulonephritis; MCD, minimal change disease), vascular (TMA, thrombotic microangiopathy), and/or tubulointerstitial (TIN, tubulointerstitial nephritis; ATI, acute tubular injury). Renal biopsy is the gold-standard examination for defining multiple etiologies of kidney impairment. Although kidney injury following HSCT has been studied, little is known about the effects of allo-HSCT on renal pathology in pediatric patients., Methods: We retrospectively analyzed renal biopsy specimens from children with kidney injury after allo-HSCT and correlated results with clinical data in the last 10 years., Results: Among 25 children (18 males and 7 females), three patients had proteinuria indicating nephrotic syndrome (24-hour urinary total protein/weight > 50 mg/kg/d), nine patients had severely reduced estimated glomerular filtration rate (eGFR < 30 ml/min/1.73 m 2 ) and four patients received kidney replacement therapy (KRT). The main pathologies identified from kidney biopsies were MSPGN (n = 12), FSGS (n = 12), MPGN (n = 5), TMA (n = 4), MCD (n = 3), diffuse glomerular fibrosis (DGF, n = 2), ATI and TIN, in isolation or combined with other pathologies. The median follow-up time was 16.5 (0.5 ~ 68.0) months. Three patients died of recurrent malignancy and/or severe infection, one child developed to end-stage renal disease (ESRD), six patients (24%) had elevated serum creatinine (SCr > 100µmol/l) and nine patients (36%) still had proteinuria., Conclusions: This study evaluates histomorphologic findings from kidney biopsies of pediatric recipients following allo-HSCT. Detailed evaluation of renal biopsy samples is helpful to elucidate the nature of renal insult, and may potentially identify treatable disease processes., (© 2023. The Author(s).)

Objective: To compare the effects of laparoscopic hepatectomy (LH) versus open hepatectomy (OH) on the short-term and long-term outcomes of patients with intrahepatic cholangiocarcinoma (ICC) through a meta-analysis of studies using propensity score-matched cohorts., Methods: The literature search was conducted in PubMed, Embase, and Cochrane Library databases until August 31, 2022. Meta-analysis of surgical (major morbidity, the length of hospital stay, 90-day postoperative mortality), oncological (R0 resection rate, lymph node dissection rate) and survival outcomes (1-, 3-, and 5-year overall survival and disease-free survival) was performed using a random effects model. Data were summarized as relative risks (RR), mean difference (MD) and hazard ratio (HR) with 95% confidence intervals (95% CI)., Results: Six case-matched studies with 1054 patients were included (LH 518; OH 536). Major morbidity was significantly lower (RR = 0.57, 95% CI = 0.37-0.88, P = 0.01) and the length of hospital stay was significantly shorter (MD = -2.44, 95% CI = -4.19 to -0.69, P = 0.006) in the LH group than in the OH group, but there was no significant difference in 90-day postoperative mortality between the 2 groups. There were no significant differences in R0 resection rate, lymph node dissection rate, 1-, 3-, and 5-year overall survival or disease-free survival between the LH and OH groups., Conclusions: LH has better surgical outcomes and comparable oncological outcomes and survival outcomes than does OH on ICC. Therefore, laparoscopy is at least not inferior to open surgery for intrahepatic cholangiocarcinoma., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objective: The effectiveness of laparoscopic repeat hepatectomy (LRH) versus open repeat hepatectomy (ORH) on recurrent hepatocellular carcinoma (RHCC) is unclear. We compared the surgical and oncological outcomes of LRH and ORH in patients with RHCC with a meta-analysis of studies based on propensity score-matched cohorts., Methods: A literature search was conducted on PubMed, Embase, and Cochrane Library with Medical Subject Headings terms and keywords until 30 September 2022. The quality of eligible studies was evaluated with the Newcastle-Ottawa Scale. Mean difference (MD) with a 95% CI was used for the analysis of continuous variables; odds ratio (OR) with 95% CI was used for binary variables; and hazard ratio with 95% CI was used for survival analysis. A random-effects model was used for meta-analysis., Results: Five high-quality retrospective studies with 818 patients were included; 409 patients (50%) were treated with LRH and 409 (50%) with ORH. In most surgical outcomes, LRH was superior to ORH: less estimated blood loss, shorter operation time, lower major complication rate, and shorter length of hospital stay (MD=-225.9, 95% CI=[-360.8 to -91.06], P =0.001; MD=66.2, 95% CI=[5.28-127.1], P =0.03; OR=0.18, 95% CI=[0.05-0.57], P =0.004; MD=-6.22, 95% CI=[-9.78 to -2.67], P =0.0006). There were no significant differences in the remaining surgical outcomes: blood transfusion rate and overall complication rate. In oncological outcomes, LRH and ORH were not significantly different in 1-year, 3-year, and 5-year overall survival and disease-free survival., Conclusions: For patients with RHCC, most surgical outcomes with LRH were superior to those of ORH, but oncological outcomes with the two operations were similar. LRH may be a preferable option for the treatment of RHCC., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Five undescribed indole alkaloids, fusarindoles A-E, together with seven known compounds were obtained from the marine-derived fungus Fusarium equiseti LJ-1. Their chemical structures and absolute configurations were determined by comprehensive analysis of the NMR, HRMS, UV, IR, ECD calculation and single-crystal X-ray diffraction data. The possible biosynthetic pathways of fusarindoles C-E were proposed. The cytotoxicities of eleven compounds, including fusarindoles A-E and six known compounds, against five human cancer cell lines A549, CNE2, SUNE1, HepG2 and QGY7701 were evaluated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Primary liver cancer is the second-most commonly occurring cancer and has resulted in numerous deaths worldwide. Hepatic resection is of two main types, i.e., anatomic resection (AR) and non-anatomic resection (NAR). The oncological outcomes of hepatocellular carcinoma (HCC) patients after AR and NAR are still considered controversial. Therefore, we aimed to compare the impact of AR and NAR on the oncological outcomes of HCC patients with tumor diameters ≤ 5 cm using the propensity score matching method and research-based evidence., Method: A systematic literature search was conducted. The main outcomes were disease-free survival (DFS), overall survival (OS), intrahepatic recurrence rate, and extrahepatic metastasis rate. Relative risk (RR) was calculated from forest plots and outcomes using random-effects model (REM)., Result: AR significantly improved DFS at 1, 3. and 5 years after surgery, compared to NAR (RR = 1.09, 95% CI = 1.04-1.15, P = 0.0003; RR = 1.16, 95% CI = 1.07-1.27, P = 0.0005; RR = 1.29, 95% CI = 1.07-1.55, P = 0.008). However, both of the difference in DFS at 7 years and OS at 1 and 3 years after AR versus that after NAR were not statistically significant. Nevertheless, the long-term OS associated with AR (5, 7, and 10 years) was superior to that associated with NAR (RR = 1.12, 95% CI = 1.03-1.21, P = 0.01; RR = 1.19, 95% CI = 1.04-1.36, P = 0.01; RR = 1.18, 95% CI = 1.05-1.34, P = 0.008). The difference in the intrahepatic recurrence rate after AR versus that after NAR was not statistically significant, but the extrahepatic metastasis rate after AR was significantly lower than that observed after NAR (RR = 0.61, 95% CI = 0.40-0.94, P = 0.03)., Conclusion: Therefore, AR should be the preferred surgical approach for HCC patients with tumor diameters ≤ 5 cm., Trial Registration: PROSPERO registration number CRD42022330596., (© 2022. The Author(s).)

Background: The outcomes of elderly (≥65 years) patients with hepatocellular carcinoma (HCC) after laparoscopic liver resection (LLR) vs open liver resection (OLR) are debated. We compared the surgical and oncological outcomes after LLR and OLR in elderly HCC patients based on matched cohort studies that performed propensity score matching (PSM)., Methods: A computer search of the PubMed, Embase, and Cochrane databases until January 31, 2022, was conducted using a combination of Medical Subject Heading (MeSH) terms and other terms. The Newcastle-Ottawa literature evaluation scale was used for quality assessment of the included studies that met the inclusion criteria and none of the exclusion criteria. The postoperative LLR and OLR markers after PSM were summarized., Results: Seven matched cohort studies were included. There were 1346 patients after PSM, of which 673 (50%) underwent LLR and 673 (50%) underwent OLR. All studies were of high quality. For surgical outcomes, the length of surgery was longer in the LLR group than in the OLR group (RR = 29.47, 95% CI = 26.55-32.39, P < 0.00001), but the length of hospitalization was significantly shorter (RR = -1.05,95% CI = -1.24 to -0.86, P < 0.00001), and the incidence of total postoperative complications and severe complications were significantly fewer (RR = 0.69,95% CI = 0.60-0.79, P < 0.00001; RR = 0.49,95% CI = 0.35-0.71, P = 0.0001, respectively). There were no significant differences in overall survival or disease-free survival between the two groups (HR = 0.87, 95% CI = 0.63-1.21, P = 0.41; HR = 0.87, 95% CI = 0.69-1.08, P = 0.20, respectively)., Conclusions: In elderly patients with HCC, LLR was associated with better surgical outcomes than OLR, but there was no significant difference in oncological outcomes. LLR should be the preferred surgical method for elderly patients with HCC., Competing Interests: Declaration of competing interest None., (Copyright © 2022 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Although early life stress (ELS) can increase susceptibility to adulthood psychiatric disorders and produce a greater inflammatory response in a stressful event, targeted preventive and therapeutic drugs still remain scarce. Ganoderma lucidum triterpenoids (GLTs) can exert anti-inflammatory effects in the periphery and central nervous systems. This study employed a combined model of "childhood maternal separation + adulthood sub-stress" to explore whether GLTs may alleviate anxiety- and depression-like behaviors in male and female mice by mitigating inflammation. Male and female pups were separated from their mothers for four hours per day from postnatal day 1 (PND 1) to PND 21; starting from PND 56, GLTs were administered intraperitoneally once daily for three weeks and followed by three days of sub-stress. Results showed that maternal separation increased the anxiety- and depression-like behaviors in both male and female mice, which disappeared after the preemptive GLTs treatment (40 mg/kg) before adulthood sub-stress. Maternal separation up-regulated the pro-inflammatory markers in the periphery and brain, and activated microglia in the prefrontal cortex and hippocampus. All the abnormalities were reversed by GLTs administration, with no adverse effects on immune organ indices, liver, and renal function. Our findings suggest that GLTs can be a promising candidate in treating ELS-induced psychiatric disorders.

Amino acid-directed strategy becomes an efficient way to explore the alkaloids' biosynthetic potential of marine fungi. The metabolites of marine fungus Monascus albidus BB3 were regulated obviously when cultured in GPY medium supplemented with L-tryptophan, L-phenylalanine, D,L-methionine, L-threonine, L-lysine, L-serine and L-valine. Four new γ-lactams, monascuslactams A-D ( 1 - 4 ), together with two known compounds pulchellalactam ( 5 ) and O -acetylperlolyrine ( 6 ) were obtained. Their structures were determined by comprehensive analysis on the 1 D and 2 D NMR, HRESIMS, UV and IR data, and their absolute configurations were assigned by the experimental and calculated ECD data analysis. Compounds 3 , 4 and 6 showed moderate cytotoxicity against human cancer cell lines SUNE1, HepG2, QGY7701, GLC82, HCT116 and MDA-MB-231.

The excess deposition of underlying extracellular matrix (ECM) in adipose tissue is defined as adipose tissue fibrosis that is a major contributor to metabolic disorder such as obesity and type 2 diabetes. Anti-fibrosis therapy has received much attention in the treatment of metabolic disorders. Orosomucoid (ORM) is an acute-phase protein mainly produced by liver, which is also an adipokine. In this study, we investigated the effects of ORM on adipose tissue fibrosis and the potential mechanisms. We showed that ORM1-deficient mice exhibited an obese phenotype, manifested by excessive collagen deposition in adipose tissues and elevated expression of ECM regulators such as metalloproteinases (MMP-2, MMP-13, MMP-14) and tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2, TIMP-3). Administration of exogenous ORM (50 mg· kg -1 · d -1 , ip) for 7 consecutive days in high-fat diet (HFD)-fed mice and leptin receptor (LepR)-deficient db/db mice attenuated these abnormal expressions. Meanwhile, ORM administration stimulated AMP-activated protein kinase (AMPK) phosphorylation and decreased transforming growth factor-β1 (TGF-β1) level in adipose tissues of the mice. In TGF-β1-treated 3T3-L1 fibroblasts, ORM (10 μg/mL) improved the impaired expression profiles of fibrosis-related genes, whereas a selective AMPK inhibitor dorsomorphin (1 μmol/mL) abolished these effects. Together, our results suggest that ORM exerts a direct anti-fibrosis effect in adipose tissue via AMPK activation. ORM is expected to become a novel target for the treatment of adipose tissue fibrosis., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Coronary atherosclerotic heart disease (CAD) is a chronic disease caused by multiple risk factors. Aberrant expression of long non-coding RNAs (lncRNAs) has been regarded as an independent risk factor of CAD. This study evaluated lncRNA myocardial infarction-associated transcription (MIAT) expression in CAD patients and its clinical significance. Totally, 155 CAD patients and 76 non-CAD controls were enrolled. MIAT expression was detected using reverse transcription quantitative polymerase chain reaction. The clinical diagnostic significance of MIAT was evaluated by plotting the receiver operating characteristic (ROC) curve. The levels of inflammatory cytokines were detected using enzyme-linked immunosorbent assay. microRNA (miR)-29b-3p expression and pregnancy-associated plasma protein A (PAPPA) level were detected. MIAT expression in CAD patients (4.23 [1.22-6.50]) was higher than that in non-CAD controls (1.64 [0.05-2.93]) (p < 0.01) and had an independent correlation with CAD. The area under ROC curve of predicting CAD was calculated as 0.790, the specificity as 71.40%, and the sensitivity as 70.00%. MIAT expression was positively correlated with the C-reactive protein level (r = 0.769, p < 0.0001) and pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and IL-8 levels, while negatively correlated with the anti-inflammatory cytokine IL-10. MIAT was positively correlated with Gensini score and had an independent correlation with it. LncRNA MIAT sponged miR-29b-3p and miR-29b-3p targeted PAPPA. In conclusion, lncRNA MIAT was upregulated in the peripheral blood of CAD patients and elicited clinical diagnostic significance. MIAT participated in the development of CAD via miR-29b-3p/PAPPA axis. This study provides insights into a potential target for the diagnosis and treatment of CAD., (© 2021 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Background: Takayasu arteritis (TAK) is a rare large vessel vasculitis, and epidemiological data on TAK are lacking in China. Thus, we designed this study to estimate the TAK prevalence and incidence in residential Shanghai, China., Methods: Data on diagnosed TAK cases aged over 16 years were retrieved from 22 tertiary hospitals in Shanghai through hospital electronic medical record systems between January 1, 2015 and December 31, 2017 to estimate the prevalence and incidence. A systematic literature review based on searches in PubMed, Ovid-Medline, Excerpta Medica Database (EMBASE), Web of Science, and China National Knowledge Infrastructure (CNKI) was performed to summarize TAK distribution across the world., Results: In total 102 TAK patients, with 64% female, were identified. The point prevalence (2015-2017) was 7.01 (95% CI 5.65-8.37) cases per million, and the mean annual incidence was 2.33 (1.97-3.21) cases per million. The average age of TAK patients was 44 ± 16 years, with the highest prevalence (11.59 [9.23-19.50] cases per million) and incidence (3.55 [0.72 3.74] cases per million) in the 16 to 34 years population. Seventeen reports were included in the system review, showing that the epidemiology of TAK varied greatly across the world. The incidence and prevalence were both relatively higher in Asian countries, with the prevalence ranging 3.3-40 cases per million and annual incidence ranging 0.34-2.4 cases per million., Conclusions: The prevalence and incidence of TAK in Shanghai was at moderate to high levels among the previous reports. The disease burden varied globally among racial populations., (© 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objectives: We aimed to construct and validate a risk assessment model to identify risk factors for heart failure (HF) in patients with Takayasu's arteritis (TAK)., Methods: Three hundred sixty-five patients with TAK were recruited in the East China Takayasu Arteritis Cohort from January 2012 to December 2019. Patients were assigned into training and validation sets following a 2:1 ratio according to the date of enrollment. Clinical characteristics were compared between heart failure (HF) and non-HF subgroups in the training set, and a risk assessment model for HF and its scoring algorithm was established based on logistic regression, which was tested in the validation set., Results: Among total of 74 (20.27%) TAK patients exhibited HF, and 55 cases (74.32%) were in the training set. The risk factors for HF of TAK patients included onset age >38 years, serum tumor necrosis factor (TNF)-α concentration >10 pg/ml, aortic valve involvement, coronary artery involvement, and pulmonary hypertension. We constructed the model without TNF-α (Model 1) and with TNF-α (Model 2). Patients in the training set with the score ≥ 3 appeared to be associated with an increased risk of HF with an area under curve (AUC) of 0.88 and 0.90 in Model 1 and Model 2 respectively. The AUC reached to 0.88 and 0.89 in the validation set that proved the accuracy of the model., Conclusions: We presented a risk assessment model of HF in TAK, which may help clinicians alert the complication of HF in the patients with specifically cardiac impairments. Key Points • Heart failure was not rare in Chinese Takayasu's arteritis patients, and there were approximately 20% of patients with heart failure in ECTA cohort. • Cardiac involvements on echocardiography include pathological valvular and atrioventricular abnormalities. • The onset age >38 years, serum tumor necrosis factor (TNF)-α concentration >10 pg/ml, aortic valve involvement, coronary artery involvement, and pulmonary hypertension were risk factors for heart failure in Takayasu's arteritis patients. • We constructed the model without TNF-α (Model 1) and with TNF-α (Model 2). Patients with the risk assessment model score of ≥ 3 appeared to be associated with an increased risk of heart failure., (© 2021. International League of Associations for Rheumatology (ILAR).)

Objective: To analyze the behavioral factors influencing of new hepatitis B virus (HBV) infection in diabetic patients, so as to provide evidence for reducing the risk of new HBV infection in diabetic patients., Methods: A nested case-control study was conducted to follow up and observe 4 586 diabetic patients. The 114 diabetic patients who newly developed HBV infection during the follow-up period were selected as the case group, and 228 diabetic patients who did not develop HBV infection in the same period were selected as the control group from the cohort population at a matching ratio of 1∶2 according to the age ±2 years. Questionnaire surveys and laboratory examinations were conducted in the cohort. The contents of the questionnaire included family history of hepatitis B, history of trauma, history of receiving/donating blood, individual-related behavioral characteristics, diabetes severity, and behavior related to diabetes treatment and management. In addition, the blood samples of the cohort were tested for hepatitis B surface antigen (HBsAg) by enzyme-linked immunosorbent assay (ELISA). The conditional logistic regression model was used to analyze the related behavioral factors affecting new HBV infection in diabetic patients., Results: The median ages of the HBV group and the control group were 64 years old and 66 years old, respectively. There was no statistically significant difference in the composition of sex, age, ethnicity, occupation and amount of formal education between the two groups ( P >0.05). Multivariate analysis showed that diabetic patients with a family history of hepatitis B ( OR =13.052, 95% CI : 3.799 to 44.847) had a higher risk of new HBV infection, while diabetic patients who used blood collection/injection devices in a standardized way ( OR =0.189, 95% CI : 0.082 to 0.436), safety locking blood glucose needles ( OR =0.142, 95% CI : 0.073 to 0.276) and venous blood collection needles ( OR =0.019, 95% CI : 0.001 to 0.262) and self-testing of blood sugar at home ( OR =0.466, 95% CI : 0.222 to 0.980) had a lower risk of new HBV infection., Conclusion: Family history of hepatitis B is an independent factor that increases the risk for new HBV infection in diabetic patients. During the process of long-term blood glucose management of diabetic patients, standardized use of blood collection/injection devices, use of safer types of blood sampling lancet, and self-testing of blood glucose help can reduce the risk of HBV infection., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Huang-Qin Decoction (HQD) is a classic prescription for diarrhea in Chinese medicine treatment. Recent studies have demonstrated that HQD and its modified formulation PHY906 could ameliorate irinotecan (CPT-11) induced gastrointestinal (GI) toxicity and enhance its anticancer therapeutic efficacy. Nevertheless, which constituents in HQD are effective is still unclear so far. The study aims to screen out the key bioactive components combination from HQD that could enhance the anticancer effect of CPT-11. First, the potential bioactive constituents were obtained through system pharmacology strategy. Then the bioactivity of each constituent was investigated synthetically from the aspects of NCM460 cell migration, TNF-α release of THP-1-derived macrophage and MTT assay in HCT116 cell. The contribution of each constituent in HQD was evaluated using the bioactive index E i, which taken the content and bioactivity into comprehensive consideration. And then, the most contributing constituents were selected out to form a key-component combination. At last, the bioefficacy of the key-component combination was validated in vitro and in vivo. As a result, a key-component combination (HB4) consisting of four compounds baicalin, baicalein, glycyrrhizic acid and wogonin was screened out. In vitro assessment indicated that HB4 could enhance the effect of CPT-11 on inhibiting cell proliferation and inducing apoptosis in HCT116. Furthermore, the in vivo study confirmed that HB4 and HQD have similar pharmacological activity and could both enhance the antitumor effect of CPT-11 in HCT116 xenograft model. Meanwhile, HB4 could also reduce the CPT-11 induced GI toxicity., (Copyright © 2021 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Objectives: To identify valuable ultrasonography findings combined with clinical markers for predicting carotid progression of Takayasu's arteritis (TAK) on imaging during a 1-year follow-up period., Methods: From May 2016 to June 2019, 77 Chinese TAK patients with carotid artery involvement were enrolled in the present study. The patients' clinical characteristics and serological test and carotid ultrasonography results were recorded at baseline and each visit. Carotid progression was evaluated by ultrasonography every 3 months during the 1-year follow-up. Baseline clinical characteristics and ultrasonography results for predicting progression on imaging were identified., Results: Sixteen (20.8%) patients presented with carotid progression on imaging during the 1-year follow-up period. The patients in the progressive group were younger (23.4±3.7 vs. 32.3±9.8 years, p<0.01) than those in the non-progressive group. At baseline, the vessel wall was thicker in the progressive group than in the non-progressive group (2.4±0.8 vs. 1.9±0.5 mm, p=0.041). Furthermore, the proportion of patients with refractory disease (87.5% vs. 16.4%, p<0.01) was higher in the progressive group than in the non-progressive group. Patients with a thickened carotid wall (≥1.9 mm), refractory disease, and younger age (≤30 years) might be at a high risk of carotid progression on imaging (75%, AUC: 0.93, sensitivity: 75%, specificity: 93.4%)., Conclusions: Younger patients with early vascular structural changes at baseline as well as refractory disease seemed more likely to show carotid progression on imaging.

Objective To investigate the current status of nutritional knowledge and skills of fast-food takeout practitioners in Chengdu City,so as to provide evidence for nutritional literacy education among takeout practitioners.Methods A questionnaire survey was conducted among 832 employees of fast-food takeout restaurants in Chengdu from April to September in 2019 through a multi-stage random sampling strategy.Results The awareness rate of nutritional knowledge of fast-food takeout practitioners in Chengdu was 77.28%,and the correct rates of answers to daily oil intake for adults,daily drinking water for adults and daily salt intake for adults in the Dietary Guidelines for Chinese Residents were respectively 17.43%,22.60% and 25.36%.In addition,the proportion of practitioners with the ability to estimate the recommended intake of food for a meal,the ability to estimate condiments intake and the ability to interpret nutrition labels were 8.77%,8.77% and 15.02%,respectively.The awareness rate of nutritional knowledge was the lowest(71.47%)in the practitioners aged≤25 and the highest(84.53%)in those aged 26-39,and the difference was statistically significant(χ 2 =14.419,P=0.001).High awareness rate of nutritional knowledge was found in the practitioners of Han ethnic group(78.45%)compared with those of ethnic minorities(57.14%)(χ 2 =10.346,P=0.001).Besides,the practitioners with a high degree of education showed high awareness rate of nutritional knowledge( [Formula: see text]=36.514,P<0.001),and the correct rate of chefs(17.86%)was higher than that(12.82%)of food matching staff(χ 2 =4.068,P=0.044).Conclusions The fast-food takeout practitioners in Chengdu generally have good nutritional knowledge while have some knowledge gaps.At the same time,the nutrition-related skills of takeout practitioners are not good.We should focus on strengthening the training of takeout restaurant employees for the Dietary Guidelines for Chinese Residents and nutrition labeling-related knowledge,carry out targeted nutritional knowledge training,and comprehensively strengthen the training of nutrition-related skills.

Objective To investigate the nutritional literacy levels of the takeaway platform practitioners in Chengdu,the takeaway food nutrients,and the correlation between them.Methods We employed a multi-stage random sampling method to investigate the nutritional literacy levels of 100 takeaway platform restaurants in the main urban area of Chengdu and examined the nutritional components of hot set meals in each restaurant.A questionnaire survey was conducted on the nutritional literacy levels of chefs and food matching staff.The correlations of nutrient energy supply rationality with nutritional literacy level and set meal price were then analyzed.Results The total pass rate of nutrition knowledge of chefs/food matching staff was 61.0%.Only 2.0% of the set meals had reasonable total energy supply.The set meals with reasonable energy supply of available carbohydrate,protein,and fat accounted for 3.0%,62.0%,and 21.0%,and those with over energy supply accounted for 97.0%,26.0%,and 73.0%,respectively.The rest set meals provided insufficient energy.There was a positive correlation between the nutritional literacy level and the rationality of protein energy supply(r=0.414,P=0.003).Conclusions The nutritional literacy levels of chefs/food matching staff of takeaway food restaurants in Chengdu are moderate.The hot set meals on the takeaway platform have the problem of excess energy supply.The nutrition knowledge of chefs/food matching staff cannot effectively satisfy rational nutrition matching.The nutritional literacy levels of chefs/food matching staff showed no significant correlation with the rationality of nutrient energy supply.

Salt-inducible kinase 2 (SIK2) is an important regulator in various intracellular signaling pathways related to apoptosis, tumorigenesis and metastasis. However, the involvement of SIK2 in gastric tumorigenesis and the functional linkage with gastric cancer (GC) progression remain to be defined. Here, we report that SIK2 was significantly downregulated in human GC tissues, and reduced SIK2 expression was associated with poor prognosis of patients. Overexpression of SIK2 suppressed the migration and invasion of GC cells, whereas knockdown of SIK2 enhanced cell migratory and invasive capability as well as metastatic potential. These changes in the malignant phenotype resulted from the ability of SIK2 to suppress epithelial-mesenchymal transition via inhibition of AKT/GSK3β/β-catenin signaling. The inhibitory effect of SIK2 on AKT/GSK3β/β-catenin signaling was mediated primarily through inactivation of AKT, due to its enhanced dephosphorylation by the upregulated protein phosphatases PHLPP2 and PP2A. The upregulation of PHLPP2 and PP2A was attributable to SIK2 phosphorylation and activation of mTORC1, which inhibited autophagic degradation of these two phosphatases. These results suggest that SIK2 acts as a tumor suppressor in GC and may serve as a novel prognostic biomarker and therapeutic target for this tumor., (© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Objective To understand the family sex education for young children in rural areas of Sichuan province and analyze the influencing factors. Methods A multi-stage random sampling method was used to select 2246 parents of kindergarten children from rural areas in Sichuan province for a questionnaire-based survey.The Chi-square test and Logistic regression model were used for data analysis. Results It was found 1132(52.33%)parents had implemented family sex education for young children and 1031(47.67%)had not.Young children having asked sex-related questions( OR =1.536,95% CI =1.257-1.878),parents thinking that early childhood sex education is necessary( OR =3.691,95% CI =2.029-6.717),and parents having the intention to know early childhood sex education( OR =1.700,95% CI =1.274-2.269),and kindergarten having implemented early childhood sex education( OR =3.316,95% CI =2.515-4.372)were promoting factors for parents to conduct early childhood sex education,whereas a total annual household income at the middle level( OR =0.664,95% CI =0.456-0.968)was a hindering factor for parents to conduct early childhood sex education. Conclusions Parents of young children in rural areas of Sichuan province have poor awareness of sex education,and the proportion of parents who have never conducted sex education for children is high.The total annual income of the family,whether the children have asked about sex-related questions,parents' attitude towards early childhood sex education,and whether the kindergarten has conducted the early childhood sex education are important factors that influence the level of children's family sex education.

Objective: To understand the status and distribution characteristics of health-related quality of life (HRQOL) of the older generation of migrant workers in Chengdu, and analyze the factors influencing the quality of life of the older generation of migrant workers, so as to provide reference for formulating relevant policies to improve the health of the older generation of migrant workers., Methods: From June 2017 to June 2018, the respondent-driven sampling (RDS) method was used to select 1 492 non-registered migrant workers born before 1980 living in Chengdu city. The investigation was performed with questionnaire including demographic characteristics, working status, economic status, disease status, living environment and HRQOL., Results: The scores of physical component summary (PCS), mental component summary (MCS) and the total score of HRQOL in the older generation of migrant workers were 50.78±7.54, 50.67±10.24 and 101.45±12.34, respectively. Multiple linear regression analysis showed that older age (standard regression coefficient ( Sβ )=-0.061, P =0.026), low education level ( Sβ =-0.053, P =0.038), being unmarried, divorced or widowed ( Sβ =-0.064, P =0.009), chronic diseases ( Sβ =-0.156, P <0.001), or two-week illness ( Sβ =-0.190, P <0.001) were the risk factors of low HRQOL; High income level ( Sβ =0.069, P =0.013), having a steady job ( Sβ =0.126, P <0.001), having endowment insurance ( Sβ =0.055, P =0.027) and satisfactory with the living environment ( Sβ =0.060, P =0.016) were the contributing factors factors of high HRQOL., Conclusion: The HRQOL of the older generation of migrant workers in Chengdu is generally good. More attention should be paid to the migrant workers of older age, having lower income, suffering from chronic diseases, being unmarried/divorced/widowed, and lacking endowment insurance. Appropriate measures should be taken to improve the health status of the key groups., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Background: Takayasu arteritis-induced renal arteritis (TARA), commonly seen in Takayasu arteritis (TA), has become one of the main causes of poor prognosis and early mortality in patients with TA. TARA progressing into Takayasu arteritis-induced renal artery stenosis (TARAS), could lead to severe complications including malignant hypertension, cardiac-cerebral vascular disease, and ischemic nephropathy. Since there existed no guidelines on treatments, this study aimed to review the comprehensive treatments for TARA., Methods: We searched systematically in databases including PubMed, Ovid-Medline, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, and SinoMed, from inception to May 2018. Literature selection, data extraction, and statistical analysis were performed., Results: Eighty-two literatures were recruited focusing on medical treatments (n = 34) and surgical treatments (n = 48). We found that combined medical treatments of glucocorticoids and conventional synthetic disease-modifying anti-rheumatic drugs could reach high rates of remission in patients with TARA, and biological disease-modifying anti-rheumatic drugs were preferred for refractory patients. After remission induction, surgical treatment could help reconstruct renal artery and recover renal function partly. Percutaneous transluminal angioplasty was the first choice for patients with TARAS, while open surgery showed a good long-term survival., Conclusions: Patients with TARA should benefit both from medical treatments and from surgical treatments comprehensively and sequentially. Multidisciplinary team coordination is recommended especially in patients with severe complications.

Objective: To compare the therapeutic effect between thunder-fire moxibustion combined with external applicaion of Shuangbai powder and thunder-fire moxibustion alone for mild and moderate knee osteoarthritis., Methods: A total of 70 patients with mild and moderate knee osteoarthritis were randomly divided into an observation group and a control group, 35 cases in each group. In the observation group, thunder-fire moxibustion combined with external applicaion of Shuangbai powder were applied, Thunder-fire moxibustion was applied at Xuehai (SP 10), Liangqiu (ST 34), Neixiyan (EX-LE 4), Yanglingquan (GB 34) and ashi point, external applicaion of Shuangbai powder was given to the affected knee after the treatment of thunder-fire moxibustion. Simple thunder-fire moxibustion was given in the control group. All patients in the two groups were treated once a day, 7 days as one course and the consecutive 4 courses were required, with an interval of 1 day between courses. Before and after treatment, the visual analogue scale (VAS) score and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score were used to assessed knee pain, stiffness and physical function in the two groups. In addition, the efficacy was evaluated., Results: Compared before treatment, the VAS scores, total scores of WOMAC, pain scores, stiffness scores and physical function scores were reduced after treatment in the two groups ( P <0.01), and the scores in the observation group were significantly lower than those in the control group ( P <0.01, P <0.05). The total effective rate was 97.0% (32/33) in the observation group, which was superior to 91.2% (31/34) in the control group ( P <0.05)., Conclusion: Thunder-fire moxibustion combined with external applicaion of Shuangbai powder are superior to simple thunder-fire moxibustion in improving the symptoms and delaying the development of the disease for mild and moderate knee osteoarthritis.

Objective: To investigate whether phenylephrine (PE) inhibits sepsis-induced cardiac dysfunction, cardiac inflammation, and mitochondrial injury through the PI3K/Akt signaling pathway., Methods: A rat model of sepsis was established by cecal ligation and puncture. PE and/or wortmannin (a PI3K inhibitor) were administered to investigate the role of PI3K/Akt signaling in mediating the effects of PE on inhibiting sepsis-induced cardiac dysfunction, cardiac inflammation, and mitochondrial injury. Hematoxylin-eosin staining, echocardiography, and Langendorff system were used to examine the myocardial injury and function. The concentrations of TNF-α and IL-6 were analyzed by enzyme-linked immunosorbent assay. Intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), myeloperoxidase, mitochondria-related fusion/fission proteins, and PI3K/Akt signaling pathway-associated proteins were analyzed by Western blotting., Results: PE improved the cardiac function and survival in septic rats. PE decreased TNF-α, IL-6, ICAM-1, VCAM-1, and myeloperoxidase contents in the myocardium of septic rats. Meanwhile, PE increased the fusion-related proteins and decreased the fission-related proteins in the myocardial mitochondria of septic rats. On the other hand, PE activated the PI3K/Akt signaling pathway in the cecal ligation and puncture-treated rats, and all the protective effects of PE were abolished by wortmannin., Conclusions: PE attenuated sepsis-induced cardiac dysfunction, cardiac inflammation, and mitochondrial injury through the PI3K/Akt signaling pathway.

Aims: To assess the value of contrast-enhanced ultrasonography (CEUS) for monitoring disease activity of Takayasu arteritis (TA)., Methods: TA patients were recruited in a Chinese TA clinical center from January 2016 to September 2017. The physician global assessment was used as the referential standard for disease activity. Clinical data, acute phase reactants, and CEUS scans were simultaneously recorded at baseline and after a 3-month therapy., Results: A total of 84 TA patients were enrolled, and 47 (55.95%) cases were active at baseline. Macaroni sign and entire artery involvement were characteristic findings of CEUS in TA. The average vascular full thickness of the carotid artery in active TA patients was significantly higher than that in inactive patients (2.36 ± 0.86 vs. 1.79 ± 0.49 mm; p = 0.001). Severe neovascularization (grade 2) was observed in 29 active cases (61.70%) and in 9 inactive cases (24.32%) (p = 0.001). Receiver operating characteristic analysis showed that the combination of CEUS parameters (cutoff of thickness was 1.75 mm or neovascularization grade 2) and erythrocyte sedimentation rate (ESR) (cutoff of 20 mm/H) could help differentiate between active and inactive TA patients with a sensitivity and specificity of 81.1% and 81.5%, respectively. Youdon's index was 0.626. Furthermore, our study found that patients with decreased ESR and C-reactive protein (CRP) still had a progression of vascular wall inflammation at 3 months of follow-up., Conclusions: The evaluation of vascular inflammation by CEUS is more sensitive than acute phase reactants. Neovascularization can still be observed in the vascular lesion sites of those who have reached clinical remission after treatment. Thus, CEUS can be used as an alternative method to assess disease activity for TA patients.

The purpose of this study was to evaluate whether FGD5-AS1 participates in oxygen-glucose deprivation and simulated reperfusion (OGD/R)-induced neurons injury and the detailed mechanism. An OGD/R model was established using the primary cortical neuron isolated from the brains of Sprague-Dawley rats. qRT-PCR and western blot were performed to de-tect the RNA and protein expression levels, respectively. Cell counting kit 8 (CCK8) and flow cytometry assays were used to evaluate the proliferation and apoptosis of neurons. The luciferase reporter assay was used to verify the interaction between lncRNA FGD5-AS1 and miRNA-223. We found that the expression of FGD5-AS1 is decreased in neurons suffering from OGD/R. Up-regulation of FGD5-AS1 could recover proliferation and inhibit apoptosis of OGD/R-injured neurons. In addition, the interaction between FGD5-AS1 and miRNA-223 were verified. The expression of miRNA-223 was negatively correlated with the level of FGD5-AS1. In turn, the expression of insulin-like growth factor-1 receptor (IGFIR, a target gene of miR-223) was positively associated with the level of FGD5-AS1. Simultaneously down-regulating miR-223 and over-expressing FGD5-AS1 as well as IGF1R exhibited an additional effect of extenuating OGD/R damage i.e. increasing neuron proliferation and reducing neuron apoptosis. In conclusion, our findings indicated that FGD5-AS1 may protect the neuron against OGD/R injury via acting as a ceRNA for miR-223 to mediate IGF1R expression, which contributes to a deeper understanding of ischemic stroke and provide a promising therapeutic target for this disease.

Objectives: To introduce a new laparoscopic splenectomy (LS) approach., Methods: Sixteen patients underwent LS with general anaesthesia and carbon dioxide pneumoperitoneum. The details of the surgery are as follows: 1. The omentum was incised along the greater curvature and retracted as much as possible to expose the pancreatic body and tail. 2. The right arteriovenous root in the gastric omentum was ligated to sufficiently expose the pancreatic body and tail. 3. The pancreatic capsula was opened along the inferior margin of the pancreatic tail, elevated and separated until the superior margin of the pancreas was grasped. The entire splenic pedicle was retracted using a string. The branching blood vessels in the splenic hilus were ligated using clamps and separated. The splenogastric and splenophrenic ligaments were transected proximally using an ultrasonic knife, and the thick short gastric blood vessels were clamped. This procedure allows complete exposure of the area above the pancreatic tail where the splenic hilus is located. The splenoportal vasculature was suspended using a 7-0 silk suture to easily manipulate this tissue. The splenic portal vessels were dissected using an ultrasonic knife, and the portal vessels were isolated individually using vascular clamps and transected. The splenogastric and lienorenal ligaments were also transected. The spleen was then placed into a bag, and the surgical port was slightly enlarged. Finally, the spleen was sectioned for removal., Results: Fifteen surgeries were successfully performed from March 2015 to January 2016. One patient underwent laparotomy. No patients developed postoperative intra-abdominal haemorrhage or infection. One patient developed subcutaneous emphysema, and one developed a wound infection. No deaths occurred., Conclusions: Active exposure of the area dorsal to the pancreatic tail is a safe and simple splenectomy method.

The quality control research of traditional Chinese medicine (TCM) is lagged far behind the space of progress in modernization and globalization. Thus the concept of quality marker (Q-marker) was proposed recently to guide the quality investigations of TCM. However, how to discover and validate the Q-marker is still a challenge. In this paper, a system pharmacology based strategy was proposed to discover Q-marker of HuangQin decoction (HQD) to attenuate Intestinal Damage. Using this strategy, nine measurable compounds including paeoniflorin, baicalin, scutellarein, liquiritigenin, norwogonin, baicalein, glycyrrhizic acid, wogonin, and oroxylin A were screened out as potential markers. Standard references of these nine compounds were pooled together as components combination according to their corresponding concentration in HQD. The bioactive equivalence between components combination and HQD was validated using wound healing test and inflammatory factor determination experiment. The comprehensive results indicated that components combination is almost bioactive equivalent to HQD and could serve as the Q-markers. In conclusion, our study put forward a promising strategy for Q-markers discovery.

Hepatocellular carcinoma (HCC) is a highly heterogeneous type of tumor, which may be caused by the stem/progenitor cell features of particular HCC cells. Recent studies have subclassified HCC into different prognostic subtypes according to just one stemness-associated marker. However, one stemness-associated marker is not sufficient to clearly define cancer stem cells, or to decipher the heterogeneous nature of HCC. For a more precise subtype classification for prognostic application, a combination of multiple stemness-associated markers is required. Cluster of differentiation 133 (CD133) and α-fetoprotein (AFP) are common stemness-associated markers for HCC that have not yet been employed for HCC subtype classification. In the present study, CD133 expression was assessed by immunohistochemistry in 127 hepatitis B virus-associated HCC tumor specimens. Based on CD133 immunostaining and serum AFP levels, the HCC cases were subclassified into four subtypes, which demonstrated different clinicopathological features and varying prognoses. Among the four subtypes, the number of tumor lesions, histological grade and vascular invasion were significantly different (P=0.002, P=0.018 and P=0.022, respectively). CD133 + AFP + HCC was associated with a relatively poor prognosis, CD133 - AFP - HCC was associated with a relatively good prognosis, while CD133 + AFP - HCC and CD133 - AFP + HCC were associated with an intermediate prognosis. These prognostic values were confirmed by borderline or statistical significance (between all groups, overall survival, P=0.061; recurrence-free survival, P=0.015). These results define a novel and simple system, based on CD133 and AFP, for classifying HCC into four distinct prognostic subtypes. This classification system may aid the assessment of patients with HCC for personalized therapy.

Objective: To investigate the effect of adipose tissue-derived mesenchymal stem cell (ADSC) transplantation in the treatment of liver fibrosis rats and possible mechanism. Methods: Subcutaneous adipose tissue in the inguinal region of rats was collected to isolate ADSCs. The rats with liver fibrosis induced by intraperitoneally injected carbon tetrachloride were divided into cell transplantation group and phosphate buffer saline (PBS) injection group, and the rats which were fed normally were enrolled as negative control group. The rats in the cell transplantation group were given tail vein injection of ADSCs, and those in the PBS injection group were given injection of 0.5 ml PBS. At 7 days after transplantation, blood samples were collected from the inferior vena cava to evaluate liver function; liver tissue was collected to measure the protein expression of hepatocyte growth factor (HGF) and alpha-smooth muscle actin (α-SMA); Masson trichrome staining was used to evaluate intrahepatic collagen deposition. Hepatic stellate cells (HSCs) were collected from the rats with liver fibrosis, and indirect co-culture of HSCs and ADSCs was performed in vitro to analyze the influence of ADSCs on the proliferation and apoptosis of HSCs. The independent samples t-test was used for comparison between groups, and an analysis of variance was used for comparison of means between multiple samples. Results: ADSCs were found in liver tissue in the transplantation group, and compared with the PBS injection group, the transplantation group had significant alleviation in hepatocyte necrosis, vacuolization, and area of fibrosis and significant reductions in the serum levels of aminotransferases, while there was no significant difference in the level of albumin between the two groups. Compared with the PBS injection group, the transplantation group had significant upregulation in the protein expression of HGF and significant downregulation in the protein expression of α-SMA (both P < 0.05). In vitro co-culture for 72 hours showed that ADSCs inhibited the proliferation of HSCs, and there was a significant difference between the co-culture group and the control group with HSCs cultured alone. Caspase-3 immunostaining showed that after co-culture for 72 hours, there was a significant difference in the apoptosis rate of HSCs between the co-culture group and the control group with HSCs cultured alone (23.42% ± 3.02% vs 14.82% ± 3.93%). Conclusion: ADSC transplantation can upregulate the expression of HGF in the liver, promote the apoptosis of HSCs, and thus alleviate liver fibrosis.

Cerebral ischemia injury seriously endangers human health and its molecular mechanism is still not fully understood. microRNA-223 (miR-223) has been reported to be involved in many physiological functions but the specific role of miRNA-223 in ischemic neuronal injury is still unclear. An oxygen-glucose deprivation and simulated reperfusion (OGD/R) model was constructed here to investigate the possible role miR-223 played in ischemic neuronal injury. The expression of miRNA-223 in the OGD/R model and its effect on cell proliferation were studied by qPCR and CCK8 assay. We observed that miR-223 was significantly over-expressed after OGD/R treatment and it suppressed significantly cortical neurons proliferation. To further study the mechanism involved, we predicted and examined the potential targets of miR-223 by targetscan, qPCR, western blot and luciferase reporter assay. We found that the expression level of type 1 insulin-like growth factor receptor (IGF1R) was negatively associated with the level of miR-223. Furthermore, the relative luciferase activity of pmirGLO-WT was inhibited obviously, while no significant change was observed in the pmirGLO-Mut group, indicating that miR-223 could bind to IGF1R. Similar cell proliferation suppression caused by miR-223 antagomir was observed when IGF1R was silenced. On the contrary, when cortical neurons were co-treated with miR-223 agomir and the cDNA of IGF1R which did not contain 3'- untranslated region, the inhibition caused by miR-223 disappeared. Our results suggested that miR-223 may suppress proliferation of cortical neurons that were treated with OGD/R via inhibiting IGF1R expression.

As a common anticancer drug, cisplatin has been widely used for treating tumors in the clinic. However, its side effects, especially its nephrotoxicity, noticeably restrict the application of cisplatin. Therefore, it is imperative to investigate the mechanism of renal injury and explore the corresponding remedies. In this study, we showed the phenotypes of the renal tubules and epithelial cell death as well as elevated cleaved-caspase3- and TUNEL-positive cells in rats intraperitoneally injected with cisplatin. Similar cisplatin-induced cell apoptosis was found in HK-2 and NRK-52E cells exposed to cisplatin as well. In both models of cisplatin-induced apoptosis in vivo and in vitro, quantitative PCR data displayed reductions in miR-30a-e expression levels, indicating that miR-30 might be involved in regulating cisplatin-induced cell apoptosis. This was further confirmed when the effects of cisplatin-induced cell apoptosis were found to be closely correlated with alterations in miR-30c expression, which were manipulated by transfection of either the miR-30c mimic or miR-30c inhibitor in HK-2 and NRK-52E cells. Using bioinformatics tools, including TargetScan and a gene expression database (Gene Expression Omnibus), Adrb1, Bnip3L, Hspa5 and MAP3K12 were predicted to be putative target genes of miR-30c in cisplatin-induced apoptosis. Subsequently, Bnip3L and Hspa5 were confirmed to be the target genes after determining the expression of these putative genes following manipulation of miR-30c expression levels in HK-2 cells. Taken together, our current experiments reveal that miR-30c is certainly involved in regulating the renal tubular cell apoptosis induced by cisplatin, which might supply a new strategy to minimize cisplatin-induced nephrotoxicity.

Irinotecan (CPT-11) is a potent chemotherapeutic agent, however, its clinical usage is often limited by the induction of severe gastrointestinal (GI) toxicity, especially late-onset diarrhea. HuangQin Decoction (HQD), commonly used for the treatment of GI ailments, has been proved could significantly ameliorate the intestinal toxicity of CPT-11. To reveal the mechanisms of CPT-11-induced toxicity and the modulation effects of HQD, a previous untargeted metabolomics study was performed and the results indicated that HQD may protect the GI tract by altering the metabolism of bile acids (BAs). Nevertheless, the untargeted assays are often less sensitive and/or efficient. In order to further confirm our previous findings, here in this paper, serum and tissues metabolic profiles of 17 BAs were analyzed using liquid chromatography-tandem mass spectrometry based targeted metabolomics. The results indicated that serum and tissues levels of most BAs were significantly decreased after CPT-11 administration, except some hydrophobic BAs. Co-treatment with HQD could markedly attenuate CPT-11-induced GI toxicity and reverse the alterations of hydrophobic BAs. Despite the fact that the BAs pool size remained unchanged, the balance of BAs had shifted leading to decreased toxicity after HQD treatment. The present study demonstrated for the first time that the precise interaction between HQD, CPT-11-induced intestinal toxicity and BAs' homeostasis.

[This corrects the article DOI: 10.1155/2017/8495326.].

Accumulating evidence suggests that the tumor microenvironment has a profound influence on tumor initiation and progression, opening a new avenue for studying tumor biology. Nonetheless, the prognostic values of the peritumoral expression of EpCAM and CD13 remain to be elucidated in hepatocellular carcinoma (HCC) patients. In this study, the expression of EpCAM and CD13 was assessed by immunohistochemistry in peritumoral liver hepatocytes from 106 hepatitis B virus- (HBV-) related HCC patients who had undergone curative hepatectomy. The peritumoral EpCAM-positive group had a significantly worse overall survival (OS) ( p = 0.003) and recurrence-free survival (RFS) ( p = 0.022) compared to the negative group. Peritumoral CD13-positive patients were also associated with poor OS ( p = 0.038), while not significantly associated with RFS. The adjusted multivariate COX proportional hazard regression analysis suggested that only the positive expression of peritumoral EpCAM precisely predicted poor OS. Being peritumoral EpCAM positive was also significantly associated with a larger tumor size, liver cirrhosis, and more frequent vascular invasion; however, no statistically significant association was observed between CD13 and any clinicopathological features. Taken together, peritumoral EpCAM and CD13 expression was associated with a poor prognosis, but EpCAM may be a better prognostic marker than CD13 in HBV-related HCC patients. In the future, peritumoral EpCAM could be a good target for adjuvant therapy after curative hepatectomy.

Background: Amyloid β (Aβ) deposits and the endoplasmic reticulum stress (ERS) are both well established in the development and progression of Alzheimer's disease (AD). However, the mechanism and role of Aβ-induced ERS in AD-associated pathological progression remain to be elucidated., Methods: The five familial AD (5×FAD) mice and wild-type (WT) mice aged 2, 7, and 12 months were used in the present study. Morris water maze test was used to evaluate their cognitive performance. Immunofluorescence and Western blot analyses were used to examine the dynamic changes of pro-apoptotic (CCAAT/enhancer-binding protein homologous protein [CHOP] and cleaved caspase-12) and anti-apoptotic factors (chaperone glucose-regulated protein [GRP] 78 and endoplasmic reticulum-associated protein degradation-associated ubiquitin ligase synovial apoptosis inhibitor 1 [SYVN1]) in the ERS-associated unfolded protein response (UPR) pathway., Results: Compared with age-matched WT mice, 5×FAD mice showed higher cleaved caspase-3, lower neuron-positive staining at the age of 12 months, but earlier cognitive deficit at the age of 7 months (all P < 0.05). Interestingly, for 2-month-old 5×FAD mice, the related proteins involved in the ERS-associated UPR pathway, including CHOP, cleaved caspase-12, GRP 78, and SYVN1, were significantly increased when compared with those in age-matched WT mice (all P < 0.05). Moreover, ERS occurred mainly in neurons, not in astrocytes., Conclusions: These findings suggest that compared with those of age-matched WT mice, ERS-associated pro-apoptotic and anti-apoptotic proteins are upregulated in 2-month-old 5×FAD mice, consistent with intracellular Aβ aggregation in neurons., Competing Interests: There are no conflicts of interest.

Objective: To observe whether adipose-derived stem cells (ADSCS), co-cultured with osteoblasts, can differentiate into osteoblasts and, if so, to study the best-induced conditions, with an ultimate goal of repairing bone defects., Materials and Methods: Adipose-derived stem cells and osteoblasts were isolated from New Zealand white rabbits, and co-cultured in media with either 5% or 10% fetal bovine serum, for up to 4 weeks. The morphology of collected cells was examined under a microscope, and histological staining with alkaline phosphatase and alizarin red was carried out after induction for 1, 2, 3 and 4 weeks. Osteogenesis identification, including mRNA expression of type I collagen and osteocalcin, and alkaline phosphatase, was also performed using RT-PCR., Results: After 7 days of co-culture, some adipose-derived stem cells became round in both groups. After 14 days of co-culture, adipose-derived stem cells were found highly-differentiated, and stained positively with alkaline phosphatase and alizarin red, similar to mature osteoblasts. The mRNA expression of type I collagen and osteocalcin increased in both groups, especially in the 10% fetal bovine serum group., Conclusions: Our findings indicate that adipose-derived stem cells co-cultured with osteoblasts can differentiate into osteoblasts when induced by a high concentration of serum culture.

Background: Amyloid β (Aβ) has been established as a key factor for the pathological changes in the brains of patients with Alzheimer's disease (AD), and cellular senescence is closely associated with aging and cognitive impairment. However, it remains blurred whether, in the AD brains, Aβ accelerates the neuronal senescence and whether this senescence, in turn, impairs the cognitive function. This study aimed to explore the expression of senescence-associated genes in the hippocampal tissue from young to aged 5XFAD mice and their age-matched wild type (WT) mice to determine whether senescent neurons are present in the transgenic AD mouse model., Methods: The 5XFAD mice and age-matched wild type mice, both raised from 1 to 18 months, were enrolled in the study. The senescence-associated genes in the hippocampus were analyzed and differentially expressed genes (DEGs) were screened by quantitative real-time polymerase chain reaction. Cognitive performance of the mice was evaluated by Y-maze and Morris water maze tests. Oligomeric Aβ (oAβ) (1-42) was applied to culture primary neurons to simulate the in vivo manifestation. Aging-related proteins were detected by Western blotting analysis and immunofluorescence., Results: In 5XFAD mice, of all the DEGs, the senescence-associated marker p16 was most significantly increased, even at the early age. It was mainly localized in neurons, with a marginal expression in astrocytes (labeled as glutamine synthetase), nil expression in activated microglia (labeled as Iba1), and negatively correlated with the spatial cognitive impairments of 5XFAD mice. oAβ (1-42) induced the production of senescence-related protein p16, but not p53 in vitro, which was in line with the in vivo manifestation., Conclusions: oAβ-accelerated neuronal senescence may be associated with the cognitive impairment in 5XFAD mice. Senescence-associated marker p16 can serve as an indicator to estimate the cognitive prognosis for AD population.

Objective: This study aimed to analyze and evaluate the diagnostic efficacy of Ishikawa's, the modified Ishikawa's criteria, 1990 American College of Rheumatology (ACR ) classification criteria and the diagnostic model based on Chinese population in Chinese TA patients., Methods: One hundred and forty-nine patients with Takayasu arteritis and 126 patients with other vascular disorders which involved aorta or its branches were recruited in this study.All the patients were admitted to the Department of rheumatism and Immunology clinic or inpatient department of Zhongshan Hospital affiliated to Fudan University from January 1(st), 2008 to June 31(st), 2015.General characteristics, clinical manifestations, laboratory results and imaging data of all the patients were collected.Sensitivity, specificity, accuracy and area under receiver operating characteristics (ROC) curve of different criteria were analyzed., Results: Sensitivity, specificity, accuracy and area under ROC curve of Chinese diagnostic model were 90.60%, 80.95%, 86.18%, and 85.80%, respectively, while those of Ishikawa criteria were 34.23%, 99.21%, 64.00%, and 66.70%, respectively.These four indicators of the modified Ishikawa criteria were 84.13%, 79.87%, 81.82%, and 82.00%, respectively and that of ACR criteria were 83.89%, 83.33%, 83.64%, and 83.60%, respectively.No significant difference was found between any two of Chinese diagnostic model, the modified Ishikawa criteria and ACR criteria in all the indicators.Sensitivity of Chinese diagnostic model was highest, while specificity of Ishikawa criteria was the highest.Among these four criteria, the diagnostic efficacy of Chinese model was the best and that of Ishikawa criteria was the worst., Conclusion: Chinese diagnostic model, which is based on Chinese population and adopts advanced imaging modality, has better diagnostic efficacy.

Background: Apolipoprotein E (ApoE) is a major lipid carrier that supports lipid transport and injury repair in the brain. The APOE ε4 allele is associated with depression, mild cognitive impairment (MCI) and dementia; however, the precise molecular mechanism through which ApoE4 influences the risk of disease development remains unknown. To address this gap in knowledge, we investigated the potential effects of chronic unpredictable mild stress (CUMS) on ApoE3 and ApoE4 target replacement (ApoE3-TR and ApoE4-TR) mice., Results: All ApoE-TR mice exposed to CUMS at 3 months old recovered from a depression-like state by the age of 12 months. Of note, ApoE4-TR mice, unlike age-matched ApoE3-TR mice, displayed impaired spatial cognitive abilities, loss of GABAergic neurons, decreased expression of Reelin, PSD95, SYN and Fyn, and reduced phosphorylation of NMDAR2B and CREB., Conclusion: These results suggest that early-life stress may mediate cognitive impairment in middle-age ApoE4-TR mice through sustained reduction of GABAergic neurons and Reelin expression, which might further diminish the activation of the Fyn/NMDAR2B signaling pathway.

The objective of this study was to evaluate a total parotidectomy performed through a face-lift incision integrated with a temporal fascia flap. We have accomplished a group of 40 cases of total parotidectomy from July 2008 to May 2013. Twenty-two cases accepted a modified performance which combined rhytidectomy incision with temporal fascia flap. The other 18 cases were fulfilled by Blair incision and no reconstruction of parotid bed as control. The patients were followed up every 6 months. In the interviews, the assessment of the operation from patients was recorded. The cosmetic gratification, presence or absence of gustatory flushing or sweating, and functional reversion of facial nerve and great auricular nerve were surveyed by 3 investigators. The criteria that integrated the subjective with objective items were stipulated for evaluation. Gustatory sweating had been identified in 0% and 44% of patients of the testing and control group, respectively. The average scale of the experimental and control group postoperatively was 7.89 and 5.93 individually. The difference of the average scale between testing and control group presented statistical significance. The author's technique is either aesthetically satisfying or efficacious to prevention of gustatory sweating in total parotidectomy.