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The global incidence of Mycobacterium abscessus (Mabc), a rapidly growing nontuberculous mycobacterial strain that causes treatment-refractory pulmonary diseases, is increasing. Despite this, the host factors that allow for protection against infection are largely unknown. In this study, we found that sirtuin 3 (SIRT3), a mitochondrial protein deacetylase, plays a critical role in host defense against Mabc infection. Mabc decreased SIRT3 and upregulated mitochondrial oxidative stress in macrophages. SIRT3 deficiency led to increased bacterial loads, histopathological, and mitochondrial damage, and pathological inflammation during Mabc infection. Administration of scavengers of mitochondrial reactive oxygen species significantly decreased the in vivo Mabc burden and excessive inflammation, and induced SIRT3 expression in infected lungs. Notably, SIRT3 agonist (resveratrol) significantly decreased Mabc growth and attenuated inflammation in mice and zebrafishes, indicating the key role for SIRT3 in metazoan host defense. Collectively, these data strongly suggest that SIRT3 is a host-directed therapeutic target against Mabc infection by controlling mitochondrial homeostasis.

We compared the efficacy and toxicity of busulfan and melphalan (BUMEL) and those of high-dose melphalan (HDMEL) as conditioning regimens for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) through a propensity score-matched analysis. No significant difference in the complete response and overall response rate after ASCT was observed between BUMEL and HDMEL. After a median follow-up of 37.3 months in the BUMEL group and 50.8 months in the HDMEL group, the median progression-free survival was calculated to be 32.9 months and 25.2 months ( p  = 0.995). With respect to non-hematologic toxicities, infections were more frequently reported in the BUMEL group ( p  < 0.001). Three patients who received BUMEL developed veno-occlusive disease (VOD), and all of them recovered without administration of defibrotide. In conclusion, BUMEL is an effective alternative conditioning regimen in terms of efficacy, but attention should be paid to toxicities.

Neovascular age-related macular degeneration (nAMD) is a common cause of irreversible vision loss in the elderly. Anti-vascular endothelial growth factor has been effective in treating pathological ocular neovascularization, but it has limitations including the need for repeated intraocular injections for the maintenance of therapeutic effects in most patients and poor or non-response to this agent in some patients. in vitro cellular studies were conducted using retinal pigment epithelial cell lines (ARPE-19 and hTERT-RPE1), human umbilical vein endothelial cells (HUVECs), and human umbilical vein smooth muscle cells (HUVSMCs). in vivo efficacy of ilimaquinone (IQ) was tested in laser-induced choroidal neovascularization mouse and rabbit models. Tissue distribution study was performed in male C57BL6/J mice. IQ, 4,9-friedodrimane-type sesquiterpenoid isolated from the marine sponge, repressed the expression of angiogenic/inflammatory factors and restored the expression of E-cadherin in retinal pigment epithelial cells by inhibiting the Wnt/β-catenin pathway. In addition, it selectively inhibited proliferation and tube formation of HUVECs by activating the p53 pathway. Topical and intraperitoneal administration of IQ significantly reduced choroidal neovascularization in rabbits and mice with laser-induced choroidal neovascularization. Notably, IQ by the oral route of exposure was highly permeable to the eyes and suppressed abnormal vascular leakage by downregulation of β-catenin and stabilization of p53 in vivo. Our findings demonstrate that IQ functions through regulation of p53 and Wnt/β-catenin pathways with conceivable advantages over existing cytokine-targeted anti-angiogenic therapies., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background and Aims: Wilson disease (WD) is caused by mutations in the copper transporter ATP7B, with its main pathology attributed to copper-mediated oxidative damage. The limited therapeutic effect of copper chelators and the early occurrence of mitochondrial deficits, however, undermine the prevalence of this mechanism., Methods: We characterized mitochondrial DNA copy number and mutations as well as bioenergetic deficits in blood from patients with WD and in livers of tx-j mice, a mouse model of hepatic copper accumulation. In vitro experiments with hepatocytes treated with CuSO 4 were conducted to validate in vivo studies., Results: Here, for the first time, we characterized the bioenergetic deficits in WD as consistent with a mitochondrial DNA depletion-like syndrome. This is evidenced by enriched DNA synthesis/replication pathways in serum metabolomics and decreased mitochondrial DNA copy number in blood of WD patients as well as decreased mitochondrial DNA copy number, increased citrate synthase activity, and selective Complex IV deficit in livers of the tx-j mouse model of WD. Tx-j mice treated with the copper chelator penicillamine, methyl donor choline or both ameliorated mitochondrial DNA damage but further decreased mitochondrial DNA copy number. Experiments with copper-loaded HepG2 cells validated the concept of a direct copper-mitochondrial DNA interaction., Conclusions: This study underlines the relevance of targeting the copper-mitochondrial DNA pool in the treatment of WD separate from the established copper-induced oxidative stress-mediated damage., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Dekkera anomala YAE-1 strain separated from "airag" (Mongolian fermented mare's milk) produces β-glucosidase, which can convert ginsenoside Rb 1 from Panax ginseng. Ginseng-derived bioactive components such as ginsenoside Rb 1 have various immunological and anticancer activities. Airag was collected from five different mare milk farms located near Ulaanbaatar, Mongolia. YAE-1 strains were isolated from airag to examine the hydrolytic activities of β-glucosidase on Korean Panax ginseng using an API ZYM kit. Supernatants of selected cultures having β-glucosidase activity were examined for hydrolysis of the major ginsenoside Rb 1 at 40°C, pH 5.0. The YAE-1 strain was found to be nearly identical at 99.9% homology with Dekkera anomala DB-7B, and was thus named Dekkera anomala YAE-1. This strain exerted higher β-glucosidase activity than other enzymes. Reaction mixtures from Dekkera anomala YAE-1 showed great capacity for converting ginsenoside Rb 1 to ginsenoside Rd. The β-glucosidase produced by Dekkera anomala YAE-1 was able to hydrolyze ginsenoside Rb 1 and convert it to Rd during fermentation of the ginseng. The amount of ginsenoside Rd was highly increased from 0 to 1.404 mg/ml in fermented 20% ginseng root at 7 days.

Background: Steep posterior tibial slope (PTS) and excessive anterior tibial translation (ATT) have been identified as important anatomic risk factors for anterior cruciate ligament (ACL) injury, which have raised concerns about clinical outcomes after primary ACL reconstruction (ACLR)., Purpose: To investigate anatomic risk factors of primary ACLR failure and to determine the cutoff values of PTS and ATT for predicting primary ACLR failure., Study Design: Case-control study; Level of evidence, 3., Methods: Between November 2015 and May 2017, a total of 215 consecutive patients with clinically diagnosed noncontact ACL injuries who underwent primary anatomic ACLR were retrospectively analyzed. Among them, 25 patients who showed complete discontinuity of ACL fibers on final follow-up magnetic resonance imaging scans were allocated into the failure group (study group). They were matched 1:2 to 50 control participants who showed clear and continuous ACL fibers on magnetic resonance imaging scans (control group). PTS and ATT were measured on preoperative weightbearing whole leg lateral radiographs and compared between the groups. The cutoff values of PTS and ATT for predicting primary ACLR failure were determined by the receiver operating characteristic curve. Moreover, predictors of primary ACLR failure were assessed by multivariate logistic regression analysis, including sex, age, body mass index, concomitant meniscal tears, degree of pivot-shift test, and KT-1000 arthrometer side-to-side difference, PTS, and ATT., Results: PTS and ATT values in the study group were significantly higher than those in the control group (mean ± SD: PTS, 17.2°± 2.2° vs 14.4°± 2.8°; ATT, 8.3 ± 3.4 mm vs 4.1 ± 3.1 mm; P < .001). The cutoff values of PTS and ATT for predicting primary ACLR failure were 17° (sensitivity, 66.7%; specificity, 90.9%) and 6 mm (sensitivity, 87.5%; specificity, 79.5%), respectively. Additionally, PTS ≥17° (odds ratio, 15.6; 95% CI, 2.7-91.5; P = .002) and ATT ≥6 mm (odds ratio, 9.9; 95% CI, 1.9-51.4; P = .006) were determined to be risk factors of primary ACLR failure, whereas sex, age, body mass index, concomitant meniscal tears, degree of the pivot-shift test, and KT-1000 arthrometer side-to-side difference were not., Conclusion: In this study, PTS ≥17° and ATT ≥6 mm, as measured on weightbearing whole leg radiographs, were identified to be predictive risk factors of primary ACLR failure. This study adds to the existing knowledge about potential surgical indications of simultaneous slope-reducing high tibial osteotomy to mitigate the primary ACLR failure rate.

Background: Galectin-3 may predict mortality for patients with aortic stenosis (AS) after transcatheter aortic valve replacement (TAVR). However, the results were inconsistent. We aimed to evaluate the association between baseline galectin and mortality after TAVR in a meta-analysis., Methods: Related follow-up studies were obtained by systematic search of PubMed, Cochrane's Library, and Embase databases. Both the fixed- and the random-effect models were used for the meta-analysis. Subgroup analyses were performed to evaluate the influences of study characteristics on the outcome., Results: Five prospective cohort studies with 854 patients were included, with a follow-up period between 1 and 1.9 years. Patients with higher baseline circulating galectin-3 had an increased risk of all-cause mortality after TAVR (random-effects model: risk ratio [RR]: 1.63, 95% confidence interval [CI]: 1.19-2.23, P=0.002; fixed-effects model: RR: 1.62, 95% CI: 1.19-2.20, P=0.002; I2 = 4%). Adjustment of estimated glomerular filtration rate (RR: 1.73, P=0.02) or B-type natriuretic peptide (BNP) or N-terminal pro-BNP (RR: 1.83, P=0.02) did not significantly affect the result. A trend of stronger association between higher baseline circulating galectin-3 and increased risk of all-cause mortality after TAVR was observed in studies with an enzyme-linked fluorescent assay (ELFA) (RR: 3.04, P=0.003) compared with those with an enzyme-linked immunosorbent assay (ELISA) (RR: 1.42, P=0.04; P for subgroup difference =0.06)., Conclusion: Higher circulating galectin-3 before the procedure may predict all-cause mortality of AS patients after TAVR., (© 2020 The Author(s).)

The hypoglycemic drug GLP-1 receptor agonist can ameliorate hepatic steatosis but the mechanism is not clear. Intake of high fructose leads to non-alcoholic fatty liver disease by stimulating lipid synthesis, and β-catenin is the key molecule for realizing GLP-1 function in extrahepatic tissues; with the discovery of GLP-1 receptor in liver, we speculate that β-catenin might mediate GLP-1 receptor agonist on ameliorating hepatic steatosis induced by high fructose. Wistar rats were fed with high fructose diet for 8 weeks and then treated with GLP-1 receptor agonist exenatide for 4 weeks; the changes of lipid synthesis pathway factors, the expression and nuclear translocation of β-catenin, and the hepatic steatosis of the rats were observed. After the intervention of exenatide, the hepatic steatosis induced by high fructose was improved, the nuclear translocation and expression of β-catenin were facilitated, and the mRNA and protein expression of the upstream regulator SREBP-1 and the downstream key enzymes ACC, FAS and SCD-1 of de novo lipogenesis were down-regulated. GLP-1 receptor agonist may ameliorate hepatic steatosis induced by high fructose by β-catenin regulating de novo lipogenesis pathway. GLP-1 receptor agonist may be a potential new drug for the treatment of non-alcoholic fatty liver disease, and the β-catenin may be an important target for the drug therapy.

CGK012 is a newly synthesized pyranocoumarin substance suppressing the activation and transcription of β-catenin related to Wnt3a-CM. A bioanalytical method for CGK012 was developed and validated in rat plasma, and the method was applied to determine the plasma concentrations after intravenous administration. Plasma was cleaned-up by protein precipitation by acetonitrile including an internal standard. The substances were separated on a reversed-phase column, and the mobile phase was a mixture of water and acetonitrile (3:7, v/v; 0.1 % formic acid). The mass transition occurred at m/z 358.2→229.2 for CGK012 [M+H] + . CGK012 was stable in the various conditions, and the present assay met the criteria of bioanalytical method validation. CGK012 bi-exponentially decayed with the half-life of 4.0 h at the terminal phase. Mean V d and clearance were 0.69 L/kg and 1.31 L/h/kg, respectively. This is the first bioanalytical method developed for quantification of CGK012 in rat plasma using LC-MS/MS, which would be useful to examine pharmacokinetic study of the substance., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Recently, the endothelial Activation and Stress Index (EASIX) score has been reported to predict overall survival (OS) after allogeneic stem cell transplantation. This study evaluated the prognostic role of EASIX score in patients with newly diagnosed multiple myeloma (MM)., Methods: This retrospective study analyzed the records of 1177 patients with newly diagnosed MM between February 2003 and December 2017 from three institutions in the Republic of Korea. Serum lactate dehydrogenase (LDH), creatinine, and platelet count at diagnosis were measured in all included patients. EASIX scores were calculated using the formula-LDH (U/L) × Creatinine (mg/dL) / platelet count (10 9 /L) and were evaluated based on log2 transformed values., Results: The median age of patients was 63 years (range, 22-92), and 495 patients (42.1%) underwent autologous stem cell transplantation (ASCT). The median log2 EASIX score at diagnosis was 1.1 (IQR 0.3-2.3). Using maximally selected log-rank statistics, the optimal EASIX cutoff value for OS was 1.87 on the log2 scale (95% CI 0.562-0.619, p < 0.001). After median follow-up for 50.0 months (range, 0.3-184.1), the median OS was 58.2 months (95% CI 53.644-62.674). Overall, 372 patients (31.6%) showed high EASIX scores at diagnosis, and had significantly inferior OS compared to those with low EASIX (log2 EASIX ≤1.87) (39.1 months vs. 67.2 months, p < 0.001). In multivariate Cox analysis, high EASIX was significantly associated with poor OS (HR 1.444, 95% CI 1.170-1.780, p = 0.001). In the subgroup analysis of patients who underwent ASCT, patients with high EASIX showed significantly inferior OS compared to those with low EASIX (52.8 months vs. 87.0 months, p < 0.001). In addition, in each group of ISS I, II, and III, high EASIX was associated with significantly inferior OS (ISS 1, 45.2 months vs. 76.0 months, p = 0.001; ISS 2, 42.3 months vs. 66.5 months, p = 0.002; ISS 3, 36.8 months vs. 55.1 months, p = 0.001)., Conclusion: EASIX score at diagnosis is a simple and strong predictor for OS in patients with newly diagnosed MM.

Objective: Exosomes have been documented to function in human diseases, yet their transfer of microRNA (miRNA) in preeclampsia (PE) has seldom been reported. This study intends to discuss the role of miR-133b derived from exosomes in human umbilical cord mesenchymal stem cells (hUC-MSCs) in trophoblast cell development in PE., Methods: Placentas from PE patients and normal pregnant women were collected. The hUC-MSCs and their exosomes were obtained and identified. Trophoblast cell HPT-8 and HTR8-S/Vneo were obtained and co-cultured with hUC-MSCs-derived exosomes that had been transfected with different miR-133b plasmids. MiR-133b and glucocorticoid-regulated kinase 1 (SGK1) expression in placental tissues and HPT-8 and HTR8-S/Vneo cells was determined. HTR8-S/Vneo and HPT-8 cell proliferation, cell cycle distribution, apoptosis rate, migration and invasion were detected., Results: MiR-133b was down-regulated and SGK1 was up-regulated in placental tissues of PE patients. MiR-133b expression was inversely related to SGK1 expression in HTR8-S/Vneo and HPT-8 cells co-cultured with hUC-MSC-derived exosomes. Exosomes promoted HTR8-S/Vneo and HPT-8 cell proliferation, migration and invasion abilities, cell cycle entry and inhibited apoptosis. Elevated exosome-derived miR-133b from hUC-MSCs boosted HTR8-S/Vneo and HPT-8 cell proliferation, cell cycle progression, migration and invasion and limited cell apoptosis. MiR-133b targeted SGK1., Conclusion: Collectively, we demonstrate that miR-133b is down-regulated and SGK1 is up-regulated in PE, and miR-133b derived from exosomes in hUM-MSCs facilitates trophoblast cell proliferation, migration and invasion in PE via constraining SGK1.

Since the introduction of an alkylator to the treatment of multiple myeloma (MM), new effective agents have been developed, such as immunomodulatory drugs including thalidomide, lenalidomide, and pomalidomide; proteasome inhibitors including bortezomib, carfilzomib, and ixazomib; monoclonal antibodies including daratumumab and elotuzumab; and deacetylase inhibitors including panobinostat. Numerous regimens with these new agents have been developed and they have contributed in improving survival outcomes in MM patients. In addition, the recommended therapies for newly diagnosed MM change every year based on the results of clinical trials. This review will discusses the appropriate induction therapies based on recent clinical trials for patients with newly diagnosed MM.

The chemical and local structures of vanadium oxide (VO x ) thin films prepared by atomic layer deposition (ALD) were investigated by soft X-ray absorption spectroscopy. It is shown that the as-deposited film was a mixture of VO 2 and V 2 O 5 in disordered form, while the chemistry changed significantly after heat treatment, subject to the different gas environment. Forming gas (95% N 2 + 5% H 2 ) annealing resulted in a VO 2 composition, consisting mostly of the VO 2 (B) phase with small amount of the VO 2 (M) phase, whereas O 2 annealing resulted in the V 2 O 5 phase. An X-ray circular magnetic dichroism study further revealed the absence of ferromagnetic ordering, confirming the absence of oxygen vacancies despite the reduction of V ions in VO 2 (V 4+ ) with respect to the precursor used in the ALD (V 5+ ). This implies that the prevalence of VO 2 in the ALD films cannot be attributed to a simple oxygen-deficiency-related reduction scheme but should be explained by the metastability of the local VO 2 structures., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

There are still controversies about the use of interim positron emission tomography/computed tomography (PET/CT) in indolent non-Hodgkin lymphoma due to the variable fluorodeoxyglucose (FDG) avidity. Therefore, this study aimed to evaluate the roles of interim PET/CT in marginal zone lymphoma (MZL), a representative indolent lymphoma. We analyzed the data of 146 MZL patients. All were treated with rituximab-containing immunochemotherapy. Interim PET/CT scan was performed after 2-3 cycles of therapy, and the response was assessed using the Deauville 5-point scales (5-PS) and a semi-quantitative assessment using the SUVmax reduction rate (ΔSUVmax). Progression-free survival (PFS) was well stratified according to a visual assessment of interim PET/CT using 5-PS (p < 0.001). Particularly, there was a significant difference in PFS between patients with interim score 1-2 and those with score 3. However, ΔSUVmax did not predict the survival outcome using 59.8% of the optimal cutoff value. In the multivariate analysis, failure to achievement of grade 1-2 in interim PET/CT was significantly associated with inferior PFS (HR, 2.154; 95% CI 1.071-4.332; p = 0.031). The interim PET/CT response based on the 5-PS is useful for predicting PFS of patients with MZL in the post-rituximab era.

Background/aim: The present study retrospectively investigated the predictive accuracy of interim positron emission tomography/computed tomography (iPET/CT) based on the Deauville 5-point scale (5-PS) and a quantitative SUV-based assessment in patients with extranodal (EN) diffuse large B cell lymphoma (DLBCL)., Patients and Methods: The Deauville 5-PS and the SUVmax reduction (ΔSUVmax) assessment for interpreting the response to iPET/CT were used., Results: A total of 163 patients were enrolled in this study. With a median follow-up of 52.5 months, ΔSUVmax successfully predicted the survival outcomes of patients with one extranodal (EN) involvement in terms of overall survival (OS) (p=0.012) and progression-free survival (PFS) (p<0.001). Visual assessment using the Deauville 5-PS did not predict survival outcomes in patients with one or more EN involvements in terms of OS and PFS., Conclusion: The quantitative SUV-based assessment with iPET/CT was a significant prognosticator for long-term survival outcomes, especially in patients with one EN involvement., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The development of heterotopic ossification (HO) might nullify any benefit of multiple-ligament reconstruction of the knee joint. The purpose of this study was to investigate the incidence and the specific explanatory factors for the development of HO after multiple-ligament reconstruction of the knee joint., Methods: From January 2011 to June 2016, 72 consecutive patients with knee dislocations received multiple-ligament reconstructions, of which 57 (79%) were available for a minimum follow up of 12 months and were included in this study. Anteroposterior (AP) and lateral radiographs were reviewed for all patients. This knee dislocation cohort was separated into two groups based on the presence or absence of HO for comparisons. In addition, the HO group was divided into three subgroups based on a modified quadrant grading system introduced by the senior author for further evaluation. Multivariate logistic regression analysis was then performed to identify specific explanatory factors predicting development of HO in patients after multiple-ligament reconstructions of the knee joint., Results: Among the 72 consecutive patients, 57 (79%) were available for the clinical evaluations with an average period of 28.4 months (range, 12-51 months). Twenty-one patients (37%) showed radiological evidence of HO. The HO group (n = 21) showed significantly inferior results of knee flexion angle compared with the non-HO group (n = 36) (HO group vs. non-HO group: 124 ± 13° vs. 132 ± 5°; P<0.01). According to the quadrant grading system, there were seven patients with grade I, nine with grade II, and five with grade III HO. Subgroup analysis further revealed that higher HO grade would lead to lower knee flexion angle. In addition, multivariate regression analysis showed that concomitant posterior cruciate ligament reconstruction was the only independent explanatory factor predicting the development of HO after multiple-ligament reconstruction of the knee joint (P=0.018; odds ratio, 8.75; 95% confidence interval, 1.69-39.7)., Conclusion: In this cohort of knee dislocations, the incidence of HO development following multiple-ligament reconstruction was 37%, with grade III HO showing the most inferior range of motion outcome. Moreover, concomitant posterior cruciate ligament reconstruction was the only independent predictor for the development of HO., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To investigate the effects of Composition of Ophiopogon polysaccharide, Notoginseng total saponins and Rhizoma Coptidis alkaloids (CONR) on myocardial apoptosis of diabetic atherosclerosis (DA) rabbits METHODS: Sixty male New Zealand white rabbits were randomly divided into 6 groups [control group, model group, CONR high-dose group (450 mg/kg), CONR medium-dose group (150 mg/kg), CONR low-dose group (50 mg/kg), and simvastatin group] by using a completely random method, 10 in each group. DA model was established by intravenously injected alloxan combined with high-fat diet and abdominal aortic balloon injury. After mediation for 10 weeks, fasting blood glucose (FBG), glycosylated hemoglobin (GHB), glycosylated serum protein (GSP), fructoseamine (FRA), aldose reductase (AR), advanced glycation end products (AGEs) in serum were measured by enzyme linked immunosorbent assay (ELISA) method; the expression of receptor of AGEs (RAGE) in myocardial tissue were observed by immunohistochemical method; and p-Jun N-terminal kinase (p-JNK), caspase-3, B-cell lymphoma-2 (bcl-2) protein expression in myocardial tissue were measured by Western blotting. The myocardial apoptosis was detected by TdT-mediated dUTPnick-end labeling (TUNEL) method, and apoptosis index (AI) was calculated., Results: Compared with the control group, serum FBG, GHB, GSP, FRA, AR, AGEs and the expression of myocardium RAGE, p-JNK, caspase-3 proteins, as well as apoptosis index (AI) were significantly increased and bcl-2 protein was significantly decreased in the model group (P<0.01). Compared with the model group, the levels of serum FBG, GHB, GSP, FRA and AR showed a significant decline in CONR high- and medium-dose groups (P<0.01). FBG and GHB showed a significant decline in CONR low-dose group (P<0.01). Compared with the model group, the expression of serum AGEs and myocardium RAGE, p-JNK and caspase-3 protein as well as AI were significantly decreased and bcl-2 protein was significantly up-regulated in all treatment groups (P<0.01); high-dose CONR had the most significant effect on abovementioned indices compared with other treatment groups (P<0.01). Middle-dose CONR had better effect on serum AGEs compared with the low-dose group (P<0.01); middle-dose CONR and simvastatin groups had better effect on the expression of caspase-3, bcl-2 protein, myocardium apoptosis compared with the CONR low-dose group (P<0.01)., Conclusion: CONR may effectively inhibit myocardial apoptosis on DA rabbits by intervening AGEs-RAGE and JNK, caspase-3, and bcl-2 protein expressions.

Background: Anterior tibial subluxation (ATS) in extension after anterior cruciate ligament (ACL) injury highlights an increased anterior position of the tibia relative to the femur. Recent studies demonstrated that subluxation is sometimes irreducible and the normal tibiofemoral relationship is not restored by ACL reconstruction (ACLR), which raises concerns regarding clinical outcomes after ACLR., Hypothesis: Excessive preoperative ATS in extension is associated with inferior knee stability after anatomic ACLR., Study Design: Cohort study; Level of evidence, 3., Methods: From March 2016 to January 2017, a total of 487 consecutive patients with clinically diagnosed noncontact ACL injuries who underwent primary anatomic ACLR were retrospectively analyzed. Of these patients, 430 met the criteria for inclusion in this study. Anterior subluxation of the lateral and medial compartments (ASLC and ASMC) in extension relative to the femoral condyles was measured on preoperative magnetic resonance imaging. Twenty patients (study group) who demonstrated excessive (>10 mm) ASLC and ASMC in extension were matched 1:2 to 40 participants (control group) who showed minimal or no (<3 mm) ASLC and ASMC in extension. The amount of ASLC and ASMC in extension relative to the femoral condyles at 2 years postoperatively was the primary outcome. Moreover, the Lysholm score, IKDC grade (International Knee Documentation Committee), and stability assessments (pivot-shift test and KT-1000 arthrometer side-to-side difference) were evaluated preoperatively and at the last follow-up visit., Results: The preoperative mean ASLC and ASMC in extension of the study group were both significantly larger than those of the control group (study group vs control group: ASLC, 13.5 mm vs 1.2 mm; ASMC, 12.4 mm vs 1.0 mm; P < .05). Moreover, patients in the study group showed significantly larger posterior tibial slope than the patients in the control group (17.8°± 2.5° vs 9.5°± 1.5°; P < .05). At the final follow-up visit, the mean ASLC and ASMC of the study group were 8.1 mm and 7.3 mm, which were significantly larger than those of the control group (ASLC, 0.9 mm; ASMC, 0.7 mm; P < .05). In addition, the study group showed inferior knee stability when compared with the control group in terms of both the pivot-shift test (study group vs control group: 2 grade 2, 10 grade 1, and 8 grade 0 vs 1 grade 1 and 39 grade 0; P < .05) and the KT-1000 arthrometer side-to-side difference (study group vs control group: 4.4 ± 1.2 mm vs 1.5 ± 0.6 mm; P < .05). Furthermore, the study group showed significantly lower mean Lysholm score (study group vs control group: 80.3 ± 6.3 vs 93.3 ± 4.3, P < .05) and IKDC grading results (study group vs control group: 3 grade C, 16 grade B, and 1 grade A vs 3 grade B and 37 grade A; P < .05) as compared with the control group., Conclusion: In this short-term study, the excessive (>10 mm) preoperative ATS in extension after ACL injury was associated with inferior knee stability after anatomic ACLR.

Background: The lateral meniscus posterior root (LMPR) lesion further decreases dynamic knee stability after anterior cruciate ligament (ACL) injury owing to the loss of the "wedge effect" maintained by the posterior horn of the lateral meniscus. However, the effect of LMPR lesions on the static tibiofemoral relationship in extension after ACL injuries is not determined., Purpose: To (1) determine the effect of LMPR lesions on anterior tibial subluxation of the lateral compartment (ATSLC) in extension in patients with ACL injuries and to (2) identify the LMPR-related factors associated with excessive ATSLC in extension., Study Design: Cohort study; Level of evidence, 3., Methods: Between January 2015 and December 2017, 405 consecutive patients with diagnosed ACL injuries who underwent primary ACL reconstructions were retrospectively reviewed. Among them, 45 patients with combined ACL injuries and LMPR lesions (ACL+LMPR group) and 51 patients with isolated ACL injuries (ACL group) were identified. Values of ATSLC in extension were measured on preoperative supine magnetic resonance imaging and classified into high grade (≥6 mm) and low grade (<6 mm). The mean ATSLC in extension and the proportion of patients with high-grade ATSLC in extension were compared between the groups by univariate analysis. In the ACL+LMPR group, predictors of high-grade ATSLC in extension-including age, sex, body mass index, affected side, cause of injury, period from injury (<12 or ≥12 weeks), LMPR lesion pattern (radial tear or root avulsion), and meniscofemoral ligament integrity (intact or impaired)-were assessed by univariate analysis and multivariate logistic regression analysis., Results: The mean ATSLC in extension in the ACL+LMPR group was significantly greater than that in the ACL group (5.6 mm vs 3.1 mm; P = .001). The proportion of patients with high-grade ATSLC in extension in the ACL+LMPR group was also significantly larger than that in the ACL group (44.4% vs 15.7%; P = .002). In addition, the root avulsion (instead of radial tear) (odds ratio, 28.750; 95% CI, 2.344-352.549; P = .009) and the period from injury ≥12 weeks (odds ratio, 17.095; 95% CI, 1.207-242.101; P = .036) were determined to be the 2 independent predictors of high-grade ATSLC in extension. However, age, sex, body mass index, affected side, cause of injury, and meniscofemoral ligament integrity were not., Conclusion: After ACL injuries, concomitant LMPR lesion further increased ATSLC in extension. Chronic LMPR avulsion was associated with high-grade ATSLC in extension.

Black ginseng (BG), which is ginseng that has been steamed and dried nine times, and its main protopanaxatriol-type ginsenosides Rg4, Rg6, Rh4, and Rg2 have been reported to exhibit various forms of biological activity, including antiseptic, antidiabetic, wound-healing, immune-stimulatory, and anti-oxidant activity. The aim of the this study was to examine the effects of [Formula: see text] (a rare protopanaxatriol-type ginsenoside fraction; Rg2, Rg4, Rg6, Rh1, and Rh4) on heme oxygenase-1 (HO-1) induction and on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-)2 in lipopolysaccharide (LPS)-activated human pulmonary artery endothelial cells (HPAECs). [Formula: see text] was tested to determine its effect on iNOS protein expression and inflammatory markers (interleukin [IL]-1[Formula: see text] and tumor necrosis factor [TNF]-[Formula: see text] in the lung tissue of LPS-treated mice. The results showed that [Formula: see text] induced the expression of HO-1, reduced LPS-activated NF-[Formula: see text]B-luciferase activity, and inhibited iNOS/NO and COX-2/PGE2, which contributed to the inhibition of STAT-1 phosphorylation. In particular, [Formula: see text] induced the translocation of Nrf2 from the cytosol to the nucleus by increasing Nrf2-ARE activity and decreased IL-1[Formula: see text] production in LPS-activated HPAECs. This reduction in iNOS/NO expression due to [Formula: see text] was reversed by siHO-1 RNA transfection. In LPS-treated mice, [Formula: see text] significantly reduced lung tissue iNOS protein levels and TNF-[Formula: see text] levels in the bronchoalveolar lavage fluid. In conclusion, these findings indicate that [Formula: see text] has a critical anti-inflammatory effect due to its ability to regulate iNOS via the inhibition of p-STAT-1 and NF-[Formula: see text]B, and thus it may be suitable for the treatment of inflammatory disease.

Plant steroid hormones brassinosteroids (BRs) regulate plant growth and development at many different levels. Recent research has revealed that stress-responsive NAC (petunia NAM and Arabidopsis ATAF1, ATAF2, and CUC2) transcription factor RD26 is regulated by BR signaling and antagonizes BES1 in the interaction between growth and drought stress signaling. However, the upstream signaling transduction components that activate RD26 during drought are still unknown. Here, we demonstrate that the function of RD26 is modulated by GSK3-like kinase BIN2 and protein phosphatase 2C ABI1. We show that ABI1, a negative regulator in abscisic acid (ABA) signaling, dephosphorylates and destabilizes BIN2 to inhibit BIN2 kinase activity. RD26 protein is stabilized by ABA and dehydration in a BIN2-dependent manner. BIN2 directly interacts and phosphorylates RD26 in vitro and in vivo. BIN2 phosphorylation of RD26 is required for RD26 transcriptional activation on drought-responsive genes. RD26 overexpression suppressed the brassinazole (BRZ)  insensitivity of BIN2 triple mutant bin2 bil1 bil2, and BIN2 function is required for the drought tolerance of RD26 overexpression plants. Taken together, our data suggest a drought signaling mechanism in which drought stress relieves ABI1 inhibition of BIN2, allowing BIN2 activation. Sequentially, BIN2 phosphorylates and stabilizes RD26 to promote drought stress response., (© 2019 The Authors The Plant Journal © 2019 John Wiley & Sons Ltd.)

Background: To describe a novel 'four-in-one' procedure - including tibial tubercle proximalization, extensive lateral release, tibial tubercle medialization, and medial patellofemoral ligament reconstruction - for treating severe habitual patellar dislocation (HPD) in adults, and to report its early clinical outcomes., Methods: Thirteen patients (13 knees) with severe primary HPD received this procedure. Results of the physical examinations, including apprehension tests and patellar tracking throughout full range of motion, were recorded pre-operatively and at final follow-up. Radiological assessments included standard anteroposterior view, true lateral view at 30° knee flexion, axial views of the patellofemoral joint at both 30° and maximum angle of knee flexion, and computed tomography scans at full knee extension pre-operatively and at final follow-up. Subjective patellofemoral functions were evaluated with the Kujala functional score before the index procedure and at final follow-up visit., Results: All 13 patients were followed for an average period of 35.5 months (range, 25-49). After the index 'four-in-one' procedure no patient reported reoccurrence of patellar dislocation at the final follow-up visit. Radiographically, there was a statistically significant improvement in the congruence angle from 75.2 ± 16.3° pre-operatively to -7.2 ± 5.4° postoperatively (P < 0.01) and in the lateral patellofemoral angle from -66.3 ± 8.3° pre-operatively to 6.3 ± 2.6° postoperatively (P < 0.01). The average pre-operative Kujala functional score was 41.4 and average postoperative score was 94.9 (P < 0.05)., Conclusion: The novel 'four-in-one' procedure effectively treated HPD in adults with severe quadriceps contracture., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: To assess the validity of using the calibration ruler for correcting magnification of linear measurements and to explore and compare the vertical and horizontal magnification of four digital cephalometric units., Methods: An acrylic box was imaged at seven sagittal positions using four digital cephalometric units: Orthopantomograph OC100, Orthopantomograph OC200, Sirona Orthophos CD, and Sirona Orthophos DS. The true linear lengths of the phantom, corrected, and uncorrected linear lengths on the images were measured and compared. The validity of measurements using the calibration ruler was assessed. The magnification values and distortion indices were calculated and compared among the four cephalometric units., Results: For linear measurements on the mid-sagittal plane and averaged linear measurements on bilateral symmetric sagittal planes, the bias 1.96 STD of the calibration ruler ranged from 1% to 2% for the four cephalometric testing units. For linear measurements on the single lateral sagittal plane, the bias 1.96 STD ranged from 3% to 6%. The vertical scanning charge-coupled device cephalometric unit produced the greatest distortion, ranging from 1.029 to 0.964., Conclusion: The metal millimeter calibration ruler is an accurate reference for linear measurement magnification correction. Because of unpredictability and machine specificity, the magnification and distortion of a cephalometric unit should be calibrated for the estimation of cephalometric measurement error., Competing Interests: None

Background: Little information about the prevalence of gastrointestinal parasites in yaks (Bos grunniens) in northwest China is available. Therefore, the objective of the study was to quantify faecal egg counts of gastrointestinal parasites (helminths and coccidia) in free-range yaks from Gannan Tibetan Autonomous Prefecture, Gansu Province, Northwest China., Results: Parasites were detected in 290 of 733 (39.56%) faecal samples. The results showed that Strongylidae, Trichuris spp. and Eimeria spp. were detected all year round, Strongyloides papillosus was detected in autumn and summer, and Nematodirus spp. was detected in both autumn and spring. In contrast, Fasciola spp. was only detected in spring. The prevalence rates of parasitic infections in different seasons were significantly different., Conclusions: To our knowledge, this is the first investigation of gastrointestinal parasites in yaks (Bos grunniens) in Gansu, China. The results demonstrated a high prevalence of gastrointestinal parasitic infections, specifically GN infections, in yaks in GTAP and these infections can cause economic losses to the local cattle industry.

Objective: Resveratrol (RSV) is a polyphenolic phytoalexin that exhibits diverse pharmacological actions, including its effect on the insulin resistance. However, the mechanism through which RSV improves insulin resistance is not fully understood yet. The aim of this study was to determine the mechanism through which RSV ameliorates insulin resistance in skeletal muscle of high-fat diet (HFD)-induced mouse model, as well as palmitic acid (PA) treated L6 cells, with a specific focus on the response of RSV on fatty acid oxidation., Materials and Methods: Male C57BL6/J mice were randomly divided into three groups: normal diet-fed mice (ND), the high-fat diet-fed mice (HFD), HFD supplemented with RSV (100 mg/kg body weight [BW]/day orally; n = 10). Fasting plasma glucose, insulin, total cholesterol, triglyceride (TG), and free fatty acid levels were determined. The intraperitoneal glucose tolerance test was used to measure blood glucose and area under the curve. The quantitative insulin sensitivity index was calculated to assess insulin resistance. Skeletal muscles were collected for histology study and protein expression measurement. L6 cells were cultured with PA and the glucose concentration in the culture medium, and the intracellular TG levels were tested. RSV, chloroquine, palmitoyltransferase and Ku-55933 were administered to differentiate L6 cells., Results: The HFD fed mice showed increased BW, hyperglycemia, and hyperlipidemia. The expressions of ataxia telangiectasia mutated (ATM), 5' adenosine monophosphate-activated protein kinase (AMPK), carnitine palmitoyltransferase 1, cytochrome oxidase subunit IV protein were significantly decreased in the skeletal muscles of HFD fed mice and PA-treated L6 cells. All these effects induced by HFD and PA were reversed by RSV treatment., Conclusions: ATM is a key factor to improve HFD-induced lipid metabolism and insulin resistance in skeletal muscles. The effects of RSV on ameliorating HFD-induced abnormal lipid metabolism and insulin resistance mediated through ATM-AMPK pathway may due to its improvement in fatty acid oxidation efficiency and sequential reduction in ROS production in skeletal muscle. These results provide important theoretical evidence for the application of RSV in the prevention and treatment of diabetes mellitus and related metabolic diseases.

Purpose: Periostin is a secreted extracellular matrix protein that is strongly associated with triglyceride metabolism, chronic inflammation, and insulin resistance. Growing evidence suggests that there is a link between periostin and ovarian function. Our aim was to ascertain whether circulating periostin levels are altered in women with polycystic ovary syndrome (PCOS) and to further explore the relationship between periostin and glucose metabolism disorder in PCOS patients., Methods: In total, 50 women with PCOS and 30 age-matched controls without PCOS were recruited for this cross-sectional study. Periostin levels were measured using ELISA as well., Results: Circulating periostin levels were significantly elevated in PCOS women compared with controls [4206.75(222.00, 4815.25) vs. 430.75(142. 13, 730.86) ng/ml, P=0. 005]. Spearman's correlation analysis showed that serum periostin levels had a positive correlation with body mass index (BMI), uric acid, homeostasis model assessment of insulin resistance (HOMA-IR), high-sensitive C reactive protein (hs-CRP), and a negative correlation with insulin sensitivity index (ISI). Logistic regression models revealed that PCOS was correlated with waist to hip ratio (WHR), fasting blood glucose (FBG), and periostin levels. In addition, multivariate linear regression analyses showed that FBG, HOMA-IR, and the lipid accumulation index (LAP) were independent factors influencing serum periostin levels., Conclusion: PCOS is associated with elevated levels of periostin., Competing Interests: No conflict of interest has been declared by the authors., (© Georg Thieme Verlag KG Stuttgart · New York.)

CXC chemokine receptor 7 (CXCR7) is highly expressed in various type of cancers and promotes cancer progression and metastasis. However, the biological role and regulation of CXCR7 in gastric cancer remains unclear, and little is known about compounds that modulate CXCR7. Here, we investigated the role of CXCR7 in gastric tumorigenesis, and the effects of decursin, which is derived from Angelica gigas Nakai, on CXCR7. Our results showed that CXCR7 significantly promoted growth of gastric cancer cells and increased migration and invasion, which was mediated by the STAT3/c-Myc pathway. We also confirmed that decursin had an antitumor effect through down-regulating the expression of CXCR7 in gastric cancer. Furthermore, apoptotic cell death was induced through the reduction of anti-apoptotic factors such as Bcl-2 in vitro and in vivo . Our findings show that CXCR7 in gastric cancer promotes cancer progression through the STAT3/c-Myc pathway and that decursin is a natural compound that may target CXCR7 in gastric cancer treatment., Competing Interests: None., (AJCR Copyright © 2019.)

Introduction: To evaluate efficacy and safety data of dulaglutide in Chinese patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with 1-2 oral antihyperglycemic medications (OAMs)., Methods: This is a subgroup analysis of a phase 3, open-label, randomized, parallel-arm, 52-week study in Chinese patients aged ≥ 18 years with T2DM who had inadequate glycemic control with OAMs (glycated hemoglobin [HbA1c] ≥ 7.0% and ≤ 11.0%). The primary endpoint was assessment of the noninferiority of dulaglutide 1.5 mg as measured by change in HbA1c, compared with insulin glargine (glargine), using a 0.4% noninferiority margin at week 26., Results: A total of 607 patients from China were randomized 1:1:1 to once-weekly dulaglutide 1.5 or 0.75 mg or once-daily glargine. At week 26, the least squares mean (LSM) change from baseline in HbA1c was greater with dulaglutide 1.5 mg (- 1.67%) and dulaglutide 0.75 mg (- 1.31%) compared with glargine (- 1.11%). The LSM (95% confidence interval) for the difference of dulaglutide 1.5 mg and 0.75 mg vs glargine was - 0.56% (- 0.75 to - 0.37) and - 0.20% (- 0.39 to - 0.01), respectively. Both doses of dulaglutide were noninferior and superior to glargine at 26 weeks and 52 weeks (two-sided P value < 0.05). The mean body weight decreased (P < 0.001) and total hypoglycemia rates were lower (P < 0.05) in the dulaglutide groups compared with the glargine group. Gastrointestinal adverse events (AEs) were the most frequently reported AEs in dulaglutide groups., Conclusion: Both doses of dulaglutide are efficacious and tolerable in Chinese patients with T2DM who had inadequate glycemic control on OAMs., Trial Registration: ClinicalTrials.gov identifier, NCT01648582., Funding: Eli Lilly and Company.

Mobilized peripheral blood-derived mesenchymal stem cells (PB-MSCs) mainly derived from bone marrow-derived MSCs (BM-MSCs) exert a similar anti-inflammatory effect. However, the mechanism of anti-inflammatory effect of mobilized PB-MSCs by a combination of G-CSF and AMD3100 remains unclear. Cultured rat PB-MSCs mobilized by G-CSF/AMD3100 have shown typical surface markers and potential for multiple differentiations, similar to non-mobilized BM-MSCs. In a co-culture system, rat M0-type macrophages co-cultured with PB-MSCs have shown higher expression of M2 markers including CD206, Arg-1, IL-10, and CCL-22 than BM-MSCs, indicating that PB-MSCs induced greater M0 polarization to M2. Furthermore, compared with BM-MSCs, PB-MSCs in a co-culture system with lipopolysaccharide-induced M1-type macrophages more efficiently promoted M1 polarization to M2, accompanied by increasing expression of CD206, Arg-1, IL-10, and CCL-22 while decreasing expression of M1 markers including iNOS, TNF-α, IL-1β and IL-6, indicating that PB-MSCs triggered greater M1 polarization to M2. Subsequently, polymerase chain reaction arrays showed higher expressions of both IL1rn and Tnfrsf11b in PB-MSCs versus BM-MSCs. In response to an inflammatory niche, such as TNF-α, PB-MSCs have shown higher expression and release of IL1RA, causing greater M2 polarization of macrophages, and the special effects may be almost entirely abolished through the neutralization antibody of IL1RA. Mechanistic studies determined that PB-MSCs showed higher levels NF-κBp65 and NF-κBp-p65 than BM-MSCs, which could be obviously enhanced by TNF-α. And the increased IL1RA expression by TNF-α in PB-MSCs could be markedly canceled by an NF-κB inhibitor PDTC. Interestingly, mimicking the mobilized PB-MSCs by a combination of G-CSF and AMD3100 in vivo , BM-MSCs were treated with G-CSF and/or AMD3100 in vitro , showing the increased expressions of NF-κBp65 and IL1RA, which could be prominently abolished by PDTC. Therefore, targeting IL1rn, gene modification or drug intervention for MSCs may provide a novel therapeutic strategy for human diseases, especially inflammatory diseases.

In the present study, several decursin analogues (KC1-3) were synthesized and evaluated in terms of their anti-septic activities on high mobility group box 1 (HMGB1)-mediated septic responses and survival rate in a mouse model of sepsis. KC1 and KC3, but not KC2, significantly reduced HMGB1 release in lipopolysaccharide (LPS)-activated human umbilical vein endothelial cells (HUVECs) and attenuated the cecal ligation and puncture (CLP)-induced release of HMGB1. Additionally, in vitro analyses revealed that KC1 and KC3 both alleviated HMGB1-mediated vascular disruptions and inhibited hyperpermeability in mice, and in vivo analyses revealed that KC1 and KC3 reduced sepsis-related mortality and tissue injury. Taken together, the present results suggest that KC1 and KC3 both reduced HMGB1 release and septic mortality and, thus, may be useful for the treatment of sepsis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Inhibition of high mobility group box 1 (HMGB1) and restoration of endothelial integrity are emerging as attractive therapeutic strategies for the management of severe vascular inflammatory diseases. Recently, we found that JH-4, a synthesized decursin derivative, exhibited a strong anti-Hutchinson-Gilford progeria syndrome by efficiently blocking progerin-lamin A/C binding. In this study, we examined the effects of JH-4 on HMGB1-mediated septic responses and the survival rate in a mouse sepsis model. The anti-inflammatory activities of JH-4 were monitored based on its effects on lipopolysaccharide- or cecal ligation and puncture (CLP)-mediated release of HMGB1. The antiseptic activities of JH-4 were determined by measuring permeability, leukocyte adhesion, migration, and the activation of proinflammatory proteins in HMGB1-activated human umbilical vein endothelial cells and mice. JH-4 inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses in human endothelial cells. JH-4 also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with JH-4 reduced CLP-induced release of HMGB1, sepsis-related mortality, and pulmonary injury in vivo. Our results indicate that JH-4 is a possible therapeutic agent to treat various severe vascular inflammatory diseases via the inhibition of the HMGB1 signaling pathway., (© 2018 Wiley Periodicals, Inc.)

Background: A habitual patellar dislocation (HPD) is a rare condition in skeletally mature patients, especially for those with severe quadriceps contracture. Until now, no study has reported the effectiveness of tibial tubercle proximalization to lengthen the extensor mechanism in treating severe HPDs in skeletally mature patients., Purpose: To describe a novel comprehensive procedure that includes tibial tubercle proximalization, extensive lateral release, tibial tubercle medialization, and medial patellofemoral ligament (MPFL) reconstruction in treating severe HPDs in skeletally mature patients and to report its early clinical outcomes., Study Design: Case series; Level of evidence, 4., Methods: From January 2014 to May 2016, a total of 43 consecutive patients (47 knees) with HPDs were surgically treated at a single institution and were retrospectively reviewed. Among them, 11 skeletally mature patients (11 knees) with severe primary HPDs underwent the index comprehensive procedure. Results of patellar tracking were recorded preoperatively and at the final follow-up. The radiological assessment included radiographs in standard anteroposterior, true lateral, and axial views and computed tomography scans at full knee extension before surgery and at the final follow-up. Subjective patellofemoral function was evaluated with the Kujala functional score before the index procedure and at the final follow-up visit., Results: The 11 included patients were evaluated for a mean period of 34.9 months (range, 25-46 months). The mean knee flexion angle when the patella dislocated laterally was 25° (range, 10°-30°) preoperatively. Radiologically, there was a statistically significant improvement in the congruence angle, from 73.4° ± 17.0° preoperatively to -7.1° ± 5.8° postoperatively ( P < .01) and in the lateral patellofemoral angle, from -65.6° ± 9.4° preoperatively to 6.1° ± 2.7° postoperatively ( P < .01). The mean preoperative Kujala functional score was 42.9, and the mean postoperative Kujala functional score was 95.2 ( P < .05). No patients reported a recurrence of patellar dislocation at the final follow-up visit., Conclusion: The novel comprehensive procedure, including tibial tubercle proximalization, extensive lateral release, tibial tubercle medialization, and MPFL reconstruction, effectively treated lateral HPDs in skeletally mature patients with severe quadriceps contracture., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: Funding for this study was received from the Beijing Municipal Administration of Hospitals (XMLX201613 to H.F.). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

The immunobiological functions of Rg6, a rare ginsenoside from ginseng, have been largely unreported. In this paper, we demonstrate that Rg6 has a significant immunosuppressive function on Toll-like receptor (TLR) 4-induced systemic inflammatory responses. Rg6 was found to negatively regulate pro-inflammatory responses and severity in vivo, and thus induced recovery in mice with lipopolysaccharide (LPS)-induced septic shock and cecal ligation and puncture (CLP)-induced sepsis. Rg6 treatment also facilitated recovery in mice with LPS-induced lung damage via reduced neutrophil infiltration and tumor necrosis factor-α expression in lung tissues. Rg6 injection also downregulated pro-inflammatory cytokines and increased the levels of interleukin (IL)-10 in the serum of septic mice. Mechanistically, Rg6 did not induce TLR negative regulators, such as A20 and IRAK-M, in bone marrow-derived macrophages (BMDMs). Instead, addition of Rg6 to LPS-activated BMDMs augmented IL-10 expression, whereas it inhibited inflammatory signaling, such as by nuclear factor κB activation and mitogen-activated protein kinases. Furthermore, Rg6 significantly induced miR-146a, an operator miRNA for anti-inflammation, in BMDMs. Collectively, these data indicate that Rg6 inhibits inflammatory responses through the induction of IL-10 and miR-146a.

High mobility group box 1 (HMGB1) is considered to be a late mediator of sepsis. The inhibition of HMGB1-mediated severe inflammatory response and restoration of endothelial integrity have emerged as attractive therapeutic strategies for the management of sepsis. Rare ginsenosides, Rk1 (SB1) and Rg5 (SB2), are among the main components of black ginseng and are prepared from ginsenoside Rd by steaming at 120 °C for 3 h. We examined the effects of SB1 and SB2 on HMGB1-mediated septic response and survival rate in a mouse model of sepsis. SB1 and SB2 were administered after challenge with HMGB1. SB1 and SB2 significantly reduced the release of HMGB1 in lipopolysaccharide (LPS)-activated primary human umbilical vein endothelial cells (HUVECS) via the SIRT1-mediated deacetylation of HMGB1. Moreover, SB1 and SB2 suppressed the production of TNF-α and IL-6 and the activation of NF-κB and ERK 1/2 by HMGB1. SB1 and SB2 also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with SB1 and SB2 reduced the cecal ligation and puncture-induced release of HMGB1, sepsis-related mortality, and tissue injury in vivo. Our results indicate that SB1 and SB2 might be useful in the treatment of sepsis by targeting HMGB1., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To investigate the significance of Silva pattern system about clinical application in invasive endocervical adenocarcinoma. Methods: Data obtained from the Maternity Affiliated Hospital of Dalian Medical University was analyzed, 78 endocervical adenocarcinoma cases were included from December, 2006 to August, 2017. The average age of patients was (45.1±9.1) years old (ranged 27-71 years old). Clinical stage: stageⅠa 26 cases and Ⅰb 49 cases and stage Ⅱa 3 cases. All pathological slides were reviewed, stratified cases into pattern A, B and C according to Silva system criteria. Clinicopathological parameters of three Silva subgroups were analyzed, χ(2) test was used to investigate the correlation of Silva system and clinicopathological parameters. Follow-up data were collected until Jan. 3rd, 2018. The median follow-up time was 41 months (ranged 5-90 months). Kruskal-Wallis H test and Fisher test were used to analyze prognoses among different Silva subgroups. Results: (1) Silva A cases accounted for 38% (30/78) of all patients, 24 cases were stageⅠa, 6 cases were stageⅠb. The median tumor thickness was 2.1 mm (ranged 1.0-10.0 mm). No lymph vascular space invasion (LVSI) and perineural invasion (PNI) was detected, and all lymph node (LN) were negative for metastatic carcinoma. All patients were alive and had no evidence of recurrence. About 21% (16/78) cases were classified as Silva B, including 2 stage Ⅰa and 14 stage Ⅰb. The median tumor thickness was 5.2 mm (ranged 2.0-11.0 mm). Several patients had LVSI (4/16), LN metastasis (1/10) or PNI (1/16), but there was no recurrence or death. Thirty two (41%, 32/78) cases were Silva C, including 29 stage Ⅰb and 3 stage Ⅱa. The median tumor thickness was 11.5 mm (ranged 4.0-21.0 mm). The incidence of LVSI (53%, 17/32), LN metastasis (31%, 8/26) or PNI (16%, 5/32) was significantly increased. There were two recurrent cases and one death cases. (2) Statistical data demonstrated that Silva pattern system was closely correlated with clinicopathological parameters, such as clinical stage ( r =0.754, P= 0.000), tumor depth ( P= 0.000) and LVSI ( r =0.534, P= 0.000). But there was no correlation between Silva system and LN metastasis or PNI (all P> 0.05). (3) Silva subgroups demonstrated no significant difference in recurrence and death ( P> 0.05). Conclusions: The application of Silva pattern system could effectively predict the prognosis of patients. It may be helpful to select reasonable operation before surgery and to realize individualized treatment of cervical adenocarcinoma.

Background: For successful autologous stem cell transplantation, the collection of a sufficient number of hematopoietic stem cells after induction therapy is essential for transplant candidates with multiple myeloma (MM)., Methods: In this study, we compared the efficacy and safety of stem cell mobilization using cyclophosphamide (CY; 3.0 g/m 2 on day 1) or etoposide (VP-16; 375 mg/m 2 on days 1 and 2) in patients with MM. Granulocyte-colony stimulating factor (G-CSF, 10 μg/kg/day, subcutaneously) was administered from the onset of neutropenia to the final day of collection., Results: Sixty-five patients were mobilized with a combination of CY and G-CSF, and 63 were mobilized with a combination of VP-16 and G-CSF. All patients were mobilized within 7 months of beginning frontline treatment. The median number of CD34 + cells collected was significantly higher in the VP-16 mobilization group than in the CY mobilization group (27.6 ×  10 6 CD34 + /kg vs. 9.6 × 10 6 CD34 + /kg, P <  0.001). The rate of mobilization failure, defined as < 2.0 × 10 6 CD34 + /kg collected in three apheresis procedures, was lower in the VP-16 group than in the CY group (1.6% vs. 10.8%, P = 0.062). Severe infections during the mobilization period were more frequent in the CY group than in the VP-16 group (18.5% vs. 7.9%, P = 0.117)., Conclusion: In conclusion, an intermediate dose of VP-16 with G-CSF appears to be an effective and tolerable chemo-mobilization method compared to CY and G-CSF, particularly in cases where use plerixafor in MM is difficult.

High mobility group box 1 (HMGB1) is considered as a late mediator of sepsis and the inhibition of HMGB1-mediated severe inflammatory responses, and restoration of endothelial integrity have emerged as attractive therapeutic strategies for the management of sepsis. Ginsenoside Rh1, a protopanaxatriol type ginsenoside, is one of the major bioactive components of Korean red ginseng, which has been increasingly used for enhancing cognition and physical health worldwide. Ginsenoside Rh1 exhibits potent biological activities such as antistress, anti-oxidant, anti-inflammatory and immunomodulatory effects. We examined the effects of ginsenoside Rh1 on HMGB1-mediated septic responses and survival rate in a mouse model of sepsis. Ginsenoside-Rh1 was administered after the HMGB1 challenge. The antiseptic activity of ginsenoside Rh1 was determined by measuring the permeability, leukocyte adhesion and migration, activation of pro-inflammatory proteins in HMGB1-activated human umbilical vein endothelial cells (HUVECs) and mice, and the survival rate in a sepsis mouse model. Ginsenoside Rh1 significantly reduced HMGB1 release in lipopolysaccharide (LPS)-activated HUVECs. Furthermore, ginsenoside Rh1 suppressed the production of tumor necrosis factor (TNF)- α , interleukin (IL)-6, activation of nuclear factor (NF)- κ B and extracellular signal-regulated kinase (ERK) 1/2 by HMGB1. Ginsenoside Rh1 also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with ginsenoside Rh1 reduced the cecal ligation and puncture (CLP)-induced release of HMGB1, sepsis-related mortality and tissue injury in vivo. Our results indicated that ginsenoside Rh1 might be useful in the treatment of sepsis by targeting HMGB1.

Inhalation of fine particulate matter ( PM 2 . 5 ) is associated with elevated pulmonary injury caused by the loss of vascular barrier integrity. Black ginseng (BG), steamed and dried ginseng nine times, exhibits various pharmacological activities such as antibacterial, antihyperglycemic, anti-atopic, antibacterial, and anti-inflammatory activities. In this study, we investigated the beneficial effects of black ginseng extract (BGE) against PM-induced lung endothelial cell (EC) barrier disruption and pulmonary inflammation. Permeability, leukocyte migration, activation of proinflammatory proteins, generation of reactive oxygen species (ROS), and histology were examined in PM 2 . 5 -treated ECs and mice. BGE significantly scavenged PM 2 . 5 -induced ROS and inhibited the ROS-induced activation of p38 mitogen-activated protein kinase (MAPK). Concurrently, BGE activated Akt, which helped maintain endothelial integrity. Furthermore, BGE reduced vascular protein leakage, leukocyte infiltration, and proinflammatory cytokine release in the bronchoalveolar lavage fluid in PM-induced lung tissues. These results indicated that BGE may exhibit protective effects against PM-induced inflammatory lung injury and vascular hyperpermeability.

Inhalation of fine particulate matter (PM 2.5 ) is associated with elevated pulmonary injury attributed to the loss of vascular barrier integrity. Black ginseng (BG), steamed 9 times and dried ginseng, and its major protopanaxatriol type ginsenosides (ginsenoside Rg4, Rg6, Rh4, Rh1, and Rg2) exhibited various biological activities including anti-septic, anti-diabetic, wound healing, immune-stimulatory, and anti-antioxidant activity. The aim of this study was to investigate the beneficial effects of Rgx365 (a protopanaxatriol type rare ginsenosides fraction) on PM-induced lung endothelial cell (EC) barrier disruption and pulmonary inflammation. Permeability, leukocyte migration, activation of proinflammatory proteins, generation of reactive oxygen species (ROS), and histology were examined in PM 2.5 -treated EC and mice. Rgx365 significantly scavenged PM 2.5 -induced ROS, inhibited ROS-induced activation of p38 mitogen-activated protein kinase (MAPK), activated Akt in purified pulmonary EC, which helped maintain endothelial integrity. Further, Rgx365 reduced vascular protein leakage, leukocyte infiltration, and proinflammatory cytokine release in bronchoalveolar lavage fluids in PM-induced mouse lung tissues. Data suggested that Rgx365 might exhibit protective effects in PM-induced inflammatory lung injury and vascular hyperpermeability.

Purpose: The purpose of the study was to quantify the patellar J sign using traditional computed tomography (CT) scans., Methods: Fifty-three patients (fifty-three knees) who suffered from recurrent patellar instability were included and analyzed. The patellar J sign was evaluated pre-operatively during active knee flexion and extension. It was defined as positive when there was obvious lateral patellar translation, and negative when there was not. The CT scans were performed in all patients with full knee extension; and the parameters including bisect offset index (BOI), patellar-trochlear-groove (PTG) distance, and patellar lateral tilt angle (PLTA) were measured on the axial slices. All the three parameters were compared between the J sign-positive group (study group) and the J sign-negative group (control group). In addition, the optimal thresholds of the three CT scan parameters for predicting the positive patellar J sign were determined with receiver operating characteristic (ROC) curves, and the diagnostic values were assessed by the area under the curve (AUC)., Result: Among the fifty-three patients (fifty-three knees), thirty-seven (70%) showed obvious lateral patellar translation, which were defined as positive J sign (study group), and the remaining sixteen (30%) who showed no lateral translation were defined as negative J sign (control group). The mean values of the three CT parameters in the study group were all significantly larger compared to the control group, including BOI (121 ± 28% vs 88 ± 12%, P = 0.038), PTG distance (5.2 ± 6.6 mm vs - 4.4 ± 5.2 mm, P < 0.05), and PLTA (34.9 ± 10.5° vs 25.7 ± 3.4°, P = 0.001). Furthermore, the evaluation of ROC analysis showed that the AUC of BOI was the largest (AUC = 0.906) among the three parameters, and the optimal threshold of BOI to predict the positive patellar J sign was 97.5% (Sensitivity = 83.3%, Specificity = 87.5%)., Conclusions: In this study, the prevalence of positive patellar J sign was 70%. The BOI measured from the axial CT scans of the knee joint can be used as an appropriate predictor to differentiate the positive J sign from the negative J sign, highlighting that the excessive lateral patellar translation on axial CT scan indicates positive patellar J sign., Level of Evidence: IV.

Background: A high consumption of fructose leads to hepatic steatosis. About 20-30% of triglycerides are synthesized via de novo lipogenesis. Some studies showed that endoplasmic reticulum stress (ERS) is involved in this process, while others showed that a lipotoxic environment directly influences ER homeostasis. Here, our aim was to investigate the causal relationship between ERS and fatty acid synthesis and the effect of X-box binding protein-1 (XBP-1), one marker of ERS, on hepatic lipid accumulation stimulated by high fructose., Methods: HepG2 cells were incubated with different concentrations of fructose. Upstream regulators of de novo lipogenesis (i.e., carbohydrate response element-binding protein [ChREBP] and sterol regulatory element-binding protein 1c [SREBP-1c]) were measured by polymerase chain reaction and key lipogenic enzymes (acetyl-CoA carboxylase [ACC], fatty acid synthase [FAS], and stearoyl-CoA desaturase-1 [SCD-1]) by Western blotting. The same lipogenesis-associated factors were then evaluated after exposure of HepG2 cells to high fructose followed by the ERS inhibitor tauroursodeoxycholic acid (TUDCA) or the ERS inducer thapsigargin. Finally, the same lipogenesis-associated factors were evaluated in HepG2 cells after XBP-1 upregulation or downregulation through cell transfection., Results: Exposure to high fructose increased triglyceride levels in a dose- and time-dependent manner and significantly increased mRNA levels of SREBP-1c and ChREBP and protein levels of FAS, ACC, and SCD-1, concomitant with XBP-1 conversion to an active spliced form. Lipogenesis-associated factors induced by high fructose were inhibited by TUDCA and induced by thapsigargin. Triglyceride level in XBP-1-deficient group decreased significantly compared with high-fructose group (4.41 ± 0.54 μmol/g vs. 6.52 ± 0.38 μmol/g, P < 0.001), as mRNA expressions of SREBP-1c (2.92 ± 0.46 vs. 5.08 ± 0.41, P < 0.01) and protein levels of FAS (0.53 ± 0.06 vs. 0.85 ± 0.05, P = 0.01), SCD-1 (0.65 ± 0.06 vs. 0.90 ± 0.04, P = 0.04), and ACC (0.38 ± 0.03 vs. 0.95 ± 0.06, P < 0.01) decreased. Conversely, levels of triglyceride (4.22 ± 0.54 μmol/g vs. 2.41 ± 0.35 μmol/g, P < 0.001), mRNA expression of SREBP-1c (2.70 ± 0.33 vs. 1.00 ± 0.00, P < 0.01), and protein expression of SCD-1 (0.93 ± 0.06 vs. 0.26 ± 0.05, P < 0.01), ACC (0.98 ± 0.09 vs. 0.43 ± 0.03, P < 0.01), and FAS (0.90 ± 0.33 vs. 0.71 ± 0.02, P = 0.04) in XBP-1s-upregulated group increased compared with the untransfected group., Conclusions: ERS is associated with de novo lipogenesis, and XBP-1 partially mediates high-fructose-induced lipid accumulation in HepG2 cells through augmentation of de novo lipogenesis., Competing Interests: There are no conflicts of interest

Secondary prevention of lung cancer by screening a high-risk population with low-dose CT (LDCT) of the chest has been shown to save lives. Our Institution offered a free screening program in 2013. The program was promoted through flyers, radio programs, face-to-face information sessions, and a multidisciplinary lung symposium. A lung navigator confirmed the eligibility of patients according to National Lung Screening Trial (NLST) criteria. Data were, prospectively, collected over a 12-month period using Lung-RADs (Lung Imaging Reporting and Data System). After one year, an online survey was sent out to all primary care and referring physicians in the network. One hundred and sixty-nine patients were found to be eligible for screening. Sixty-five per cent were black, 44 per cent white, 9 per cent Hispanic, and 6 per cent were Asian. Sixty per cent patients were referred by their physician. Thirty-one were Lung-RADs 1 (18.3%), 116 were Lung-RADs 2 (68.6%), 16 were Lung-RADs 3 (9.5%), and six were Lung-RADs 4 (3.6%). At the end of the study period, the survey showed that 100 per cent of the providers were aware of the screening program but 15 per cent never referred a patient. Time constraints and requirement for precertification were cited as potential barriers to referral. Twenty-six per cent of providers were unaware that LDCT was recommended by the U.S. Preventive Services Task Force on par with colonoscopy and mammography. The NLST showed that screening with LDCT could reduce lung cancer mortality by 20 per cent. Significant concerns exist about the generalizability of these results and the applicability of screening programs in the community.

Objective: To investigate the impact of aortic root morphology on the implantation depth of aortic valve prosthesis during trans-catheter aortic valve replacement (TAVR) in bicuspid aortic valve patients. Methods: Clinical data of 40 patients with native bicuspid aortic valve stenosis who underwent TAVR using the self-expandable prosthesis (the Venus A-valve) from 2014 to 2017 in Fuwai Hospital was retrospectively analyzed. The patients were divided into non-deep implantation group (implant depth ≤10 mm by instant angiogram after implantation,29 cases) and deep implantation group (implant depth> 10 mm by instant angiogram after implantation,11 cases).Pre-procedural aortic root characteristics (e.g. calcification, angle and dimensions) were assessed by CT. The impact of aortic root morphology on the implantation depth and clinical outcomes were also evaluated. Results: The age was (75.1±5.9) years with equal representation from the raphe-type and non-raphe type (52.5%(21/40) and 47.5%(19/40)).The bigger aorta angle ((56.5±4.5)° vs. (47.4±9.4)°, P= 0.004),more frequent mild-calcification (HU850, <200 mm(3)) or severe-calcification(HU850, >1 000 mm(3)) of aortic leaflets (7/11 vs. 4/29, P= 0.006), as well as higher ratio of left ventricular outflow tract perimeter to annulus perimeter ((109.2±7.5)% vs. (101.5±6.5)%, P= 0.004) were found in the deep implantation group compared to the non-deep implantation group. The new in-hospital onset of bundle-branchheart-block or atrioventricular block conduction disturbance rate was higher in the deep implantation group than in the non-deep implantation group (6/11 vs. 2/29, P= 0.030).Left ventricular ejection fraction was similar between deep implantation group and non-deep implantation group at baseline((49.9±8.9)% vs. (55.8±10.4)%, P= 0.117), and was significantly lower in the deep implantation group than in the non-deep implantation group at 30 days after implantation ((51.6±12.8)% vs. (60.9±8.1)%, P= 0.020). Conclusion: Aortic root morphology of bicuspid aortic valve patients is associated with implantation depth of the prosthesis during TAVR, which affects the conduction system and left ventricular function during and post TAVR.

Background: Static anterior tibial subluxation of the lateral compartment after an anterior cruciate ligament (ACL) injury highlights an increased anterior position of the tibia relative to the femur. However, the precise cause of this phenomenon is not entirely clear. Recently, an increased posterior tibial slope (PTS) has been identified as an independent risk factor for noncontact ACL injuries., Hypothesis: An increased PTS is associated with an increased anterior position of the lateral compartment of the tibia relative to the femur after acute ACL injuries., Study Design: Case-control study; Level of evidence, 3., Methods: From March 2016 to March 2017, a total of 154 patients with clinically diagnosed noncontact ACL injuries who underwent primary ACL reconstruction were retrospectively analyzed. Static anterior subluxation of the lateral compartment relative to the lateral femoral condyle was measured on preoperative magnetic resonance imaging. Among them, 23 patients (study group) who demonstrated ≥6-mm anterior subluxation of the lateral compartment were matched in a 1:1 fashion to 23 control participants (control group), who showed <6-mm anterior subluxation of the lateral compartment. The PTS was measured on routinely available preoperative weightbearing lateral knee radiographs. Predictors of increased (≥6 mm) static anterior subluxation of the lateral compartment, including body mass index (BMI), PTS, injuries to the anterolateral ligament (ALL), and concomitant lateral meniscal lesions, were assessed by multivariable conditional logistic regression analysis., Results: The mean PTS in the study group was 15.4°, which was significantly larger than that in the control group (8.8°) ( P < .001). In addition, an abnormal degree of PTS (≥10.0°) was determined to be an independent risk factor (odds ratio, 8.0 [95% CI, 2.7-29.2]; P < .001) associated with ≥6-mm anterior subluxation of the lateral compartment after acute ACL injuries. However, BMI, presence of concomitant lateral meniscal lesions, and presence of ALL ruptures were not., Conclusion: An increased PTS was identified to be an independent anatomic risk factor of increased (≥6 mm) anterior subluxation of the lateral compartment in acute noncontact ACL injuries. For patients with obviously increased anterior tibial subluxation of the lateral compartment after ACL injuries, the PTS should be measured.

The expression level of microRNA-802 (miR-802) is increased in livers of high-fat diet (HFD)-fed mice and obese human subjects; however, the function of miR-802 in the development of obesity-associated insulin resistance remains incompletely understood. Here we studied the potential role of miR-802 in regulating hepatic glucose metabolism and insulin sensitivity. Mice were fed either a standard chow diet or HFD for 12 weeks, and then the HFD mice were infected by injection with an adeno-associated virus expressing miR-802 or miR-802-SP. Six weeks after the injection, we measured blood glucose, plasma insulin, and insulin sensitivity in the mice. In addition, hepatic glucose levels and PI3K-Akt pathway gene expression were analyzed. Adeno-associated viral-mediated overexpression of miR-802 in the livers of HFD mice caused impaired glucose homeostasis and insulin sensitivity, thus giving rise to decreased protein level of pAkt s473 and pPI3K, and increased protein levels of pPTEN, G6PC, and GluT2. In contrast, loss of miR-802 function in the liver of HFD mice led to increased pAkt s473 and pPI3K, and decreased levels of pPTEN, G6PC, and GluT2, thereby improving glucose metabolism and insulin resistance. Our findings confirmed MiR-802 as a regulator of liver glucose metabolism and insulin signaling., Competing Interests: None., (IJCEP Copyright © 2018.)

Macrosomia, not only is closely associated with short-term, birth-related problems, but also has long-term consequences for the offspring. We investigated the expression of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in the placenta of macrosomia births using a microarray profile. The data showed that 2929 lncRNAs and 4574 mRNAs were upregulated in the placenta of macrosomia births compared with the normal birth weight group (fold change ⩾2.0, P<0.05), and 2127 lncRNAs and 2511 mRNAs were downregulated (fold change ⩾2.0, P<0.05). To detect the function of the differentially expressed lncRNAs and their possible relationship with the differentially expressed mRNAs, we also performed gene ontology analysis and pathway analysis. The results demonstrated that the PI3K-AKT signalling pathway, the mitogen-activated protein kinase (MAPK) signalling pathway, the focal adhesion pathway, the B cell receptor signalling pathway, and the protein processing in endoplasmic reticulum and lysosome pathway were significantly differentially expressed in the macrosomia placenta. Four lncRNAs were randomly chosen from the differentially expressed lncRNAs to validate the microarray data by quantitative polymerase chain reaction (qPCR). The qPCR results were consistent with the microarray data. In conclusion, lncRNAs were significantly differentially expressed in the placenta of macrosomia patients, and may contribute to the pathogenesis of macrosomia.

Objective: Suicide is a significant public health concern worldwide. Social media data have a potential role in identifying high suicide risk individuals and also in predicting suicide rate at the population level. In this study, we report an advanced daily suicide prediction model using social media data combined with economic/meteorological variables along with observed suicide data lagged by 1 week., Methods: The social media data were drawn from weblog posts. We examined a total of 10,035 social media keywords for suicide prediction. We made predictions of national suicide numbers 7 days in advance daily for 2 years, based on a daily moving 5-year prediction modeling period., Results: Our model predicted the likely range of daily national suicide numbers with 82.9% accuracy. Among the social media variables, words denoting economic issues and mood status showed high predictive strength. Observed number of suicides one week previously, recent celebrity suicide, and day of week followed by stock index, consumer price index, and sunlight duration 7 days before the target date were notable predictors along with the social media variables., Conclusion: These results strengthen the case for social media data to supplement classical social/economic/climatic data in forecasting national suicide events.

Background : The study examined the difference in the expression of the receptor for activated C kinase 1 (RACK1) between anaesthesia with propofol and isoflurane in rats with myocardial ischemia-reperfusion injury (IRI). Methods : Male Sprague-Dawley rats were studied. Anaesthesia was induced with xylazine 20 µg/g by intraperitoneal injection and maintained with propofol or isoflurane. Myocardial IRI was induced by ligating the left anterior descending artery for 1 hour. Reactive oxygen species (ROS), cardiomyocyte apoptosis, the expression of RACK1 and toll-like receptor 4 (TLR4), and the heart injury score were compared between the two groups. Results : Cardiomyocyte apoptosis with ROS was significantly lower in the propofol group than in the isoflurane group. The propofol group had significantly higher RACK1 expression and lower TLR4 expression, compared with the isoflurane group (RACK1, 1970.50 ± 120.50 vs . 1350.20 ± 250.30, p <0.05; TLR4, 980.50 ± 110.75 vs . 1275.50 ± 75.35, p <0.05). However, the heart injury scores in the two groups did not differ significantly (3.56 ± 0.29 vs . 4.33 ± 0.23 in the propofol and isoflurane groups, respectively, p =0.33). Conclusion : There were significant differences in inflammation and apoptosis, including the expression of RACK1 and TLR4, after myocardial IRI between the propofol and isoflurane groups. However, both groups had similar heart injury scores., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

The picture of human immunodeficiency virus (HIV)-infected patients has changed dramatically since the original description in 1981. The introduction of antiretroviral drugs in 1987 and combination antiretroviral therapy has decreased mortality by as much as 80%. We now see patients in their 60s and 70s, having lived decades with HIV and living a normal live. As outlined in the article, despite good viral control, patients with HIV may present with solid organ cancers earlier than noninfected patients and are also prone to other complications of their disease that may require the attention of a thoracic surgeon., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of transcatheter aortic valve replacement(TAVR) using Venus-A valve for treating patients with severe aortic stenosis. Methods: In this prospective study, 101 consecutive severe aortic stenosis patients with high surgical risk(Society of Thoracic Surgeon(STS) score ≥4%) or at prohibitive surgical risk were enrolled from 5 academic cardiovascular centers in China(Fuwai hospital, the second affiliated hospital of Zhejiang university school of medicine, West China hospital of Sichuan university, the first affiliated hospital of Nanjing medical university, Ruijin hospital of Shanghai Jiaotong university school of medicine) from September 2012 to January 2015, and Venus-A valves were used in TAVR for these patients. The primary endpoints were death from any cause and major stroke in 1 year. The secondary endpoints included efficacy and safety of TAVR in 1 year. Results: TAVR success rate was 97.9%(98/101), and 3 patients were transferred to receive surgical AVR. There were 85 patients using 1 Venus-A valve, and 13 patients underwent valve-in-valve implantation using 2 Venus-A valves. There were 1 case(1.0%) of stroke, 2 cases(2.0%)of acute myocardial infarction, 5 cases(5.0%) of pericardial effusion, 6 cases(5.9%) of severe vascular complication, and 2 cases(2.0%) of death after 7 days of TAVR. Meanwhile, aortic pressure gradient derived from echocardiography was significantly reduced when compared with pre-procedure level(11(8, 15) mmHg (1 mmHg=0.133 kPa) vs. 59(45, 71)mmHg, P <0.01), and there was no aortic root rupture or leaflets thrombosis. Rate of NYHA functional class ≤Ⅱ improvements were observed at 6 months follow-up when compared with pre-procedure(94.4%(84/89)vs. 21.3%(21/89), P <0.01). The primary endpoint was 7.9%(8/11), and the incidence of all cause death and stroke was 5.9%(6/101) and 2.0%(2/101) respectively at 1 year after the procedure. Kaplan-Meier survival analysis showed that cumulative survival rate was 94.1% at 1 year after the procedure. Conclusion: TAVR using Venus-A valve for treating patients with severe aortic stenosis is effective and safe in the early and medium term post procedure.