[Application of Padua prediction score and serum albumin level in evaluating venous thromboembolism in rheumatic inpatients].

OBJECTIVE: To investigate the status of venous thromboembolism (VTE) in rheumatic inpatients, and to explore the efficiency of Padua prediction score (PPS) in the patient population. In addition, to analyze the relationship between serum albumin and VTE in rheumatic inpatients. METHODS: Data of inpatients with rheumatology were retrospectively collected and analyzed at Sichuan Provincial People's Hospital from September 2018 to September 2019. Occurrence of VTE was compared between high (PPS≥4) and low (PPS < 4) risk groups. PPS were analyzed in the VTE and non-VTE patients. Multivariate Logistic regression model was used to analyze the risk factors in PPS and the relationship between serum albumin and VTE. RESULTS: A total of 1 547 patients were included in this study, and 27 (1.7%) had symptomatic VTE. Among the symptomatic VTE cases, 19 (1.2%) had deep vein thrombosis (DVT) only, 6 (0.4%) had pulmonary thromboembolism (PTE) only, and 2 (0.1%) were diagnosed with DVT and PTE. PPS in the VTE and non-VTE groups were 3.33±1.78 and 1.80±0.97 respectively (P < 0.05).The number of patients with PPS≥4 in the VTE group and non-VTE group was 37.0% and 4.3% respectively (P < 0.01). The average serum albumin level in the VTE group was lower than that in non-VTE group [(29.79±6.36) g/L vs. (35.17±6.31) g/L, P < 0.001]. Seventy-six cases was divided into high-risk group of VTE, while 1 471 cases were in the low-risk group, and the incidence of VTE was 13.2% and 1.2% respectively (P < 0.001). Logistic regression analysis showed that ongoing hormonal treatment, age≥70 years, trauma and/or surgery ≤30 d, reduced mobility and previous VTE were risk factors of VTE in the rheumatology patients, OR values were 7.11, 7.07, 3.40, 2.40 and 2.00, respectively. Lower serum albumin level was the risk factor of VTE in the rheumatology patients [OR=0.88 (95%CI: 0.82-0.94)]. CONCLUSION: The incidence of VTE was relatively higher in the hospitalized patients in Department of Rheumatology and Immunology. Glucocorticoid therapy was the highest risk factor of VTE and lower serum albumin level also was the risk factor. Although the PPS can reflect the risk of VTE in rheumatic inpatients to some extent, its effectiveness is limited. PPS can be optimized for quantitative VTE risk assessment of rheumatic inpatients in the future.

[Clinical observation of microsurgical removal of the hemilateral tuberculum sellae meningiomas through contralateral eyebrow arch approach].

The current study aimed to investigate the clinical feasibility of microscopic resection of hemilateral tuberculum sellae meningiomas (TSM) via the contralateral eye brow arch approach. The clinical data of 34 patients with TSM who underwent microsurgery from January 2016 to June 2021 in the Neurosurgery Department of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine and the First Affiliated Hospital of Henan University were collected and reviewed. The postoperative visual acuity improvement rate was 88.5% (23/26), and the total tumor resection rate was 88.2% (30/34); the postoperative visual acuity improvement in patients with total tumor resection was better than that of patients with partial resection [90.9% (20/22) vs 3/4]. Meanwhile, the postoperative visual acuity improvement in patients with the superior optic nerve and laterl-superior optic nerve was better than that of patients with the lateral optic nerve type (12/14, 8/8 vs 3/4). Supraorbital skin numbness occurred in 3 cases after operation, and the symptoms disappeared during follow-up; 2 cases had mild disturbance of hormone level, and urine output of 2 cases increased after operation, which returned to normal level after symptomatic treatment; 1 case had subcutaneous effusion which was absorbed after treatment. There were no complications such as olfactory disturbance and intracranial infection. During follow-up for 3-60 (33±6) months, recurrence occurred in 2 cases and reoperation was performed. For the hemilateral TSM, according to the preoperative evaluation of the origin of the TSM and the side with visual impairment, the contralateral eyebrow approach is selected to fully expose the tumor base below the optic nerve. It is beneficial to fully resect the tumor under direct vision, and the symptoms of postoperative visual impairment are significantly improved, indicating that the current surgical method can be used in the clinical setting.

Characterizing the critical role of metabolism in osteosarcoma based on establishing novel molecular subtypes.

OBJECTIVE: Osteosarcoma is the third most frequently diagnosed cancer among adolescents. Immunotherapy is an effective curative treatment for metastatic osteosarcoma patients. This study aimed to further reveal the significance of metabolism in tumor progression, and to categorize molecular subtypes for guiding personalized therapy. MATERIALS AND METHODS: Univariate Cox regression analysis was performed to screen metabolism-related genes associated with osteosarcoma prognosis. A molecular subtyping system was developed by unsupervised consensus clustering. Survival analysis and functional analysis were used to evaluate the performance of subtyping and characterize the TME of subtypes. Stepwise Akaike information criterion (stepAIC) was employed to optimize the prognostic model. RESULTS: C1 and C2 subtypes showed distinct prognosis, with more favorable survival in C2 subtype. C2 subtype presented a higher immune infiltration and active anti-tumor response. Notably, C2 subtype was predicted to have better immune response to immune checkpoint blockade. In addition, a 5-gene prognostic signature with robust ability to classify patients into high-risk and low-risk groups was developed. CONCLUSIONS: The study revealed the critical role of metabolism in tumorigenesis by comparing the features between the two subtypes. Oncogenic pathways including epithelial mesenchymal transition (EMT), glycolysis and hypoxia may be closely involved in the correlation with metabolism. Importantly, we developed a novel subtyping system and a 5-gene signature with high potential to be applied in clinical practice.

PARP inhibitors as maintenance therapy in newly diagnosed advanced ovarian cancer: a meta-analysis.

BACKGROUND: Up to 70% of patients with advanced ovarian cancer have a relapse after primary therapy. New agents and approaches are urgently needed to avoid or slow down this recurrence. OBJECTIVES: To investigate the efficacy of PARP inhibitors (PARPis) as maintenance treatment in patients with newly diagnosed advanced ovarian cancer. SEARCH STRATEGY: PubMed, MEDLINE, EMBASE, Cochrane Library and Web of Science databases. SELECTION CRITERIA: All randomised clinical trials (RCTs) that compared PARPis with placebo as first-line maintenance therapy in ovarian cancer. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data. Pooled hazard ratio (HR) and risk ratio (RR) with 95% confidence interval (CI) were calculated. MAIN RESULTS: PARPis were associated with significant improvement of progression-free survival (PFS) in advanced epithelial ovarian cancer (AeOC) (HR = 0.53, 95% CI 0.40-0.71; P < 0.0001). The benefit was not only in women with BRCA mutations (HR = 0.35, 95% CI 0.29-0.42; P < 0.00001) and homologous recombination deficiency (HRD) (HR = 0.43, 95% CI 0.32-0.60; P < 0.00001), but also in those with nonmutated BRCA (HR = 0.72, 95% CI 0.63-0.82; P < 0.00001) and even non-HRD (HR = 0.83, 95% CI 0.70-0.99; P = 0.04). CONCLUSIONS: PARP inhibitors are effective as maintenance therapy among patients with newly diagnosed advanced ovarian cancer after platinum-based chemotherapy, regardless of BRCA mutation or HRD status. TWEETABLE ABSTRACT: PARPis provide a significant PFS benefit as first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer.

Over-expression of DJ-1 attenuates effects of curcumin on colorectal cancer cell proliferation and apoptosis.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Over-expression of DJ-1 attenuates effects of curcumin on colorectal cancer cell proliferation and apoptosis, by H. Shang, T. Wang, F. Shang, M. Li, Y. Luo, K.-M. Huang, published in Eur Rev Med Pharmacol Sci 2019; 23 (7): 3080-3087-DOI: 10.26355/eurrev_201904_17591-PMID: 31002157" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17591.

Glutamine protects myocardial ischemia-reperfusion injury in rats through the PI3K/Akt signaling pathway.

OBJECTIVE: To study the protective mechanism of glutamine (Gln) on myocardial ischemia-reperfusion (IR) injury in rats through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. MATERIALS AND METHODS: A total of 30 healthy SD rats weighing 200-300 g were used in this experiment. They were randomly divided into 3 groups: sham group (n=10), myocardial IR injury group (IR group, n=10), IR+Gln group (n=10). The protein expression levels of phosphorylated Akt (p-Akt), total Akt (t-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), mTOR, proliferating cell nuclear antigen (PCNA), P21, and Tubulin were determined by Western blotting (WB). Quantitative Polymerase Chain Reaction (qPCR) was applied to detect the messenger ribonucleic acid (mRNA) levels of Akt and mTOR. 3-(4,5)-dimethylthiazol(-z-y1)-3,5-diphenyl tetrazolium bromide (MTT) test was utilized to examine the proliferation ability of cardiomyocytes in vitro. Besides, the contents of the inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) were measured via enzyme-linked immunosorbent assay (ELISA). Cell apoptosis in each group was examined through Hoechst staining. RESULTS: Compared with those in the sham group, ratios of p-AKT/AKT, p-mTOR/mTOR, and the level of PCNA extremely significantly decreased, but the level of P21 notably increased in IR group (p<0.01). In comparison with those in the IR group, ratios of p-AKT/AKT, p-mTOR/mTOR, and the level of PCNA were remarkably raised, while the level of P21 was remarkably reduced in IR+Gln group (p<0.05). QRT-PCR results manifested that there were no significant differences in the mRNA levels of Akt and mTOR among the three groups [no significant difference (NS)]. Moreover, the cell proliferation ability in IR group was remarkably lower than that in the sham group (p<0.01), while it was enhanced in the IR+Gln group compared with that in the IR group (p<0.05). Additionally, IR group had significantly elevated expression levels of TNF-α and IL-6 compared with the sham group (p<0.01), whereas the IR+Gln group had notably decreased expression levels of TNF-α and IL-6 compared with IR group (p<0.05). In comparison with that in the sham group, the apoptosis in IR group was significantly raised (p<0.01), and compared with that in the IR group, the apoptosis in the IR+Gln group prominently decreased (p<0.05). The contents of the inflammatory cytokines, TNF-α, and IL-6 presented the same trends among the three groups. CONCLUSIONS: Gln activates the PI3K/Akt signaling pathway by increasing the levels of p-AKT and p-mTOR. Gln can increase the PCNA level and reduce the P21 level, so as to enhance the proliferation ability of cardiomyocytes. Besides, Gln reduces the levels of inflammatory cytokines, TNF-α, and IL-6, and inhibits cell apoptosis. Finally, Gln can protect cells from myocardial IR injury by activating the PI3K/Akt signaling pathway.

Inhibition of microRNA-875-5p promotes radioiodine uptake in poorly differentiated thyroid carcinoma cells by upregulating sodium-iodide symporter.

BACKGROUND AND AIM: Poorly differentiated thyroid carcinoma (PDTC) is an endocrine malignancy that is challenging to treat due to its limited radioiodine uptake. microRNAs (miRNAs or miRs) have been shown to be useful in treating many types of tumors, including PDTC. This study aims to evaluate the potential effect of miR-875-5p on the radioiodine uptake of PDTC and to clarify the underlying mechanisms. METHODS: Expression of miR-875-5p and sodium-iodide symporter (NIS) in tissues and cell lines was determined using RT-qPCR. The binding relationship between miR-875-5p and NIS was predicted through in silico analysis and verified by dual-luciferase reporter gene assay. A series of miR-875-5p mimic, miR-875-5p inhibitor, shRNA against NIS, and overexpressed NIS plasmids were introduced into PDTC cells. We then evaluated the cell viability, colony formation, apoptosis, and radioiodine uptake of each PDTC sample via CCK-8 assay, clonogenic assay, flow cytometry, and γ counter, respectively. RESULTS: miR-875-5p was found to be highly expressed, but NIS was poorly expressed in DTC tissues and PDTC cell lines. NIS was verified to be a target gene of miR-875-5p. Upregulation of miR-875-5p was found to induce PDTC cell proliferation, and reduce apoptosis and radioiodine uptake in vitro through down-regulation of NIS. In an in vivo orthotopic model, the enhancement of miR-875-5p led to the reduction of NIS expression and radioiodine uptake in the thyroid tumors. CONCLUSIONS: Altogether, the findings of the current study suggest that down-regulated miR-875-5p expression could promote its target gene NIS to increase radioiodine uptake in PDTC, constituting a preventive strategy against PDTC.

Over-expression of DJ-1 attenuates effects of curcumin on colorectal cancer cell proliferation and apoptosis.

OBJECTIVE: The phosphatase and tensin homologue deleted on chromosome ten (PTEN) acts as a tumor suppressor gene by inhibiting the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. DJ-1, a negative regulator of PTEN, is associated with the pathogenesis of a variety of tumors. Curcumin (Cur) is a phenolic compound that is extracted from various plant rhizomes with various anti-tumor pharmacological effects. This study aimed to investigate the effects of Cur on proliferation and apoptosis of colorectal cancer cells. MATERIALS AND METHODS: Human normal colorectal epithelial cell line (NCM460) and colorectal cancer cell line (SW480 and SW620) were cultured in vitro. Real-time quantitative PCR (RT-PCR) and western blot were used to detect DJ-1 and PTEN mRNA and protein, respectively. Cell apoptosis was determined with flow cytometry. SW480 cells were divided into control, 20 µM Cur treatment group, Cur+pcDNA3.1-Blank group and Cur+pcDNA3.1-DJ-1 group. Cell proliferation activity was evaluated with EdU staining. RESULTS: Comparing with NCM460 cells, DJ-1 was significantly increased, while PTEN was significantly declined in SW480 and SW620 cells (p<0.05). Cur treatment significantly inhibited SW480 and SW620 cell proliferation and significantly induced apoptosis compared to control group (p<0.05) but showed no significant effects on NCM460 cells. Cur down-regulated DJ-1 level and enhanced PTEN expressions in SW480 cells with dose dependence. The pcDNA3.1-DJ-1 transfection significantly declined PTEN expression, enhanced p-AKT levels, reduced cell apoptosis, and strengthened cell proliferation in SW480 cells treated by Cur (p<0.05). CONCLUSIONS: Cur can inhibit colorectal cancer cell proliferation and promote apoptosis by down-regulating DJ-1 expression to regulate the activity of PTEN/PI3K/AKT signaling pathway.

High levels of long non-coding RNA DICER1-AS1 are associated with poor clinical prognosis in patients with osteosarcoma.

OBJECTIVE: Long noncoding RNA DICER1-AS1 (DICER1-AS1) has been reported to be upregulated in osteosarcoma cells and to serve as a tumor promoter. However, the clinical significance of DICER1-AS1 in osteosarcoma remains unclear. The aim of this study was to investigate the association of DICER1-AS1 expression with prognosis of osteosarcoma. PATIENTS AND METHODS: The expression of DICER1-AS1 was measured in 214 osteosarcoma samples and normal bone samples by using Real-time PCR. The correlations between DICER1-AS1 expression and clinical features were statistically analyzed. Overall survival (OS) and disease-free survival (DFS) were examined using Kaplan-Meier curves. Multivariate analyses were performed to analyze the prognostic significance of DICER1-AS1 expression. RESULTS: It was found that the expression levels of DICER1-AS1 in osteosarcoma tissues were significantly higher than those in corresponding noncancerous bone tissues (p < 0.01). Higher DICER1-AS1 had significant association with clinical stage (p = 0.005) and distant metastasis (p = 0.000). Kaplan-Meier survival analysis showed that patients with high DICER1-AS1 expression had a shorter OS and DFS compared with the low DICER1-AS1 expression group (p = 0.007 and p < 0.0001). In a multivariate Cox model, our results showed that DICER1-AS1 expression was an independent poor prognostic factor for both 5-year OS (HR = 3.236, 95% CI: 1.148-5.347; p = 0.004) and 5-year DFS (HR = 3.935, 95% CI: 1.556-6.349; p = 0.001). CONCLUSIONS: DICER1-AS1 is up-regulated in osteosarcoma and may serve as a potential prognostic biomarker for osteosarcoma.

[Improvement and effect analysis of a new neuroendoscopic trans-nasal-sphenoidal pituitary tumor resection approach].

Objective: To modify the individual neuroendoscopic surgical approach of pituitary tumors with specific imaging features, and to analyze the clinical outcomes. Methods: The clinical data of 116 patients with pituitary tumors who underwent surgical treatment at the pituitary tumor diagnosis and treatment center of Ruijin Hospital from April 2014 to December 2017 were collected, then the resection effects and complication rates of pituitary tumors from three different kinds of transsphenoidal approaches (e.g. classical single nostril approach, bilateral approach, "one-and-a-half" approach) were compared. Results: Pituitary tumor resection with "one-and-a-half" trans-nasal-sphenoidal approach achieved the same surgical effects with the bilateral approach, which was difficult to resect with the single-nostril classical approach. And it had significant advantages in the average length of postoperative hospitalization ( "one-and-a-half" : 6.9 days, bilateral: 12.5 days, P<0.01), the average postoperation VAS of olfactory retention ( "one-and-a-half" : 8.6, bilateral: 7.0, P<0.01) and preventing posterior nasal septum perforation (the occurrence rate of "one-and-a-half" : 0%, bilateral: 27%). Conclusion: The "one and a half" approach increases the ability to control and completely resect the lesion beyond the medial edge of the internal carotid artery on the same side of the nostril involving endoscope. It is a good supplement and improvement to the bilateral approach.

Effects of oat protein supplementation on skeletal muscle damage, inflammation and performance recovery following downhill running in untrained collegiate men.

The positive influence of animal-based protein supplementation during muscle-damaging exercise has been widely studied. However, the effects of plant-based proteins remain unclear and require further clarification. This study investigated the protective role of oat protein against exercise induced muscle damage (EIMD), subsequent inflammation, and loss of performance induced by downhill running. Subjects consumed either oat protein (25 g protein) or a placebo for 14 days prior to a downhill running test and then for 4 days thereafter. Treatments with oat protein for 19 days markedly alleviated eccentric exercise induced skeletal muscle soreness, and reduced the elevation of plasma IL-6 concentrations and serum creatine kinase, myoglobin and C reactive protein contents. In addition, oat protein supplementation significantly inhibited limb edema following damaging exercise, and the adverse effects on muscle strength, knee-joint range of motion, and vertical jump performance were lessened. Furthermore, the administration of oat protein facilitated recovery from exhaustive downhill running in this study. These findings demonstrated that oat protein supplementation has the potential to alleviate the negative effects of eccentric exercise in untrained young males.

Vascular risk factors and depression in Parkinson's disease.

BACKGROUND AND PURPOSE: The aim of this study was to address the vascular depression hypothesis in Parkinson's disease (PD) from a large cohort of Chinese population. METHODS: A cross-sectional analysis of 1784 Chinese patients with PD was conducted. Patients were divided into absence of depression (score ≤ 20) and presence of depression (score > 20) based on assessment of the Hamilton Depression Rating Scale. Other clinical assessments included the Unified PD Rating Scale (UPDRS), the Hamilton Anxiety Rating Scale, the frontal assessment battery (FAB) and the Montreal Cognitive Assessment (MoCA). RESULTS: Patients with depression showed a higher proportion of women, longer disease duration, higher UPDRS part III score, higher levodopa equivalent daily dose use, higher occurrences of motor fluctuation and dyskinesia, lower FAB score and lower MoCA score than those without depression (P < 0.05). The proportions of drinking and overweight/obesity in the depression group were significantly lower than those in the non-depression group (P < 0.05). A forward binary logistic regression model indicated that depression in PD was associated with female sex [odds ratio (OR) 1.376, P = 0.025], higher UPDRS part III score (OR 1.042, P < 0.001), lower FAB score (OR 0.937, P = 0.015), anxiety (OR 18.156, P < 0.001) and overweight/obesity (OR 0.700, P = 0.019), whereas no associations were found with hypertension, diabetes, smoking, drinking, hyperlipidaemia and heart disease. CONCLUSIONS: Our study failed to verify the vascular depression hypothesis in PD. On the contrary, it was demonstrated that overweight/obesity is negatively associated with the presence of depression in PD.

A potential strategy for counteracting age-related sarcopenia: preliminary evidence of combined exercise training and leucine supplementation.

Previous research has demonstrated the positive effects of concurrent/combined aerobic and resistance exercise or leucine supplementation on skeletal muscle protein synthesis (MPS) and hypertrophy in aging organisms. However, the effects of a multimodal intervention which combines both aerobic and resistance exercise and leucine supplementation has not been fully elucidated. Eighteen month old and 2 month old C57BL/6 mice were assigned to aging control (AC, n = 8), aging and multimodal intervention (AMI, n = 8) and young control (YC, n = 8). Mice in the YC and AC groups were fed an alanine-rich diet (3.4%), and mice in the AMI group received an isonitrogenous leucine-supplemented (5%) diet in combination with combined aerobic (30 minutes swimming) and resistance exercise training (incremental jumping submersed in water with overload corresponding to 40%-50% body weight) for a total of 4 weeks. The gastrocnemius muscles were dissected for western blotting detection (signaling proteins involved in MPS) and the ex vivo determination of protein synthesis and protein content. The muscle strength of the hind limbs was measured pre-experiment and repeated once per week on Sunday for 4 weeks. Mice in the AC and AMI groups showed lower ex vivo protein synthesis, protein content, expression of signaling proteins involved in MPS, maximal grip strength but higher plasma cortisol compared with the YC group post intervention. When compared to AC mice, the multimodal treatment led to lower activity of Sestrin2, higher expression of PI3K III and the phosphorylation of mTOR, p70S6K and 4E-BP1, as well as higher plasma leucine, wet gastrocnemius muscle weight and muscle weight to body weight ratio. Furthermore, the multimodal intervention induced more pronounced anabolic response such as higher ex vivo protein synthesis rate, total protein content, and myofibrillar fractions in gastrocnemius muscle, and greater maximum grip strength. The present research shows that a multimodal intervention including combined both aerobic and resistance exercise training and 5% leucine supplementation has the potential to maintain skeletal muscle protein synthesis and attenuate losses in muscular strength during the aging process.

Expression and significance of miR-21 in multiple myeloma patients.

The aim of the present study is to examine the expression level of peripheral mir-21 in multiple myeloma (MM) patients and to determine its clinical significance. MM patients (30), monoclonal gammopathy of undetermined significance (MGUS) patients (14), and normal controls (20) were recruited to determine the serum level of ß2-MG, IgA and IgM, IgG, λ, κ, TP, ALB, Hb, LDH, and Ca(2+). Gene expression of mir-21 was quantified by SYBR green real-time fluorescent quantitative PCR. We found that the expression level of serum mir-21 in the MM group was significantly higher than the MGUS group and the NC group (P < 0.01). According to the ISS installment, the level of mir-21, lgG, κ, and ALB in the MM group in stage I differed from that in stages II and III. The level of IgA, ß2-MG in stage III was higher as compared with stage I and II (P < 0.05 and P < 0.01).The levels of mir-21, κ, (κ+λ), IgG, (IgG + IgA + IgM), and ß2-MG in MM patients were positively correlated with ALB (P < 0.01). Based on the results, miR-21 plays an important role as an oncogene. Mir-21 may be important in the occurrence, development, and disease prognosis of MM.

An association analysis of the rs1572931 polymorphism of the RAB7L1 gene in Parkinson's disease, amyotrophic lateral sclerosis and multiple system atrophy in China.

BACKGROUND AND PURPOSE: Recently, the rs1572931 single-nucleotide polymorphism (SNP) of the putative promoter of the member RAS oncogene family-like 1 (RAB7L1) gene was reported to be associated with reduced risk for Parkinson's disease (PD) in the Ashkenazi Jewish population. Ethnic-specific effects are an important consideration in genome-wide association studies. Considering that the clinical manifestations and pathological characteristics overlap between PD, amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA), the possible associations between the rs1572931 SNP and these three diseases were studied in the Chinese population. METHODS: A total of 1011 PD patients, 778 sporadic ALS (SALS) patients, 264 MSA patients and 516 healthy controls (HC) were included in this study. All subjects were genotyped for the rs1572931 SNP by using polymerase chain reaction and direct sequencing. RESULTS: Significant differences were observed in the genotype and minor allele frequency (MAF) of rs1572931 between PD and HC (P = 0.0001 and P = 1.08E-04, respectively) and between late-onset PD and matched controls (P = 0.0011 and P = 0.0002, respectively). However, no differences were observed between early-onset PD and HC. The number of minor allele carriers was significantly lower in PD patients than in HC (P = 2.96E-05, odds ratio 0.63, 95% confidence interval 0.51-0.78). No differences were observed between groups with respect to sex, onset symptoms, absence or presence of cognition impairment, anxiety or depression. In addition, no differences were found in the genotype and MAF of rs1572931 between SALS and HC or between MSA and HC. CONCLUSION: Our results suggest that rs1572931 decreases the risk for PD but not for ALS and MSA in the Chinese population. However, the polymorphism is unlikely to be a common cause of SALS and MSA in the Chinese population.

Diagnostic value of glypican-3 in alpha fetoprotein negative hepatocellular carcinoma patients.

BACKGROUND: The prognosis of patients with hepatocellular carcinoma(HCC) is generally very poor with a 5-year survival rate of less than 15% since most of them are diagnosed clinically at their late stage. However, the differential diagnosis between alpha fetoprotein(AFP) negative HCC and cirrhotic nodules is still difficult. OBJECTIVES: To evaluate the diagnostic value of glypican-3(GPC3) in patients with AFP negative hepatitis B related HCC. METHODS: The liver tissue GPC3 (GPC3L) expression was tested from 426 for surgery and 179 of needle biopsies of hepatitis B related HCC patients using immunohistochemistry staining. Serum GPC3 (GPC3S) and AFP were also measured. RESULTS: Among surgical HCC samples, 80.0% of GPC3L expression was positive, however, in paracarcinomatous and cirrhotic nodules were negative. In needle biopsy tissues, GPC3L positively expression was in 74.9%. The sensitivity of AFP>400 µg/L was 25.4%. The GPC3S >3.5 µg/L was determined as a positive. The area of ROC curve of GPC3S was 0.68(95% CI 0.56-0.79,P<0.05) in all HCC patients,0.81 (95% CI 0.62 -0. 98, P<0.05) in AFP greater or equal to 400 µg/L and 0.64 (95% CI 0.51-0.77, P=0.051) in AFP negative patients. The GPC3S was positive in 48.8% of patients with AFP negative. No difference was observed between GPC3L/GPC3S and serum AFP. CONCLUSIONS: GPC3 may be helpful in improving diagnosis of HCC and in differentiating diagnosis between AFP negative HCC and cirrhotic nodules.

Expression of Toll-like receptors 2 and 4 and the OPG-RANKL-RANK system in inflammatory external root resorption and external cervical resorption.

AIM: To investigate and compare the expression of the pathogen recognition receptors Toll-like receptor (TLR) 2 and TLR4, and the hard tissue resorption triad osteoprotegerin (OPG)-receptor activator of nuclear factor kappa-B ligand (RANKL)-receptor activator of nuclear factor kappa-B (RANK) in external inflammatory root resorption of endodontic origin (ER) and external cervical root resorption (ECR) by immunohistochemistry. METHODOLOGY: Formalin-fixed, paraffin-embedded archival specimens collected from teeth that were diagnosed clinically, radiographically and histopathologically with either ER (n = 9) or ECR (n = 9) were processed for immunohistochemistry to investigate and compare levels of TLR2, TLR4, OPG, RANKL, RANK, CD3, CD19 and CD83 expression. The histological features were evaluated via haematoxylin and eosin stain. Taylor's modification of the Brown and Brenn Gram stain was used for examining the presence and distribution of bacteria. All stained slides were digitally photographed and qualitatively analysed, and F test and unpaired Student's t-test were used for statistical analysis. RESULTS: Both ER and ECR showed similar immuno-histopathology characteristics of a fibrovascular connective tissue with varying degrees of inflammatory infiltrate consisting of T and B lymphocytes, dendritic cells, polymorphonuclear lymphocytes and plasma cells. Colonies of bacteria were identified in the majority of lesions, and this correlated with the cellular expression of TLR2 and TLR4 in all lesions. Similarly, all lesions showed a significantly higher (P < 0.05) level of cells expressing RANKL than OPG, indicating hard tissue resorption processes where active in the lesions. CONCLUSION: The immunohistopathology patterns of ECR samples were consistent with the bacteria-driven ER specimens, suggesting bacteria-induced inflammation may be involved in ECR.

Time course of Keap1-Nrf2 pathway expression after experimental intracerebral haemorrhage: correlation with brain oedema and neurological deficit.

Oxidative stress (OS) is involved in the progression of intracerebral haemorrhage (ICH)-induced secondary brain injury. The pathway involving Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2) is currently recognised as the major endogenous regulatory system against oxidative injury. Although its beneficial role has been described for ICH, the time course of Keap1-Nrf2 pathway expression, the activity of downstream antioxidative enzymes, and the association with brain oedema and neurological deficits have not been fully investigated. In this study, we investigated the temporal changes in expression of Keap1, Nrf2, and their downstream antioxidative proteins in the ICH rat brain. We additionally quantified the relationship between these gene and protein changes with brain water content and neurological behaviour scores. After blood infusion, Keap1 showed decreased expression starting at 8 h, whereas Nrf2 began to show a significant increase at 2 h with a peak at 24 h. Keap1 and Nrf2 are chiefly expressed in neuronal cells but not in glial cells. The downstream antioxidative enzymes such as haemeoxygenase-1 (HO-1), glutathione (GSH), thioredoxin (TRX), and glutathione-S-transferase (GST-α1) increased to different degrees during the early stages of ICH. Among these enzymes, HO-1 showed a significant time-dependent increase starting 8 h after ICH. In addition, there was a positive correlation between the HO-1 level and brain water content. In combination, these results suggest that activation of the Keap1-Nrf2 pathway may play an important endogenous neuroprotective role during OS after ICH. Because HO-1 expression is temporally associated with brain oedema - reflective of the severity of brain injury - it may be used as a biomarker of haeme-mediated oxidative damage after ICH.

Bax and Bcl-xL exert their regulation on different sites of the ceramide channel.

The present study demonstrates the important structural features of ceramide required for proper regulation, binding and identification by both pro-apoptotic and anti-apoptotic Bcl-2 family proteins. The C-4=C-5 trans-double bond has little influence on the ability of Bax and Bcl-xL to identify and bind to these channels. The stereochemistry of the headgroup and access to the amide group of ceramide is indispensible for Bax binding, indicating that Bax may interact with the polar portion of the ceramide channel facing the bulk phase. In contrast, Bcl-xL binding to ceramide channels is tolerant of stereochemical changes in the headgroup. The present study also revealed that Bcl-xL has an optimal interaction with long-chain ceramides that are elevated early in apoptosis, whereas short-chain ceramides are not well regulated. Inhibitors specific for the hydrophobic groove of Bcl-xL, including 2-methoxyantimycin A3, ABT-737 and ABT-263 provide insights into the region of Bcl-xL involved in binding to ceramide channels. Molecular docking simulations of the lowest-energy binding poses of ceramides and Bcl-xL inhibitors to Bcl-xL were consistent with the results of our functional studies and propose potential binding modes.