Objective To examine the expression variation of toll-like receptor 2 (TLR 2)in peripheral blood monocytes of patients with rheumatoid arthritis (RA)and explore its role in pathogenesis of RA.Methods Mean fluorescence intensity of TLR 2 expression on the surface of peripheral blood monocytes were detected by flow cytometry and independent samples t-test was used for statistical analysis.Results Mean fluorescence intensity of TLR 2 expression on the surface of peripheral blood CD14+ CD45+ cell of RA patients was 357.68±86.97,while in normal control it was 223.71±87.70.It indicates that the expression of TLR 2 on peripheral blood monocytes in patients with active disease was higher than in normal indi-viduals (t=5.478,P=0.005,P<0.01).Conclusion Increase of the TLR 2 expression on peripheral blood monocytes in patients with active disease suggests its import role in pathogenesis of RA.

Objective: To observe the preventive effect of alkaline drinking water on hyperuricemia in mice. Methods: Sixty male SPF Kunming mice were randomly divided into six groups: pH 7.3, pH 8.0, pH 9.3 intervention groups, in which the mice were given water with pH values of 7.3±0.5, 8.0±0.5 and 9.3±0.6, respectively; the control group, model group and positive drug group ( with 2 g/L allopurinol ) were given double distilled water. Except for the control group, the mice in each group were given yeast by gavage (1.5 g/mL) for 13 days. On the 14th day, the mice were injected with 300 mg/kg potassium oxyzinate by intraperitoneal injection, and then fasted for 1 day. On the 16th day, serum uric acid, creatinine and urea nitrogen were detected, and renal tissues were stained to observe the morphology.The expression levels of neutrophil gelatinase-associated lipocalin ( NGAL ), tissue inhibitor of metalloproteinase 1( TIMP1 ), organic anion transporter 1 ( OAT1 ) and urate transporter 1 ( URAL-1 ) in renal tissues were determined bywestern blotting. The mRNA expression levels of URAL-1 and OAT1 were detected by real-time fluorescent quantita⁃tive polymerase chain reaction. Results: The level of serum uric acid was higher in the model group than in the control group and in the pH 9.3 intervention group (both P<0.05). The number and area of renal tubular lesions were less in the pH 9.3 intervention group than in the model group (all P<0.05). The relative expression levels of NGAL and URAT-1 proteins were lower in the pH 9.3 intervention group than in the model group, and the relative expression level of OAT1 protein was higher in the pH 9.3 intervention group than in the model group ( all P<0.05). The relativeexpression level of URAT-1 mRNA was lower in the pH 9.3 intervention group than in the model group, and the rela⁃tive expression level of OAT1 mRNA was higher in the pH 9.3 intervention group than in the model group ( all P<0.05 ). Conclusion Alkaline drinking water with pH value of 9.3±0.6 can effectively prevent hyperuricemia and acute kidney injury in mice.

Background and Objectives: This study was to investigate the role of microRNA-29a-3p (miR-29a-3p) in human bone marrow mesenchymal stem cells (hBMSCs), and its relationship with steroid-associated osteonecrosis. Methods: and Results: The online tool GEO2R was used to screen out the differentially expressed genes (DEGs) in GSE123568 dataset. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-29a-3p, forkhead box O3 (FOXO3), alkaline phosphatase (ALP), bone gamma-carboxyglutamate protein (OCN) and RUNX family transcription factor 2 (Runx2) in the hBMSCs isolated from the patients with steroid-associated osteonecrosis. CCK-8 assay was executed to measure cell viability; western blot assay was utilized to detect FOXO3, ALP, Runx2, OCN and β-catenin expression. Cell apoptosis and cell cycle were detected by flow cytometry. Immunofluorescence assay was used to detect the sub-cellular localization of β-catenin. Bioinformatics analysis and luciferase reporter gene assay were performed to confirm whether miR-29a-3p can combine with FOXO3 3’UTR. MiR-29a-3p was markedly up-regulated in the hBMSCs of patients with steroid-associated osteonecrosis, while FOXO3 mRNA was significantly down-regulated. Transfection of miR-29a-3p mimics significantly inhibited the hBMSCs’ proliferation, osteogenic differentiation markers’ expressions, including ALP, Runx2, OCN, and repressed the ALP activity, as well as promoted cell apoptosis and cell-cycle arrest. FOXO3 was identified as a target gene of miR-29a-3p, and miR-29a-3p can inhibit the expression of FOXO3 and β-catenin, and inhibition of miR-29a-3p promoted translocation of β-catenin to the nucleus. Conclusions MiR-29a-3p can modulate FOXO3 expression and Wnt/β-catenin signaling to inhibit viability and osteogenic differentiation of hBMSCs, thereby promoting the development of steroid-associated osteonecrosis.

Carcinoma, Hepatocellular ; diagnosis ; surgery ; therapy ; Hepatectomy ; Humans ; Liver Neoplasms ; diagnosis ; surgery ; therapy

Hereditary spastic paraplegia is a heterogeneous group of genetic neurodegenerative disorders of the nervous system. It is classified into four subtypes based on the mode of inheritance; and among them, most autosomal recessive hereditary spastic paraplegia cases are due to type SPG11 and SPG15 gene mutations. Autosomal recessive hereditary spastic paraplegia cases with SPG30 gene mutation have never been reported in China. Herein, we present our experience with a case of hereditary spastic paraplegia with SPG30 gene mutation in our hospital from North East China. In this patient we detected a missense mutation of c.499 C>T (p.Arg167Cys) in gene KIF1A, a causative gene of type SPG30.

BACKGROUND:Hyperbaric oxygen (HBO) therapy can aleviate the skin flap congestion by improving the angiogenesis and increasing the oxygen content of blood in skin flaps. Although the HBO therapy ability to increase flap survival has been wel described, the research on the application of HBO pretreatment in skin flap transplantation does not arouse adequate concern.
OBJECTIVE: To investigate the effect of HBO pretreatment on early-stage flap congestion in the rat model of over-length dorsal random skin flaps.
METHODS: Thirty-six SD rats were randomly divided into control group (n=12), HBO pretreatment group (n=12) and HBO treatment group (n=12). Rats in the HBO pretreatment group received 4 days of HBO therapy prior to transplantation, once a day. Rats in the HBO treatment group received 4 days of HBO therapy after transplantation. Rats in the control group were raised in the normal conditions after flap transplantation. At postoperative days 3 and 5, rats were sacrificed and the samples were colected. The inflammation of flap tissues was detected using hematoxylin-eosin staining. The expression of vascular endothelial growth factor and transforming growth factor-β was analyzed by immunohistochemistry staining. The flap survival rate was calculated at postoperative day 5.
RESULTS AND CONCLUSION:The flap survival area of the HBO pretreatment group and HBO treatment group was larger than that of the control group (P < 0.05). At postoperative days 3 and 5, the expression levels of vascular endothelial growth factor and transforming growth factor-β in the flap tissue were higher in the HBO pretreatment group and HBO treatment group than the control group (P < 0.05). However, there was no significant difference in the flap survival area and the expression of vascular endothelial growth factor and transforming growth factor-β between HBO pretreatment and HBO treatment groups (P > 0.05). HBO pretreatment can increase the expression of vascular endothelial growth factor and transforming growth factor-β and promotes angiogenesis in random pattern flaps,thereby improving skin flap survival.

Objective To study the clinical efficacy and adverse reactions of the preoperative neo-adjuvant chemotherapy with oxaliplatin plus fluorouracil and calcium folinate (FOLFOX) in the treatment of advanced gastric carcinoma that was difficult to undergo radical operation. Methods We enrolled 16 patients with advanced gastric carcinomas that were unable to undergo radical operation admitted to our hospital from April 2008 to October 2009. The neo-adjuvant chemotherapy regimen was oxaliplatin 130 mg/m~2 for first one, fluorouracil 500 mg/m~2 and calcium folinate 200 mg/m~2 from first day to fifth day,and one treatment course was three weeks and the patients underwent two courses.The changes of the primary lesion and the adverse reactions of the patients were observed. Results Carcinomas of 13 patients were degraded after the treatment, of which, 11 patients underwent radical resections after 4-6 weeks after operation.There were two cases of complete remission (CR) , 10 cases of partial remission (PR), three cases of stable disease(SD) and one case of progress disease(PD) , and the total effective rate was 75.0% (12/16). Adverse reactions included bone marrow suppression, diarrhea, nausea and vomiting and paresthesia, which were relieved after appropriate symptomatic treatment. Conclusions Neoadjuvant chemotherapy with FOLFOX can improve the resection rate of the advanced gastric carcinoma that is unable to undergo radical resection, and the patients' tolerability to this regimen is favorable.Thus, the regimen is worthy of generalizing.

Objective:To investigate the characteristics of the sleep quality and health-related quality of life (HRQoL), and analyze the different effects of sleep quality on HRQoL among young and middle-aged people.Methods:A cross-sectional study recruited 1 976 participants.All participants completed a self-designed questionnaire for the adults' general condition, the Pittsburgh sleep quality index (PSQI) and Short-Form health survey (SF-36). All participants were divided into 3 age groups: 18-29-year-old group( n=1 148), 30-44-year-old group( n=586) and 45-59-year-old group ( n=242). SPSS 23.0 software was used for statistical analysis.Chi-square test was used to analyze the general characteristics of the three age groups.Non-parametric test was used to analyze the scores of the three age groups in different dimensions of sleep quality. One-way ANOVA was used to analyze the mean scores of the three age groups in different dimensions of HRQoL. Stepwise regression analysis was used to analyze the effect of sleep quality on HRQoL among the three groups after control the confounding factors such as marital status, education, smoking, drinking and exercise habits and past medical history. Results:In terms of sleep quality, the total PSQI scores of 18-29-year-old, 30-44-year-old and 45-59-year-old groups(4(2, 6), 4(2, 6), 4(2, 6)) showed statistically significant differences ( Z=10.951, P=0.004). In terms of HRQoL, there were statistically significant differences in physical component summary scores (18-29-year-old: 82.51±12.62, 30-44-year-old: 80.72±13.63, 45-59-year-old: 82.04±13.07, F=3.667, P=0.026) and mental component summary scores(18-29-year-old: 76.09±15.46, 30-44-year-old: 77.20±16.14, 45-59-year-old: 81.82±14.14, F=13.649, P<0.001) among young and middle-aged people in different age groups.Regression analysis found that daytime dysfunction was an independent influencing factor for HRQoL in young and middle-aged population ( β=-0.308--0.425, all P<0.01). Sleep disorders significantly decreased Physical Component Summary of HRQoL in young-aged people ( β=-0.127--0.215, all P<0.01). The use of hypnotic drugs significantly reduced the scores in the physiological field in the young adults aged 30-44 ( β=-0.076, P<0.05). The duration of sleep significantly decreased the scores in the mental domain of young adults aged 30-44 ( β=-0.112, P<0.01). Subjective sleep quality was an independent factor that significantly decreased HRQoL in young adults aged 18-29 and 30-44 years ( β=-0.089--0.169, all P<0.01). Conclusion:Sleep quality and HRQoL of young and middle-aged people in different age groups show different characteristics.The effect of sleep quality on HRQoL is different among people in different ages.Taking targeted interventions for people of different ages to improve the sleep quality may be an effective way to improve their HRQoL.

Epilepsy is a clinical syndrome caused by highly synchronized abnormal discharges of brain neurons due to various causes. Studies have shown that abnormal hippocampal neurogenesis is observed in both human epilepsy patients and animal models of epilepsy， and abnormal neurogenesis can alter normal neural circuits in the hippocampus and promote the development of hippocampal sclerosis， ultimately leading to the development and progression of epilepsy. The low-pressure hypoxic environment unique to the plateau affects hippocampal neurogenesis by regulating hypoxia-inducible factors， the Wnt signaling pathway， the Notch signaling pathway， and EPO， thereby affecting the susceptibility to epilepsy and the development and progression of epilepsy. This article reviews the mechanism of interaction between hippocampal neurogenesis and epilepsy in high-altitude hypoxic environments， in order to provide potential strategies and targets for the treatment of epilepsy.
Neurogenesis ; Hippocampus

Objective: To investigate the expression of ALC1 protein during esophageal squamous cell carcinoma (ESCC) development and progression, so as to explore its association with clinicopathological characteristics and overall survival of ESCC patients, and the effect of ALC1 overexpression on malignant biological behavior of esophageal squamous cells. Methods: Immunohistochemistry (IHC) was used to detect ALC1 protein expression in 245 primary ESCC tissues and their paired normal esophageal mucous membranes, and to determine its correlation to gender, age, tumor cell differentiation, invasion, TNM stage, lymph nodes metastasis, and overall surviv-al rate of ESCC patients. MTT assay, colony formation assay, transwell invasion, and wound healing assay were used to observe the ef-fect of ALC1 on ESCC cell proliferation, invasion, and migration. Results: The expression ratio of ALC1 in esophageal squamous cell car-cinoma was higher compared with that in their paired normal esophageal mucous membranes (41.6% vs . 21.2% , P<0.05). Upregula-tion of ALC1 was associated with ESCC invasion, TNM stage, and lymph node metastasis (P<0.05). The overall survival of ESCC patients with ALC1 overexpression was significantly lower than that in patients with downregulated ALC1 expression (P=0.002). Therefore, ALC1 may promote the proliferation, invasion, and migration of ESCC cells. Conclusions: ALC1 upregulation may play an important role in the progression and development of ESCC. Upregulation of ALC1 leads to poorer disease prognosis, and could promote the prolifera-tion, invasion, and migration of the KYSE30 ESCC cells. Therefore, ALC1 may have potential prognostic value for ESCC patients.