BACKGROUND: Cancer stem-like cells (CSCs) are a small subset of cells in tumors that exhibit self-renewal and differentiation properties. CSCs play a vital role in tumor formation, progression, relapse, and therapeutic resistance. B7-H3, an immunoregulatory protein, has many protumor functions. However, little is known about the mechanism underlying the role of B7-H3 in regulating gastric cancer (GC) stemness. Our study aimed to explore the impacts of B7-H3 on GC stemness and its underlying mechanism. METHODS: GC stemness influenced by B7-H3 was detected both in vitro and in vivo . The expression of stemness-related markers was examined by reverse transcription quantitative polymerase chain reaction, Western blotting, and flow cytometry. Sphere formation assay was used to detect the sphere-forming ability. The underlying regulatory mechanism of B7-H3 on the stemness of GC was investigated by mass spectrometry and subsequent validation experiments. The signaling pathway (Protein kinase B [Akt]/Nuclear factor erythroid 2-related factor 2 [Nrf2] pathway) of B7-H3 on the regulation of glutathione (GSH) metabolism was examined by Western blotting assay. Multi-color immunohistochemistry (mIHC) was used to detect the expression of B7-H3, cluster of differentiation 44 (CD44), and Nrf2 on human GC tissues. Student's t -test was used to compare the difference between two groups. Pearson correlation analysis was used to analyze the relationship between two molecules. The Kaplan-Meier method was used for survival analysis. RESULTS: B7-H3 knockdown suppressed the stemness of GC cells both in vitro and in vivo . Mass spectrometric analysis showed the downregulation of GSH metabolism in short hairpin B7-H3 GC cells, which was further confirmed by the experimental results. Meanwhile, stemness characteristics in B7-H3 overexpressing cells were suppressed after the inhibition of GSH metabolism. Furthermore, Western blotting suggested that B7-H3-induced activation of GSH metabolism occurred through the AKT/Nrf2 pathway, and inhibition of AKT signaling pathway could suppress not only GSH metabolism but also GC stemness. mIHC showed that B7-H3 was highly expressed in GC tissues and was positively correlated with the expression of CD44 and Nrf2. Importantly, GC patients with high expression of B7-H3, CD44, and Nrf2 had worse prognosis ( P = 0.02). CONCLUSIONS B7-H3 has a regulatory effect on GC stemness and the regulatory effect is achieved through the AKT/Nrf2/GSH pathway. Inhibiting B7-H3 expression may be a new therapeutic strategy against GC.
Humans ; Cell Line, Tumor ; Neoplasm Recurrence, Local ; NF-E2-Related Factor 2/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Stomach Neoplasms

Cholestatic liver disease is a common disease that causes bile flow dysfunction due to various reasons. The etiology of cholestatic liver disease is complexed, and therapeutic drugs are extremely limited. To date, ursodeoxycholic acid is the only FDA-approved drug for treating primary biliary cirrhosis, whereas its efficacy is limited to early stage of the disease, therefore novel drugs are urgently needed. Nuclear receptors become therapeutic hotspot target in cholestasis since these receptors play a key role in regulating bile acid homeostasis. Peroxisome proliferator-activated receptor (PPAR) is an important nuclear receptor involved in regulating multiple mechanisms of cholestasis in vivo. It can improve intrahepatic cholestasis by inhibiting bile acid synthesis, reducing bile acid toxicity, affecting the expression of bile acid metabolic enzymes and transporters, and can play an anti-inflammatory, anti-oxidation and anti-fibrosis role. A number of studies have shown that PPAR agonists represented by fibrates alone or in combination can improve liver function indexes, inflammatory factors and fibrosis markers in patients with cholestasis. This review analyzes and summarizes the lastest advances in the molecular mechanism of PPAR as a therapeutic target for cholestasis and drug treatment in development or have been used in clinical.

BACKGROUND: Synovectomy has been introduced into total knee arthroplasty (TKA) with the aim of relieving pain and inflammation of the synovium. However, there are no long-term, comparative data to evaluate the effect of synovectomy in TKA. This study was aimed at assessing pain, function, and complications in patients undergoing synovectomy during TKA for osteoarthritis (OA) at long-term follow-up. METHODS: This was a prospective randomized controlled trial of 42 consecutive patients who underwent staged bilateral TKA. Patients undergoing the first-side TKA were allocated to receive TKA with or without synovectomy followed by a 3-month washout period and crossover to the other strategy for the opposite-side TKA. The overall efficacy of both strategies was evaluated by determination of blood loss, the Knee Society score (KSS), and knee inflammation conditions during a 3-month postoperative period. The postoperative pain, range of motion (ROM), and complications were sequentially evaluated to compare the two groups until 10 years after surgery. RESULTS: At the 10-year follow-up, both groups had a similarly significantly improved ROM (114.88 ± 9.84° vs. 114.02 ± 9.43°, t  = 0.221, P  = 0.815) and pain relief with no differences between the two groups (1.0 [1.0] vs. 1.0 [1.5], U  = 789.500, P  = 0.613). Similar changes in total blood loss, KSS, and knee inflammation were found in both groups during 3 months postoperatively ( P  > 0.05). Additionally, there was no significant difference regarding complications and satisfaction between the two groups ( P  > 0.05). CONCLUSIONS: Synovectomy in conjunction with TKA for primary OA does not seem to provide any benefit regarding postoperative pain, ROM, and satisfaction during a 10-year follow-up. In addition, it may not result in more blood loss and increased incidence of long-term complications. Based on our long-term findings, it should not be performed routinely. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR-INR-16008245; https://www.chictr.org.cn/showproj.aspx?proj=13334 .
Humans ; Arthroplasty, Replacement, Knee/methods* ; Synovectomy/methods* ; Osteoarthritis, Knee/surgery* ; Prospective Studies ; Pain, Postoperative ; Inflammation/etiology* ; Range of Motion, Articular ; Knee Joint/surgery* ; Treatment Outcome ; Knee Prosthesis/adverse effects*

Objective:To investigate the relationship between painful tonic spasm (PTS) and spinal cord injury in patients with neuromyelitis optica spectrum disorder (NMOSD).Methods:The clinical data, serum AQP4-IgG antibody levels and magnetic resonance data of 138 patients with NMOSD were analyzed. Those with spinal cord involvement were assessed using the American Spinal Injury Association Impairment Scale (AIS) to investigate the relationship between PTS and spinal cord injury.Results:The prevalence of PTS among the NMOSD patients was 36% (51/138), and all of the 51 NMOSD patients with PTS showed spinal cord lesions, an incidence significantly different from those without PTS. However, there were no significant differences in the age of onset, gender, disease duration, AQP4-IgG levels, lesion location, range of spinal cord lesions, or AIS grade between the NMOSD patients with and without PTS.Conclusion:PTS is a prevalent concomitant of NMOSD. As a common symptom of remission and recurrent remission, PTS is associated with myelopathy. This study failed to find any correlation between PTS and the affected spinal cord site or segment range. There was also no correlation between PTS and AIS grading among these subjects.

OBJECTIVE：To investigate the effects of gypenosides （GPs）on gene expression of major urinary proteins （Mups） in liver tissue of hypercholesterolemia model mice. METHODS ：C57BL/6J mice were divided into control （ND）group，model （HFD）group and GPs therapy （GP）group according to body weight （BW），with 11 mice in each group. Except for ND group ， other groups were given high-lipid diet to induce hypercholesterolemia model. From the 17th week of feeding ，ND group and HFD group were given constant volume of 0.1％CMC-Na solution intragastrically ；GP group were given GPs suspension （250 mg/kg） intragastrically，once a day ，for consecutive 22 weeks. BW ，the levels of blood glucose （BG）and blood lipid （TC，LDL-C）were detected in each group. Total RNA of liver tissue was extracted ，and reverse transcription library was constructed and RNA-seq sequencing was performed. The differentially expressed genes were screened by PCA ，volcano map and scatter plot. RT-qPCR was used for verification for differentially expressed genes. The correlation between the expression of differentially expressed genes and the above pharmacodynamic indexes was analyzed by bivariate analysis. RESULTS ：Compared with ND group ，BW，the levels of BG，TC and LDL-C in HFD group were increased significantly （P＜0.05）. Compared with HFD group ，above indexes of GP group were decreased significantly except for BW （P＜0.05）. PCA showed that the data of ND group and HFD group distributed in different quadrants ，and the data distribution of GP group was between above two groups. mRNA of Mup4，Mup5，Mup11，Mup15 and Mup21 in liver tissue of mice were increased significantly after treated with high-fat diet （P＜0.05）. mRNA of Mup3，Mup4， Mup5，Mup8，Mup12 and Mup21 were decreased significantly after treated with GPs （P＜0.05）. In ND group vs. HFD group and HFD group vs. GP group ，mRNA of Mup4，Mup5 and Mup21 genes changed significantly and the trend was opposite. Results of RT-qPCR verification showed that compared with ND group ，relative mRNA expression of Mup4，Mup5 and Mup21 gene were increased significantly in HFD group （P＜0.05）. Correlation analysis revealed that mRNA expression of Mup5 was positively correlated with the levels of TC and BG （r＝0.727 1，0.670 6，P＜0.05），mRNA expression of Mup4 and Mup21 were positively correlated with the level of BG （r＝0.737 8，0.721 5，P＜0.05）. CONCLUSIONS ：GPs can regulate the expression of Mups genes in liver tissue of hypercholesterolemia model mice ， and reduce glucose and lipid level through regulating the mRNA over-expression of Mup4，Mup5 and Mup21.

Objective Study on the absorption,distribution,transformation,excretion and toxicity of four forms of arsenic in rats.Methods Four thousand and fifty data were obtained from 28 days animal metabolism experiments of 81 rats exposed to the four As species.Distribution,metabolism,excretion,and subacute toxicity of 4 As species were compared by analyzing the arsenate [As(V)],arsenite [As(Ⅲ)],methyl arsenate (MMAV) and dimethyl arsenate (DMAV) content of rat feces (excrement and urine),blood,seven organs,and liver and kidney pathology.Results After oral administration of each As species,82.9％ of As(Ⅲ),85.1％ of As(V),95.0％ of MMAV and 96.2％ of DMAV were accumulatively secreted via feces and urine,while 16.2％ of As(Ⅲ),14.1％ of As(V),4.65％ of MMAV and 0.120％ of DMAV were detected in blood.The DMAV accumulated in blood and urine after dosing As(Ⅲ),As(V) and MMAV,and the content of DMAV in the blood was 8 times greater than urine.Four kinds of arsenic had effects on rat liver and kidney function,the influence on liver was acute phase effect while that on renal was cumulative effects.The effect of As(Ⅲ) was the most significant,followed by MMAV.Four kinds of arsenic could cause tissue deformation and inflammatory cells infiltration,but showed no difference between groups.Conclusion The distribution,metabolism,excretion,and toxicity of the four kinds of arsenic in rats were different in varying degrees.The research of health risk for arsenic should consider its different forms.

Objective To compare the impact of bowel preparation on postoperative complications of patients undergoing radical cystectomy(RC) with ileal conduit diversion(ICD) by meta-analysis.Methods All literature were collected from VIP,CNKI,WanFang Data,CBMdisc,Pubmed,Medline,Embase dated from inception to April 2016.Then literature were grouped into mechanical bowel preparation and nonmechanical bowel preparation,whose differences in the wound,intestinal function,infection and other complications were compared.Results Three RCTs,four cohort studies and 656 cases were taken into account.No statistical difference was observed in the wound infection,wound dehiscence,fascia dehiscence,intestinal obstruction,anastomosis fistula,intestinal fistula,urinary leakage,death of indicators between the two groups.Conclusion Preoperative mechanical bowel preparation did not reduce the occurrence of postoperative complications of the patients with RC undergoing ICD.

Objective To make specific clear labels which can lead us to easily distinguish tube category,function,the drainage of fluid properties and so on,and to improve the safety of patients tube management.Methods Using BarTender software to create labels format,and printing out all kinds of the labels by bar code printer,pasting around at suitable locations.Results Labels designed and printed by Bar-Tender software could be more efficient,accurate and clear to mark patients’drain,which avoided illegible writing.Conclusion Labels de-signed and printed by BarTender software can help doctors and nurses identifying the tube and handover management.

Objective To investigate the correlation between hemorrhage in transurethral resection of prostate ( TURP) and cystospasm and psychonosema of the patients with hyperplasia of prostate. Methods All clinic data of 322 patients with hyperplasia of prostate who have had TURP from 2009 to 2013 were reviewed. These patients were divided into four groups according to the volume of hemorrhage( H):H<400 mL, 400≤H<600 mL, 600≤H<800 mL, H≥800 mL. The quantity of cystospasm and psychonosema was measured by three catego-ries:no symptom, light symptom without treatment, severe symptom with treatment. The differences of the four groups were compared through statistical methods. Results The incidence rates of cystopasm and severity degree of psychonosema were increased with the raise of hemorrhage . Conclusion There is a positive correlation between the incidence rates of cystopasm and psychonosema and the volume of hem-orrhage in the patients with hyperplasia of prostate who have had TURP.

OBJECTIVETo investigate the expression of TMEM16A in gastric carcinoma and its clinical implications.

METHODSA total of 72 surgical specimens of gastric carcinoma were collected for examination of TMEM16A expression with immunohistochemical staining.

RESULTSTMEM16A expression was detected in the cytoplasm and cell membrane of the tumor cells. Of the 72 specimens of the tumor tissues, the total positivity rate of TMEM16A expression was 80.56% (58/72), significantly higher than the rate in the adjacent tissues (4.17%, 3/72, P<0.005).

CONCLUSIONAberrant expression of TMEM16A occurs in the majority of gastric carcinoma cases. TMEM16A can be used as a new candidate target for diagnosis and treatment of gastric carcinoma.

Adult ; Aged ; Anoctamin-1 ; Carcinoma ; metabolism ; pathology ; Chloride Channels ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Proteins ; metabolism ; Stomach Neoplasms ; metabolism ; pathology