Curcumin inhibits advanced glycation end products-induced cell apoptosis and mitochondrial dysfunction via elevating PPARγ in chondrocyte / 中国药理学通报

Aim To explore the mechanism of the protective effect of curcumin on advanced glycation end products (AGEs)-induced chondrocyte apoptosis and mitochondrial dysfunction whether by elevating peroxisome proliferators-activated receptor-γ (PPARγ) or not.Methods The ratio of apoptotic cells was assayed by TUNEL;the mitochondrial membrane potential(△Ψm) was evaluated by Rhodamine-123 fluorescence.The ATP content was assayed by related kits.The activity of caspase-3 was detected by spectrophotometry.The expression of cytochrome C,Bax,and Bcl-2 was detected by Western blot.The PPARγ expression was determined by Western blot and real-time PCR;in addition,its activity was assayed by DNA-binding method.Results AGEs could induce chondrocyte apoptosis and up-regulate the levels of cytochrome C and caspase-3.Simultaneously,AGEs decreased the levels of △ Ψm and ATP production.Mitochondrial permeability conversion pore inhibitor cyclosporine A could significantly protect the cells from apoptosis.In addition,both PPARγ specific agonist pioglitazone and curcumin significantly inhibited AGEs-induced chondrocytes apoptosis and mitochondrial dysfunction.However,pretreatment with PPARγ specific inhibitor GW9662 (10 μ mol · L-1) could significantly antagonize the protective effect of curcumin on mitochondrial damage induced by AGEs.Curcumin could also significantly increase PPARγtranscriptional activity induced by AGEs,together with a significant induction of PPARγprotein and mRNA expression.Conclusion Curcumin could effectively protect AGEs-induced chondrocyte mitochondrial dysfunction by upregulating PPARγ,thus protecting chondrocytes from apoptosis.

Analgesic effect of femoral nerve block versus adductor canal block after total knee arthroplasty: a meta-analysis / 中国组织工程研究

BACKGROUND: In recent years, extensive studies on the pain management after total knee arthroplasty (TKA) have identified different ways of analgesia. Among which, femoral nerve block (FNB) is the standard antalgic method post-TKA for its effective analgesia, but it may reduce the muscle strength of the quadriceps after TKA and cause serious consequences. Adductor canal block (ACB) is a novel antalgic method that provides fast functional recovery and good ability of pain control after TKA. OBJECTIVE: To compare the functional recovery and ability of pain control of ACB and FNB after TKA through a meta-analysis. METHODS: Databases of WanFang, CNKI, PubMed, Web of Science, and Embase were searched for the literature concerning the analgesia and functional recovery after TKA published before March 2017. The articles were evaluated according to the Cochrane system and a meta-analysis was conducted on Revman 5.1. RESULTS AND CONCLUSION: (1) Twelve articles were included involving 802 patients with 872 knees. (2) Meta-analysis results showed that compared with FNB, ACB significantly reduced the Visual Analogue Scale scores at rest at 8 hours postoperatively (P < 0.001) and significantly improved the muscle strength of quadriceps femoris (P < 0.001) and motor capacity (Timed Up and Go test) (P < 0.05); but the scores at rest at 24 and 48 hours postoperatively, and the scores in activity at postoperative different time points, usage of opioids, and hospitalization time did not differ significantly between two groups. (3) ACB can achieve better analgesia at the early period (8 hours) after TKA, better motor capacity and stronger muscle strength of the quadriceps femoris; thereafter, it is a substitute for FNB after TKA.

Down-regulation of Notch1 by small interfering RNA enhances chemosensitivity to gemcitabine in pancreatic cancer cells through activating apoptosis activity / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of down-regulation of Notch1 by Notch1 small interfering RNA (siRNA) on chemosensitivity to gemcitabine in pancreatic cancer cells and its mechanism.</p><p><b>METHODS</b>Notch1 siRNA was transfected to pancreatic cancer cell lines AsPC-1, BxPC-3, MIAPaCa-2 and Panc-1. The transfected pancreatic cancer cells were treated with 10 μmol/L gemcitabine in vitro. The relative quantity of Notch1 mRNA of pancreatic cancer cells was detected by real-time PCR. The inhibition rates of gemcitabine-treated cells were evaluated by CCK-8 method. The expression of Bax protein was examined by Western blot, and the caspase 3 activity was detected by CaspACETM assay system kit.</p><p><b>RESULTS</b>The relative quantity of Notch1 mRNA was the highest in BxPC-3 cell line and the lowest in Panc-1 cells. The inhibition rates of gemcitabine treated-cells were significantly higher in Notch1 siRNA transfection groups than in corresponding siRNA control groups (AsPC-1: 67.5±6.7 vs 47.5±6.8; BxPC-3: 90.5±4.4 vs 70.2±4.2; MIAPaCa-2: 80.9±5.7 vs 58.1±6.0; Ps<0.05), with the overexpression of protein Bax. The activity of caspase 3 was also significantly increased in Notch1 siRNA transfection groups compared with corresponding siRNA control groups (AsPC-1: 28.90±2.70 vs 12.82±3.44; BxPC-3: 59.87±6.77 vs 27.27±11.88; MIAPaCa-2: 29.34±4.06 vs 14.59±4.25; P<0.05).</p><p><b>CONCLUSION</b>Inhibition of Notch signaling pathway by Notch1 siRNA can enhance chemosensitivity to gemcitabine in pancreatic cancer cells through activating apoptosis activity．</p>

Clinicopathological characteristics and surgical treatment of duodenal gastrointestinal stromal tumor / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological characteristics and surgical treatment of duodenal gastrointestinal stromal tumor (GIST).</p><p><b>METHODS</b>Clinicopathological data of 25 cases with duodenal GIST from January 2007 to July 2011 in West China hospital were retrospectively analyzed.</p><p><b>RESULTS</b>All the patients were identified by pathological examination without specific symptoms. Tumors were located in the bulb area in 2 cases, descending portion in 11 cases, transverse portion in 8 cases, and ascending portion in 4 cases. Two cases were at very low risk, 7 at low risk, 6 at intermediate risk, and 10 at high risk. All the patients received surgical resection, including 11 pancreaticoduodenectomies, 10 local tumor resections, 2 duodenal segmental resections, and 2 distal subtotal gastrectomies. Eighteen patients were followed up from 16 to 39 months and 3 patients recurred 18, 30, and 35 months after operation respectively.</p><p><b>CONCLUSIONS</b>Duodenal GIST exhibits no distinct clinical characteristics. Complete removal of the tumor is the main choice of treatment.</p>

A meta-analysis of bone morphogenetic protein for the treatment of open tibial fractures / 中国骨伤

<p><b>OBJECTIVE</b>To systematically assess the clinical efficacy of bone morphogenetic proteins in the treatment of open tibial fractures.</p><p><b>METHODS</b>Based on the principles and methods of Cochrane systematic reviews, the Cochrane Library, PubMed, EMBASE, Chinese Bio-medicine Database, China Journal Full-text Database, VIP database were searched from their establishment to April 2012 in whatever language. Related journals were handsearched as well. Randomized controlled trials (RCTs) of bone morphogenetic protein for the treatment of open tibial fractures were included. The quality of the included trials according to the Cochrane Handbook for Systematic Reviews of Interventions Version was assessed. The Cochrane Collaboration's software RevMan 5.1 was used for meta-analysis.</p><p><b>RESULTS</b>Three RCTs totaling 851 patients were included. The results showed that bone morphogenetic protein had no significant differences in fracture healing [RR = 1.16, 95% CI (0.95,1.41), P = 0.15], but lower secondary interventions incidence rate [RR = 0.72, 95% CI (0.58, 0.89), P = 0.003]. There were no significant differences between the two groups in the incidence of adverse events of infection [RR = 1.31, 95% CI (0.94, 1.81), P = 0.11] and pain [RR = 0.92, 95% CI (0.79, 1.08), P = 0.30].</p><p><b>CONCLUSION</b>Bone morphogenetic protein has certain advantages in treating open tibial fractures. It needs more high-quality articles to assess the long-term effect of different courses of treatments. The above conclusion still needs more high-quality randomized controlled trails to be verified owing to the limitations of the number and quality of systematic review included studies.</p>

Screening the hepatitis B virus PreS1 associated protein by the yeast two-hybrid system / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To screen the hepatitis B virus PreS1 associated protein from normal human liver cDNA library by the yeast two-hybrid system and explore the role of PreS1 protein in the infection of hepatitis B virus (HBV).</p><p><b>METHODS</b>PCR was preformed to amplify the PreS1 gene containing EcoRI and PstI from HBV positive serum, and the production was inserted into plasmid pAS2-1 after digesting with the former two restricted endonuclease, then the bait vector pAS2-1-PreS1 was verified by auto-sequencing assay. The PreS1-BD fusion protein expressed in the yeast cells was confirmed by western blot, after pAS2-1-PreS1 was transfected into the yeast cell AH109. Yeast cells co-transfected with pAS2-1-PreS1 and the normal human liver cDNA library grew in selective SC/-trp-leu-his-ade2 medium, and the second screening was performed with LacZ report gene. Furthermore, segregation analysis and mating experiment were done to eliminate the false positive, then the true positive clones were submitted for PCR and sequencing. The results were submitted to the BLAST notebook of World Wide Wed Site NCBI to seek homologous sequence.</p><p><b>RESULTS</b>Bait vector pAS2-1-PreS1 included the anticipated fragment of PreS1 gene. Western blot showed that pAS2-1-PreS1 could correctly express PreS1-BD fusion protein in the yeast cells. After yeast cells co-transfected with pAS2-1-PreS1 and the normal human liver cDNA library, 97 colonies grew in the selective SC/-trp-leu-his-ade2 medium, only one clone was positive and showed high homology with Homo sapiens nascent-polypeptide-associated complex alpha polypeptide.</p><p><b>CONCLUSION</b>Bait vector pAS2-1-PreS1 is successfully constructed, and nascent-polypeptide-associated complex alpha polypeptide protein expressed in hepatocyte can interact with PreS1 by the yeast two-hybrid system.</p>

The role of T-type calcium channel in the pathogenesis of neuropathic pain in rats / 中华麻醉学杂志

Objective To investigate the effect of intrathecal(IT)mibefradil on the mechanical and thermal hyperalgesia following chronic compression of dorsal mot ganglion(CCD)in rats,trying to elucidate the role of T-type calcium channels in the nociceptive signal transmission at spinal level.Methods Forty-eight male SD rats weighing 230-250 g were randomly divided into 6 groups(n=8 each):group Ⅰ sham operation;group Ⅱ CCD;group Ⅲ CCD+normal saline(N.S.)and group Ⅳ,Ⅴ,Ⅵ CCD+mibefradil 50 ?g(Ⅳ),100 ?g (Ⅴ),200 ?g(Ⅵ).The animals were anesthetized with intraperitoneal(IP)1% pentobarbital 40 mg?kg~(-1). Intrathecal catheter was placed according to the technique described by Yaksh et al.Five days after IT catheter placement L_4 and I_5 dorsal root ganglion(DRG)compression(CCD)was performed in group Ⅱ-Ⅵ.In sham operation group(Ⅰ)only L_(4-5) transverse processes and intervertebral foramina were exposed but DRGs were not compressed.In group Ⅳ,Ⅴ,and Ⅵ 5 days after CCD model was established a bolus of mibefradil 50,100 and 200 ?g in 10 ?l NS was given IT.In group Ⅲ NS 10 ?l was given IT instead of mibefradil.Mechanical withdrawal threshold(MWT)using Von Frey filament and thermal withdrawal latency(TWL)using radiant heat applied to the plantar surface were measured before CCD(baseline)and 1,3,5,7,14 and 21 days after CCD in group Ⅰ and Ⅱ and before and 30,60,120,240 and 480 min after IT mibefradil in group Ⅲ-Ⅵ.Results The animals in group Ⅱ(CCD group)developed mechanical and thermal hyperalgesia from the 1st day after operation to the end of the experiment.IT mibefradil 50,100 and 200 ?g can all attenuate both mechanical and thermal hyperalgesia induced by CCD.Conclusion Spinal T-type calcium channel may play an important role in the pathogenesis of neuropathic pain.