[Spinal transcription factor GATA4 mediated adenosine A1 receptor activation contributes to electroacupuncture analgesia in neuropathic pain rats].

OBJECTIVE: To investigate the effect of electroacupuncture (EA) on pain behaviors and expression of spinal transcription factor GATA-binding Protein 4 (GATA4) and adenosine A1 receptor in neuropathic pain rats, so as to explore its mechanism underlying pain relief. METHODS: The present study includes 2 parts. In the first part, 18 SD rats were randomly divided into control, adenovirus short-hairpin interference RNA for GATA4 (AV-shGATA4 RNA) and adenovirus empty vector (AV-control short-hairpin RNA, AV-shCTRL) groups, with 6 rats in each group. The expression of GATA4 protein in the lumbar spinal cord (L4-L6) was detected to evaluate the transfection efficiency of AV-shGATA4 RNA (silencing GATA4 expression). In the second part, thirty SD rats were randomly divided into 5 groups, namely sham operation, CCI model, EA, EA+AV-shGATA4 RNA, and EA+AV-shCTRL groups, with 6 rats in each group. The neuropathic pain model was established by chronic constriction injury (CCI) of the right sciatic nerve. On the 7th day following modeling, EA was applied to the right "Zusanli"(ST36) and "Taichong"(LR3) (1 mA，2 Hz /100 Hz) for 30 min. Rats of the EA+AV-shGATA4 RNA and EA+AV-shCTRL groups received intrathecal injection of AV-shGATA4 RNA and AV-shCTRL(1×1011 PFU/mL，10 µL)at the spinal L4-L6 segments, separately, 48 h before EA intervention. The mechanical pain threshold and thermal pain threshold of the affected limb were detected before molding, 7 days following molding and 60 min after EA. The expressions of adenosine A1 receptor and GATA4 protein in the spinal cord (L4-L6) were detected by Western blot. RESULTS: Outcomes of the first part showed that compared with the control group, no significant changes were found in the mechanical and thermal pain thresholds in both AV-shCTRL and AV-shGATA4 RNA groups and in the expression of spinal GATA4 protein of the AV-shCTRL group (P＞0.05). The expression of spinal GATA4 protein of the AV-shGATA4 RNA group was significantly lower than that of the AV-shCTRL group (P<0.05). In the second part of the study, before CCI modeling, there were no significant differences among the five groups in the mechanical and thermal pain thre-sholds (P> 0.05). On the 7th day following modeling, the mechanical and thermal pain thresholds were significantly lowered in compa-rison with their own pre-modeling of each group and with the sham operation group (P<0.05). At 60 min after EA and compared with the model group, the mechanical and thermal pain thresholds were significantly increased in both the EA and EA+AV-shCTRL groups (P<0.05) but not in the EA+AV-shGATA4 RNA group (P>0.05), suggesting a critical involvement of GATA4 in EA analgesia. The expression levels of adenosine A1 receptor and GATA4 protein were significantly increased in the model group than in the sham operation group (P<0.05), and considerably further up-regulated in both EA and EA+AV-shCTRL groups (P< 0.05), rather than in the EA+AV-shGATA4 RNA group (P>0.05), suggesting that the effects of EA in up-regulating the expression of A1 receptor and GATA4 were eliminated after silencing GATA4 protein. CONCLUSION: EA of ST36 and LR3 can relieve pain by increasing the expression of adenosine A1 receptor of the lumbar spinal cord in neuropathic pain rats, which is probably mediated by GATA4 protein.

[Effect of acupoint stimulation on the quality of recovery in patients with radical thyroidectomy under the concept of enhanced recovery after surgery: a randomized controlled trial].

OBJECTIVE: To observe the effect of acupoint stimulation on the quality of recovery in patients with radical thyroidectomy under the concept of enhanced recovery after surgery (ERAS). METHODS: A total of 62 patients with radical thyroidectomy were randomized into an observation group and a control group, 31 cases in each one. In both of the two groups, general anesthesia with tracheal intubation was applied, the same anesthesia induction and maintenance medication were given. In the observation group, auricular point pressing with magnetic beads was adopted at bilateral shenmen (TF4) and transcutaneous electrical acupoint stimulation (dilatational wave, 2 Hz/100 Hz in frequency, 6 to 12 mA) was performed at bilateral Hegu (LI 4) and Neiguan (PC 6) from 30 min before anesthesia induction to the end of the anesthesia. In the control group, medical adhesive plaster was pasted at bilateral shenmen (TF4) and the electrodes were plastered at bilateral Hegu (LI 4) and Neiguan (PC 6) with no corresponding stimulation. In both of the two groups, visual analogue scale for anxiety (VAS-A) score was observed to evaluate the anxiety severity before anesthesia induction; the total intraoperative dosages of sufentanil, remifentanil and propofol were recorded; the numerical rating scale (NRS) score was used to assess the pain severity of instant time (T0) and 30 min (T1) of entering post-anesthesia recovery room (PACU), motor and static mode at 2 h (T2), 6 h (T3), 12 h (T4), 24 h (T5) after surgery; time of first anal exhaust, time of getting out of bed after surgery, total hospitalization time and the incidences of postoperative nausea and vomiting were observed; the quality of recovery was assessed by the 40-item quality of recovery score (QoR-40). RESULTS: The VAS-A score and the total intraoperative dosage of remifentanil in the observation group were reduced compared with the control group (P<0.05). The NRS scores at T0-T4 in the observation group were lower than those in the control group (P<0.01, P<0.05), while the difference between the two groups in NRS score at T5 was not significant (P>0.05). The time of first anal exhaust and getting out of bed after surgery in the observation group were advanced than those in the control group (P<0.05), there was no significant difference between the two groups in total hospitalization time and incidences of postoperative nausea and vomiting (P>0.05). Compared with the control group, the QoR-40 score was increased in the observation group (P<0.05). CONCLUSION: Acupoint stimulation can improve the preoperative anxiety in patients with radical thyroidectomy, reduce the intraoperative anesthetic dosage and postoperative pain, advance the time of anal exhaust and getting out of bed, improve the quality of postoperative recovery and enhance the recovery process.

BRAF kinase inhibitor exerts anti-tumor activity against breast cancer cells via inhibition of FGFR2.

Most anti-angiogenic therapies currently being evaluated in clinical trials targetvascular endothelial growth factor (VEGF) pathway; however, the tumor vasculature can acquire resistance to VEGF-targeted therapy by shifting to other angiogenesis mechanisms. Therefore, other potential therapeutic agents that block non-VEGF angiogenic pathways need to be evaluated. Here we identified BRAF kinase inhibitor, vemurafenibas an agent with potential anti-angiogenic and anti-breast cancer activities. Vemurafenib demonstrated inhibition of endothelial cell proliferation, migration, and tube formation in response to basic fibroblast growth factor (bFGF). In ex vivo and in vivo angiogenesis assays, vemurafenib suppressed bFGF-induced microvessel sprouting of rat aortic rings and angiogenesis in vivo. To understand the underlying molecular basis, we examined the effects of vemurafenib on different molecular components in treated endothelial cell, and found that vemurafenib suppressed bFGF-triggered activation of FGFR2 and protein kinase B (AKT). Moreover, vemurafenib directly inhibited proliferation and blocked the oncogenic signaling pathways in breast cancer cell. In vivo, using xenograft models of breast cancer cells MDA-MB-231, vemurafenib showed growth-inhibitory activity associated with inhibition of tumor angiogenesis. Taken together, our results indicate that vemurafenib targets the FGFR2-mediated AKT signaling pathway in endothelial cells, leading to the suppression of tumor growth and angiogenesis.

Diagnostic value of interleukin-8 in colorectal cancer: a case-control study and meta-analysis.

AIM: To assess the diagnostic value of serum interleukin-8 (IL-8) in the detection of colorectal cancer (CRC). METHODS: An original study was conducted to explore the potential value of IL-8 in CRC diagnosis. Receiver operating characteristic (ROC) analysis was performed and the area under the curve (AUC) value was calculated. PUBMED and EMBASE were searched (to October, 2013), supplemented with manual screening for relevant publications. Meta-analysis methods were applied to pool sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratios and to construct a summary receiver-operating characteristic (sROC) curve. Heterogeneity across studies was checked by the I(2) test and Deek's funnel plot method was applied to test publication bias. RESULTS: In our original study, serum IL-8 yielded an AUC of 0.742 [95%CI: 0.635-0.849]. The sensitivity and specificity were 85.42% and 54.05%, respectively, at a cut-off value of 5.39. In this meta-analysis, we included five studies with 668 CRC patients and 374 controls and one study in our own center with 48 CRC patients and 37 controls. The pooled sensitivity and specificity of IL-8 were 0.69 (95%CI: 0.42-0.87) and 0.85 (95%CI: 0.68-0.94) for CRC detection. Besides, the area under the sROC curve was 0.86 (95%CI: 0.82-0.88). Subgroup analysis suggested that there was no heterogeneity in the Asian subgroup but some in the European subgroup. In addition, no publication bias was found according to the Deek's funnel plot asymmetry test. CONCLUSION: Serum IL-8 is a promising biomarker for CRC detection and may become a clinically useful tool to identify high-risk patients.

Exploration of molecular mechanisms of diffuse large B-cell lymphoma development using a microarray.

OBJECTIVE: We aimed to identify key genes, pathways and function modules in the development of diffuse large B-cell lymphoma (DLBCL) with microarray data and interaction network analysis. METHODS: Microarray data sets for 7 DLBCL samples and 7 normal controls was downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified with Student's t-test. KEGG functional enrichment analysis was performed to uncover their biological functions. Three global networks were established for immune system, signaling molecules and interactions and cancer genes. The DEGs were compared with the networks to observe their distributions and determine important key genes, pathways and modules. RESULTS: A total of 945 DEGs were obtained, 272 up-regulated and 673 down-regulated. KEGG analysis revealed that two groups of pathways were significantly enriched: immune function and signaling molecules and interactions. Following interaction network analysis further confirmed the association of DEGs in immune system, signaling molecules and interactions and cancer genes. CONCLUSIONS: Our study could systemically characterize gene expression changes in DLBCL with microarray technology. A range of key genes, pathways and function modules were revealed. Utility in diagnosis and treatment may be expected with further focused research.

[Effects of combined enteral nutrition support on hemorrheologic parameters and the level of inflammatory factors in rabbits with severe acute pancreatitis].

OBJECTIVE: To explore the effects of combined enteral nutrition (CEN) on the hemorheologic parameters and the changing levels of inflammatory factors in an animal model of severe acute pancreatitis (SAP). METHODS: The experimental animals were divided randomly into 3 groups, i.e. early enteral nutrition (EEN) group, CEN group and parenteral nutrition(PN)group (n = 20 each). Enteral nutrition was administered to the EEN and CEN group animals at 24 h and 72 h post-modeling respectively. The PN group animals were supported by parenteral nutrition all time. Hemorrheologic indices of all experimental animals were examined on Days 1, 3 and 7 post-modeling. And the inflammatory factors were examined on Days 1 and 7. RESULTS: Compared with the EEN and PN groups, some hemorrheologic indices of the CEN group decreased significantly (P < 0.05) on Day 7 post-modeling. They included blood sedimentation, hematocrit (HCT), whole blood high-cut reduction viscosity and whole blood low-cut reduction viscosity. As compared within the CEN group, each hemorrheologic index was lower on Day 7 than that on Day 1 (P < 0.05). Except for whole blood high-cut reduction viscosity and erythrocyte aggregation index in the EEN group after a 7-day nutrition support, there was no significant change for all hemorrheologic indices in the PN group. As to the level of inflammatory factors, the values of interleukin 8 (IL-8) and tumor necrosis factor-α (TNF-α) in the CEN group were lower than those in the PN group on Day 7 post-modeling (P < 0.05). The values of IL-8 and IL-6 in the CEN group were lower than those in the EEN group on the same day (P < 0.05). As compared within the CEN group, the values of IL-6 and TNF-α were lower on Day 7 than those on Day 1 post-modeling (P < 0.05). CONCLUSION: The modulatory mechanism of EN over SAP should be achieved by correcting hemorrheologic index change and lowering the level of inflammatory factors. A proper timing of EN is probably the most optimal nutrition support mode of SAP therapy.

[Efficacy observation on acupoint catgut embedding therapy combined medication for treatment of chronic urticaria induced by Helicobacter pylori infection].

OBJECTIVE: To observe the efficacy of acupoint catgut embedding therapy combined medication on chronic urticaria induced by Helicobacter pylori (HP) infection. METHODS: Ninety-two cases were randomly divided into 3 groups, named a medication group (group A, 31 cases), an acupoint catgut embedding group (group B, 30 cases) and a medication combined acupoint catgut embedding group (group C, 31 cases). In group A, the medication was administered orally for antihistamine and anti-HP infection. In group B, catgut embedding was applied on Quchi (LI 11), Xuehai (SP 10), Zusanli (ST 36), etc. In group C, acupoint catgut embedding therapy was applied in combination with medication (medication as group A, acupoint catgut embedding as group B). After 3-month treatment, the efficacy, recurrence rate and HP negative rate were compared among 3 groups. RESULTS: Separately, the effective rates of group A, B, C were 61.3% (19/31), 53.3% (16/30) and 90.3% (28/31); the recurrence rates were 27.3% (3/11), 33.3% (3/9) and 5.9% (1/17); and HP negative rates were 31.3% (10/31), 26.7% (9/30) and 77.4% (24/31). The clinical efficacy and HP negative rate in group C were superior to those in group A and B (P < 0.01, P < 0.05). CONCLUSION: Acupoint catgut embedding therapy combined medication is significant in efficacy and low in recurrence rate in treatment of chronic urticaria caused by HP infection.

[Pregnant women hepatitis B markers investigation and analysis of intrauterine infection].

OBJECTIVE: To investigate the relationship between the hepatitis B virus (HBV) infection in pregnant women and intrauterine infection in local region. METHODS: The markers of hepatitis B (HBVM) were determined by time-resolved fluoroimmunoassay and HBV-DNA were determined by FQ-PCR. RESULTS: A total of 1262 pregnant women were examined the HBVM, 2.6%, 38.2%, 0.9%, 22.6%, 23.1% subjects were identified HBsAg, HBsAb, HBeAg, HBeAb, HBcAb positive respectively. In 33 cases of serum HBsAg-positive pregnant women, HBV-DNA were observed in most of 11 cases of pregnant women with HBeAg-positive and intrauterine infection rates were 6/11. In contrast, 22 cases of pregnant women with HBeAg negative, HBV-DNA were detected lowly-loaded and intrauterine infection rates were 2/22 (P < 0.01). Intrauterine infection rates of HBV in pregnant women with HBsAg-positive were 24.2% (8/33). CONCLUSION: HBV infective rates in pregnant women in the local region were low. Pregnant women with serum HBeAg positive and HBV-DNA high-loaded were prone to intrauterine infection.