Systematic Review and Sequential Analysis on Efficacy of Modified Buyang Huanwu Tang in Treatment of Chronic Heart Failure / 中国实验方剂学杂志

Objective:To systematically evaluate the efficacy and safety of modified Buyang Huanwu Tang in the treatment of chronic heart failure. Method:CNKI database，Wanfang database，VIP database，Pubmed，MEDLINE，EMBASE and Cochrane database were retrieved systematically. The literature retrieval period is from no limit to December 2019，with "Buyang Huanwu Tang" and "chronic heart failure" "heart failure" as the key words for full-text retrieval of Chinese and English databases. Literatures of randomized controlled trials（RCTs） for chronic heart failure were included， and the data were extracted. Cochrane system evaluation method was used to score the quality of literature. Stata 14.0 was applied in Meta-analysis on the retrieval results. TSA0.9 was applied in test sequential analysis. Sensitivity analysis was made to explain heterogeneity，and funnel chart was used to evaluate publication bias. Result:A total of 2 037 patients were included in 21 RCT studies. The article quality risk assessment was generally unclear risk of bias. The results of meta-analysis showed that the left ventricular ejection fraction （LVEF） in the experimental group was significantly higher than that in the control group，with statistically significant differences ［MD=0.901，95% CI （0.772，1.029），P<0.01］，the left ventricular end diastolic diameter （LVEDd） in the experimental group was significantly lower than that in the control group，with statistically significant differences ［OR=-0.650，95% CI=（-0.854，-0.446），P<0.01］，BNP in the experimental group was significantly lower than that in the control group，with statistically significant differences ［MD=-1.212，95% CI=（-1.359，-1.066），P<0.01］，6-minute walk test （6MWT） in the experimental group was significantly higher than that in the control group，with statistically significant differences ［MD=0.797， 95% CI=（0.447，1.146），P<0.01］，and the effective rate in the experimental group was significantly improved，with statistically significant differences ［OR=1.840，95% CI=（1.680，2.016），P<0.01］. Conclusion:Modified Buyang Huanwu Tang combined with conventional western medicine treatment of chronic heart failure is more effective than single administration of western medicine treatment，and can improve clinical efficacy， effectively improve the LVEF of patients with chronic heart failure，reduce the LVEDd reduces plasma BNP levels，prolong the 6-minute walking distance，and reduce the incidence of adverse reactions.

CXCL10/CXCR3 Signaling in the DRG Exacerbates Neuropathic Pain in Mice / 神经科学通报·英文版

Chemokines and receptors have been implicated in the pathogenesis of chronic pain. Here, we report that spinal nerve ligation (SNL) increased CXCR3 expression in dorsal root ganglion (DRG) neurons, and intra-DRG injection of Cxcr3 shRNA attenuated the SNL-induced mechanical allodynia and heat hyperalgesia. SNL also increased the mRNA levels of CXCL9, CXCL10, and CXCL11, whereas only CXCL10 increased the number of action potentials (APs) in DRG neurons. Furthermore, in Cxcr3

TLR8 in the Trigeminal Ganglion Contributes to the Maintenance of Trigeminal Neuropathic Pain in Mice / 神经科学通报·英文版

Trigeminal neuropathic pain (TNP) is a significant health problem but the involved mechanism has not been completely elucidated. Toll-like receptors (TLRs) have recently been demonstrated to be expressed in the dorsal root ganglion and involved in chronic pain. Here, we show that TLR8 was persistently increased in the trigeminal ganglion (TG) neurons in model of TNP induced by partial infraorbital nerve ligation (pIONL). In addition, deletion or knockdown of Tlr8 in the TG attenuated pIONL-induced mechanical allodynia, reduced the activation of ERK and p38-MAPK, and decreased the expression of pro-inflammatory cytokines in the TG. Furthermore, intra-TG injection of the TLR8 agonist VTX-2337 induced pain hypersensitivity. VTX-2337 also increased the intracellular Ca

CCL2/CCR2 Contributes to the Altered Excitatory-inhibitory Synaptic Balance in the Nucleus Accumbens Shell Following Peripheral Nerve Injury-induced Neuropathic Pain / 神经科学通报·英文版

The medium spiny neurons (MSNs) in the nucleus accumbens (NAc) integrate excitatory and inhibitory synaptic inputs and gate motivational and emotional behavior output. Here we report that the relative intensity of excitatory and inhibitory synaptic inputs to MSNs of the NAc shell was decreased in mice with neuropathic pain induced by spinal nerve ligation (SNL). SNL increased the frequency, but not the amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs), and decreased both the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in the MSNs. SNL also decreased the paired-pulse ratio (PPR) of evoked IPSCs but increased the PPR of evoked EPSCs. Moreover, acute bath application of C–C motif chemokine ligand 2 (CCL2) increased the frequency and amplitude of sIPSCs and sEPSCs in the MSNs, and especially strengthened the amplitude of N-methyl-D-aspartate receptor (NMDAR)-mediated miniature EPSCs. Further Ccl2 overexpression in the NAc in vivo decreased the peak amplitude of the sEPSC/sIPSC ratio. Finally, Ccr2 knock-down improved the impaired induction of NMDAR-dependent long-term depression (LTD) in the NAc after SNL. These results suggest that CCL2/CCR2 signaling plays a role in the integration of excitatory/inhibitory synaptic transmission and leads to an increase of the LTD induction threshold at the synapses of MSNs during neuropathic pain.

Clinical Value of Serum Amyloid A and Misfolded Transthyretin for Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients / 中国实验血液学杂志

OBJECTIVE@#To evaluate the clinical value of serum amyloid A (SAA1/2) and misfolded transthyretin (TTR) for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) patients.@*METHODS@#30 R/R DLBCL patients were enrolled as observation group, 20 remission/stabilization DLBCL and 10 chronic lymphadenitis patients were enrolled as control group. SELDI technique, Tris-Tricine sodium dodecyl sulfate-polyacrylamide gel electro-phoresis, the shotgun-LTQ-MS method, and bioinformatics technique were used to detected and analyzed SAA and TTR in R/R DLBCL patients. SPSS 21.0 software was used to analyze the relationship between the high expression of SAA, misfolded TTR in serum and the clinicopathological features, survival time of R/R DLBCL. patients Chi-square test was used to analyze clinical count data, Kaplan-Meier curve was used for survival analysis, and Log-Rank test was used to compare single-factor survival differences.@*RESULTS@#The high expression of SAA and TTR (SAA@*CONCLUSION@#Both SAA and misfolded TTR are poor prognosis factors of R/R DLBCL patients.

Increased CXCL13 and CXCR5 in Anterior Cingulate Cortex Contributes to Neuropathic Pain-Related Conditioned Place Aversion / 神经科学通报·英文版

Pain consists of sensory-discriminative and emotional-affective components. The anterior cingulate cortex (ACC) is a critical brain area in mediating the affective pain. However, the molecular mechanisms involved remain largely unknown. Our recent study indicated that C-X-C motif chemokine 13 (CXCL13) and its sole receptor CXCR5 are involved in sensory sensitization in the spinal cord after spinal nerve ligation (SNL). Whether CXCL13/CXCR5 signaling in the ACC contributes to the pathogenesis of pain-related aversion remains unknown. Here, we showed that SNL increased the CXCL13 level and CXCR5 expression in the ACC after SNL. Knockdown of CXCR5 by microinjection of Cxcr5 shRNA into the ACC did not affect SNL-induced mechanical allodynia but effectively alleviated neuropathic pain-related place avoidance behavior. Furthermore, electrophysiological recording from layer II-III neurons in the ACC showed that SNL increased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs), decreased the EPSC paired-pulse ratio, and increased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor/N-methyl-D-aspartate receptor ratio, indicating enhanced glutamatergic synaptic transmission. Finally, superfusion of CXCL13 onto ACC slices increased the frequency and amplitude of spontaneous EPSCs. Pre-injection of Cxcr5 shRNA into the ACC reduced the increase in glutamatergic synaptic transmission induced by SNL. Collectively, these results suggest that CXCL13/CXCR5 signaling in the ACC is involved in neuropathic pain-related aversion via synaptic potentiation.

Effect of P53 Expression on Prognosis of Patients with Double Expressor Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of P53 expression on prognosis of patients with double expressor lymphoma(DEL) and the interaction between the expression of MYC, BCL2 and P53 in diffuse large B-cell lymphoma(DLBCL).@*METHODS@#Eighty-eight patients with newly diagnosed DLBCL from 1st September 2012 to 31th May 2018 in Shanxi Dayi Hospital affiliated to Shanxi Medical University were selected. The expressions of MYC、BCL2、P53、CD10、BCL6、MUM and Ki-67 were tested by immunohistochemistry method. The overall survival of patients was analyzed by the Kaplan-Meier method and compared by the log-rank test. The prognostic effect of MYC, BCL2 and P53 expression was analyzed by univariate and multivariate analysis.@*RESULTS@#Compared with patients without P53 expression, the patients with P53 expression had higher LDH level, higher NCCN-IPI scores, lower response to chemotherapy，poorer overall survival(OS) and a higher rate of death(P0.05). Among lymphoma patients with MYC/P53, MYC/BCL2 and BCL2/P53 co-expression, the patients with MYC/P53 co-expression had the worse OS (3 year OS rate：31.6%), followed by the subgroup of patients with MYC/BCL2/P53(3 year OS rate：46.2%), patients with MYC/BCL2/P53 expression(3 year OS rate： 636%) showed a longer OS compared with the other two subgroups（P<0.05）. Multivariate analysis demonstrated that P53 expression and NCCN-IPI were independent prognostic factors in this patient cohort.@*CONCLUSION@#P53 and MYC expressions have a synergistically negative prognostic effect in DLBCL patients. P53 expression augments the negative prognostic effect of MYC/BCL2 double expression. Patients with MYC/P53 co-expression have a worse prognosis in comparison with the patients with MYC/BCL2 double expression.

Chemokine Receptor CXCR3 in the Spinal Cord Contributes to Chronic Itch in Mice / 神经科学通报·英文版

Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis (ACD). CXCR3 in the spinal cord also contributes to the maintenance of neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic itch remains unclear. Here, we report that Cxcr3 mice showed normal scratching in acute itch models but reduced scratching in chronic itch models of dry skin and ACD. In contrast, both formalin-induced acute pain and complete Freund's adjuvant-induced chronic inflammatory pain were reduced in Cxcr3 mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal cord in the dry skin model induced by acetone and diethyl ether followed by water (AEW). Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch. Furthermore, touch-elicited itch (alloknesis) after compound 48/80 or AEW treatment was suppressed in Cxcr3 mice. Finally, AEW-induced astrocyte activation was inhibited in Cxcr3 mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.

The effects of the autologous venous external stents on intimal hyperplasia of the vein grafts in rabbits / 中华外科杂志

<p><b>OBJECTIVE</b>To assess the effect of the autologous venous external stents on intimal hyperplasia of the vein grafts in rabbits.</p><p><b>METHODS</b>Thirty-six male New Zealand white rabbits, aged 5 months and weighing 2.8 to 3.0 kg, were randomly divided into 3 groups: group A, group B and group C, with 12 rabbits in each group. First, a section about 6 cm long of vein was cut from the right external jugular vein of each rabbit and severed to have 3 equal-length segments. Next, each distal segment prepared for anastomosis. The proximal segment invaginating middle segment in group A and only middle segment in group B were used for the external stent. Later, the left common carotid artery was separated from surrounding tissue, from it a section about 0.5 cm long was cut away. Finally, the vein graft was inverted and end-to-end anastomosed to the two ends of the artery with a 9-0 suture. After bloodstream re-established, the diameter of each vein graft was measured. At 2 and 4 weeks postoperative, the graft veins were cut off and histologically examined by the means of HE staining and Masson staining. The smooth muscle cells (SMC) proliferation was studied by the immunohistochemical detection of proliferating cell nuclear antigen.</p><p><b>RESULTS</b>After bloodstream re-established, the diameters of vein graft of group A and group B and group C were (1.6 +/- 0.3) mm, (2.2 +/- 0.4) mm and (2.6 +/- 0.6) mm respectively (P < 0.05). At 4 weeks postoperative, the data of the ratio of intima to media thickness and the index of the proliferating cells of the intima were as follow: group A (1.01 +/- 0.07 and 6.84 +/- 1.98), group B (1.32 +/- 0.08 and 11.01 +/- 2.61), group C (1.55 +/- 0.03 and 14.96 +/- 4.14). Both the data of group A were obviously less than that in group B, and that of group B was less than group C (P < 0.05).</p><p><b>CONCLUSION</b>The autologous venous two-layer external stents inhibit intimal hyperplasia of the vein grafts.</p>

Phase space reconstruction of mastication muscles surface electromyography signal based on nonlinear dynamics / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To calculate the delay times and embedding dimensions of surface electromyogragh (sEMG) signal of the masseter and temporal muscle during clenching at intercuspal position (ICP), and to reconstruct the space phase of sEMG signal with method of nonlinear dynamics.</p><p><b>METHODS</b>Ten male and 10 female young volunteers with normal masticatory system were included in the study, the signals of surface sEMG of bilateral masseter and temporal muscles in the position of ICP were collected, and the delay times and embedding dimensions of the sEMG signals were calculated using C-C method, the space phase of the sEMG signals was reconstructed.</p><p><b>RESULTS</b>A program of nonlinear dynamic analysis of mastication muscles sEMG signals was developed base on the platform of Matlab. The signals of the sEMG of the masseters and temporals were analyzed with nonlinear dynamic methods, the delay times and embedding dimensions of each muscles sEMG signals were obtained, and the space phase of each sEMG signals were reconstructed. The graphs of the space phase indicated the typical characteristic of chaotic attractor.</p><p><b>CONCLUSIONS</b>The signals of the masseter and temporal muscles of surface sEMG during clenching at ICP of normal masticatory system show the typical characters of chaos, the methods of nonlinear dynamics are effective to analyze the sEMG signals of mastication system.</p>