Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway / 中西医结合学报

OBJECTIVE@#This work explores the impact of electroacupuncture (EA) on acute postoperative pain (APP) and the role of stimulator of interferon genes/type-1 interferon (STING/IFN-1) signaling pathway modulation in the analgesic effect of EA in APP rats.@*METHODS@#The APP rat model was initiated through abdominal surgery and the animals received two 30 min sessions of EA at bilateral ST36 (Zusanli) and SP6 (Sanyinjiao) acupoints. Mechanical, thermal and cold sensitivity tests were performed to measure the pain threshold, and electroencephalograms were recorded in the primary somatosensory cortex to identify the effects of EA treatment on APP. Western blotting and immunofluorescence were used to examine the expression and distribution of proteins in the STING/IFN-1 pathway as well as neuroinflammation. A STING inhibitor (C-176) was administered intrathecally to verify its role in EA.@*RESULTS@#APP rats displayed mechanical and thermal hypersensitivities compared to the control group (P < 0.05). APP significantly reduced the amplitude of θ, α and γ oscillations compared to their baseline values (P < 0.05). Interestingly, expression levels of proteins in the STING/IFN-1 pathway were downregulated after inducing APP (P < 0.05). Further, APP increased pro-inflammatory factors, including interleukin-6, tumor necrosis factor-α and inducible nitric oxide synthase, and downregulated anti-inflammatory factors, including interleukin-10 and arginase-1 (P < 0.05). EA effectively attenuated APP-induced painful hypersensitivities (P < 0.05) and restored the θ, α and γ power in APP rats (P < 0.05). Meanwhile, EA distinctly activated the STING/IFN-1 pathway and mitigated the neuroinflammatory response (P < 0.05). Furthermore, STING/IFN-1 was predominantly expressed in isolectin-B4- or calcitonin-gene-related-peptide-labeled dorsal root ganglion neurons and superficial laminae of the spinal dorsal horn. Inhibition of the STING/IFN-1 pathway by intrathecal injection of C-176 weakened the analgesic and anti-inflammatory effects of EA on APP (P < 0.05).@*CONCLUSION@#EA can generate robust analgesic and anti-inflammatory effects on APP, and these effects may be linked to activating the STING/IFN-1 pathway, suggesting that STING/IFN-1 may be a target for relieving APP. Please cite this article as: Ding YY, Xu F, Wang YF, Han LL, Huang SQ, Zhao S, Ma LL, Zhang TH, Zhao WJ, Chen XD. Electroacupuncture alleviates postoperative pain through inhibiting neuroinflammation via stimulator of interferon genes/type-1 interferon pathway. J Integr Med. 2023; 21(5): 496-508.

Cinnamaldehyde Derivatives Inhibit Coxsackievirus B3-Induced Viral Myocarditis

The chemical property of cinnamaldehyde is unstable in vivo, although early experiments have shown its obvious therapeutic effects on viral myocarditis (VMC). To overcome this problem, we used cinnamaldehyde as a leading compound to synthesize derivatives. Five derivatives of cinnamaldehyde were synthesized: 4-methylcinnamaldehyde (1), 4-chlorocinnamaldehyde (2), 4-methoxycinnamaldehyde (3), α-bromo-4-methylcinnamaldehyde (4), and α-bromo-4-chlorocinnamaldehyde (5). Neonatal rat cardiomyocytes and HeLa cells infected by coxsackievirus B3 (CVB3) were used to evaluate their antiviral and cytotoxic effects. In vivo BALB/c mice were infected with CVB3 for establishing VMC models. Among the derivatives, compound 4 and 5 inhibited the CVB3 in HeLa cells with the half-maximal inhibitory concentrations values of 11.38 ± 2.22 μM and 2.12 ± 0.37 μM, respectively. The 50% toxic concentrations of compound 4 and 5-treated cells were 39-fold and 87-fold higher than in the cinnamaldehyde group. Compound 4 and 5 effectively reduced the viral titers and cardiac pathological changes in a dose-dependent manner. In addition, compound 4 and 5 significantly inhibited the secretion, mRNA and protein expressions of inflammatory cytokines TNF-α, IL-1β and IL-6 in CVB3-infected cardiomyocytes, indicating that brominated cinnamaldehyde not only improved the anti-vital activities for VMC, but also had potent anti-inflammatory effects in cardiomyocytes induced by CVB3.

Correlations between MELD score and left ventricular function in patients with end-stage liver disease / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the correlations between MELD score and left ventricular function in patients with end-stage liver disease.</p><p><b>METHODS</b>A total of 92 patients who prepared for orthotopic liver transplantation from January 2002 to May 2008 were enrolled in this study. Of these Patients, 75 were males and 17 were females, and the mean age was 50.3+/-9.5 years; 85 were cirrhosis, 7 were cirrhosis with primary liver cancer. Preoperative information, including biochemical parameters, coagulation parameters, indicators of hepatitis virology, two-dimensional echocardiography and electrocardiogram were collected. According to MELD (the Model for End-stage Liver Disease) scoring system, these subjects were categorized into three groups: MELD score is less than or equal to 9 points (31 cases, 33.7%); 10 is less than or equal to MELD score is less than or equal to 19 points (45 cases, 48.9%); MELD score is more than or equal to 20 points (16 cases, 17.4%). The relationships between MELD score and classification and cardiac function were determined by chi-square test, analysis of variance, rank sum test and correlation analysis, et al.</p><p><b>RESULTS</b>MELD score was significantly correlated with left atrial diameter (LAD), interventricular septum thickness (IVST), left ventricular end-diastolic diameter (LVEDD), aortic flow (AF), cardiac output (CO), QRS interval (QRSI) and corrected QT interval (QTc) (r = 0.317, 0.341, 0.228, 0.387, 0.325, 0.209 and 0.347, respectively; P value less than 0.01, respectively); except QRSI, these variables and left ventricular posterior wall thickness (LVPWT) were also correlated with INR (a MELD component) (r = 0.282, 0.319, 0.322, 0.435, 0.275, 0.320 and 0.237, respectively; P value less than 0.01, respectively); LAD, LVEDD, AF, CO and QTc were correlated with serum total bilirubin (r = 0.241, 0.219, 0.357, 0.246 and 0.253, respectively; P value less than 0.05, respectively); IVST and E/A ratio (A blood flow [from left atrium to left ventricular] velocity ratio between early diastole [E wave] and late diastole[A wave] ) were correlated with serum creatinine (r = 0.216 and -0.343; P value less than 0.05 and 0.01); the proportion of E/A is less than or equal to 1 in all subjects was 46.7% (43/92), and 48.4% (15/31), 35.6% (16/45) and 75.0% (12/16) in each group, besides, there was statistically significant difference between 10 is less than or equal to MELD score is less than or equal to 19 points group and MELD score is more than or equal to 20 points group (X2 = 7.359, P = 0.009).</p><p><b>CONCLUSIONS</b>There are different degrees of left ventricular structure, function and electrophysiological changes in patients with end-stage liver disease, these anomalies also will be increased with the MELD score increasing.</p>

Association of the PADI4 gene polymorphism and HLA-DRB1 shared epitope alleles with rheumatoid arthritis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of single nucleotide polymorphisms (SNPs) of the peptidylarginine deiminase IV (PADI4) and HLA-DRB1 shared epitope (SE) alleles with rheumatoid arthritis(RA) in a Chinese population.</p><p><b>METHODS</b>Four exonic SNPs of the PADI4 gene (PADI 4_89*A/G, PADI 4_90*C/T, PADI 4_92*C/G and PADI 4_104*C/T) were genotyped in 67 unrelated patients with RA and 81 healthy controls, using cDNA sequencing and T vector cloning. HLA-DRB 1*01, *04 and *10 subtypes were determined by polymerase chain reaction with sequence specific primers (PCR-SSP).</p><p><b>RESULTS</b>The distributions of the 4 SNPs were different in the two groups, and increased RA susceptibility was significantly associated with the minor alleles of PADI 4_89*G (P was 0.023), PADI 4_90*T (P was 0.004), PADI 4_104*T (P was 0.003), and the haplotypes carrying the 4 minor alleles (P was 0.008). HLA-DRB1 SE alleles are composed of HLA-DRB 1*0101, *0102, *0401, *0404, *0405, *0408, *0409, *0410 and *1001. Individuals carrying the SE alleles were associated with increased RA susceptibility (P was 0.002). Individuals carrying both the SE alleles and minor alleles of the 4 SNPs were more susceptible to RA than individuals carrying neither the minor SNP alleles nor the SE alleles.</p><p><b>CONCLUSION</b>The PADI4 SNPs and haplotypes are associated with RA susceptibility in Chinese. HLA-DRB1 shared epitope is also an important risky factor for RA. There may exist certain synergistic effect between the PADI4 minor alleles and the HLA-DRB1 shared epitope.</p>