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High-grade hemorrhoids are usually recommended to receive operational treatments. However, these traditional surgeries are associated with severe postoperative pain. A procedure for prolapse and hemorrhoids (PPH), a circular staple device, has been developed to improve short-term outcomes, including reducing the severity of postoperative pain. PPH, compared to conventional surgery, has been associated with the incidence of anatomical anal stenosis. The causes of stenosis after PPH are not yet clear. We first analyzed the complications of our patients with PPH, and then developed a rat model to verify the tension force of PPH using Hematoxylin-eosin, Masson's trichrome, immunohistochemistry, and immunofluorescence staining. Our clinical data showed that PPH significantly improved postoperative pain, but that it resulted in higher incidences of complications, including anal stenosis, than hemorrhoidectomy. We simulated the status of PPH and developed a rat model to verify PPH's tension force, including the scarring area and the deposition of proinflammatory factors, angiogenic factors, and fibrotic factors. The tension wound histological data showed more extensive granulation tissue and inflammatory cell infiltration and a thicker epidermis than the control group on day 12 post-operation and tension treatment. In addition to IL-1ß and IL-10 cytokines on day 3 and IL-1ß, IL-6, and IL-10 cytokines on day 12 post-operation in the tension group, two angiogenic factors, CD31 and VEGF-A, were found to have a more significant expression on day 7 post-operation in the tension group. The mean scar area was larger and the distribution of fibrotic proteins (collagen 1, α-SMA, CTGF, and MMP2) in the tension group was significantly broader than in the control on day 12 post-operation and tension treatment. Based on the findings of our animal model, the development of a lesser tensile force for PPH to decrease the deposition of proinflammatory factors, angiogenic factors, and fibrotic factors is urgently required.

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The cryptoglandular perianal fistula is a common benign anorectal disorder that is managed mainly with surgery and in some cases may be an extremely challenging condition. Perianal fistulas are often characterized by significantly decreased patient quality of life. Lack of fully recognized pathogenesis of this disease makes it difficult to treat it properly. Recently, adipose tissue hormones have been proposed to play a role in the genesis of cryptoglandular anal fistulas. The expression of adipose tissue hormones and epithelial-to-mesenchymal transition (EMT) factors were characterized based on 30 samples from simple fistulas and 30 samples from complex cryptoglandular perianal fistulas harvested during surgery. Tissue levels of leptin, resistin, MMP2, and MMP9 were significantly elevated in patients who underwent operations due to complex cryptoglandular perianal fistulas compared to patients with simple fistulas. Adiponectin and E-cadherin were significantly lowered in samples from complex perianal fistulas in comparison to simple fistulas. A negative correlation between leptin and E-cadherin levels was observed. Resistin and MMP2 levels, as well as adiponectin and E-cadherin levels, were positively correlated. Complex perianal cryptoglandular fistulas have a reduced level of the anti-inflammatory adipokine adiponectin and have an increase in the levels of proinflammatory resistin and leptin. Abnormal secretion of these adipokines may affect the integrity of the EMT in the fistula tract. E-cadherin, MMP2, and MMP9 expression levels were shifted in patients with more advanced and complex perianal fistulas. Our results supporting the idea of using mesenchymal stem cells in the treatment of cryptoglandular perianal fistulas seem reasonable, but further studies are warranted.

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Knee osteoarthritis (KOA) is one of the most common degenerative diseases and is characterized by cartilage degeneration, synovial inflammation, joint stiffness and even loss of motor function. In the clinical treatment of arthritis, conventional analgesic and anti-inflammatory drugs have great side effects. We have evaluated the possibility of the endogenous transcription regulator Ski as an anti-inflammatory alternative in OA through experimental studies in animal models and in vivo and in vitro. Male Sprague‒Dawley rats were injected with monosodium iodoacetate (MIA) into the knee joints to induce symptoms identical to those of human OA. We isolated knee synovial tissue under sterile conditions and cultured primary synovial cells. In vitro, Ski inhibits the proinflammatory factors IL-1ß, IL-6 and TNF-α mRNA and protein expression in lipopolysaccharide (LPS)-stimulated fibroblast-like synoviocytes (FLSs) and U-937 cells. In addition, Ski attenuates or inhibits OA-induced synovial inflammation by upregulating the protein expression of the anti-inflammatory factor IL-4 and downregulating the protein expression of downstream molecules related to the NF-κB inflammatory signaling pathway. In vivo, Ski downregulated proinflammatory factors and p-NF-κB p65 in KOA synovial tissue and alleviated pain-related behaviors in KOA rats. These experimental data show that Ski has strong anti-inflammatory activity. Ski is an endogenous factor, and if used in the clinical treatment of OA, the side effects are small. However, the anti-inflammatory mechanism of Ski must be further studied.

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Aims: HIF1-α is an important transcription factor in the regulation of the immune response. The protective function of HIF1-α in the host epithelial immune response to Aspergillus fumigatus requires further clarification. Methods: In this study we demonstrated the effect of upregulation of HIF1-α expression in A549 cells and mouse airway cells exposed to A. fumigatus in vivo. Results: The killing capacity was enhanced by boosting proinflammatory factors both in vitro and in vivo. Moreover, airway inflammation was reduced in the HIF1-α-upregulated mice. Conclusion: We identified a protective role for HIF1-α in anti-A. fumigatus immunity. Modulation of HIF1-α might be a target for the development of aspergillosis therapy.

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Lycium barbarum (LB) is a traditional Chinese medicine that has been demonstrated to exhibit a wide variety of biological functions, such as antioxidation, neuroprotection, and immune modulation. One of the main mechanisms of Alzheimer's disease is that microglia activated by amyloid beta (Aß) transform from the resting state to an M1 state and release pro-inflammatory cytokines to the surrounding environment. In the present study, immortalized microglial cells were pretreated with L. barbarum extract for 1 hour and then treated with oligomeric Aß for 23 hours. The results showed that LB extract significantly increased the survival of oligomeric Aß-induced microglial cells, downregulated the expression of M1 pro-inflammatory markers (inducible nitric oxide synthase, tumor necrosis factor α, interleukin-6, and interleukin-1ß), and upregulated the expression of M2 anti-inflammatory markers (arginase-1, chitinase-like protein 3, and interleukin-4). LB extract also inhibited the oligomeric Aß-induced secretion of tumor necrosis factor α, interleukin-6, and interleukin-1ß in microglial cells. The results of in vitro cytological experiments suggest that, in microglial cells, LB extract can inhibit oligomeric Aß-induced M1 polarization and concomitant inflammatory reactions, and promote M2 polarization.

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We have previously reported that the activation of astrocytes and microglia may lead to the overproduction of proinflammatory mediators, which could induce neuroinflammation and cause brain edema in 1,2-dichloroethane (1,2-DCE)-intoxicated mice. In this research, we further hypothesized that astrocyte-microglia crosstalk might trigger neuroinflammation and contribute to brain edema in 1,2-DCE-intoxicated mice. The present research revealed, for the first time, that subacute intoxication with 1,2-DCE might provoke the proinflammatory polarization of microglia, and pretreatment with minocycline, a specific inhibitor of microglial activation, may attenuate the enhanced protein levels of ionized calcium-binding adapter molecule1 (Iba-1), cluster of differentiation 11b (CD11b), glial fibrillary acidic protein (GFAP), soluble calcium-binding protein 100B (S100B), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), inducible nitric oxide synthase (iNOS), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase-9 (MMP-9), Toll-like receptor 4 (TLR4), MyD88, and p-p65, and ameliorate the suppressed protein expression levels of occludin and claudin 5; we also observed changes in water content and made pathological observations on edema in the brains of 1,2-DCE-intoxicated mice. Moreover, pretreatment with fluorocitrate, an inhibitor of reactive astrocytes, could also reverse the alteration in protein expression levels of GFAP, S100B, Iba-1, CD11b, TNF-α, IL-6, iNOS, VCAM-1, ICAM-1, MMP-9, occludin, and claudin 5 in the brain of 1,2-DCE intoxicated mice. Furthermore, pretreatment with melatonin, a well-known anti-inflammatory drug, could also attenuate the above-mentioned changes in the brains of 1,2-DCE-intoxicated mice. Altogether, the findings from this research indicated that microglial activation might play an important role in triggering neuroinflammation, and hence may contribute to brain edema formation; additionally, the findings suggested that molecular crosstalk between reactive astrocytes and activated microglia may amplify the neuroinflammatory reaction, which could induce secondary brain injury in 1,2-DCE-intoxicated mice.

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The launch of novel chemotherapeutic agents-in particular, proteasome inhibitors and immunomodulatory drugs-dramatically changed multiple myeloma (MM) therapy, improving the response rate and prolonging progression-free survival. However, none of the anti-MM drugs are deprived of side effects. Peripheral neuropathy (PN) seems to be one of the most pressing problems. Despite extensive research in this area, the pathogenesis of drug-induced peripheral neuropathy (DiPN) has not yet been fully elucidated. In the present study, we aimed to assess the potential relationship between proinflammatory factors and the development of PN in MM patients with particular emphasis on the application of VTD (bortezomib, thalidomide, dexamethasone) regimen. Our analysis identified increased concentrations of CCL2, IL-1ß, and IFN-γ in plasma of MM patients during treatment, both with and without symptoms of PN, compared with untreated neuropathy-free MM patients. At the same time, the plasma concentration of IL-1ß in patients with neuropathy was significantly increased compared with patients without PN before and during treatment. Moreover, the results were enhanced at the transcript level by performing global mRNA expression analysis using microarray technology. The most significant changes were observed in the expression of genes responsible for regulating immunological and apoptotic processes. An in-depth understanding of the mechanisms responsible for the development of DiPN might in the future reduce the incidence of PN and accelerate diagnosis, allowing the choice of neuropathy-free treatment strategies for MM.

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Neurotensin (NT) acts as a primary neurotransmitter and neuromodulator in the CNS and has been involved in a number of CNS pathologies including epilepsy. NT mediates its central and peripheral effects by interacting with the NTSR1, NTSR2, and Sort1/NTSR3 receptor subtypes. To date, little is known about the precise expression of the NT receptors in brain neural cells and their regulation in pathology. In the present work, we studied the cellular distribution of the NTSR2 protein in the rat hippocampus and questioned whether its expression was modulated in conditions of neuroinflammation using a model of temporal lobe epilepsy induced by pilocarpine. This model is characterized by a rapid and intense inflammatory reaction with reactive gliosis in the hippocampus. We show that NTSR2 protein is expressed in hippocampal astrocytes and its expression increases together with astrocyte reactivity following induction of status epilepticus. NTSR2 immunoreactivity is also increased in astrocytes proximal to blood vessels and their end-feet, and in endothelial cells. Proinflammatory factors such as IL1ß and LPS induced NTSR2 mRNA and protein in cultured astroglial cells. Antagonizing NTSR2 with SR142948A decreased NTSR2 expression as well as astroglial reactivity. Together, our results suggest that NTSR2 is implicated in astroglial and gliovascular inflammation and that targeting the NTSR2 receptor may open new avenues in the regulation of neuroinflammation in CNS diseases.

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BACKGROUND: Nucleus pulposus cells' (NPCs') degeneration is mainly responsible for the intervertebral disc degeneration (IDD), which is closely related to inflammatory response. Among the major proinflammatory factors that are related to NPCs' degeneration, interleukin-6 (IL-6) and its downstream JAK/STAT3 pathway have received recent attention. The goal of our study is to figure out whether or how resveratrol (RSV) can protect NPCs from degeneration by affecting IL6/JAK/STAT3 pathway. METHODS: Different concentrations of RSV were added to NPCs' mediums. Cell viability was measured by MTT assay and crystal violet staining. Cell cycle and apoptosis were analyzed by flow cytometry. Protein expression level was determined by western blot. mRNA expression level was measured by qPCR. RESULTS: Our study showed that RSV improved NPCs' cell viability. It also inhibited cell apoptosis and cell cycle arrest, which were accompanied by the increased expression level of heat shock protein 90 (HSP90) and N-Cadherin. What' more, RSV also improved the NPCs' degeneration which was reflected in the increase of extracellular matrix (collagen II, Aggrecan). Moreover, RSV significantly attenuated the level of IL-6 secretion, which was accompanied by less phosphorylation of the transcription factors Janus kinase 1 (JAK1) and signal transducer and activator of transcription 3 (STAT3). CONCLUSION: RSV exerted its protective effect on HNPCs' degeneration by improving cell survival and function. The possible mechanism may be associated with the suppression of JAK/STAT3 phosphorylation and the decreased IL-6 production, which could be explained by a blockage of the positive feedback control loop between IL-6 and JAK/STAT3 pathway.

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Cryptoglandular perianal fistula is a common benign anorectal disorder that is managed mainly with surgery. A fistula is typically defined as a pathological communication between two epithelialized surfaces. More specifically, perianal fistula manifests as an abnormal tract between the anorectal canal and the perianal skin. Perianal fistulas are often characterized by significantly decreased patient quality of life. The cryptoglandular theory of perianal fistulas suggests their development from the proctodeal glands, which originate from the intersphincteric plane and perforate the internal sphincter with their ducts. Involvement of proctodeal glands in the inflammatory process could play a primary role in the formation of cryptoglandular perianal fistula. The objective of this narrative review was to investigate the current knowledge of the pathogenesis of cryptoglandular perianal fistula with the specific aims of characterizing the potential role of proinflammatory factors responsible for the development of chronic inflammation. Further studies are crucial to improve the therapeutic management of cryptoglandular perianal fistulas.

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Objective:To investigate the efficacy of enhanced recovery after surgery(ERAS)combined with laparoscopy for the treatment of colorectal cancer in the elderly and its effects on proinflammatory factors and immune responses.Methods:A total of 158 elderly patients with colorectal cancer treated with surgery were retrospectively analyzed.According to different treatment methods, they were divided into the control group(76 cases)and the study group(82 cases). The control group received traditional open surgery and routine perioperative care.The study group received laparoscopic radical resection of colorectal cancer plus perioperative ERAS.Surgery parameters, complications, postoperative immune function and proinflammatory factor levels were compared between the two groups.Results:The operation duration of the study group was significantly longer than that of the control group[(128.5±33.7)min vs.(117.4±28.7)min, t=2.220, P=0.028], whereas the intraoperative blood loss[(100.8±20.5)ml vs.(250.7±62.3)ml, t=20.621, P<0.01]and the incision length[(4.5±1.2)cm vs.(17.5±3.0)cm, t=36.243, P<0.01]were significantly less than those in the control group.The time to first flatus[(2.0±0.9)d vs.(3.8±1.8)d, t=8.037, P<0.01], time to first defecation[(2.8±0.8)d vs.(4.5±1.1)d, t=11.167, P<0.01], time to first ambulation[(1.2±0.2)d vs.(3.8±1.3)d, t=17.888, P<0.01]and hospitalization length[(7.1±0.2)d vs.(11.4±2.2)d, t=17.625, P<0.01]were also significantly shorter than those in the control group.The incidences of surgical site infections(2.4% vs.10.5%, χ2=4.351, P=0.037), abdominal distension(7.3% vs.19.7%, χ2=5.279, P=0.023)and intestinal obstruction(9.8% vs.22.4%, χ2=4.711, P=0.030)in the study group were significantly lower than those in the control group.The levels of C-reactive protein, interleukin-6 and tumor necrosis factor-α in the study group were significantly lower than those in the control group at 1 d, 3 d and 7 d after surgery( t= 9.612, 7.300, 5.446, 8.762, 12.138, 15.370, 10.186, 10.432, 13.512, respectively, all P<0.05). The levels of CD3 + , CD4 + and CD4 + /CD8 + in the study group were significantly higher than those in the control group at 1 d, 3 d and 7 d after surgery( t= 2.128, 2.957, 2.313, 2.914, 2.937, 2.809, 5.089, 5.623, 5.409, respectively, P<0.05 for all), and the levels of CD8 + were significantly lower than those of the control group( t= 2.008, 2.580, 4.902, all P<0.05). Conclusions:Laparoscopy combined with ERAS for the treatment of colorectal cancer in the elderly can reduce surgical injury and complications and mitigate inflammatory responses with little impact on immune responses.

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Purpose: To investigate the change in cytokine microenvironment of the aqueous humor (AH) after surgery in children with congenital or developmental cataracts. Methods: AH samples were obtained from 59 eyes diagnosed with a congenital or developmental cataract. Thirty-three of these eyes were aphakic following previous cataract surgery and were scheduled for secondary intraocular lens (IOL) implantation. Additionally, AH samples from 26 eyes that had not undergone surgery were taken. AH samples were then analyzed for 16 different inflammatory immune mediators using multiplex bead immunoassays and enzyme-linked immunosorbent assay (ELISA). Results: The mean interval between secondary IOL implantation and original cataract surgery was 24.85 months (range, 9-60 months). Levels of IL-6, IP-10 (CXCL10), MCP-1 (CCL2), and IL-2 were significantly elevated in the AH of eyes after surgery compared to eyes that did not undergo surgery (P < 0.001, P = 0.047, P = 0.006, P = 0.012, respectively). There was significant correlation between the levels of TGF-ß2 and intraocular pressure (IOP) in postsurgical and nonsurgical eyes (r = 0.532, P = 0.006; r = 0.57, P = 0.001). Postsurgical outcomes, such as iris adhesions, capsular fibrosis, and capsular contraction, were found not to be significantly associated with cytokine levels in the AH after surgery; however, IL-6 levels in capsular exposure eyes were significantly higher than those in cortical closure eyes (P = 0.023). Conclusions: To our knowledge, this is the first study to report significantly increased proinflammatory cytokine levels in the AH after congenital cataract extraction in children. Our study also suggests that this proinflammatory state may be maintained for a prolonged period of time. Overall, these results give us insight into the relationship between the inflammatory cytokine microenvironment of the aqueous humor and potential long-term complications following congenital cataract surgery. Translational Relevance: The inflammatory cytokine microenvironment of the aqueous humor might help explain potential long-term complications after surgery in patients with congenital or developmental cataracts.

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BACKGROUND: This study aimed to investigate the protective effect and mechanism of lentinan (LNT) on acute kidney injury (AKI) in septic rats. METHODS: A total 72 male SD rats were randomly divided into 6 groups with 12 rats in each group. Except for the sham group, all groups, including the burn sepsis group (BS group), the positive drug control group (dexamethasone, 5 mg/kg, PC group), the LNT low-concentration group (LNT-L group) (50 mg/kg), the LNT medium-concentration group (LNT-M group) (100 mg/kg), and the LNT high-concentration group (LNT-H group) (200 mg/kg), were intraperitoneally injected with the same amount of normal saline 30 min before injury. The levels of serum interleukin (IL)-4, IL-6, IL-10, and tumor necrosis factor alpha (TNF-α); the indexes of blood urea nitrogen (BUN) and creatinine (Cr); and the protein expression levels of inducible nitric oxide synthase (iNOS), intercellular adhesion molecule 1 (ICAM-1), and nuclear factor-κB (NF-κB) in renal tissue were detected 24 hours after the model was established. RESULTS: Compared with the sham group, the BUN and Cr of the other groups were significantly higher, while those of the LNT group with different concentrations were significantly lower than those of the BS group (P<0.05). Compared with the sham group, the protein expression levels of NF-κB, iNOS, and ICAM-1 along with the levels of pro-inflammatory factors TNF-α and IL-6 in serum were significantly increased, while the levels of anti-inflammatory factors IL-4 and IL-10 were obviously lower in the BS group. Compared with the BS group, the protein expression levels of NF-κB, iNOS, and ICAM-1 along with the levels of pro-inflammatory factors TNF-α and IL-6 in serum were significantly decreased, while the levels of anti-inflammatory factors IL-4 and IL-10 were obviously increased in the LNT group with different concentrations.. CONCLUSIONS: LNT has a certain protective effect on AKI in septic rats, and its mechanism may involve inhibiting the activation of NF-κB, which suppresses the expression of proinflammatory factors in turn, thus promoting the release of anti-inflammatory factors.

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We previously reported that expression of matrix metalloproteinase-9 (MMP-9) mRNA and protein was upregulated during 1,2-dichloroethane (1,2-DCE) induced brain edema in mice. We also found that the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway resulted in MMP-9 overexpression and nuclear factor-κB (NF-κB) activation in mice treated with 1,2-DCE. In this study, we further hypothesized that inflammatory reactions mediated by the p38 MAPK/ NF-κB signaling pathway might be involved in MMP-9 overexpression, blood-brain barrier (BBB) disruption and edema formation in the brain of 1,2-DCE-intoxicated mice. Our results revealed that subacute poisoning by 1,2-DCE upregulates protein levels of glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba-1), interleukin-1ß (IL-1ß), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthase (iNOS) and p-p65 in mouse brains. Pretreatment with an inhibitor against p38 MAPK attenuates these changes. Moreover, pretreatment with an inhibitor against NF-κB attenuates alterations in brain water content, pathological indications notable in brain edema, as well as mRNA and protein expression on levels of MMP-9, VCAM-1, ICAM-1, iNOS, and IL-1ß, tight junction proteins (TJs), GFAP and Iba-1 in the brain of 1,2-DCE-intoxicated mice. Furthermore, pretreatment with an inhibitor against MMP-9 obstructs the decrease of TJs in the brain of 1,2-DCE-intoxicated mice. Lastly, pretreatment with an antagonist against the IL-1ß receptor also attenuates changes in protein levels of p-p38 MAPK, p-p65, p-IκB, VCAM -1, ICAM-1, IL-1ß, and Iba-1 in the brain of 1,2-DCE-intoxicated-mice. Taken together, findings from the current study indicate that the p38 MAPK/ NF-κB signaling pathway might be involved in the activation of glial cells, and the overproduction of proinflammatory factors, which might induce inflammatory reactions in the brain of 1,2-DCE-intoxicated mice that leads to brain edema.

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Evidence indicates that adverse experiences in early life may be a factor for immune disturbances leading to the depression in adulthood. Recently, a pivotal role in the pathogenesis of depression has been assigned to the activation of the brain Nod-like receptor pyrin-containing 3 (NLRP3) inflammasome. We investigated the impact of chronic treatment with antidepressant drugs on the behavioral disturbances and the levels of proinflammatory factors in the hippocampus and frontal cortex of adult male rats after prenatal stress exposure. Next, we explored the involvement of the NLRP3 inflammasome-related pathways in the mechanism of antidepressant action. Our study confirmed that chronic antidepressant treatment attenuated depression-like disturbances and exerted an anxiolytic action. All antidepressants diminished the prenatal stress-induced increase in IL-1ß in both brain areas, while IL-18 only in the hippocampus. Moreover, tianeptine administration diminished the increase in CCR2 levels in both brain areas, while in the hippocampus, tianeptine, along with venlafaxine CCL2 and iNOS levels. Next, we observed that in the hippocampus, tianeptine and fluoxetine suppressed upregulation of TLR4. Furthermore, venlafaxine suppressed NFкB p65-subunit phosphorylation, while fluoxetine enhanced the IкB level. Importantly, in the hippocampus, all antidepressants normalized evoked by stress changes in caspase-1 level, while tianeptine and venlafaxine also affect the levels of ASC and NLRP3 subunits. Our results provide new evidence that chronic administration of antidepressants exerts anti-inflammatory effects more pronounced in the hippocampus, through suppression of the NLRP3 inflammasome activation. These effects are accompanied by an improvement in the behavioral dysfunctions evoked by prenatal stress.

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OBJECTIVES: Renal mesangial expansion has been identified as a major factor contributing to glomerulosclerosis, a typical symptom of diabetic nephropathy. It is unclear whether microvesicles, known as a mediator for cross-talk between cells and organs, are involved in a profibrotic process. In this study, we are the first to investigate the effect of monocyte-derived microvesicles induced by high glucose on renal mesangial cells. METHODS: THP1 cells were evoked by high glucose to generate microvesicles, quantified by ELISA. Glucose uptake by THP1 cells was measured using fluorescently-labeled deoxyglucose analog 2-NBDG as a probe. The contents of inflammatory cytokines in microvesicles were detected by western blot. The expressions of HIF-1α and VEGF in human renal mesangial cells after treatment with THP1-derived microvesicles were examined by western blot. RESULTS: The glucose uptake by THP1 cells was significantly increased after high glucose treatment. High glucose significantly evoked MV generation, which contained increased protein level of IL-6, 8 and MCP-1. The expressions of HIF-1α and VEGF in HRMC were augmented by microvesicles. CONCLUSIONS: Our study indicates that monocyte-derived MVs induced by high glucose can carry proinflammatory factors, and enhance the expression of the HIF/VEGF pathway in human renal mesangial cells. Our findings may provide a novel potential mechanism in the progression of diabetic nephropathy.

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Objective: To observe the clinical efficacy of addition and subtraction therapy of Taohong Siwutang combined with Chaihu Shugansan to unstable angina pectoris with type A behavior pattern (Qi stagnation and blood stasis syndrome), and investigate its effects on proinflammatory factors and serotonin (5-HT). Method: One hundred twenty-four patients were randomly divided into control group (60 cases) and observation group(64 cases) by random number table. Patients in control group got Aspirin enteric-coated tablets, 100 mg/time, 1 time/day. Tigrillo tablets, 90 mg/time, 2 times/days. Metoprolol tartrate tablets, 50 mg/time, 2 times/days. Simvastatin tablets, 10 mg/time, 1 time/day. Nitroglycerin tablets, 0.5 mg/time. Based on the treatment in control group, patients in observation group also received addition and subtraction therapy of Taohong Siwutang combined with Chaihu Shugansan, 1 dose/day. The treatment course was 8 weeks in both groups. Number of attacks, duration, degree of pain and usage of nitroglycerin were recorded for every week. Before and after treatment, electrocardiogram was also recorded. And levels of triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), hypersensitive C-reactive protein and 5-HT were detected. In addition, scores of Seattle Angina Scale (SAQ) and Qi stagnation and blood stasis syndrome were graded. Result: In the rank sum test, the curative effect in electrocardiogram of observation group was better than that of control group (Z=1.965, PPPPα and 5-HT in observation group were lower than those in control group (PPConclusion: On the basis of conventional western medicine, addition and subtraction therapy of Taohong Siwutang combined with Chaihu Shugansan can further control angina attack, relieve clinical symptoms, improve quality of life, regulate lipid metabolism, and can inhibit expression of proinflammatory factors and 5-HT, so it can play a role in stabilizing the disease.

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Objective: To discuss the clinical effect of Dahuang Zhechong Wan on pelvic pain caused by endometriosis with Qi stagnation and blood stasis syndrome and study the mechanism of action. Method: One hundred and twenty-six patients were randomly divided into control group (64 cases) and observation group (62 cases) by random number table. Both groups' patients got Duphaston from the 5th to 25th days of menstrual cycle, 1 tablet/day, 2 times/days. Patients in control group got Sanjie Zhentong Jiaonang at the first day of menstruation, 4 grains/time, 3 times/days. Patients in observation group got Dahuang Zhechong Wan, 3 g/time, 2 times/days. The treatment in two groups continued for 3 menstrual cycles. Before treatment and at the first, second and third menstrual cycles after the treatment, visual analogue score (VAS) of pain was used for dysmenorrheal. Before AND after the treatment, scores of symptoms, signs, Qi stagnation and blood stasis syndrome and endometriosis were scored by endometriosis health profile-5 (EHP-5). And hemorheology was detected, and levels of matrix metalloproteinases-2 (MMP-2), MMP-9, tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), prostaglandin E2 (PGE2), prostaglandin F2α(PGF2α) and substance P (SP) were detected. Result: By rank sum test, the clinical effect of disease in observation group was better than that in control group (Z=2.198, PPPPα, IL-1, PGF2α and SP were lower than those in control group (P2 was higher than that in control group (PConclusion: In addition to treatment of progestogen, Dahuang Zhechong Wan can relieve pelvic pain, improve quality of life and clinical effect, and regulate levels of prostaglandins, matrix metalloproteinases and proinflammatory factors.

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OBJECTIVE: To characterize the microenvironment following blood-spinal cord barrier (BSCB) damage and to evaluate the role of BSCB disruption in secondary damage of spinal cord injury (SCI). METHODS: A model of BSCB damage was established by co-culture of primary microvascular endothelial cells and glial cells obtained from rat spinal cord tissue followed by oxygen glucose deprivation/re-oxygenation (OGD/R). Permeability was evaluated by measuring the transendothelial electrical resistance (TEER) and the leakage test of Fluorescein isothiocyanate-dextran (FITC-dextran). The expression of tight junction (TJ) proteins (occludin and zonula occludens-1 (ZO-1) were evaluated by Western blot and immunofluorescence microscopy. Proinflammatory factors (TNF-α, iNOS, COX-2 and IL-1ß), leukocyte chemotactic factors (MIP-1α, MIP-1ß) and leukocyte adhesion factors (ICAM-1, VCAM-1) were detected in the culture medium under different conditions by enzyme-linked immuno sorbent assay (ELISA). RESULTS: The model of BSCB damage induced by OGD/R was successfully constructed. The maximum BSCB permeability occurred 6-12 hours but not within the first 3 h after OGD/R-induced damage. Likewise, the most significant period of TJ protein loss was also detected 6-12 hours after induction. During the hyper-acute period (3 h) following OGD/R-induced damage of BSCB, leukocyte chemotactic factors and leukocyte adhesion factors were significantly increased in the BSCB model. Pro-inflammation factors (TNF-α, IL-1ß, iNOS, COX-2), leukocyte chemotactic factors (MIP-1α, MIP-1ß) and leukocyte adhesion factors (ICAM-1, VCAM-1) were also sharply produced during the acute period (3-6 hours) and maintained plateau levels 6-12 hours following OGD/R-induced damage, which overlapped with the period of BSCB permeability maximum. A negative linear correlation was observed between the abundance of proinflammatory factors and the expression of TJ proteins (ZO-1 and occludin) and transepithelial electrical resistance (TEER), and a positive linear correlation was found with transendothelial FITC-dextran. CONCLUSIONS: Secondary damage continues after primary BSCB damage induced by OGD/R, exhibiting close ties with inflammation injury.

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OBJECTIVE: We have repeatedly demonstrated that electroacupuncture (EA) stimulation of "Shenmen" (HT 7)- "Tongli" (HT 5) segment of the Heart Meridian can improve acute myocardial ischemia (AMI). This study aimed at observing the effect of EA on contents of hippocampal norepinephrine (NE), and interleukin 6 (IL-6), IL-1 ß and tumor necrosis factor- α (TNF-α) in AMI rats, so as to explore its underlying mechanism. METHODS: SD rats were randomly divided into 3 groups: sham operation (sham), model and EA(n=6 rats in each). The anterior descending branch (ADB) of the left coronary artery was occluded to make an AMI model. For rats of the sham group, a surgical suture was simply threaded beneath the ADB without ligation. EA (2 Hz/15 Hz, 1 mA) was applied to bilateral "Shenmen" (HT 7)- "Tongli" (HT 5) and the middle-point between HT 7 and HT 5 for 30 min, once daily for 3 days. Electrocardiogram (ECG) of the neck-thoracic lead was recorded by using PowerLab 16. The contents of serum creatine kinase (CK), hippocampal IL-6, IL-1 ß and TNF-α were assayed by ELISA. The concentration of NE in hippocampal CA 1 area was detected by microdialysis combined with electrochemical detector. RESULTS: Compared with the sham group, the ECG-ST height, serum CK, hippocampal NE, IL-6, IL-1 ß and TNF-α contents of the CA 1 region were significantly increased in the model group (P<0.001). Whereas, after EA intervention, the serum CK, hippocampal NE, IL-6, IL-1 ß and TNF-α contents were obviously down-regulated relevant to the model group (P<0.05, P<0.001), and the IL-6, IL-1 ß and TNF-α contents were positively correlated with the NE level (P<0.001, P<0.01). CONCLUSION: EA stimulation of the Heart Meridian may improve ischemic myocardial injury in AMI rats, probably by reducing the proinflammatory factors and hippocampal NE.

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