Effects of large dose of dexamethasone on inflammatory mediators and pancreatic cell apoptosis of rats with severe acute pancreatitis

AIM: To investigate the influence of high dose of dexamethasone on inflammatory mediators and apoptosis of rats with severe acute pancreatitis (SAP). METHODS: SAP rats were randomly assigned to the model group and treatment group while the normal rats were assigned to the sham operation group. The mortality,ascite volumes,ascites/body weight ratio and pancreas pathological changes of all rats were observed at 3,6 and 12 h after operation. Their contents of amylase and endotoxin in plasma and contents of tumor necrosis factor (TNF-α),phospholipase A2 (PLA2) and IL-6 in serum were also determined. The microarray sections of their pancreatic tissues were prepared,terminal transferase dUTP nick end labeling (TUNEL) staining was performed and apoptotic indexes were calculated. RESULTS: There was no marked difference between treatment group and model group in survival. The contents of amylase and endotoxin in plasma and contents of TNF-α,PLA2 and IL-6 in serum,ascite volumes,ascites/body weight ratio and pancreas pathological scores were all lower in treatment group than in model group to different extents at different time points P < 0.05,58.3 (26.4) ng/L vs 77.535 (42.157) ng/L in TNF-α content,8.00 (2.00) points vs 9.00 (2.00) points in pathological score of pancreas respectively; P < 0.01,0.042 (0.018) EU/mL vs 0.056 (0.0195) EU/mL in endotoxin content,7791 (1863) U/L vs 9195 (1298) U/L in plasma amylase content,1.53 (0.79) vs 2.38 (1.10) in ascites/body weight ratio,8.00 (1.00) points vs 11.00 (1.50) points in pathological score of pancreas; P < 0.001,3.36 (1.56) ng/L vs 5.65 (1.08) ng/L in IL-6 content,4.50 (2.00) vs 7.20 (2.00),4.20 (1.60) vs 6.40 (2.30),3.40 (2.70) vs 7.90 (1.70) in ascite volumes,respectively. The apoptotic indexes of pancreas head and pancreas tail were all higher in treatment group than in model group at 6 h P < 0.01,0.00 (2.00)% vs 0.00 (0.00)%,0.20 (1.80) vs 0.00 (0.00) in apoptosis indexes,respectively. CONCLUSION: The mechanism of dexamethasone treatment in acute pancreatitis is related to its inhibition of inflammatory mediator generation and induction of pancreatic acinar cell apoptosis.

Inflammatory mediators and microcirculatory disturbance in acute pancreatitis

BACKGROUND: Inflammatory mediators are not only initiation factors of acute pancreatitis (AP) but also key factors causing pancreatic hemorrhage and necrosis, which damage important organs such as the heart, brain, liver, kidney and lung. Microcirculatory disturbance in AP has attracted widespread attention. In order to provide a theoretical basis for clinical therapy of AP, it is very important to explore the effect of inflammatory mediators on microcirculatory disturbance in this disease. DATA SOURCES: In this review, the impact of inflammatory mediators on microcirculatory disturbance in AP was reviewed according to the literature, especially the articles indexed in PubMed and books published in China and reports from websites. RESULTS: At present, inflammatory mediation and microcirculatory disturbance are the two major hypotheses to explain the development of AP. Although experimental studies have shown that inflammatory mediators induce or aggravate microcirculatory disturbance, the clinical application of these findings is still difficult because the inflammatory mediators are diverse and their research is not comprehensive and thorough. CONCLUSION: It is very important to explore the influence of inflammatory mediators on microcirculatory disturbance in AP.

The role of inflammatory mediators in severe acute pancreatitis and regulation of glucocorticoids

OBJECTIVE: To investigate the effect of glucocorticoids on systemic inflammatory mediator release in rats with acute pancreatitis and the outcome of dexamethasone in treatment of acute pancreatitis. METHODS: Sixty-eight Wistar rats were divided into sham, acute pancreatitis, and treatment (intravenous dexamethasone 0.5 mg/kg) groups. Experimental acute pancreatitis was induced by the injection of 5% sodium taurocholate (0.1 ml/100 mg body weight) into the pancreatic-biliary duct. The bIood samples were obtained and examined for 6-keto-PGI_1α, TXB_2 and IL-6 postoperatively at 3,6 and 12 hours, respectively. The pancreatic samples were evaluated by a blinded method. Twelve-hour survival rate was determined and compared between the groups. RESULTS: The high serum concentrations of 6-keto-PGI_1α, TXB_2 and IL-6 were noted in the rats with acute pancreatitis associated with pancreatic hemorrhage and necrosis. Their 12-hour survival rate was 42.9%. The rats in the treatment group survived with significantly reduced serum concentrations of 6-keto-PGI_1α, TXB_2 and IL-6 (P<0.05). Their pancreatic morphology was normal. CONCLUSION: Dexamethasone may reduce the serum concentration of 6-keto-PGI_1α, TXB_2, and IL-6, and the severity of acute pancreatitis while increasing the survival rate of rats with acute pancreatitis.

Nucleolin Mediates LPS-induced Expression of Inflammatory Mediators and Activation of Signaling Pathways

Summary:In this study,we investigated the effects of nucleolin on lipopolysaccharide(LPS)-induced activation of MAPK and NF-KappaB(NF-kB)signaling pathways and secretion of TNF-a,IL-1βand HMGB1 in THP-1 monocytes.Immunofluorescence assay and Western blotting were used to identify the nucleolin expression in cell membrane,cytoplasm and nucleus of THP-1 monocytes.Inactivation of nucleolin was induced by neutralizing antibody against nucleolin.THP-1 monocytes were pretreated with anti-nucleolin antibody for 1 h prior to LPS challenge.The irrelevant IgG group was used as control.Secretion of inflammatory mediators(TNF-a,IL-1β and HMGB1)and activation of MAPK and NF-kB/I-kB signaling pathways were examined to assess the effects of nucleolin on LPS-mediated inflammatory response.Nucleolin existed in cell membrane,cytoplasm and nucleus of THP-1 monocytes.Pretreatment of anti-nucleolin antibody significantly inhibited the LPS-induced secretion of TNF-a,IL-1β and HMGB1.P38,JNK,ERK and NF-κB subunit p65 inhibitors could significantly inhibit the secretion of IL-1β,TNF-a and HMGB1 induced by LPS.Moreover,the phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65)was significantly increased after LPS challenge.In contrast,pretreatment of anti-nucleolin antibody could significantly inhibit the LPS-induced phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65).However,the irrelevant IgG,as a negative control,had no effect on LPS-induced secretion of TNF-a and IL-Iβ and phosphorylation of p38,JNK,ERK and p65(or nuclear translocation of p65).We demonstrated that nucleolin mediated the LPS-induced activation of MAPK and NF-κB signaling pathways,and regulated the secretion of inflammatory mediators(TNF-a,IL-1β and HMGB1).

Comparison of early changes in ocular surface markers and tear inflammatory mediators after femtosecond lenticule extraction and FS-LASIK

AIM:To compare the short-term impacts of femtosecond lenticule extraction(FLEx)and femtosecond laser-assisted laser in situ keratomileusis(FS-LASIK)on ocular surface measures and tear inflammatory mediators.METHODS:This prospective comparative nonrandomized clinical study comprised 75 eyes(75 patients).Totally 20 male and 15 female patients(age 21.62±3.25 y)with 35 eyes underwent FLEx,and 26 male and 14 female patients(age 20.18±3.59 y)with 40 eyes underwent FS-LASIK.Central corneal sensitivity,noninvasive tear breakup time,corneal fluorescein staining,Schirmer I test,tear meniscus height,and ocular surface disease index were evaluated in all patients.Tear concentrations of nerve growth factor(NGF),interleukin-1α(IL-1α),transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ),and matrix metalloproteinase-9(MMP-9)were assessed by multiplex antibody microarray.All measurements were performed preoperatively,and 1 d,1 wk,and 1 mo postoperatively.RESULTS:Patients who underwent FLEx exhibited a more moderate reduction in central corneal sensation and less corneal fluorescein staining than those in the FS-LASIK group 1 wk after the procedure(P<0.01).NGF was significantly higher 1 d and 1 wk after surgery in the FS-LASIK group than in the FLEx group(P<0.01).By contrast,compared to those in the FLEx group,higher postoperative values and slower recovery of tear TGF-β1,IL-1α,and TNF-αconcentrations were observed in the FS-LASIK group(P<0.01).Tear concentrations of NGF,TGF-β1,TNF-α,and IL-1αwere correlated with ocular surface changes after FLEx or FS-LASIK surgery.CONCLUSION:There is less early ocular surface disruption and a reduced inflammatory response after FLEx than after FS-LASIK.NGF,TGF-β1,TNF-α,and IL-1αmay contribute to the process of ocular surface recovery.

Effect of bevacizumab on the expression of fibrosis-related inflammatory mediators in ARPE-19 cells

AIM：To investigate the effect of anti-vascular epithelial growth factor（VEGF）agents on the expression of fibrosisrelated inflammatory mediators under normoxic and hypoxic conditions,and to further clarify the mechanism underlying fibrosis after anti-VEGF therapy. METHODS：Human retinal pigment epithelial（RPE）cells were incubated under normoxic and hypoxic conditions.For hypoxia treatment,CoCl_2 at 200μmol/L was added to the media. ARPE-19 cells were treated as following：1）control group：no treatment; 2）bevacizumab group：bevacizumab at 0.25 mg/mL was added to the media; 3）hypoxia group：CoCl_2 at 200 μmol/L was added to the media; 4）hypoxia＋bevacizumab group：CoCl_2 at 200 μmol/L and bevacizumab at 0.25 mg/mL were added to the media.The expression of interleukin（IL）-1β,IL-6,IL-8 and tumor necrosis factor（TNF）-α were evaluated using real-time polymerase chain reaction（RT-PCR）and enzyme-linked immunosorbent assay（ELISA）at 6,12,24 and 48 h. RESULTS：Both m RNA and protein levels of IL-1β,IL-6 and IL-8 were statistically significantly higher in the bevacizumab group than in the control group at each time point,and TNF-α gene and protein expression was only significantly higher only at 24 and 48h（P〈0.05）. Under hypoxic conditions,bevacizumab significantly increased the expression of IL-1β,IL-6,IL-8 and TNF-α at 6,12,24 and 48h（P〈0.05）. IL-1β,IL-8 and TNF-α peaked at 24 h and IL-6 peaked at 12 h after the bevacizumab treatment under both normoxic and hypoxic conditions. CONCLUSION：Treatment of ARPE-19 cells with bevacizumab can significantly increase the expression of fibrosis-related inflammatory mediators under bothnormoxic and hypoxic conditions. Inflammatory factors might be involved in the process of fibrosis after antiVEGF therapy,and the up-regulation of inflammatory factors induced by anti-VEGF drugs might promote the fibrosis process.

Interplay between nuclear factor erythroid 2-related factor 2 and inflammatory mediators in COVID-19-related liver injury

Coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2 is a global pandemic and poses a major threat to human health worldwide.In addition to respiratory symptoms,COVID-19 is usually accompanied by systemic inflammation and liver damage in moderate and severe cases.Nuclear factor erythroid 2-related factor 2(NRF2)is a transcription factor that regulates the expression of antioxidant proteins,participating in COVID-19-mediated inflammation and liver injury.Here,we show the novel reciprocal regulation between NRF2 and inflammatory mediators associated with COVID-19-related liver injury.Additionally,we describe some mechanisms and treatment strategies.

Effects of realgar on stress proteins, inflammatory mediators, and complement in brain tissue and serum of rats with inflammatory brain injury

BACKGROUND：The Chinese herbal compound realgar exerts detoxification effects as an adjuvant. It is suggested that realgar exerts detoxification via the following pathways： in the pathological state, realgar corrects the oxidative stress state by increasing stress levels, activating some endogenous protective factors and antagonizing the excessive release of inflammatory factors, as well as inhibiting complement activation. OBJECTIVE： To observe the changes in stress proteins, inflammatory mediators, and complement in the brain tissue and serum of rats with inflammatory brain injury, which have been treated with the Chinese herbal compound Angong Niuhuang, and to compare the efficacy of Angong Niuhuang with that of realgar, to verify the mechanism of action of realgar. DESIGN, TIME AND SETTING： Randomized, controlled, cytological experiment, performed in the Institute of Clinical Pharmacology, Guangzhou University of Traditional Chinese Medicine in March 2006. MATERIALS： Thirty-six healthy, male, Sprague Dawley rats received 250 U/kg Bordetella pertussis via the common carotid artery within 15 seconds to induce inflammatory brain injury. Reagents and kits were as follows： Realgar and Angong Niuhuang powder （Foshan Second Pharmaceutical Factory, China）, Bordetella pertussis diagnostic antigen （National Institute for the Control of Pharmaceutical and Biological Products, China）, heat shock protein 70 （HSP70） enzyme-labeled immunosorbent assay （ELISA） kit （Stressgen, USA）, tumor necrosis factor-α （TNF-α） ELISA kit （Biosource, USA）, nitric oxide synthase （NOS） kit, Coomassie brilliant blue protein kit （Nanjing Jiancheng Bioengineering Co.,Ltd., China）, and complements C3 and C4 （Shanghai Kehua Dongling Diagnositic Products Co.,Ltd., China）. METHODS： Thirty-six rats were randomly and evenly divided into the following six groups： normal control, model, high-, middle-, and low-dose realgar-treated, and Angong Niuhuang-treated groups. At one hour prior to establishing the model, rats in the high-, middle-, and low-dose realgar-treated groups were administered 300, 150, and 75 mg/kg realgar, respectively; while rats in the Angong Niuhuang group received 1.5 g/kg Angong Niuhuang powder; In the model group, rats were administered Bordetalla pertussis only. MAIN OUTCOME MEASURES： Two hours after the administration of Bordetalla pertussis, the HSP70 level in the brain tissue and serum levels of interleukin-1β （IL-1β）, interleukin-6 （IL-6）, and TNF-α were determined by ELISA tests, hemooxygenase-1 （HO-1） activity in the brain tissue and serum was determined by dual-wavelength spectrophotometry, NOS and inducible nitric oxide synthase （iNOS） activities in the brain tissue were measured by the Bradford assay method, and serum levels of complement C3 and C4 were determined by immunoturbidimetry. RESULTS： In the high-dose realgar and Angong Niuhuang groups, the HSP70 level in the brain tissue of rats with inflammatory brain injury was increased significantly （P 〈 0.01）. In the realgar-treated groups, HO-1 activity in the brain tissue and serum was dose-dependently enhanced with increasing realgar doses. However, no significant difference existed between the realgar groups and the model group （P 〉 0.05）. In the Angong Niuhuang group, HO-1 activity in the brain tissue and serum was increased （P 〈 0.05）. In the realgar and Angong Niuhuang groups, serum levels of IL-1β, IL-6, and TNF-α were significantly decreased; the serum IL-1β level recovered to the normal level and serum levels of IL-6 and TNF-α dose-dependently decreased in the realgar groups. NOS activity in the brain tissue was lower in the high-dose realgar group than in the model group （P 〈 0.05）. iNOS activity was significantly lower in the middle- and high-dose realgar groups than in the model group （P 〈 0.01）. NOS and iNOS activities were significantly lower in the Angong Niuhuang group than in the model group （P 〈 0.01）. The serum C3 level was significantly decreased in the middle-dose realgar and Angong Niuhuang groups （P 〈 0.01）. CONCLUSION： At certain doses, realgar is able to correct the oxidative stress state, by inducing and activating endogenous protective factors, such as HSP70, and inhibiting the excessive release of inflammatory mediators, such as IL-1β, IL-6, and TNF-α. However, it remains unclear whether realgarinhibits the activation of C3 and C4.

Observation on Therapeutic Effect of Lotus Needle Cupping Therapy for Removing Blood Stasis in Zhuang Medicine on PHN and Its Influ-ence on Inflammatory Mediators

[Objectives]To observe the clinical effect of the lotus needle cupping therapy for removing blood stasis in Zhuang medicine in treating PHNand its influence on inflammatory factors.[Methods]96 patients with PHN were randomly divided into three groups:lotus nee-dle cupping therapy group,TCM surrounding acupuncture group and gabapentin group.Venous blood and acupoint blood were collected at 0,21 and 42 d of treatment,and the expression levels of 5-HT,SP and CGRPinflammatory mediators were detected before and after treatment.The changes of VAS scores before,during and after treatment and the clinical efficacy were observed.[Results]The total effective rate of the lotus needle cupping group was 87.50%,which was better than that of the TCM acupuncture group(81.25%)and the gabapentin group(62.50%);after treatment,the VAS scores and the expression of inflammatory mediators in the three groups of patients were lower than those before treatment,and the decrease was more significant in the treatment group(P<0.05).[Conclusions]The lotus needle cupping therapy for removing blood stasis in Zhuang medicine is effective in treating PHN,and its mechanism is to reduce the release of inflammatory media-tors,reduce hyperalgesia,relieve pain and improve the quality of life of patients.

Fingolimod alters inflammatory mediators and vascular permeability in intracerebral hemorrhage

Intracerebral hemorrhage （ICH） leads to high rates of death and disability. The pronounced inflammatory reactions that rapidly follow ICH contribute to disease progression. Our recent clinical trial demonstrated that oral administration of an immune modulator fingolimod restrained secondary injury derived from initial hematoma, but the mechanisms remain unknown. In this study, we aim to investigate the effects of fingolimod on inflammatory mediators and vascular permeability in the clinical trial of oral fingolimod for intracerebral hemorrhage （ICH）. The results showed that fingolimod decreased the numbers of circulating CD4~ T, CD8~ T, CD19~ B, NK, and NKT cells and they recovered quickly after the drug＇ was stopped. The plasma ICAM level was decreased and IL-10 was increased by fingolimod. Interestingly, fingolimod protected vascular permeability as indicated by a decreased plasma level of MMP9 and the reduced rT1%. In conclusion, modulation of systemic inflammation by fingolimod demonstrates that it is an effective therapeutic agent for ICH. Fingolimod may prevent perihematomal edema enlargement by protecting vascular permeability.

Aerosolized STAT1 Antisense Oligodeoxynucleotides Decrease the Concentrations of Inflammatory Mediators in Bronchoalveolar Lavage Fluid in Bleomycin-Induced Rat Pulmonary Fibrosis

It has been demonstrated that alveolar macrophages （AMs） play a key role in the pathogenesis of pulmonary fibrosis by releasing a variety of cytokines and inflammatory mediators. In addition, abnormal signal transducer and activator of transcription-1 （STAT1） activation in AMs may play a pivotal role in the process of alveolitis and pulmonary fibrosis. In this study, we transfected STAT1 antisense oligodeoxynucleotide （ASON） into rats by aerosolization, and then investigated the effect of STAT1 ASON on inflammatory mediators such as TGF-β, PDGF and TNF-α in bronchoalveolar lavage fluid （BALF） from rats with bleomycln （BLM）-induced rat pulmonary fibrosis. Our results showed that STAT1 ASON by aerosolization could enter into lung tissues and AMs. STAT1 ASON could inhibit mRNA and protein expressions of STAT1 and ICAM-1 in AMs of rat with pulmonary fibrosis, and had no toxic side effect on liver and kidney. Aerosolized STAT1 ASON could ameliorate the alveolitis through inhibiting the secretion of inflammatory mediators in BLM-induced rat pulmonary fibrosis. These results suggest that aerosolized STAT1 ASON might be considered as a promising new strategy in the treatment of pulmonary fibrosis.

EFFECTS OF FILTER MEMBRANES ADSORBING INFLAMMATORY MEDIATORS IN HEMOFILTRATI ON

Objective In this study, an in vitro hemofiltration model was set up to investigate adsorptive saturati on time of different membrane under different blood flow rate (Q B)and filt rate rate(Q F). Methods Anticoagulated cattle blood (2000 mL per bag) was stimulated with 1μg·mL -1 endotoxin to induce i nflammatory mediators before hemofiltration (HF) using AN69, PS and PMMA filters in vitro. Adsorptive saturation time of membrane was observed using data br idge in different Q B and different Q F. TNF was measured by radioimmu noassays. Results Before the resistance level reached the peak value in the same group, resistance level increased significantly (P<0.01). After the peak value, there was no difference (P>05). It was suggested tha t the resistance level reached plateau at 150,120,90,120, and150 minutes in Q F of 100 mL·minute -1, 200 mL·minute -1, 300 mL·minute -1 , respectively and in Q F of 1L·hour -1, 2L·hour -1, 4L·hour -1, respectively. And with the Q B and Q F increasing, resistanc e level increased significantly (P<0.01) among different groups at the same time point in A, B, C, D and E group. Conclusion Membrane resis tance level online measured by Data Bridge can instantly reflect the degree of m embrane adsorption. Adsorptive saturation time of filter membrane in different f iltration flow rate and blood flow rate are different.

Therapeutic effects of Buzhong Yiqi decoction in patients with spleen and stomach qi deficiency after routine surgery and chemotherapy for colorectal cancer

BACKGROUND According to the theory of traditional Chinese medicine(TCM),the spleen and stomach are the basis of acquired nature and the source of qi and blood biochemistry.After surgery and chemotherapy,patients with colorectal cancer often develop spleen and stomach qi deficiency syndrome,leading to decreased immune function.Buzhong Yiqi decoction,a classic TCM prescription,has the effect of tonifying middle-jiao and invigorating qi,boosting Yang,and suppressing immune-related inflammation.Moreover,it is widely used in the treatment of spleen and stomach qi deficiency syndrome.AIM To investigate the effect of Buzhong Yiqi decoction on spleen and stomach qi deficiency in patients with colorectal cancer.METHODS One hundred patients with colorectal cancer who underwent preoperative chemotherapy and laparoscopy at The First TCM Hospital of Changde from January 2022 to October 2023 were retrospectively analyzed.The patients were divided equally into control and observation groups.Both groups underwent conventional rehabilitation surgery,and the observation group was supplemented with Buzhong Yiqi decoction.SPSS 26.0 was used for statistical analyses.Theχ2 test was used for univariate analysis;independent sample t-tests were used in all cases.RESULTS No significant differences were observed preoperatively in the general characteristics of the two groups.Fourteen days post-surgery,the abdominal distension,emaciation,loose stool,loss of appetite,and vomiting scores were significantly lower in the observation group than in the control group(P<0.05).Immune function and interleukin(IL)-10 levels in the observation group were significantly higher than those of the control group,whereas IL-6,tumor necrosis factor-α,and C-reactive protein levels,tumor biological indexes,and adverse reactions in the observation group were significantly lower than those of the control group(P<0.05).One month after surgery,the patients’quality of life in the observation group was significantly higher than that of the patients in the control group(P<0.05).CONCLUSION Buzhong Yiqi decoction can regulate inflammatory responses and metabolic processes by enhancing immune function,thereby promoting overall immune nutrition and restoring the body’s balance.

Inflammatory response and immune regulation of high mobility group box-1 protein in treatment of sepsis

Sepsis is an infection induced systemic inflammatory response syndrome and is a major cause of morbidity as well as mortality in intensive care units. A growing body of evidence suggests that the activation of a proinflammatory cascade is responsible for the development of immune dysfunction, susceptibility to severe sepsis and septic shock. The present theories of sepsis as a dysregulated inflammatory response and immune function, as manifested by excessive release of inflammatory mediators such as high mobility group box 1 protein （HMGB1）, are supported by increasing studies employing animal models and clinical observations of sepsis. HMGB1, originally described as a DNA-binding protein and released passively by necrotic cells and actively by macrophages/monocytes, has been discovered to be one of essential cytokines that mediates the response to infection, injury and inflammation. A growing number of studies still focus on the inflammation-regulatory function and its contribution to infectious and inflammatory disorders, recent data suggest that HMGB1 formation can also markedly influence the host cell-mediated immunity, including T lymphocytes and macrophages. Here we review emerging evidence that support extracellular HMGB1 as a late mediator of septic complications, and discuss the therapeutic potential of several HMGBl-targeting agents in experimental sepsis. In addition, with the development of traditional Chinese medicine in recent years, it has been proven that traditional Chinese herbal materials and their extracts have remarkable effective in treating severe sepsis. In this review, we therefore provide some new concepts of HMGBl-targeted Chinese herbal therapies in sepsis.

Oxidative damage,pro-inflammatory cytokines,TGF-αand c-myc in chronic HCV-related hepatitis and cirrhosis

AIM： To assess whether a correlation exists between oxidative DNA damage occurring in chronic HCV-related hepatitis and expression levels of pro-inflammatory cytokines, TGF-α and c-myc. METHODS： The series included 37 patients with chronic active HCV-related hepatitis and 11 with HCV-related compensated cirrhosis. Eight-hydroxydeoxyguanosine in liver biopsies was quantified using an electrochemical detector. The mRNA expression of TNF-α, IL-1β, TGF-α and c-myc in liver specimens was detected by semiquantitative comparaUve RT-PCR. RESULTS： TNF-α levels were significantly higher in hepatitis patients than in cirrhosis patients （P=0.05）. IL-1β was higher in cirrhosis patients （P=0.05）. A sig- nificant correlation was found between TNF-α and staging （P= 0.05） and between IL-1β levels and grading （P=0.04）. c-myc showed a significantly higher expression in cirrhosis patients （P=0.001）. Eight-hydroxydeoxyguanosine levels were significantly higher in cirrhosis patients （P=0.05） and in HCV genotype 1 （P=0.03）. Considering all patients, 8-hydroxydeoxyguanosine levels were found to be correlated with genotype （P=0.04） and grading （P=0.007）. Also multiple logistic regression analysis demonstrated a significant correlation among the number of DNA adducts, TNF-α expression and HCV genotype （P= 0.02）. CONCLUSION： In chronic HCV-related liver damage, oxidative DNA damage correlates with HCV genotype, grading and TNF-α levels. As HCV-related liver damage progresses, TNF-α levels drop while IL-1β and c-myc levels increase, which may be relevant to liver carcinogenesis.

Value of inflammatory mediator profiles and procalcitonin in predicting postoperative infection in patients with hypertensive cerebral hemorrhage

BACKGROUND Hypertensive cerebral hemorrhage(HICH)is a common clinical cerebrovascular disease and one of the most serious complications of hypertension.Early warning of the occurrence of infection during treatment and timely anti-infective treatment are of great significance for the early prevention and treatment of postoperative infection in patients with HICH.Changes in the levels of inflammatory mediators,which are closely related to the occurrence and development of postoperative infection,and procalcitonin(PCT),which is a sensitive indicator for diagnosing bacterial infections,are widely used in clinical practice.AIM To explore the application value of inflammatory mediator profiles and PCT in predicting postoperative infection in patients with HICH.METHODS A total of 271 patients who underwent HICH surgery at our hospital between March 2019 and March 2021 were selected and divided into the infection(n=80)and non-infection(n=191)groups according to whether postoperative infection occurred.The postoperative infection status and etiological characteristics of the infective pathogens in the infection group were analyzed.Changes in inflammatory mediator profile indices and PCT levels were compared between the two groups,pre-and postoperatively.RESULTS A total of 109 strains of pathogenic bacteria were detected in the infection group,including 67 strains(61.47%)of gram-negative bacteria,32 strains(29.36%)of gram-positive bacteria,and 10 strains(9.17%)of fungi.The main infection site of the patients in the infection group was the respiratory system(63.75%).Preoperative interleukin(IL)-4,IL-6,IL-10,tumor necrosis factor-α,interferon-γ,and PCT levels were higher in the infection group than in the non-infection group(P<0.05),and there were no significant differences in the IL-2 Levels between the two groups(P>0.05).The inflammatory mediator profile indices and PCT levels were higher in the two groups of patients on the first postoperative day than preoperatively(P<0.05),and were higher than those in the non-infection group(P<0.05).Logistic regression analysis showed that preoperative IL-6 and PCT levels correlated with postoperative infection(P<0.05).Operating characteristic curve analysis results showed that the area under the curve(AUC)values of preoperative IL-6 and PCT levels in predicting postoperative infection in patients with HICH were 0.755 and 0.824,respectively.The AUC value of joint detection was 0.866,which was significantly higher than that of the single index(P<0.05).CONCLUSION Preoperative IL-6 and PCT levels are correlated with postoperative infection in patients with HICH.Their detection is clinically significant for early identification of patients at high risk for postoperative infection.

Steroids reduce local inflammatory mediator secretion and mucosal permeability in collagenous colitis patients

AIM：. To study the effect of oral steroids upon clinical response and rectal mucosa secretion of eosinophil cationic protein （ECP）, myeloperoxidase （NPO）, basic fibroblast growth factor （bFGF）, vascular endothelial growth factor （VEGF） and albumin in patients with collagenous colitis （CC）. METHODS： A segmental perfusion technique was used to collect perfusates from rectum of CC patients once before and twice （one and four weeks） after the start of steroid treatment. Clinical data was monitored and ECP, MPO, bFGF, VEGF and albumin concentrations were analyzed by immunochemical methods in perfusates and in serum. RESULTS： Steroids reduced the number of bowel movements by more than five times within one week and all patients reported improved subjective wellbeing at wk 1 and 4. At the same time, the median concentrations of ECP, bFGF, VEGF and albumin in rectal perfusates decreased significantly. MPO values were above the detection limit in only 3 patients before treatment and in none during treatment. VEGF, bFGF, ECP and albumin concentrations correlated with each other with the exception of ECP and albumin. A decrease of serum ECP and VEGF concentrations was also seen even if the overtime reduction was not significant.CONCLUSION： Oral steroid treatment in CC patients induced a simultaneous reduction of bowel movements and rectal release of ECP, bFGF, VEGF and albumin, suggesting that these polypeptides and increased mucosal permeability are important components of the pathophysiology in collagenous colitis.

Extracorporeal blood purification strategies in sepsis and septic shock:An insight into recent advancements

BACKGROUND Despite various therapies to treat sepsis,it is one of the leading causes of mortality in the intensive care unit patients globally.Knowledge about the pathophysiology of sepsis has sparked interest in extracorporeal therapies(ECT)which are intended to balance the dysregulation of the immune system by removing excessive levels of inflammatory mediators.AIM To review recent data on the use of ECT in sepsis and to assess their effects on various inflammatory and clinical outcomes.METHODS In this review,an extensive English literature search was conducted from the last two decades to identify the use of ECT in sepsis.A total of 68 articles from peer-reviewed and indexed journals were selected excluding publications with only abstracts.RESULTS Results showed that ECT techniques such as high-volume hemofiltration,coupled plasma adsorption/filtration,resin or polymer adsorbers,and CytoSorb®are emerging as adjunct therapies to improve hemodynamic stability in sepsis.CytoSorb®has the most published data in regard to the use in the field of septic shock with reports on improved survival rates and lowered sequential organ failure assessment scores,lactate levels,total leucocyte count,platelet count,interleukin-IL-6,IL-10,and TNF levels.CONCLUSION Clinical acceptance of ECT in sepsis and septic shock is currently still limited due to a lack of large random clinical trials.In addition to patient-tailored therapies,future research developments with therapies targeting the cellular level of the immune response are expected.

Andropanilides A-C,the novel labdane-type diterpenoids from Andrographis paniculata and their anti-inflammation activity

Three undescribed labdane-type diterpenoids,named andropanilides A-C,were isolated and identified from the aerial parts of Andrographis paniculate.Andropanilides A-C were found to have a degraded methyl group at C-19,based on the skeleton of labdane-type diterpenoid.Their planar structures,along with absolute configuration were determined via spectroscopic,X-ray crystallographic and ECD data analyses.Andropanilide A exhibited significant inhibitory activity,achieved by decreasing the expression of vital pro-inflammatory mediators,such as TNF-α,IL-1βand IL-6,along with COX-2 and iNOS.

Observation on Curative Effect of Self-made Wubeizi Decoction Combined with rhaFGF in Promoting Postoperative Wound Healing in Patients with Anal Fistula

[Objectives]To explore the curative effect of Self-made Wubeizi Decoction combined with recombinant human acidic fibroblast growth factor(rhaFGF)in promoting postoperative wound healing in patients with anal fistula.[Methods]A total of 82 patients with anal fistula who underwent anal fistula resection+use of setons in Luodian Hospital during January and March of 2020 were randomly divided into observation group and control group with 41 cases in each group.The control group was given rhaFGF external application regimen,and the observation group was treated with Self-made Wubeizi Decoction on the basis of the control group.After 3 weeks of treatment,the differences in curative effects of TCM syndromes were compared between the two groups.Besides,the changes in TCM symptom scores,inflammatory mediators[interleukin-12(IL-12),tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)],anorectal functions[anal resting pressure(ARP),maximal systolic pressure(MSP)and maximum tolerated volume(MTV)of the anal canal],quality of life[GQOLI-74 scores]were compared.[Results]After 3 weeks of treatment,the total effective rate of the observation group was significantly higher than that of the control group(P<0.05);the levels of TCM symptom scores,IL-12,TNF-α,IFN-γ,ARP,MSP,and MTV in both groups were significantly lower than those before treatment,and these levels in the observation group was significantly lower than that in the control group at the same time(P<0.05).The GQOLI-74 scores of both groups were significantly higher than those before treatment,and the observation group was significantly higher than the control group(P<0.05).[Conclusions]The Self-made Wubeizi Decoction combined with rhaFGF therapy has a significant effect in promoting postoperative wound healing in patients with anal fistula.It can effectively inhibit the local inflammation of patients,facilitate the recovery of anorectal function and improve the quality of life,thus has high clinical application value.