CTLA-4 and MDR1 polymorphisms increase the risk for ulcerative colitis:A meta-analysis

AIM:To evaluate the correlations between cytotoxic T lymphocyte-associated antigen-4(CTLA-4) and multidrug resistance 1(MDR1) genes polymorphisms with ulcerative colitis(UC) risk.METHODS:Pub Med,EMBASE,Web of Science,Cochrane Library,CBM databases,Springerlink,Wiley,EBSCO,Ovid,Wanfang database,VIP database,China National Knowledge Infrastructure,and Weipu Journal databases were exhaustively searched using combinations of keywords relating to CTLA-4,MDR1 and UC. The published studies were filtered using our stringent inclusion and exclusion criteria,the quality assessment for each eligible study was conducted using Critical Appraisal Skill Program and the resultant high-quality data from final selected studies were analyzed using Comprehensive Meta-analysis 2.0(CMA 2.0) software. The correlations between SNPs of CTLA-4 gene,MDR1 gene and the risk of UC were evaluated by OR at 95%CI. Z test was carried out to evaluate the significance of overall effect values. Cochran's Q-statistic and I2 tests were applied to quantify heterogeneity among studies. Funnel plots,classic fail-safe N and Egger's linear regression test were inspected for indication of publication bias.RESULTS:A total of 107 studies were initially retrieved and 12 studies were eventually selected for metaanalysis. These 12 case-control studies involved 1860 UC patients and 2663 healthy controls. Our major result revealed that single nucleotide polymorphisms(SNPs) of CTLA-4 gene rs3087243 G > A and rs231775 G > A may increase the risk of UC(rs3087243 G > A:allele model:OR = 1.365,95%CI:1.023-1.822,P = 0.035; dominant model:OR = 1.569,95%CI:1.269-1.940,P < 0.001; rs231775 G > A:allele model:OR = 1.583,95%CI:= 1.306-1.918,P < 0.001; dominant model:OR = 1.805,95%CI:1.393-2.340,P < 0.001). In addition,based on our result,SNPs of MDR1 gene rs1045642 C > T might also confer a significant increases for the risk of UC(allele model:OR = 1.389,95%CI:1.214-1.590,P < 0.001; dominant model:OR = 1.518,95%CI:1.222-1.886,P < 0.001).CONCLUSION:CTLA-4 gene rs3087243 G > A and rs231775 G > A,and MDR1 gene rs1045642 C > T might confer an increase for UC risk.

Appendix is a priming site in the development of ulcerative colitis

AIM： The role of the appendix has been highlighted in the pathogenesis of ulcerative colitis （UC）. The aims of this study were to elucidate the immuno-imbalances in the appendix of UC patients, and to clarify the role of the appendix in the development of UC. METHODS： Colonoscopic biopsy specimens of the appendix, transverse colon, and rectum were obtained from 86 patients with UC： active pancolitis （A-Pan; n = 15）, active letf-sided colitis （A-Lt; n = 25）, A-Lt with appendiceal involvement （A-Lt/Ap; n = 10）, inactive pancolitis （I-Pan; n = 14）, and inactive left-sided colitis （I-Lt; n = 22）, and from controls. In the isolated mucosal T cells, the CD4/CD8 ratio and proportion of activated CD4＋ T ceils were investigated, and compared with controls. RESULTS： in the appendix, the CD4/CD8 ratio significantly increased in A-Lt and A-Lt/Ap. The ratio in the appendix also tended to increase in A-Pan. In the rectum, the ratio significantly increased in all UC groups. In the appendix, the proportion of CD4＋CD69＋ （early activation antigen） T cells significantly increased in all UC groups. In the rectum, the proportion of CD4＋CD69＋ T cells significantly increased only in A-Pan. The proportion of CD4＋HLADR＋ （mature activation antigen） T cells significantly increased only in the rectum of A-Pan, but not in the otherareas of any groups. CONCLUSION： The increased CD4/CD8 ratio and predominant infiltration of CD4＋CD69＋ T cells in the appendix suggest that the appendix is a priming site in the development of UC.

Nicotine protects against ulcerative colitis through regulating microRNA-124 and STAT3

OBJECTIVE Although it is generally believed that nicotine accounts for the beneficial effect of smoking on ulcerative colitis,the underlying mechanisms remain not well-understood.Our previous finding that nicotine inhibits inflammatory responses through inducing miRNA-124 prompted us to ask whether the miRNA is involved in the protective action of nicotine on UC.METHODS Mi R-124 expression in colon tissues and cells was determined by q-PCR and in situ hybridization.The effect of miR-124 on protective role of nicotine in ulcerative colitis was evaluated in DSS-treated mice and IL-6-treated Caco-2 colon epithelial cells.Expression of p-STAT3/STAT3 was detected by immunohistochemistry and Western blot analysis.RESULTS miR-124 expression is upregulated in colon tissues from patients and DSS-induced colitis.Nicotine treatment further elevated miR-124 level in colon tissues of the mice,in infiltrated lymphocytes and epithelial cells,and augmented miR-124 expression in lymphocytes isolated from human ulcerative colon tissues.Administration of nicotine also reduced weight loss,improved DAI and decreased HE score in DSS-induced colitis.Moreover,knockdown of miR-124 in vivo significantly diminished the beneficial effect of nicotine,and in vitro on IL-6-treated Caco-2 colon epithelial cells.Further analysis indicated that nicotine inhibited STAT3 activation in vivo and in IL-6-treated Caco-2 colon epithelial cells and Jurkat human T lymphocytes,in whichmiR-124 knockdown led to increased activation of STAT3.CONCLUSION These data indicated that nicotine exerts its protective action in UC through inducing miR-124 and its effect on STAT3,suggesting that the miR-124/STAT3 system is a potential target for the therapeutic intervention of UC.

Selective decrease in colonic CD56^+ T and CD161^+ T cells in the inflamed mucosa of patients with ulcerative colitis

AIM： To investigate the role of local colonic mucosal NK receptor-positive T （NKR＋ T） cells in the regulation of intestinal inflammation, we analyzed the population and function of these cells in ulcerative colitis （UC）. METHODS： Colonic mucosal tissues were obtained from colonoscopic biopsies of the descending colon from 96 patients with UC （51 endoscopically uninflamed, 45 inflamed） and 18 normal controls. Endoscopic appearance and histologic score at the biopsied site were determined by MaLts＇ classification. A single cell suspension was prepared from each biopsy by collagenase digestion. Two NKR^＋ T cell subsets, CD56^＋ （CD56^＋CD3^＋） T cells and CD161＋ （CD161^＋CD3^＋） T cells, were detected by flow cytometric analysis. Intracellular cytokine analysis for anti-inflammatory cytokine interleukin-10 （IL-10） was performed by in vitro stimulation with phorbol-myristateacetate （PMA） and ionomycin. RESULTS： CD56^＋ T cells and CD161^＋ T cells are present in the normal human colon and account for 6.7% and 21.3% of all mononuclear cells, respectively. The populations of both CD56＋ T cells and CD161^＋ T cells were decreased significantly in the inflamed mucosa of UC. In contrast, the frequency of conventional T cells （CD56 CD3^＋ cells and CD161CD3^＋ cells） was similar among the patient and control groups. The populations of NKR^＋ T cells were correlated inversely with the severity of inflammation, which was classified according to the endoscopic and histologic Marts＇ criteria. Interestingly, approximately 4% of mucosal NKR＋ T cells expressing IL-10 were detected by in vitro stimulation with PMA and ionomycin.CONCLUSION： Selective reduction in the population of colonic mucosal NKR＋T cells may contribute to the development of intestinal inflammation in UC.

Aberrant activation of nuclear factor of activated T cell 2 in lamina propria mononuclear cells in ulcerative colitis

AIM:To investigate the role of nuclear factor of activated T cell 2(NFAT2),the major NFAT protein in peripheral T cells,in sustained T cell activation and intractable inflammation in human ulcerative colitis(UC). METHODS:We used two-dimensional gel-electrophoresis, immunohistochemistry,double immunohistochemical staining,and confocal microscopy to inspect the expression of NFAT2 in 107,15,48 and 5 cases of UC, Crohn's disease(CD),non-specific colitis,and 5 healthy individuals,respectively. RESULTS:Up-regulation with profound nucleo- translocation/activation of NFAT2 of lamina propria mononuclear cells(LPMC)of colonic mucosa was found specifically in the affected colonic mucosa from patients with UC,as compared to CD or NC(P<0.001,Kruskal- Wallis test).Nucleo-translocation/activation of NFAT2 primarily occurred in CD8+T,but was less prominent in CD4+T cells or CD20+B cells.It was strongly associated with the disease activity,including endoscopic stage (τ=0.2145,P=0.0281)and histologic grade(τ=0.4167, P<0.001). CONCLUSION:We disclose for the first time the nucleo-translocation/activatin of NFAT2 in lamina propria mononuclear cells in ulcerative colitis.Activation of NFAT2 was specific for ulcerative colitis and highly associated with disease activity.Since activation of NFAT2is implicated in an auto-regulatory positive feedback loop of sustained T-cell activation and NFAT proteins play key roles in the calcium/calcineurin signaling pathways,our results not only provide new insights into the mechanism for sustained intractable inflammation,but also suggest the calcium-calcineurin/NFAT pathway as a new therapeutic target for ulcerative colitis.

Biological therapy for ulcerative colitis:An update

Of the diverse biological agents used for patients with ulcerative colitis, the anti-tumor necrosis factor-&#x003b1; agents infliximab and adalimumab have been used in large-scale clinical trials and are currently widely used in the treatment of inflammatory bowel disease patients. Recent studies have indicated that golimumab, oral tofacitinib and vedolizumab reportedly achieved good clinical response and remission rates in ulcerative colitis patients. Thus, we believe that the detailed investigation of various studies on clinical trials may provide important information for the selection of appropriate biological agents, and therefore, we have extensively reviewed such trials in the present study.

Effect of Bifidobacterium triple live bacteria on inflammatory factors, oxidative stress and T lymphocyte subsets in patients with ulcerative colitis

Objective: To explore the effect of Bifidobacterium triple live bacteria on inflammatory factors, oxidative stress and T lymphocyte subsets in patients with ulcerative colitis (UC). Method: A total of 90 patients with UC treated in our hospital were selected and randomly divided into the observation group and the control group each with 45 cases. The control group was given Mesalazin Enteric-coated Tablets 1 g/times, 4 times/d, continuous treatment for 1 months:when the clinical symptoms were stable, switched to 500 mg/times, 3 times/d, continuous treatment for 3 months. The observation group on the basis of conventional treatment to give Bifidobacterium triple live bacteria scattered adjuvant therapy (Bifico capsule), 0.84 g/time, 2 times/d, continuous treatment for 3 months. In the two groups, the levels of inflammatory factors (IL-6, IL-10, CRP, TNF-α), oxidative stress markers (MDA, SOD) and T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+/CD8+) were compared pre and post treatment. Results: The levels of IL-6, CRP, MDA, TNF-α, CD8+ in both two groups were significantly decreased compared with treatment before;the levels of IL-10, SOD, CD3+, CD4+ and CD4+/CD8+were significantly increased compared with treatment before. After treatment, the levels of serum IL-6, CRP, TNF-α, MDA and CD8+ in observation group with the data (72.17±15.18) pg/mL, (21.52±10.21) mg/mL, (15.98±4.12) pg/mL respectively were decreased more significantly than those data in control group which were (86.55±17.26) pg/mL, (43.02±12.27) mg/L, (22.35±3.67) pg/mL, MDA level (5.89±0.56) nmol/mL in observation group was decreased more significantly than the level in the control group (6.75±0.68) nmol/mL;CD8+level (17.24±3.06)% in observation group was decreased more significantly than the level (19.01±2.62)% in the control group. After treatment, IL-10 level (70.21±6.03) pg/mL in observation group was increased more significantly than the level in the control group (56.48+ 8.67) pg/mL;SOD level (1.84±0.06) U/mL in observation group was increased more significantly than the level in the control group (1.32±0.05) U/mL;the levels of CD3+, CD4+, CD4+/CD8+ in the observation group (57.84±6.07)%;(36.78±4.32)%;(1.92±0.29) were increased more significantly than the level in the control group (54.93±6.87)%;(35.42±5.27)%;(1.89±0.12). Conclusion: Bifidobacterium triple live bacteria scattered adjuvant treatment of ulcerative colitis helps regulate oxidative stress and inflammatory cytokines inhibiting inflammatory reaction and improving enhance function, and can effectively improve the clinical symptoms of patients with UC.

Atopic Dermatitis Deteriorates Dextran Sodium Sulfate-Induced Ulcerative Colitis via Thymic Stromal Lymphopoietin in Mice

It has been reported that atopic dermatitis (AD) and ulcerative colitis are related. However, the mechanism underlying this association has not been clarified. We therefore explored how AD induces ulcerative colitis. We developed an AD mouse model (NC/Nga mice) with ulcerative colitis by administering dextran sodium sulfate (DSS) for five days. DSS-induced ulcerative colitis was deteriorated in our conventional AD mouse model compared with specific-pathogen-free (SPF) mice. The plasma levels of thymic stromal lymphopoietin (TSLP) and tumor necrosis factor-α increased the most in DSS-treated conventional mice. Furthermore, the expression of dendritic cells (DC), retinoid-related orphan receptor (ROR)γt (marker of T helper 17 cells [Th17]), interleukin (IL)-17, GATA binding protein 3 (GATA3) (marker of Th2), and IL-4 increased the most in the colon of the DSS-treated conventional mice compared with DSS-treated SPF mice. In addition, TSLP inhibitor (TSLP neutralizing antibody) did not exacerbate ulcerative colitis in DSS-treated conventional mice. These results indicate that TSLP/DC/Th2 and Th17 play major roles in the exacerbation of ulcerative colitis by AD.

Curcumin alleviated dextran sulfate sodium-induced colitis by recovering memory Th/Tfh subset balance

BACKGROUND Restoration of immune homeostasis by targeting the balance between memory T helper(mTh)cells and memory follicular T helper(mTfh)cells is a potential therapeutic strategy against ulcerative colitis(UC).Because of its anti-inflammatory and immunomodulatory properties,curcumin(Cur)is a promising drug for UC treatment.However,fewer studies have demonstrated whether Cur can modulate the mTh/mTfh subset balance in mice with colitis.AIM To explore the potential mechanism underlying Cur-mediated alleviation of colitis induced by dextran sulfate sodium(DSS)in mice by regulating the mTh and mTfh immune homeostasis.METHODS Balb/c mice were administered 3%and 2%DSS to establish the UC model and treated with Cur(200 mg/kg/d)by gavage on days 11-17.On the 18th d,all mice were anesthetized and euthanized,and the colonic length,colonic weight,and colonic weight index were evaluated.Histomorphological changes in the mouse colon were observed through hematoxylin-eosin staining.Levels of Th/mTh and Tfh/mTfh cell subsets in the spleen were detected through flow cytometry.Western blotting was performed to detect SOCS-1,SOCS-3,STAT3,p-STAT3,JAK1,p-JAK1,and NF-κB p65 protein expression levels in colon tissues.RESULTS Cur effectively mitigates DSS-induced colitis,facilitates the restoration of mouse weight and colonic length,and diminishes the colonic weight and colonic weight index.Simultaneously,it hinders ulcer development and inflammatory cell infiltration in the colonic mucous membrane.While the percentage of Th1,mTh1,Th7,mTh7,Th17,mTh17,Tfh1,mTfh1,Tfh7,mTfh7,Tfh17,and mTfh17 cells decreased after Cur treatment of the mice for 7 d,and the frequency of mTh10,Th10,mTfh10,and Tfh10 cells in the mouse spleen increased.Further studies revealed that Cur administration prominently decreased the SOCS-1,SOCS-3,STAT3,p-STAT3,JAK1,p-JAK1,and NF-κB p65 protein expression levels in the colon tissue.CONCLUSION Cur regulated the mTh/mTfh cell homeostasis to reduce DSS-induced colonic pathological damage,potentially by suppressing the JAK1/STAT3/SOCS signaling pathway.

溃疡性结肠炎患者血清Chemerin与Th9/Treg细胞失衡的相关性分析

目的探究溃疡性结肠炎(ulcerative colitis,UC)患者血清趋化素(Chemerin)水平与Th9/Treg细胞失衡的相关性。方法选取2020年11月至2021年11月于我院确诊为UC的患者85例(UC组)和健康体检者80名(对照组)。流式细胞术检测Th9/Treg的比例;采用ELISA法检测血清中IL-9、CRP、IL-10、IL-17的含量。统计学分析Chemerin表达与Mayo评分的相关性;与Th9、Treg、Th9/Treg以及相关细胞因子之间的相关性。结果UC组Chemerin水平和Mayo评分均显著高于对照组,UC患者重度组Chemerin水平和Mayo评分均显著高于中度组和轻度组,中度组显著高于轻度组(P<0.05);Chemerin表达与Mayo评分之间呈正相关(P<0.05);流式细胞术结果显示,UC患者血清中Th9/CD4+的比例显著升高,Treg/CD4+比例显著降低,Th9/Treg比例显著升高(P<0.05);UC组Treg比例以及IL-10水平显著低于对照组,Th9比例、Th9/Treg以及IL-9、CRP、IL-17水平显著高于对照组(P<0.05);UC患者重度组的Treg比例、IL-10水平显著低于中度组和轻度组,中度组显著低于轻度组(P<0.05);UC患者重度组的Th9比例、Th9/Treg、IL-9、CRP、IL-17水平显著高于中度组和轻度组,中度组显著高于轻度组(P<0.05);UC组患者血清Chemerin表达与Th9比例、Th9/Treg、CRP、IL-17、IL-9水平呈正相关,与Treg比例、IL-10水平呈负相关(P<0.05)。结论UC患者血清Chemerin水平与Th9/Treg细胞失衡有密切关系。

芍药汤治疗湿热内蕴型溃疡性结肠炎疗效及对患者炎症因子和T淋巴细胞亚群的影响

目的:观察芍药汤治疗溃疡性结肠炎(UC)患者(湿热内蕴证)的临床疗效及对患者炎症因子和T淋巴细胞亚群的影响。方法:选择接受治疗的110例UC患者作为研究对象,掷硬币法分为两组,各55例。对照组采取美沙拉秦治疗,观察组在对照组基础上采取芍药汤治疗,两组均连续治疗3个月。治疗3个月时比较两组患者临床疗效;比较两组治疗前、治疗3个月时临床症状、Mayo、Geboes指数评分、炎症因子、T淋巴细胞亚群(CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))及肠道菌群水平;统计并比较两组治疗期间不良反应发生情况。结果:治疗后,观察组总有效率高于对照组(P<0.05);治疗后,两组主症、次症及总分低于治疗前,观察组低于对照组(P<0.05);治疗后,两组Mayo活动指数、Geboes指数评分低于治疗前,观察组低于对照组(P<0.05);治疗后,两组超敏C反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平低于治疗前,观察组低于对照组(P<0.05);治疗后,两组CD4^(+)、CD4^(+)/CD8^(+)高于治疗前,CD8^(+)低于治疗前,观察组CD4^(+)、CD4^(+)/CD8^(+)高于对照组,CD8^(+)低于对照组(P<0.05);治疗后,两组双歧杆菌、乳酸杆菌高于治疗前,大肠杆菌低于治疗前,观察组大肠杆菌低于对照组(P<0.05);观察组发生1例恶心,1例皮肤瘙痒,对照组未发生不良反应(P>0.05)。结论:芍药汤能够有效改善湿热内蕴证UC患者临床症状,促进肠黏膜愈合,降低机体炎症反应,提高免疫功能,恢复胃肠道菌群平衡,提升临床疗效。

Probiotics increase T regulatory cells and reduce severity of experimental colitis in mice

AIM:To investigate the effect of probiotics on regulating T regulatory cells and reducing the severity of experimental colitis in mice. METHODS:Forty C57/BL mice were randomly divided into four groups.Colitis was induced in the mice using 2,4,6-trinitrobenzene sulfonic acid(TNBS).After 10-d treatment with Bifico capsules(combined bifidobacterium,lactobacillus and enterococcus),body weight,colonic weight,colonic weight index,length of colon,and histological scores were evaluated.CD4+CD25+Foxp3+T cell in mesenteric lymph nodes were measured by flow cytometry,and cytokines in colonic tissue homogenateswere analyzed by a cytometric bead array. RESULTS:The colonic weight index and the colonic weight of colitis mice treated with Bifico were lower than that of TNBS-induced mice without treatment. However,colonic length and percent of body weight amplification were higher than in TNBS-induced mice without treatment.Compared with TNBS-induced mice without treatment,the level of CD4+CD25+Foxp3+T cells in mesenteric lymph nodes,the expression of interleukin(IL)-2,IL-4 and IL-10 in colonic tissues from colitis mice treated with Bifico were upregulated,and tumor necrosis factor-αand interferon-γwere downregulated. CONCLUSION:Probiotics effectively treat experimental colitis by increasing CD4+CD25+Foxp3+T cell and regulating the balance of Th1 and Th2 cytokines in the colonic mucosa.

Increased CD4^+CD45RA^-FoxP3^(low) cells alter the balance between Treg and Th17 cells in colitis mice

AIM To investigate the role of regulatory T cell(Treg) subsets in the balance between Treg and T helper 17(Th17) cells in various tissues from mice with dextran sulfate sodium-induced colitis.METHODS T r e g c e l l s, T r e g c e l l s u b s e t s, T h 1 7 c e l l s, a n d CD4+CD25+FoxP 3+IL-17+ cells from the lamina propria of colon(LPC) and other ulcerative colitis(UC) mouse tissues were evaluated by flow cytometry. Forkhead box protein 3(FoxP 3), interleukin 17A(IL-17A), and RORC m RNA levels were assessed by real-time PCR, while interleukin-10(IL-10) and IL-17 A levels were detected with a Cytometric Beads Array.RESULTS In peripheral blood monocytes(PBMC), mesenteric lymphnode(MLN), lamina propria of jejunum(LPJ) and LPC from UC mice, Treg cell numbers were increased(P < 0.05), and FoxP 3 and IL-10 mR NA levels were decreased. Th17 cell numbers were also increased in PBMC and LPC, as were IL-17 A levels in PBMC, LPJ, and serum. The number of FrI subset cells(CD4+CD45RA+FoxP 3low) was increased in the spleen, MLN, LPJ, and LPC. FrI I subset cells(CD4+CD45RA-Fox P3high) were decreased among PBMC, MLN, LPJ, and LPC, but the number of Fr III cells(CD4+CD45RA-FoxP 3low) and CD4+CD25+FoxP 3+IL-17A+ cells was increased. Fox P3 m RNA levels in CD4+CD45RA-Fox P3 low cells decreased in PBMC, MLN, LPJ, and LPC in UC mice, while IL-17 A and RORC mR NA increased. In UC mice the distribution of Treg, Th17 cells, CD4+CD45RA-FoxP 3high, and CD4+CD45RA-FoxP 3low cells was higher in LPC relative to other tissues.CONCLUSION Increased numbers of CD4+CD45RA-FoxP 3low cells may cause an imbalance between Treg and Th17 cells that is mainly localized to the LPC rather than secondary lymphoid tissues.

复方芩柏颗粒对溃疡性结肠炎大鼠Th1/Th2、Th17/Treg细胞稳态影响

目的 探讨复方芩柏颗粒对葡聚糖酸钠(dextran sulfate, DSS)诱导的溃疡性结肠炎(ulcerative colitis, UC)大鼠CD4~+T细胞稳态的调节作用。方法 42只SPF级雄性SD大鼠,随机均分为正常组、模型组、美沙拉嗪组、复方芩柏颗粒组,DSS诱导UC模型。连续灌胃干预3周后观察大鼠一般情况;检测各组大鼠结肠组织病理改变;通过流式细胞仪检测各组大鼠辅助性T细胞(helper T cell, Th)1/Th2、Th17/调节性T细胞(regulatory T cells, Treg)细胞亚群比例;通过RT-PCR检测各组大鼠肠道组织中逆转录因子的mRNA表达;通过Western blot法测定逆转录因子的蛋白表达。结果 与正常组相比,模型组Th1、Th17细胞比例上升,Th2、Treg细胞比例下降(均P<0.05);与模型组相比,美沙拉嗪组及复方芩柏颗粒组中Th1、Th17细胞比例回调下降,Th2、Treg细胞比例回升(均P<0.05)。结论 复方芩柏颗粒能有效改善UC大鼠的一般症状及肠道黏膜情况,可能是通过调节相关细胞因子及Th1/Th2、Th17/Treg细胞稳态以调节促炎细胞因子水平实现的。

以口腔黏膜溃疡为首发表现的结外鼻型NK/T细胞淋巴瘤的多学科诊疗1例

结外鼻型NK/T细胞淋巴瘤(extranodal nasal type NK/T-cell lymphoma,ENKTL)是一种以破坏面部中份结构为主的NK/T细胞来源的非霍奇金淋巴瘤,临床少见。以口腔黏膜溃疡为首发症状的病例罕见且易与其他疾病相混淆,在诊断上极其困难。本文报道1例以颊黏膜及牙龈溃疡为首发表现的ENKTL的多学科诊疗,并分析该疾病的临床病理学特征、诊断、鉴别诊断和治疗,以期为临床诊治相关病例提供参考。

口腔洁含漱液对脾胃伏火型复发性口腔溃疡患者口腔菌群、血清炎症因子和T细胞亚群水平的影响

目的探讨口腔洁含漱液对脾胃伏火型复发性口腔溃疡患者口腔菌群、血清炎症因子和T细胞亚群水平的影响。方法选取2022年4月至2023年3月成都中医药大学附属医院口腔科和四川大学华西口腔医院口腔黏膜科收治的脾胃伏火型复发性口腔溃疡患者64例为研究对象,按照随机数字表法分为试验组(32例)和对照组(32例),对照组患者给予醋酸曲安奈德乳膏治疗,试验组在对照组基础上联合口腔洁含漱液含漱、吞服,每日3次,持续治疗7 d。观察两组患者临床疗效,评价两组治疗前后,以及治疗后组间的中医证候积分、疼痛指数、疼痛持续时间和溃疡愈合时间;实时荧光定量PCR法分析口腔菌群(链球菌、韦荣氏菌、奈瑟氏菌)DNA浓度;ELISA法检测血清炎症因子[肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-6、IL-8]含量;流式细胞术测定血清T细胞亚群水平[T淋巴细胞(CD3^(+))、辅助性T淋巴细胞(CD4^(+))、CD4^(+)/细胞毒性T淋巴细胞(CD8^(+))]。同时记录治疗期间不良反应,比较6个月后复发情况。结果试验组临床疗效、疼痛抑制效果和溃疡愈合速率均优于对照组(P<0.05);两组患者治疗后口腔内链球菌和韦荣氏菌DNA浓度明显高于治疗前,且试验组高于对照组,差异均有统计学意义(P<0.05);两组患者治疗后血清炎症因子TNF-α、IL-6、IL-8含量相较治疗前降低,CD3^(+)、CD4^(+)、CD4^(+)/CD8^(+)相较治疗前升高,且试验组改善程度优于对照组,差异均有统计学意义(P<0.05)。试验组复发率显著低于对照组(P<0.05)。结论口腔洁含漱液治疗脾胃伏火型复发性口腔溃疡患者,可显著提高临床疗效,改善口腔菌群构成,抑制血清炎性反应水平,提高细胞免疫功能,降低复发率,值得临床推广应用。

化浊解毒抑溃煎对溃疡性结肠炎大鼠Th1/Th2平衡、应激反应及肠黏膜的影响

目的探讨化浊解毒抑溃煎对溃疡性结肠炎大鼠Th1/Th2平衡、应激反应及肠黏膜的影响。方法SPF级别Wistar大鼠随机分为对照组、模型组、化浊解毒抑溃煎低、中、高剂量(1.25、2.5、5 kg·L^(-1))组及阳性药美沙拉嗪(0.05 kg·L^(-1))组,共6组。除对照组外,其余各组大鼠均建立溃疡性结肠炎动物模型,分别灌胃给予相应药物。ELISA法检测TNF-α、IL-8、IL-13、IL-10、IFN-γ及IL-4水平;相关试剂盒检测SOD、MDA及GSH-Px水平;HE染色观察肠道组织病理形态并计算评分;TUNEL法检测肠道上皮细胞凋亡率;免疫印迹检测肠组织NF-B、TLR4、MyD88、Bcl-2及Bax蛋白水平。结果与模型组相比,化浊解毒抑溃煎组TNF-α、IL-8、IL-13、MDA、IFN-γ、病理评分、肠上皮细胞凋亡率、NF-B、TLR4、MyD88及Bax水平降低(P<0.05),IL-10、IL-4、SOD、GSH-Px、Bcl-2水平升高(P<0.05)。结论化浊解毒抑溃煎可明显抑制溃疡性结肠炎大鼠氧化应激及炎症反应,促使Th1/Th2平衡,并发挥肠黏膜保护作用,其作用机制与抑制NF-B/TLR4/MyD88信号通路相关。

血管活性肠肽调控滤泡辅助性T细胞/滤泡调节性T细胞平衡治疗溃疡性结肠炎的研究进展

溃疡性结肠炎(UC)是以结肠黏膜屏障持续损伤为病理基础的自身免疫性疾病。滤泡辅助性T(Tfh)细胞和滤泡调节性T(Tfr)细胞的异常表达与UC的发生发展密切相关,Tfh细胞具有分泌促炎因子、辅助B细胞产生抗体等作用,能够促进UC的发展,Tfr细胞则具有抑制Tfh细胞活性、分泌抗炎因子等作用,如何调节两者平衡已成为UC的潜在治疗靶点之一。血管活性肠肽(VIP)对UC具有防治作用,其机制与调控Tfh/Tfr细胞平衡密切相关,可对UC的治疗提供思路。

消化性溃疡患者HMGB1、PINP和CD_(4)^(+)T细胞变化及与Hp感染的关系

目的探讨消化性溃疡患者高迁移率族蛋白B1(HMGB1)、I型原胶原N端前肽(PINP)和CD_(4)^(+)T细胞变化及与幽门螺杆菌(Hp)感染的关系。方法选择2019年9月—2021年9月我院收治的消化性溃疡患者97例作为研究对象,根据是否Hp感染分为Hp阳性组(n=63)与Hp阴性组(n=34);另选择同期我院健康体检者60例作为对照组。采用酶联免疫吸附法测定HMGB1和PINP水平;采用流式细胞仪测定CD_(4)^(+)T细胞水平。比较消化性溃疡组与对照组HMGB1、PINP和CD_(4)^(+)T细胞水平;不同Hp感染HMGB1、PINP和CD_(4)^(+)T细胞水平;采用Pearson分析Hp感染与HMGB1、PINP和CD_(4)^(+)T细胞相关性;采用多因素Logistic回归分析HMGB1、PINP和CD_(4)^(+)T细胞与Hp感染的关系。结果消化性溃疡组HMGB1水平高于对照组,PINP和CD_(4)^(+)T细胞水平低于对照组(P<0.05)。Hp阳性组HMGB1水平高于Hp阴性组,PINP和CD_(4)^(+)T细胞水平低于Hp阴性组(P<0.05)。经Pearson分析,HMGB1与Hp感染呈线性正相关,PINP和CD_(4)^(+)T细胞与Hp感染呈线性负相关(P<0.05)。经多因素Logistic回归分析HMGB1、PINP和CD_(4)^(+)T细胞为影响Hp感染危险因素。结论消化性溃疡患者HMGB1水平升高,PINP和CD_(4)^(+)T细胞水平下降,且与Hp感染密切相关,为影响Hp感染的危险因素。

基于组织驻留记忆CD4^(+)T细胞探讨溃疡性结肠炎复发过程中“伏邪”的生物学基础

从组织驻留记忆CD4^(+)T细胞(CD4^(+)TRM)细胞入手,综述其生理病理特点及其在溃疡性结肠炎(UC)复发中的作用,探讨UC复发过程中“伏邪”的生物学基础,为中医药抗UC复发提供新策略。CD4^(+)TRM细胞在UC的发病机制中具有核心作用,参与了UC肠道炎症的反复发作。伏邪是感邪后藏伏于体内不立即发病的邪气,或湿热瘀血等邪气并未随疾病治愈根除而是潜伏于内的病邪,是UC反复发作、迁延难愈的主要病因。伏邪的致病特点与CD4^(+)TRM细胞免疫记忆、感而引动、待机而发的特性暗相契合,因此CD4^(+)TRM细胞可能是UC“伏邪”的生物学基础之一。