贝飞达对原发性胆汁性肝硬化患者细胞因子的影响

目的探讨微生态调节剂对原发性胆汁性肝硬化（PBC）的影响。方法34例PBC患者为我院住院患者,均有肝功能异常,随机分为2组,一组为常规治疗组,给予糖皮质激素类、熊去氧胆酸及其他免疫抑制／增强剂药物治疗,另一组为贝飞达治疗组,在常规治疗基础上加用贝飞达。经过1个月的治疗,采血检测细胞因子及肝功能,对结果进行统计学处理。结果贝飞达治疗组同常规治疗组进行比较,在降低细胞因子水平改善肝功能方面差异有显著性。结论贝飞达通过调整肠道菌群,控制内毒素血症,可以调整原发性胆汁性肝硬化患者的免疫功能,改善肝功能。     

结肠途径治疗机辅助治疗急性黄疸性肝炎的临床研究

目的探讨结肠途径治疗机辅助治疗急性黄疸性肝炎的临床疗效.方法选择60例急性黄疸性肝炎患者,随机分成2组,分别给予常规治疗及常规治疗加肠疗,观察时间为15 d,30例健康人为正常对照组.分析2组患者治疗前后血液生化指标和肠道菌群变化,并观察临床症状和体症的改善情况.结果肠疗组患者的肝功能的恢复程度好于常规治疗组,且临床症状的改善较常规治疗组差异有显著性(P＜0.01);与正常对照组相比,肠疗组双歧杆菌、乳酸杆菌含量明显下降(P＜0.05).结论肠疗能有效改善患者临床症状及血液生化指标;肠疗治疗后肠道菌群仍轻度失调.     

贝飞达治疗小儿迁延性腹泻的临床研究

目的评价贝飞达治疗小儿迁延性腹泻的临床疗效,为合理应用贝飞达治疗小儿迁延性腹泻提供科学依据。方法选取60例1个月～2岁的迁延性腹泻患儿为研究对象,把他们随机分为贝飞达组和常规组。另30例1个月-2岁的健康儿作为对照组;3组均进行治疗前后粪便中的4种常驻的正常菌群的测定和60例迁廷性腹泻患儿疗效、住院时间及费用的观察。结果贝飞达组总有效率明显高于常规组,且住院时间及费用也明显减少。治疗前60例迁延性腹泻患儿的粪便菌群中双歧杆菌、乳杆菌明显减少,肠球菌、肠杆菌增加,与健康同龄儿比t〈0．05,治疗后贝飞达组粪便菌群中的4种菌群数比常规组增加明显结论贝飞达具有调整肠道菌群失调的作用,从而提高疗效。     

健脾渗湿汤对脾虚湿盛泄泻患者肠道微生态及舌部菌群影响的研究

目的观察中药健脾渗湿汤对脾虚湿盛泄泻的患者肠道微生态及舌象变化的影响。方法选取脾虚湿盛泄泻的患者90例及正常健康人30例为研究对象,90例患者随机分为健脾渗湿汤治疗组30例,双歧三联活菌制剂贝飞达治疗组30例,氟哌酸治疗组30例,30例正常健康人作为对照组;观察治疗前后的舌象等临床表现,测定粪便中4种肠道常驻菌及舌部菌群的变化情况。结果健脾渗湿汤组和贝飞达组总有效率明显高于氟哌酸组。90例脾虚湿盛泄泻的患者粪便中双歧杆菌比健康人明显减少(P<0.05),并且其舌部(腻苔)的菌群构成与健康人(薄白苔)差异有显著性。治疗后健脾渗湿汤组和贝飞达组粪便中双歧杆菌增加明显,白腻苔及舌部菌群改善明显,说明健脾渗湿汤和贝飞达均具有调整肠道菌群及舌部菌群平衡的作用。结论(1)健脾渗湿汤具有调整肠道菌群及舌部菌群失调的作用,治疗脾虚湿盛泄泻疗效显著。(2)健脾渗湿汤是一理想的微生态调节剂,可起到益生元的作用,与益生菌合用可达到合生元的效果;与抗生素合用,可起到边抗边调的作用,应用前景广阔。     

贝飞达对慢性肝病患者纤维化指标及TNF-α的影响

目的探讨贝飞达在治疗慢性肝病患者时,对血清HA、NL、IV-C及TNF-α的影响。方法血清HA、LN、IV-及TNF-α检测采用放免法。结果60例肝功能减退者,经3个月贝飞达治疗与对照组比较。HA、LN、IV-C及TNF-α值下降水平平均低于对照组,经统计学处理差异有显著性。结论应用微生态调节剂贝飞达对慢性肝病患者进行抗纤维化治疗。通过调整肠道菌群失调。控制内毒素血症,可以降低血清HA、LN、IV-C及TNF-α水平,从而达到预防和控制纤维化的目的。     

联合疗法对慢性乙型肝炎患者红细胞免疫功能的影响

目的观察拉米夫定与氧化苦参碱单用及联合治疗对慢性乙型肝炎(CHB)患者红细胞免疫功能的影响.方法 77例CHB患者随机分成拉米夫定组、氧化苦参碱组和两者联合治疗组,分别对其红细胞膜CD35、CD44s分子定量、红细胞天然免疫粘附功能(CR1分子粘附活性)、红细胞CR1分子密度相关基因型进行测定.结果各组CHB患者红细胞粘附肿瘤细胞能力治疗后较治疗前明显上升(P＜0.05);3组药物对CHB患者红细胞CR1和CD44s分子数量有明显提高作用(P＜0.01),联合组最显著;77例CHB患者治疗前后CR1分子密度相关基因多态性表达型别比率无变化,但CR1分子数量发生明显变化(P＜0.05).结论联合疗法可明显提高CHB患者红细胞免疫功能.     

金银花水提物对肠道微生态失调大鼠的调整作用

目的研究金银花水提取物作为微生态调节剂对肠道微生态失调大鼠肠道菌群的调整作用。方法结扎大鼠胆总管造成肠道菌群失调模型后分别以金银花、丽珠肠乐、金银花与丽珠肠乐合剂、生理盐水灌胃,于灌胃4d后测定各组大鼠肠道菌群组分、乙酸含量及肝脏中肠杆菌易位情况。结果大鼠肠道菌群失调得到恢复,肠道内乙酸含量增加,易位至肝脏的肠杆菌数量减少,与自然恢复组相比,差异有统计学意义（P〈0.05）,金银花与丽珠肠乐合剂组效果最佳。结论金银花水提物作为益生元对大鼠肠道菌群失调具有调整作用。     

复方树舌液对肠道微生态失调小鼠的调节作用

目的应用复方树舌液作为微生态调节剂对肠道微生态失调小鼠进行调节。方法用盐酸林可霉素造成菌群失调模型,用复方树舌液进行治疗,在治疗期间分别检测各组小鼠的肠道优势菌群、乙酸、内毒素含量及肝脏肠杆菌易位。结果小鼠肠道菌群失调得到恢复、小鼠肠道内乙酸含量增加、内毒素含量下降、易位至肝脏的肠杆菌数量减少,与自然恢复组相比,差异有统计学意义（P〈0.05）,树舌组优于丽珠肠乐组。结论复方树舌液作为益生元对小鼠肠道菌群失调具有调节作用。     

生态调节剂防治抗生素相关性腹泻

本文了生态调节剂防治抗生素相关性腹泻的效果并调查抗生素对肠菌群的影响。结果表明,预防组ＡＡＤ的发生率明显低于对照组,预防组肠道菌群失调较轻而对照组肠道菌群明显失调,应用生态调节剂治疗ＡＡＤ有效率为８０．３％,治疗后ＡＡＤ病人肠道菌失调 明显好转。提示生态调节剂能维护肠道微生态平衡减少ＡＡＤ的发生。     

肠易激综合征患者肠道灌洗液菌群特点

目的探讨肠易激综合征(IBS)患者肠道灌洗液菌群特点及其临床意义。方法选择2018年10月至2019年10月我院收治的87例肠易激综合征患者为病例组,选择同期我院健康体检者87例为对照组,比较两组对象肠道灌洗液菌群分布,比较不同类型及不同严重程度肠易激综合征患者肠道灌洗液菌群失调情况。采用Spearman相关分析肠易激综合征患者肠道灌洗液菌群失调与疾病类型、症状严重程度的相关性。结果病例组患者肠道乳杆菌、双歧杆菌、双歧杆菌与肠杆菌数量之比(B/E值)显著低于对照组(t=8.097、8.370、8.255,均P0.001),而肠球菌、肠杆菌数量显著高于对照组(t=11.577、8.424,均P0.001)。不同类型肠易激综合征患者I度、Ⅲ度肠道灌洗液菌群失调比例差异具有统计学意义(t=30.548、19.145,均P0.001),而不同类型肠易激综合征患者Ⅱ度肠道灌洗液菌群失调比例差异无统计学意义(t=2.435,P=0.296)。不同严重程度肠易激综合征患者Ⅰ度、Ⅲ度肠道灌洗液菌群失调比例差异有统计学意义(t=8.460、14.872,均P0.001),而不同严重程度肠易激综合征患者Ⅱ度肠道灌洗液菌群失调比例差异无统计学意义(t=0.923,P=0.631)。肠易激综合征患者肠道灌洗液菌群失调与疾病类型、症状严重程度具有显著相关性(r=0.452、0.586,均P0.001)。结论肠易激综合征患者存在肠道灌洗液菌群失调情况,不同疾病类型及症状严重程度的患者肠道灌洗液菌群失调情况存在明显差异,临床可根据其肠道灌洗液菌群变化情况给予针对性治疗。     

腹泻小儿便中双歧杆菌含量变化和红细胞免疫功能关系的探讨

目的：研究腹泻小儿便中双歧杆菌含量变化与红细胞免疫的关系。方法：对42例腹泻小儿和38例正常小儿进行了粪便双歧杆菌含量、红细胞CR1数量及红细胞自然粘附肿瘤花环率（NTRR）的测定。结果：与正常小儿相比,腹泻小儿粪便中双歧杆菌含量明显下降,红细胞CR1数量无明显改变,NTRR明显下降。结论：小儿肠道内双歧杆菌含量与其红细胞CR1免疫活性有相关关系。     

Complement receptor 1 gene variants are associated with erythrocyte sedimentation rate

The erythrocyte sedimentation rate (ESR), a commonly performed test of the acute phase response, is the rate at which erythrocytes sediment in vitro in 1 hr. The molecular basis of erythrocyte sedimentation is unknown. To identify genetic variants associated with ESR, we carried out a genome-wide association study of 7607 patients in the Electronic Medical Records and Genomics (eMERGE) network. The discovery cohort consisted of 1979 individuals from the Mayo Clinic, and the replication cohort consisted of 5628 individuals from the remaining four eMERGE sites. A nonsynonymous SNP, rs6691117 (Val→IIe), in the complement receptor 1 gene (CR1) was associated with ESR (discovery cohort p = 7 × 10(-12), replication cohort p = 3 × 10(-14), combined cohort p = 9 × 10(-24)). We imputed 61 SNPs in CR1, and a "possibly damaging" SNP (rs2274567, His→Arg) in linkage disequilibrium (r(2) = 0.74) with rs6691117 was also associated with ESR (discovery p = 5 × 10(-11), replication p = 7 × 10(-17), and combined cohort p = 2 × 10(-25)). The two nonsynonymous SNPs in CR1 are near the C3b/C4b binding site, suggesting a possible mechanism by which the variants may influence ESR. In conclusion, genetic variation in CR1, which encodes a protein that clears complement-tagged inflammatory particles from the circulation, influences interindividual variation in ESR, highlighting an association between the innate immunity pathway and erythrocyte interactions.     

Complement Receptor 1 Is a Sialic Acid-Independent Erythrocyte Receptor of Plasmodium falciparum

Plasmodium falciparum is a highly lethal malaria parasite of humans. A major portion of its life cycle is dedicated to invading and multiplying inside erythrocytes. The molecular mechanisms of erythrocyte invasion are incompletely understood. P. falciparum depends heavily on sialic acid present on glycophorins to invade erythrocytes. However, a significant proportion of laboratory and field isolates are also able to invade erythrocytes in a sialic acid-independent manner. The identity of the erythrocyte sialic acid-independent receptor has been a mystery for decades. We report here that the complement receptor 1 (CR1) is a sialic acid-independent receptor for the invasion of erythrocytes by P. falciparum. We show that soluble CR1 (sCR1) as well as polyclonal and monoclonal antibodies against CR1 inhibit sialic acid-independent invasion in a variety of laboratory strains and wild isolates, and that merozoites interact directly with CR1 on the erythrocyte surface and with sCR1-coated microspheres. Also, the invasion of neuraminidase-treated erythrocytes correlates with the level of CR1 expression. Finally, both sialic acid-independent and dependent strains invade CR1 transgenic mouse erythrocytes preferentially over wild-type erythrocytes but invasion by the latter is more sensitive to neuraminidase. These results suggest that both sialic acid-dependent and independent strains interact with CR1 in the normal red cell during the invasion process. However, only sialic acid-independent strains can do so without the presence of glycophorin sialic acid. Our results close a longstanding and important gap in the understanding of the mechanism of erythrocyte invasion by P. falciparum that will eventually make possible the development of an effective blood stage vaccine.     

Hematin promotes complement alternative pathway-mediated deposition of C3 activation fragments on human erythrocytes: potential implications for the pathogenesis of anemia in malaria

Childhood malaria caused by Plasmodium falciparum is often characterized by severe anemia at low parasite burdens; the mechanism(s) responsible for this pathology remain to be defined. We have reported, based on clinical observations and in vitro models, that complement control proteins on erythrocytes such as CR1, the immune adherence receptor specific for C3b, may be reduced in childhood malaria, suggesting a possible role for complement in erythrocyte destruction. Intravascular lysis of iE by P. falciparum leads to release of erythrocyte breakdown products such as hemoglobin and hematin, which have inflammatory properties. In the present article, we demonstrate that in serum and in anticoagulated whole blood, moderate concentrations of hematin activate the alternative pathway of complement and promote deposition of C3 activation and breakdown products on erythrocytes. The degree of C3 fragment deposition is directly correlated with erythrocyte CR1 levels, and erythrocytes opsonized with large amounts of C3dg form rosettes with Raji cells, which express CR2, the C3dg receptor which is expressed on several types of B cells in the spleen. Thus, the reaction mediated by hematin promotes opsonization and possible clearance of the youngest (highest CR1) erythrocytes. A mAb specific for C3b, previously demonstrated to inhibit the alternative pathway of complement, completely blocks the C3 fragment deposition reaction. Use of this mAb in nonhuman primate models of malaria may provide insight into mechanisms of erythrocyte destruction and thus aid in the development of targeted therapies based on inhibiting the alternative pathway of complement.     

Complement-regulatory proteins in severe malaria: too little or too much of a good thing?

Data from several laboratories suggest that erythrocyte complement-regulatory proteins, in particular complement receptor 1 (CR1), are important in the pathogenesis of severe malaria. Additional studies suggest that the levels of expression of CR1 and the complement regulator CD55 on erythrocytes vary with age, being low in young children and increasing with age. It is proposed that the interplay between the rate at which immunity develops during malaria exposure and the changes in levels of erythrocyte complement-regulatory proteins that occur with age might contribute to the differences in epidemiology of severe malaria-associated anaemia and cerebral malaria.     

The chimpanzee and cynomolgus monkey erythrocyte immune adherence receptors are encoded by CR1-like genes

The human erythrocyte immune adherence (IA) receptor is the Mr 220,000 type one complement receptor, or CR1. Nonhuman primate IA receptors are comprised of a family of smaller erythrocyte complement receptors (E-CRs) of unknown origin. Recently, the Mr 65,000 baboon E-CR was identified as a glycophosphatidylinositol (GPI)-linked protein encoded by a partially duplicated CR1 gene termed CR1-like. The purpose of this study was to determine the genetic origin of the Mr 75,000 chimpanzee E-CR. Two previously identified cDNAs, an alternative splice product of CR1 termed CR1a and a chimpanzee form of CR1-like, were synthesized and amplified from chimpanzee bone marrow RNA, and transiently expressed in COS-7 cells. By SDS-PAGE, the CR1a protein had a relative mobility slightly greater than chimpanzee E-CR, whereas that of the CR1-like protein was slightly less. Affinity chromatography demonstrated that little chimpanzee CR1a bound to human C3i linked to activated thiol-Sepharose (C3i-ATS), while over 50% of both chimpanzee CR1-like and chimpanzee E-CR bound to C3i-ATS. Treatment with phosphatidylinositol-specific phospholipase C (PIPLC) to assess GPI linkage released E-CR from chimpanzee erythrocytes, and E-CR from cynomolgus monkey erythrocytes. Based on size, ligand-binding specificity, and PIPLC sensitivity, we conclude that the chimpanzee E-CR is encoded by the CR1-like gene. Furthermore, based on PIPLC sensitivity, the cynomolgus monkey E-CR is also likely encoded by a CR1-like sequence. Thus, CR1-like, which is a genetic element of unknown significance in humans, is the gene that encodes the erythrocyte IA receptor of many nonhuman primates.     

Quantitative alleles of CR1: coding sequence analysis and comparison of haplotypes in two ethnic groups.

The quantitative expression of complement receptor type 1 (CR1) on erythrocytes is regulated by two CR1 alleles that differ in having genomic HindIII fragments of either 7.4 or 6.9 kb and that determine high (H allele) or low (L allele) CR1 expression, respectively, across a 10-fold range. To investigate whether the product of the L allele may contain amino acid substitutions that make it more susceptible to proteolysis, cDNA sequence spanning the CR1 coding region was analyzed in two donors who were homozygous for the H and L alleles and differed by 7-fold in their mean numbers of CR1 per erythrocyte. Sequence differences were detected at 10 nucleotide positions, including 6 that would cause amino acid substitutions. The HindIII RFLP and 3 of the latter 6 sites were analyzed in genomic DNA of 85 Caucasians and 75 African Americans; sites encoding the other amino acid substitutions were analyzed less extensively. Two major haplotypes defined prototypic H and L alleles in both ethnic groups, suggesting that these alleles existed before the African and European populations diverged. Decreased erythrocyte CR1 expression is associated with impaired clearance of immune complexes from blood. Persistence of the L allele in all populations that have been analyzed may suggest a compensatory survival advantage, perhaps related to malaria or another infectious disease.     

Identification of human erythrocyte blood group antigens on the C3b/C4b receptor.

The Knops/McCoy (Kn/McC) human erythrocyte blood group system belongs to the category of blood group Ag that generate so-called "high titer low avidity" antibodies in immunized transfusion recipients. Screening of red cells lacking certain high titer low avidity Ag demonstrated markedly diminished CR1 expression on McC(d-) and Kn/McC "null" (Kn(a-)McC(a-b-c-d-e-f-] erythrocytes. Additional testing by other methods confirmed these data, and biochemical assays demonstrated no detectable immunoreactive CR1 protein in membranes from Kn/McC null red cells. Human antisera to various Kn/McC Ag were then used to demonstrate that many of these antisera could be used to isolate a protein of identical m.w. to that isolated from the same cells using murine mAb CR1 antisera. Finally, protein isolated by using murine mAb anti-CR1 reacted specifically with anti-Kn/McC antibodies, demonstrating the identity of the Kn/McC and CR1 proteins. Thus, CR1 protein bears the human erythrocyte Kn/McC blood group Ag.