甲烷氢呼气试验对原发性肾病综合征患儿小肠细菌过度生长的检测

通过甲烷氢呼气试验对原发性肾病综合征（PNS）患儿小肠细菌过度生长情况进行评估,探索PNS患儿小肠细菌情况。

本研究于2021年3月至2022年3月招募30例PNS患儿（PNS组）和34例体检者（对照组）为研究对象,采用甲烷氢呼气试验检测受试者小肠的菌群生长情况。分析PNS与小肠细菌生长情况的相关性。

PNS组共有16名PNS患儿合并小肠细菌过度生长（SIBO）,SIBO患病率为53.3%（95% CI：11.1%～89.7%）;而对照组有26.5%的儿童患有SIBO,组间差异有统计学意义（χ² = 4.831 4,P = 0.027 9）。两组儿童年龄、性别、常住地比较差异均无统计学意义（均P＞0.05）。PNS合并SIBO的患儿白细胞水平显著低于未合并SIBO的患儿（F = 6.279 7,P = 0.020 1）。Pearson分析显示,PNS组中SIBO阳性患儿服用乳果糖后呼出气体变化量与血清中胆固醇水平具有相关性（P＜0.05）。

PNS患儿更容易发生SIBO,临床可对此类患者进行针对性治疗。

     

Microecological aspects of small intestinal bacterial overgrowth syndrome

Small intestinal bacterial overgrowth syndrome (SIBOS) means chronic recurrent diarrhea with malabsorption, intoxication and increased risk of endogenous infection. This syndrome are accompanied by increase of overall bacterial burden in biotope >10(5) CFU/ml in adults and >10(4) CFU/ml in children, emergence of different species of enterobacteria, bacteroides, clostridia and fusobacteria et al. in small intestine. Such characteristics of the syndrome allow to consider it as syndrome of disturbances of intestinal microflora (dysbacteriosis). Microecological changes are accompanied by B12 vitamin deficiency anemia, hypovitaminosis, protein deficiency, translocation of bacteria and their toxins from intestine in blood, emergence of endotoxinemia and possible generalization of infection. SIBOS is diagnosed by concentration of hydrogen in expiratory flow (lactulosa load test) or by bacteriological study of aspirate from proximal part of small intestine. Complex treatment includes containing lacto- and bifidobacteria probiotics and, in more severe cases, antimicrobial agents (vancomycine, metronidazole, aminoglycosides, amoxicillin clavulanate, tetracycline, and cephalosporines of 2nd generation) with following correction of disturbed microbiocenosis by different probiotics.     

应用质子泵抑制剂导致小肠细菌过度生长发生的可能性

目的观察应用质子泵抑制剂(PPI)患者,在强效抑酸状态下小肠细菌过生长(SIBO)的发生情况。方法用葡萄糖呼气H2试验,检测57例服用PPI制剂患者,30名健康志愿者作为对照。结果 PPI制剂组中呼气H2检测SIBO阳性28例,阴性29例;健康对照组中SIBO阳性3例,阴性27例。PPI组与健康对照组比较差异有统计学意义(P0.01),PPI制剂使用时间与SIBO阳性率存在正相关性。结论长期服用PPI制剂的患者可并发SIBO,且SIBO的发病率与PPI制剂使用时间呈正相关。     

Bacteria-lectin interactions in phytohemagglutinin-induced bacterial overgrowth of the small intestine

The mechanism of phytohemagglutinin-induced bacterial overgrowth of the small bowel in the rat was studied. Interaction of the lectin with bacterial isolates selected at random from those that comprised the major population of the overgrowth was determined. In both bacterial agglutination assays and glycocalyx stabilization, no specific association between lectin and bacteria was seen. In three independent binding assays phytohemagglutinin was not found to increase bacterial adherence to washed intestinal mucosa. Phytohemagglutinin would not appear to act, therefore, as a direct ligand to mediate bacterial adherence or to modify the mucosal surface to increase bacterial adherence.     

米曲菌胰酶片对功能性消化不良合并小肠细菌过度生长患者的治疗

目的 了解功能性消化不良（FD）中小肠细菌过度生长（SIBO）的发生率,推测临床预测因子并观察米曲菌胰酶片对FD合并SIBO的疗效。方法 对112例符合罗马Ⅲ标准的FD患者进行第1次LHBT（f-LHBT）,其结果使用Logistic回归分析LHBT阳性的预测因子。26例f-LHBT阳性者随机接受加酶或非加酶治疗,2周后复查LHBT（LHBT-2w）,对LHBT-2w持续阳性者继续加酶治疗2周后再次复查LHBT（LHBT-4w）。比较加酶组与非加酶组间症状改善情况及复查LHBT情况。结果 112例FD中,33例（29.46%）f-LHBT阳性,Logistic回归提示上腹胀程度（OR=1.759,95%CI：1.187~2.609）、恶心程度（OR＝1.634,95%CI：1.029~2.594）是LHBT阳性的独立预测因子。治疗2周后,两组共17例患者（65.38%）出现LHBT-2w阴转,其症状改善率高于LHBT-2w持续阳性组（t=－2.833,P=0.009）。加酶组（n=14）症状改善率为（75.89±21.92）%、非加酶组（n=12）为（53.84±31.39）%,差异有统计学意义（t=2.100,P=0.046）。加酶组LHBT-2w阴转率为71.4%,非加酶组为58.3%,差异无统计学意义（P=0.683）,但加酶组高峰呼气H2浓度减少率显著高于非加酶组（U=－2.315,P=0.021）。7例LHBT-2w持续阳性者经继续加酶治疗2周后复查LHBT-4w,结果4例阴转,3例仍持续阳性,但高峰呼气H2浓度均有所下降。结论 大约29% FD患者会合并SIBO,上腹胀程度及恶心程度是独立预测因子。SIBO转阴后消化不良症状改善,提示FD症状可能与SIBO有关。短期使用米曲菌胰酶片可促进这些患者的症状改善,可能与减少SIBO有关。     

Altered transit and bacterial overgrowth in the cystic fibrosis mouse small intestine

Small intestinal bacterial overgrowth (SIBO) may play an important role in the gastrointestinal complications of cystic fibrosis (CF). This work explored two potential factors in development of SIBO in the CF (cftr(tm1UNC)) mouse: impaired Paneth cell innate defenses and altered gastrointestinal motility. Postnatal differentiation of Paneth cells was followed by Defcr, Lyzs, and Ang4 gene expression, and SIBO was measured by quantitative PCR of the bacterial 16S rRNA gene. Paneth cell gene expression was low in 4-day-old CF and wild-type (WT) mice and increased similarly in both groups of mice between 12 and 16 days. Peak Paneth cell gene expression was reached by 40 days of age and was less for Defcr and Lyzs in CF mice compared with WT, whereas Ang4 levels were greater in CF mice. SIBO occurred by postnatal day 8 in CF mice, which is before Paneth cell development. With the use of gavaged rhodamine-dextran to follow motility, gastric emptying in CF mice was slightly decreased compared with WT, and small intestinal transit was dramatically less. Since antibiotics improve weight gain in CF mice, their effects on gastric emptying and small intestinal transit were determined. Antibiotics did not affect gastric emptying or transit in CF mice but did significantly slow intestinal transit in WT mice, suggesting a potential role of normal microflora in regulating transit. In conclusion, small intestinal transit was significantly slower in CF mice, and this is likely a major factor in SIBO in CF.     

腹泻型IBS患者小肠细菌过度生长和抗菌素的影响

目的观察腹泻型肠易激综合征(IBS-D)患者乳果糖氢呼气试验(LHBT)的阳性率、以及短期抗菌素治疗的疗效。方法 89例符合罗马Ⅲ标准的IBS-D患者接受LHBT检测,分析LHBT结果与肠易激综合征(IBS)症状的相关性;16例LHBT阳性IBS-D患者接受"替硝唑或司帕沙星"治疗1周,观察LHBT阴转率及其与症状改善的关系。结果 89例IBS-D患者中,46例(51.7%)LHBT阳性。LHBT阳性组与LHBT阴性组IBS患者在腹痛程度和频率、腹胀程度和频率的差异有统计学意义(P0.05)。16例LHBT阳性的IBS-D患者经1周抗菌素治疗后10例(62.5%)LHBT阴转,IBS症状改善率(Y)与H2呼出量减少率(X)存在正相关关系(回归方程Y=31.3+0.34X,r=0.61,P=0.03)。结论 51.7%IBS-D患者存在小肠细菌过生长(SIBO),SIBO与IBS-D患者的腹痛、腹胀症状有关;短程抗菌素治疗后可以使IBS-D的部分症状获得缓解。     

Single breath of CO2 as a clinical test of the peripheral chemoreflex

Peripheral chemoreceptor responsiveness is usually examined clinically by hypoxic testing, but the usefulness of this approach is limited by safety considerations, and the interpretation of results may be confounded by the direct central nervous system effects of hypoxia. Therefore we examined the single-breath (SB) CO2 test to determine its reproducibility and applicability as a clinical test of peripheral chemoreceptor function. The technique involved the inhalation of a SB of 13% CO2 in air. The ventilatory response was determined from the increase in ventilation (VE) during the first 20 s after the test breath and from the difference in end-tidal PCO2 between the test breath and preceding control breaths. The peak increase in VE occurred during the second or third breath after the test breath, corresponding to a delay of approximately 10 s. The mean of 10 SB tests administered at 2- to 3-min intervals was taken as the subject's response. Five healthy subjects were tested in this manner on each of 6 consecutive days with the response having an interday coefficient of variation of 25 +/- 6% (SD). The response in 26 healthy females (aged 22-61 yr) was 0.32 +/- 0.11 l.min-1.Torr-1, and in 26 healthy males (aged 24-69 yr) the response was 0.38 +/- 0.14 (P NS). No significant correlation was found between the age of the subjects and their ventilatory response. Thirty-six of the subjects also underwent hyperoxic CO2 rebreathing tests, the response to which is dependent on central chemoreceptor function. No correlation was found between rebreathing and SB tests.(ABSTRACT TRUNCATED AT 250 WORDS)     

Synthesis and screening of a small library of proline-based biodendrimers for use as delivery agents

A small library of defined peptide dendrimers based on polyproline sequences was designed to demonstrate the feasibility of generating a new type of polymeric agent for therapeutic use. Structural modifications to dendrimer surfaces further enriched the diversity of the library. Data show that the prolinerich dendrimers can be internalized in human epithelial (HeLa) cells, demonstrating the importance of the dendrimeric motif. The promising results described herein suggest that controlled modification of the dendrimer surface should eventually yield proline dendrimers with therapeutic potential.     

Mutagen screening by a simplified bacterial fluctuation test: use of microsomal preparations and whole liver cells for metabolic activation.

We describe the use of a simplified bacterial fluctuation test to detect induced mutation, either incorporating liver microsomal or whole liver cell preparations. We have evaluated both types of test using three agents. The fluctuation assay seems somewhat slower, simpler and more sensitive than a conventional plating test with microsomes. A whole cell preparation appears marginally more effective than a microsomal fraction for metabolic activation of 9,10-dimethyl-1,2-benzanthracene, but rather less effective for benz(a)pyrene and 2-acetamidofluorene. Ultimately the usefulness of activation by whole cells may depend upon whether the method can give a correlation with carcinogenicity that is more quantitative than microsome methods and better reflects organ and species specificity.     

Surrogate genetics: the use of bacterial hybrids as a genetic tool

Experimental dissection of bacterial genomes requires a well-developed set of genetic tools, but many bacteria lack the essential tools required for genetic analysis. Recombination of a region of chromosomal DNA from poorly characterized donor bacteria with the chromosome of a suitable surrogate host creates a genetically malleable hybrid, providing a short-cut for the detailed genetic analysis of the substituted genes. However, recombination between closely related but nonidentical DNA sequences ("homeologous recombination") is strongly inhibited, posing a powerful barrier to gene exchange between bacteria and a major impediment to the construction of genetic hybrids. By taking advantage of mutS and recD mutant recipients, it is possible to effectively overcome the recombination barrier, allowing construction of genetic hybrids in a related surrogate host. Once stably recombined into the recipient chromosome, the donor DNA can be studied with all the genetic tools available in the surrogate host. In addition to facilitating standard genetic analysis, use of a surrogate host can provide novel approaches to study the physiological roles of unique genes from poorly characterized bacteria.     

13C-urea breath test for the diagnosis of Helicobacter pylori infection in children: a systematic review and meta-analysis

Background: The ¹³C‐urea breath test (¹³C‐UBT) is a safe, noninvasive and reliable method for diagnosing H. pylori infection in adults. However, the test has shown variable accuracy in the pediatric population, especially in young children. We aimed to carry out a systematic review and meta‐analysis to evaluate the performance of the ¹³C‐UBT diagnostic test for H. pylori infection in children. Methods: We conducted a systematic review of the PubMed, Embase and Liliacs databases including studies from January 1998 to May 2009. Selection criteria included studies with at least 30 children and reporting the comparison of ¹³C‐UBT against a gold standard for H. pylori diagnosis. Thirty‐one articles and 135 studies were included for analysis. Children were stratified in subgroups of <6 and ≥6 years of age, and we considered variables such as type of meal, cutoff value, tracer dose, and delta time for the analysis. Discussion: The ¹³C‐UBT performance meta‐analyses showed 1, good accuracy in all ages combined (sensitivity 95.9%, specificity 95.7%, LR+ 17.4, LR? 0.06, diagnostic odds ratio (DOR) 424.9), 2, high accuracy in children >6 years (sensitivity 96.6%, specificity 97.7%, LR+ 42.6, LR? 0.04, DOR 1042.7), 3, greater variability in accuracy estimates and on average a few percentage points lower, particularly specificity, in children ≤6 years (sensitivity 95%, specificity 93.5%, LR+ 11.7, LR? 0.12, DOR 224.8). Therefore, the meta‐analysis shows that the ¹³C‐UBT test is less accurate for the diagnosis of H. pylori infection in young children, but adjusting cutoff value, pretest meal, and urea dose, this accuracy can be improved.     

胰腺癌中小肠细菌过度生长及炎症介质异常表达分析

目的 本研究通过检测胰腺癌患者小肠细菌过度生长(SIBO)、癌组织中IL 1β、IL 6和TNF α的表达水平,探讨胰腺癌患者是否更易发生SIBO及SIBO伴随的炎症介质水平变化。 方法 采用葡萄糖氢呼气试验(HBT)检测40例胰腺癌患者和40例健康查体人群的SIBO的发生情况。采用免疫组织化学技术(IHC)测定胰腺癌组织中IL 1β、IL 6和TNF α的表达情况,分析与胰腺癌临床病理的关系。 结果 胰腺癌组SIBO阳性率为60.0%,健康对照组SIBO阳性率为15.0%,胰腺癌组SIBO阳性率显著高于对照组(P结论 胰腺癌患者较健康人更容易发生SIBO,SIBO可能通过促进IL 1β、IL 6及TNF α的表达影响胰腺癌的发生发展。     

The use of SAX-HPLC-CD as a heparin screening strategy

Heparin, a heterogeneous polysaccharide, has been widely used as an anticoagulant for decades. Recently, however, international events involving the sudden onset of allergic-type reactions following heparin administration led to numerous fatalities, and demanded the use of multiple laborious, time consuming techniques to identify an economically motivated adulterant. Using these methods cooperatively, the semi-synthetic molecule known as oversulfated chondroitin sulfate (OSCS), was found to be present at significant concentrations. Since the discovery of this adulterant, several analytical methods have been put forth or updated to advance the process of screening pharmaceutical heparins; of these, strong anion exchange high performance liquid chromatography (SAX-HPLC) methods have now become routine. In this preliminary work, we report the use of circular dichroism (CD) detection in conjunction with existing SAX-HPLC methods to quantitate various sulfated polysaccharides. The proposed strategy exploits the selectivity associated with CD detection of heparin and heparin-like polysaccharides, while taking advantage of the method's insensitivity to the use of mobile phase additives and programmed gradients. The limit of detection of heparin by CD was found to be ～0.22 mg/mL, whereas traditional UV/Vis detection yielded a detection limit of ～1.09 mg/mL. The success of CD detection varied for other polymers, however no significant modifications were made to the separations method to capitalize on the advantages of CD detection.     

The use of spiroarteriocardiorhythmography as a functional test for estimating the state of the cardiorespiratory system in adults and children

The heart rate, peripheral arterial blood pressure (BP), and respiration parameters were simultaneously recorded in adult subjects and young schoolchildren in two modes of testing: using a mask with airflow sensors that did not restrict air inflow but increased the pulmonary dead space and without the mask. It was demonstrated that wearing the mask was a functional test for the state of the cardiorespiratory system in both age groups; however, the responses of the children’s and adults’ bodies differed from each other, probably, because of the functional immaturity of the sympathetic component of the autonomic control. In adults, the parameters of the cardiovascular system did not change, except that the heart rate variability spectrum was redistributed toward an enhancement of the high-frequency component. In children, testing with the mask on decreased the systolic BP; increased the heart rate; and, as evidenced by the spectral characteristics of BP variability, activated the sympathetic nervous system.