OBJECTIVE:To investigate the distribution of Traditional Chinese Medicine(TCM)constitution among individuals with functional constipation,which would provide insights for developing constitution-targeted prevention and treatment strategies. METHODS:A systematic search was conducted across eight databases(China National Knowledge Infrastructure Database,Wanfang Database,China Science and Technology Journal for Chinese Technical Periodicals,SinoMed,PubMed,Web of Science,Embase,and the Cochrane Library)to identify relevant observational studies assessing Traditional Chinese Medicine(TCM)constitution types among people with functional constipation.The protocol for this review has been registered on International Prospective Register of Systematic Reviews(registration number:CRD42022345996). RESULTS:A total of sixteen cross-sectional studies involving 2976 participants were included in this review.Among functional constipation patients,the proportions of Yin-deficiency,Yang-deficiency,and Qi-deficiency constitution were 27.0%[95%confidence interval(CI)19.9%to 36.7%],25.2%(95%CI 17.5%to 35.0%)and 23.7%(95%CI 15.8%to 34.0%),respectively.Besides,females accounted for a higher percentage of the population with functional constipation in the included studies,and most patients were aged 45 years or older.These findings may reflect the demographic characteristics of the general functional constipation population,where older adults and women are more commonly affected.The impact of gender and age on TCM constitution distribution merits further exploration. CONCLUSION:Our finding revealed that Yin-deficiency,Yang-deficiency,and Qi-deficiency are the predominant TCM constitution types in people with functional constipation.This study suggests that clinicians should focus on patients with these TCM constitution types in the prevention and management of functional constipation.Larger sample sizes and more rigorous methodological designs are needed in future studies.Furthermore,future researches should also focus on developing individualized prevention and treatment strategies based on different TCM constitution types.
Background:Anxiety disorders and depressive disorders are the most prevalent mental disorders worldwide. Their diagnosis has long relied on clinical symptom assessment, and objective blood-based biomarkers remain lacking. Sex is a critical risk factor for these disorders; however, sex-specific divergence in blood biochemical profiles has yet to be systematically characterized. Methods:This retrospective study enrolled 778 patients diagnosed with anxiety-depressive state at China-Japan Friendship Hospital. Demographic data, complete blood count parameters, and blood biochemical parameters were collected. Following missing value processing and multiple imputation, Mann-Whitney U tests were applied to identify sex-differentially expressed biomarkers. A random forest classifier was constructed to evaluate the discriminative capacity of combined multi-marker panels, with model performance comprehensively assessed through receiver operating characteristic curve analysis, SHAP-based explainability analysis, and multi-classifier probability projection. Age-stratified analyses were performed with a threshold of 50 years to explore the potential modifying effect of age on sex differences. Results:Several biomarkers exhibiting significant differences between males and females were identified (FDR < 0.05), among which creatinine, hemoglobin, hematocrit, red blood cell count, and uric acid demonstrated the largest effect sizes. The random forest model achieved an area under the receiver operating characteristic curve of 0.902 on the independent test set. Multi-classifier probability projection following hyperparameter tuning yielded a Silhouette coefficient of 0.464 in the two-dimensional space, with permutational multivariate analysis of variance confirming highly significant centroid differences between groups (p < 0.001). Age-stratified analysis using hemoglobin as an example revealed that levels in males were significantly higher than those in females across both age strata, with the magnitude of the sex difference attenuated in the ≥50-year group compared with the <50-year group. Conclusions:Robust sex-related signals are embedded in routine blood biochemical markers. Although complete separation is difficult to achieve under unsupervised dimensionality reduction, these signals can be efficiently integrated through ensemble learning algorithms. This study provides a molecular phenotypic basis related to sex in patients with anxiety-depressive state and underscores the importance of fully considering sex as a variable in clinical laboratory testing.
Introduction:Refractory Helicobacter pylori infection (RHPI) poses a clinical challenge due to its treatment resistance. The gastric microbiota characteristics in patients with RHPI remain unclear. This study analyzed gastric fluid samples to explore the structural and functional differences in the gastric microbiota of patients with RHPI and their association with clinicopathological features, providing a theoretical basis for precision treatment of RHPI. Methods:Eighty-four patients who underwent gastroscopy were prospectively and consecutively divided into the Nhp (H. pylori-negative, n = 32), Php (H. pylori-positive at first diagnosis without treatment, n = 32), and Rhp (RHPI, n = 20) groups. Gastric fluid and mucosal biopsy samples were collected for 16S rRNA gene sequencing, pathological evaluation, and bioinformatic analysis. Differences in gastric microbiota and clinical data were compared among the three groups. Results:The Rhp group exhibited more gastric mucosal atrophy, inflammation, and inflammatory activity than Nhp and Php groups. Rhp also showed lower microbial richness and diversity. β-diversity analysis revealed distinct microbial communities between the Nhp and Php/Rhp groups. Rhp was enriched with H. pylori PZ5004 and Pseudoalteromonas sp. C_8, among others, while Php was enriched with Lactobacillus sp. CY1 and other species and Nhp with Prevotella melaninogenica and other species. The Rhp group also had higher H. pylori PZ5004/P79 abundance, more complex microbial interactions, and enriched sulfur relay pathways than the other groups. Conclusion:H. pylori infection disrupts the diversity, structure, and function of gastric microbiota. The close interaction between characteristic microbiota and H. pylori subspecies may be a key factor contributing to the difficulty in treating RHPI.
Upper gastrointestinal motility disorders are common during anesthesia induction and are closely related to reflux aspiration; however, there is a lack of research on gastroesophageal reflux during anesthesia induction. In this study, we applied high-resolution impedance measurement (HRIM) to characterize gastroesophageal reflux during anesthesia induction. A total of 28 patients participated in this study, with 14 patients receiving anesthesia induction with propofol and succinylcholine, and 14 patients receiving anesthesia induction with propofol and rocuronium. A HRIM catheter was used to collect esophageal impedance and pressure data throughout the anesthesia induction process. Prior to anesthesia induction, none of the 28 patients experienced gastroesophageal reflux. Within 10 min of anesthesia induction, 12 patients experienced gastroesophageal reflux (n = 12/28; 42.9
ABSTRACTBackgroundOpinions about the impact of bowel preparation on the gut microbiota are divided. This study investigated the effects of different regimens on the gut microbiota post‐bowel preparation and the differences in responses across different age groups.MethodsThis single‐center, prospective, randomized, controlled clinical trial included 194 patients. Patients were categorized into two groups: one group receiving polyethylene glycol (n = 108) and one receiving sodium picosulfate (n = 86) for bowel preparation. Fecal samples were collected at baseline and on days 7 and 14 post‐bowel preparation. The microbiota's diversity and composition were analyzed using 16S ribosomal RNA gene sequencing, followed by comparative analyses.ResultsThe gut microbiota's abundance and diversity in patients significantly decreased post‐bowel preparation, which did not recover to the level of pre‐bowel preparation on Day 14. When comparing different regimens, the polyethylene glycol and sodium picosulfate groups recovered faster in richness and diversity, respectively. Patients aged < 65 years had higher richness and diversity of the gut microbiota, whereas the microbiota structure in those aged ≥ 65 years returned to the baseline state faster. The structure of beta diversity is significantly altered and did not return in the short term. However, in the elderly population aged ≥ 65 years, it can rebound quickly. This study also identified a number of significantly altered bacterial genera.ConclusionsFollowing the use of different bowel preparation regimens, the gut microbiota recovers in diverse ways, with older people over 65 experiencing a faster recovery of the microbial structure.
The emergence of multidrug-resistant Escherichia coli (MDR E. coli), particularly enteropathogenic E. coli, is closely associated with therapeutic interventions for irritable bowel syndrome (IBS) and ulcerative colitis (UC) in clinical practice. However, a comprehensive characterization of their resistome differences remains limited. Exploring their resistance profiles and virulence gene repertoires is crucial for informing improved treatment strategies and controlling the dissemination of MDR E. coli in healthcare settings. Here, we analyzed 70 E. coli strains isolated from a single-center, case-control cohort enrolled between 2022 and 2023 at a tertiary care hospital in Beijing, China. Through integrated phenotypic and genomic approaches, we investigated their antimicrobial resistance (AMR) patterns and transmission dynamics. These strains exhibited high resistance to sulfonamides (34.3 %) and fluoroquinolones (32.9 %) in general. Incremental trends in β-lactam resistance were observed in the IBS-D and UC groups compared to the HC group, reflecting both phenotypic resistance and the presence of ESBL genes. Significant intergroup differences in the prevalence of β-lactam resistance gene blaTEM-1B, rifamycin resistance gene ARR-3, and ExPEC-related nutritional/metabolic factors (e.g. chuA, chuU, iroD, iroE, kpsM) were observed. Notably, the co-existence of blaCTX−M-55 and tet(X4) was first identified in IBS-D patients. The emergence of high-risk ST10, ST1193, and ST131 clones occurred in IBS-D and UC patients. Positive correlations were observed between the number of antibiotic resistance genes, virulence factor genes, and antibiotic usage history. This study underscores escalating AMR and virulence trends across patient groups and highlights the urgent need for tailored antimicrobial stewardship in managing IBS-D and UC.
Depression is a common mood disorder characterized by persistent sadness, loss of interest or pleasure, and a range of cognitive and physical symptoms such as gastrointestinal dysfunction that significantly impair daily functioning. Electroconvulsive Therapy (ECT) remains the treatment of choice and a critical last-resort intervention for patients with severe, treatment-resistant depression, particularly those at high risk of suicide. Evidence suggests that the gut-brain axis, a complex bidirectional communication network, plays a key role in the development of these multifaceted symptoms. This study explores the possibility that ECT may exert its therapeutic effects by modulating gastrointestinal function. In clinical investigation, a notable proportion of patients with major depressive disorder experienced significant alleviation of gastrointestinal symptoms, particularly constipation, following ECT. In preclinical research, Electroconvulsive Shock (ECS) is commonly applied to animal models as an experimental analogue to explore the mechanisms and efficacy of ECT. Complementary experiments in mice revealed that daily ECS not only reversed depressive-like behaviors but also restored colonic motility. This effect was closely associated with the normalization of neural activity in the hypothalamic paraventricular nucleus (PVN), a key brain region involved in autonomic nervous regulation. Importantly, these benefits were abolished by subdiaphragmatic vagotomy, underscoring the pivotal role of the vagus nerve in mediating gut-brain interactions. These findings offer insights into the neural pathways underpinning the gut-brain connection, highlighting the potential of ECT not only as a last line of defense against severe depression but also as a means to address associated gastrointestinal dysfunction.
Fluorinated liquid-crystal monomers (FLCMs) are widespread environmental contaminants with potential endocrine-disrupting effects. Infants are particularly vulnerable, yet their exposure remains unclear. This study analyzed FLCMs in urine samples from 190 paired mothers and infants in Beijing, detecting 34 and 35 FLCMs, respectively. Median creatinine-corrected concentrations were 1.83 μg/g (unadjusted concentrations: 1.28 ng/mL) for mothers and 3.28 μg/g (0.60 ng/mL) for infants. 1-butoxy-2,3-difluoro-4-(trans-4-propylcyclohexyl) benzene (BDPrB) and 1-ethyl-4-[(4-fluorophenyl) ethynyl] benzene (EFPEB) were identified as the primary detected contaminants. A significant positive correlation in urine concentrations between mothers and infants was observed only for 2'-Fluoro-4″-propyl-[1,1':4',1″-terphenyl]-4-carbonitrile (FPTC) (rs = 0.23, p = 0.023). Certain FLCMs were associated with infant feeding patterns, maternal parity, and environmental exposure, including dust and cleaning frequency (p < 0.05). The results of the study showed that the median estimated daily intakes (EDIs) of ∑FLCMs for mothers and infants were 526 and 425 ng/kg bw/day, respectively, with no significant difference between them (p > 0.05). Further stratification of the data by sex revealed that for male infants, the EDI values for BDPrB and EFPEB were greater (p < 0.05). These findings emphasize the need for greater research on the health effects of FLCMs on infants, particularly considering gender differences.
Background: In East Asia,Helicobacter pylori (H. pylori) infection and related diseases are common, primarily during childhood and adolescence. The rates of primary antibiotic resistance inH. pylori among East Asian children and adolescents have not been extensively explored; few relevant systematic reviews or meta-analyses have been conducted. We evaluated the rates of antibiotic resistance inH. pylori among East Asian children and adolescents, with the goal of facilitating individualized treatment recommendations.Methods: We searched PubMed, Embase, and the Cochrane Library for studies in any language published up to February 2023 that explored antibiotic resistance inH. pylori among East Asian children and adolescents. We used MeSH and non-MeSH terms related to the topic, including terms related to children, adolescents, antibiotic resistance,H. pylori, and nations or regions. Additionally, we reviewed the reference lists of relevant articles. Studies that matched our strict predefined eligibility criteria were included in the screening process. Using established assessment methods, we evaluated the quality of the included studies.Results: We identified 15 observational studies involving 4831H. pylori isolates, all published between 2001 and 2022. There was substantial primary antibiotic resistance inH. pylori isolates from East Asian children and adolescents. The rates of primary resistance were 51% (95% confidence interval [CI]: 40–62%) for metronidazole; 37% (95% CI: 20–53%) for clarithromycin; 19% (95% CI: 11–28%) for levofloxacin; and less than 3% each for amoxicillin, tetracycline, and furazolidone. Subgroup analysis revealed a prominent increase in metronidazole resistance over time. Clarithromycin and levofloxacin resistance rates fluctuated between 2005 and 2015, then remained stable; other antibiotic resistance rates were generally stable. Metronidazole, clarithromycin, and levofloxacin resistance rates were significantly higher in the Chinese mainland than in other East Asian regions. The rates of dual and multiple antibiotic resistance were 28% (95% CI: 21–36%) and 10% (95% CI: 7–14%), highlighting the potential for diverse resistance patterns.Conclusions: H. pylori isolates from East Asian children and adolescents exhibit high levels of metronidazole and clarithromycin resistance, particularly in the Chinese mainland. The non-negligible rates of dual and multiple resistance highlight the complexity of this problem.Registration: PROSPERO, No. CRD42023402510.
BackgroundThe eradication regimen for Helicobacter pylori (H. pylori) infection can induce gut dysbiosis. In this open-label, prospective, and randomized clinical trial, we aimed to assess the effects of fucoidan supplementation on the eradication rate and gut microbial homeostasis in the context of quadruple therapy, as well as to investigate the combined effects of fucoidan and synbiotics supplementations.MethodsEighty patients with H. pylori infection were enrolled and randomly assigned to one of four treatment groups: the QT (a 2-week quadruple therapy alone), QF (quadruple therapy plus a 6-week fucoidan supplementation), QS (quadruple therapy plus a 6-week synbiotics supplementation), and QFS (quadruple therapy with a 6-week fucoidan and synbiotics supplementation), with 20 patients in each group. The QT regimen included rabeprazole, minocycline, amoxicillin, and bismuth potassium citrate. The synbiotics supplementation contained three strains of Bifidobacterium, three strains of Lactobacillus, along with three types of dietary fiber. All of the patients underwent 13C-urea breath test (13C-UBT) at baseline and at the end of the 6th week after the initiation of the interventions. Fresh fecal samples were collected at baseline and at the end of the 6th week for gut microbiota analysis via 16S rRNA gene sequencing.ResultsThe eradication rates among the four groups showed no significant difference. In the QT group, a significant reduction in α-diversity of gut microbiota diversity and a substantial shift in microbial composition were observed, particularly an increase in Escherichia-Shigella and a decrease in the abundance of genera from the Lachnospiraceae and Ruminococcaceae families. The Simpson index was significantly higher in the QF group than in the QT group. Neither the QS nor QFS groups exhibited significant changes in α-diversity or β-diversity. The QFS group was the only one that did not show a significant increase in the relative abundance of Escherichia-Shigella, and the relative abundance of Klebsiella significantly decreased in this group.ConclusionThe current study provided supporting evidence for the positive role of fucoidan and synbiotics supplementation in the gut microbiota. The combined use of fucoidan and synbioticss might be a promising adjuvant regimen to mitigate gut dysbiosis during H. pylori eradication therapy.
INTRODUCTION:The imbalance in gut microbiota is contributing to the development and progression of IBS. FMT can improve the gut microbiota, and donor-recipient-matched FMT can help develop individualized treatment plans according to different enterotypes. This study aimed to explore the efficacy of donor-recipient-matched FMT in IBS with predominant diarrhoea (IBS-D) and evaluate its effects on gut microbiota. METHODS:Twenty-seven patients with IBS-D were randomly divided into donor-recipient-matched FMT group (group P), random-donor FMT group (group R), and placebo group (group B). All participants received corresponding FMT treatment after filling in IBS-S, IBS-QoL, GSRS, and HADS questionnaires and having their stool samples collected at 4, 8, and 12 weeks after treatment. The improvement in the symptoms and the changes in the bacterial flora were analysed for three groups. RESULTS:The IBS-SSS, IBS-QoL, GSRS, and anxiety scores of group P were significantly lower after treatment (p < 0.05). The IBS-QoL scores of group R were significantly lower after treatment (p < 0.05). Beta diversity analysis showed that the gut microbiota of group P had an obvious trend of classification after treatment. Seven bacterial genera were related to the differences in the IBS-SSS scores before and after treatment. CONCLUSION:Donor-recipient-matched FMT significantly improved the clinical symptoms, quality of life, and anxiety scores of the patients with IBS-D than random-donor FMT.
Hepatocellular carcinoma (HCC) is a prevalent and deadly form of cancer globally with typically unfavorable outcomes. Increasing research suggests that lactate serves as an important carbon contributor to cellular metabolism and holds a crucial part in the progression, sustenance, and treatment response of tumors. However, the contribution of lactate-related genes (LRGs) in HCC is still unclear. In this study, we analyzed TCGA datasets and screened 21 differentially expressed LRGs related to long-term survivals in HCC patients. Pan-cancer assays revealed that 21 LRGs expression exhibited a dysregulated level in man types of tumors and associated with clinical prognosis of tumor patients. The analysis of 21 LRGs successfully classified HCC samples into two molecular subtypes, and these two subtypes showed significant differences in clinical information, gene expression, and immune characteristics. Subsequently, based on the aforementioned 21 LRGs, a novel prognostic signature (DTYMK, IRAK1, POLRMT, MPV17, UQCRH, PDSS1, SLC16A3, SPP1 and LDHD) was generated by LASSO-Cox regression analysis. Survival assays demonstrated that the signature performed well in predicting the overall survival of patients with HCC. The results of Gene Set Variation Analysis indicated that the high GSVA scores were associated with poor prognosis. Moreover, we also investigated the correlation between GSVA scores and various signaling pathways in HCC. Among the nine prognostic genes, our attention focused on POLRMT which was highly expressed in HCC specimens based on TCGA datasets and several HCC cell lines. In addition, functional assays indicated that POLRMT distinctly promoted the proliferation, migration and energy metabolism of HCC cells via regulating Wnt/β-Catenin signaling. Overall, through the establishment of a novel prognostic signature, we have provided potential clinical value for assessing the prognosis of HCC patients. Furthermore, our study has identified the high expression of POLRMT in HCC and demonstrated its crucial role in HCC cell proliferation. These findings hold great importance in advancing our understanding of the pathophysiology of HCC, identifying new therapeutic targets, and improving patient survival rates.
Overlapping clinical manifestations of irritable bowel syndrome (IBS) and IBS-like symptoms in patients with inflammatory bowel disease (IBD-IBS) present challenges in diagnosis and management. Both conditions are associated with alterations in metabolites, but few studies have described the lipid profiles. Our aim was to pinpoint specific lipids that contribute to the pathogenesis of IBS and IBD-IBS by analyzing multiple biologic samples. Diarrhea-predominant IBS (IBS-D) patients (n = 39), ulcerative colitis in remission with IBS-like symptoms patients (UCR-IBS) (n = 21), and healthy volunteers (n = 35) were recruited. IBS-D patients meet the Rome IV diagnostic criteria, and UCR-IBS patients matched mayo scores ≤ two points and Rome IV diagnostic criteria. Serum, feces, and mucosa were collected for further analysis. Lipid extraction was carried out by ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Lipidomics of mucosa and serum samples significantly differed among the three groups. Feces showed the most altered lipid species, and the enrichment analysis of 347 differentially abundant metabolites via KEGG pathway analysis revealed that alpha-linolenic acid metabolism was significantly altered in the two groups (P < 0.01). The ratio of omega-6/omega-3 fatty acid were imbalance in serum samples. This study revealed a comprehensive lipid composition pattern between IBS-D patients and UCR-IBS patients. We found several distinctive lipids involved in alpha-linolenic acid metabolism, reflecting an imbalance in the omega-6/omega-3 fatty acid ratio. Compared to mucosa and serum samples, fecal samples might have more advantages in lipidomics studies due to the convenience of sample collection and effectiveness in reflecting metabolic information.
Helicobacter pylori (H. pylori) infection correlates closely with gastric diseases such as gastritis, ulcers, and cancer, influencing more than half of the world's population. Establishing a rapid, precise, and automated platform for H. pylori diagnosis is an urgent clinical need and would significantly benefit therapeutic intervention. Recombinase polymerase amplification (RPA)-CRISPR recently emerged as a promising molecular diagnostic assay due to its rapid detection capability, high specificity, and mild reaction conditions. In this work, we adapted the RPA-CRISPR assay on a digital microfluidics (DMF) system for automated H. pylori detection and genotyping. The system can achieve multi-target parallel detection of H. pylori nucleotide conservative genes (ureB) and virulence genes (cagA and vacA) across different samples within 30 min, exhibiting a detection limit of 10 copies/rxn and no false positives. We further conducted tests on 80 clinical saliva samples and compared the results with those derived from real-time quantitative polymerase chain reaction, demonstrating 100% diagnostic sensitivity and specificity for the RPA-CRISPR/DMF method. By automating the assay process on a single chip, the DMF system can significantly reduce the usage of reagents and samples, minimize the cross-contamination effect, and shorten the reaction time, with the additional benefit of losing the chance of experiment failure/inconsistency due to manual operations. The DMF system together with the RPA-CRISPR assay can be used for early detection and genotyping of H. pylori with high sensitivity and specificity, and has the potential to become a universal molecular diagnostic platform.
BackgroundUlcerative colitis (UC) is a persistent inflammatory bowels disease (IBD) characterized by immune response dysregulation and metabolic disruptions. Tryptophan metabolism has been believed as a significant factor in UC pathogenesis, with specific metabolites influencing immune modulation and gut microbiota interactions. However, the precise regulatory mechanisms and key genes involved remain unclear.MethodsAUCell, Ucell, and other functional enrichment algorithms were utilized to determine the activation patterns of tryptophan metabolism at the UC cell level. Differential analysis identified key genes associated with tryptophan metabolism. Five machine learning algorithms, including Random Forest, Boruta algorithm, LASSO, SVM-RFE, and GBM were integrated to identify and categorize disease-specific characteristic genes.ResultsWe observed significant heterogeneity in tryptophan metabolism activity across cell types in UC, with the highest activity levels in macrophages and fibroblasts. Among the key tryptophan metabolism-related genes, CTSS, S100A11, and TUBB were predominantly expressed in macrophages and significantly upregulated in UC, highlighting their involvement in immune dysregulation and inflammation. Cross-analysis with bulk RNA data confirmed the consistent upregulation of these genes in UC samples, highly indicating their relevance in UC pathology and potential as targets for therapeutic intervention.ConclusionsThis study is the first to reveal the heterogeneity of tryptophan metabolism at the single-cell level in UC, with macrophages emerging as key contributors to inflammatory processes. The identification of CTSS, S100A11, and TUBB as key regulators of tryptophan metabolism in UC underscores their potential as biomarkers and therapeutic targets.
患者女,65岁.因左上臂半球形丘疹1年,伴局部皮肤萎缩8个月,于2018年1月10日来我院皮肤科就诊.患者1年前无明显诱因左上臂出现一粟粒大黄红色丘疹,并逐渐增大.患者8个月前发现丘疹外周皮肤皮纹变浅,随时间进展皮纹变浅明显.自发病以来患者无自觉症状,未予诊治.发病部位既往无任何皮损,否认糖皮质激素外用史.既往体健,家族中无类似疾病患者.
Irritable bowel syndrome (IBS) is one of the most common functional bowel disorders, but its pathogenesis remains unknown. Its development may be linked to intestinal dysmetabolism, directly and indirectly. The present study aimed to screen the differentially expressed small molecular substances in the mucosa of the colon between IBS with diarrhea (IBS-D) patients and healthy subjects and explore the pathogenesis of IBS-D. In this pilot study, the metabolites of colonic mucosa in ten patients with IBS-D and six healthy controls (HC) were analyzed by DESI-MSI. We also mapped the spatial distribution of the screened differential metabolites from samples of the IBS-D group and HC group. The results showed that 20 metabolites in the colonic mucosa of IBS-D were significantly more abundant, while the other 77 substances were significantly reduced. Enrichment analysis of 97 differential metabolites and KEGG pathway analysis revealed that six medium-chain and long-chain fatty acids were determined to be most overrepresented in the IBS-D group compared to the HC group. Four of these six fatty acids are all PUFAs. The DESI–MSI results suggested that these fatty acids were localized in the colonic mucosa and confirmed the differences in these fatty acids between IBS-D and HC. Medium-chain and long-chain fatty acids localized in the colonic mucosa are likely to be potential indicators for the differentiation of IBS-D from healthy subjects which may have implications in the mechanisms and possible preventive measures against IBS. ChiCTR2200060224.
目的 观察氧化苦参碱(oxymatrine,OMT)通过免疫负调控机制对小鼠胶原诱导性关节炎(collagen-in-duced arthritis,CIA)的缓解作用.方法 将DBA/1J小鼠随机分为正常组、模型组、OMT组和地塞米松组,每组9只.采用胶原和佐剂等体积混合背部皮下多点注射诱导DBA/1J小鼠,构建CIA小鼠模型.OMT组和地塞米松组分别用氧化苦参碱和地塞米松进行腹腔注射,正常组注射同等剂量的生理盐水.采用实时荧光定量PCR(RT-qPCR)法检测脾淋巴细胞叉头样转录因子P3(forkhead box protein3,Foxp3)、细胞毒性T淋巴细胞相关蛋白-4(cytotoxic T-lymphocyte-associated protein-4,CTLA-4)和程序性死亡受体-1(programmed cell death protein-1,PD-1)的mRNA表达水平.采用苏木精-伊红染色法(hematoxylin-eosin staining,HE)观察关节滑膜组织的异位生发中心.采用免疫组织化学法和Western blot检测Foxp3及CTLA-4和PD-1的表达.结果 OMT可缓解CIA小鼠关节肿胀度并降低其关节评分,增加脾淋巴细胞和关节组织Foxp3及CTLA-4的表达,降低PD-1的表达(P均<0.05),并减少炎性细胞大面积浸润.结论 OMT可能经增加调节性(Foxp3+)T细胞CT-LA-4的表达但降低PD-1的表达而缓解RA.
非劣效性设计临床试验是一类检验试验组治疗手段是否不劣于对照组治疗手段的随机对照临床试验.本文简要介绍非劣效性设计临床试验的基本概念、设计要点及其与等效性和优效性设计临床试验的差异,并通过具体案例解读,帮助读者全面了解、实施和评价非劣效性设计方法.