Identifying hub genes in response to ustekinumab and the impact of ustekinumab treatment on fibrosis in Crohn's disease.

Introduction: Crohn's disease (CD) is a chronic inflammatory disease. Approximately 50% of patients with CD progressed from inflammation to fibrosis. Currently, there are no effective drugs for treating intestinal fibrosis. Biologic therapies for CD such as ustekinumab have benefited patients; however, up to 30% of patients with CD have no response to initial treatment, and the effect of ustekinumab on intestinal fibrosis is still uncertain. Therefore, it is of great significance to explore the predictive factors of ustekinumab treatment response and the effect of ustekinumab on intestinal fibrosis. Materials and methods: Public datasets-GSE207465 (blood samples) and GSE112366 and GSE207022 (intestinal samples)-were downloaded and analyzed individually (unmerged) based on the treatment response. Differentially expressed genes (DEGs) were identified by the "limma" R package and changes in immune cell infiltration were determined by the "CIBERSORT" R package in both blood and intestinal samples at week 0 (before treatment). To find predictive factors of ustekinumab treatment response, the weighted gene co-expression network analysis (WGCNA) R package was used to identify hub genes in GSE112366. Hub genes were then verified in GSE207022, and a prediction model was built by random forest algorithm. Furthermore, fibrosis-related gene changes were analyzed in ileal samples before and after treatment with ustekinumab. Results: (1) Our analysis found that MUC1, DUOX2, LCN2, and PDZK1IP1 were hub genes in GSE112366. GSE207022 revealed that MUC1 (AUC:0.761), LCN2 (AUC:0.79), and PDZK1IP1 (AUC:0.731) were also lower in the response group. Moreover, the random forest model was shown to have strong predictive capabilities in identifying responders (AUC = 0.875). To explore the relationship between intestinal tissue and blood, we found that ITGA4 had lower expression in the intestinal and blood samples of responders. The expression of IL18R1 is also lower in responders' intestines. IL18, the ligand of IL18R1, was also found to have lower expression in the blood samples from responders vs. non-responders. (2) GSE112366 revealed a significant decrease in fibrosis-related module genes (COL4A1, TUBB6, IFITM2, SERPING1, DRAM1, NAMPT, MMP1, ZEB2, ICAM1, PFKFB3, and ACTA2) and fibrosis-related pathways (ECM-receptor interaction and PI3K-AKT pathways) after ustekinumab treatment. Conclusion: MUC1, LCN2, and PDZK1IP1 were identified as hub genes in intestinal samples, with lower expression indicating a positive prediction of ustekinumab treatment response. Moreover, ITGA4 and IL18/IL18R1 may be involved in the treatment response in blood and intestinal samples. Finally, ustekinumab treatment was shown to significantly alter fibrotic genes and pathways.

Cyclosporine A alleviates colitis by inhibiting the formation of neutrophil extracellular traps via the regulating pentose phosphate pathway.

BACKGROUND: The aberrant formation of neutrophil extracellular traps (NETs) has been implicated in ulcerative colitis (UC), a chronic recurrent intestinal inflammation. Cyclosporine A (CsA) is now applied as rescue therapy for acute severe UC. In addition, it has been certained that CsA inhibits the formation of NETs in vitro and the mechanism of which was still vague. The study aimed to explore the mechanism CsA inhibits the NETs formation of colitis in vivo and in vitro. METHODS: NETs enrichment in clinical samples was analyzed using databases from Gene Expression Omnibus and verified in our center. Dextran sulfate sodium (DSS)-induced acute colitis mice model was used to investigate the effect of CsA on NETs of colonic tissue expression. To clarify the mechanism, intracellular energy metabolites were examined by Liquid Chromatograph Mass Spectrometer, and reactive oxygen species (ROS) levels were examined by fluorescence intensity in neutrophils treated with CsA after LPS stimulation. The transcriptional level and activity of G6PD of neutrophils were also assessed using qRT-PCR and WST-8. RNA Sequencing was used to detect differentially expressed genes of neutrophils stimulated by LPS with or without CsA. The expression levels of related proteins were detected by western blot. RESULTS: NETs enrichment was especially elevated in moderate-to-severe UC patients compared to HC. NETs expression in the colon from DSS colitis was decreased after CsA treatment. Compared with neutrophils stimulated by LPS, NETs formation and cellular ROS levels were decreased in LPS + CsA group. Cellular ribulose 5-phosphate and NADPH/NADP + related to the pentose phosphate pathway (PPP) were reduced in LPS + CsA group. In addition, CsA could decrease G6PD activity in neutrophils stimulated with LPS, and the results were further verified by inhibiting G6PD activity. At last, P53 protein was highly expressed in LPS + CsA group compared with the LPS group. Intracellular G6PD activity, ROS level and NETs formation, which were downregulated by CsA, could be reversed by a P53 inhibitor. CONCLUSION: Our results indicated CsA could alleviate the severity of colitis by decreasing the formation of NETs in vivo. In vitro, CsA reduced ROS-dependent NETs release via downregulating PPP and cellular ROS levels by decreasing G6PD activity directly by activating the P53 protein.

Release and impact of China's "Second List of Rare Diseases".

On September 18, 2023, the National Health Commission of China officially announced the "Second List of Rare Diseases". This list of 86 rare diseases, drafted in accordance with the "Working Procedures for Drafting the List of Rare Diseases", marks the second release of a rare disease list since the initial list was issued in May 2018. Following the release of the first batch, the Chinese Government introduced various policies to enhance the diagnosis and treatment of rare diseases, to promote the research on, development of, production of, and availability of rare disease medications in China, and to improve medication access for patients with rare diseases. Consequently, this has elevated the level of rare disease diagnosis and treatment, ensuring greater accessibility to treatment for affected individuals. The expansion of the rare disease list through the release of the "Second List of Rare Diseases" will further enhance rare disease management, increase awareness, improve diagnosis and treatment, facilitate the development and availability of more rare disease medications, establish a comprehensive support system for patients with rare diseases, and ultimately benefit a larger number of individuals affected by rare diseases. The definition of rare diseases in China should be refined by explicitly establishing corresponding criteria based on incidence, prevalence, or the number of affected individuals. Additionally, the mechanism for removal of diseases from rare disease lists should be enhanced, and prompt adjustments should be made regarding diseases that do not align with the selection principles of the list, taking into consideration environmental changes.

The initiation, exploration, and development of hospital-based health technology assessment in China: 2005 ‒ 2022.

A hospital-based health technology assessment (HB-HTA) can provide the evidence needed to inform clinical decisions at the administrative level. With the implementation of a new round of medical and health care system reforms in China, such as the abolition of medical mark-ups, adoption of modern hospital management systems, reform of diagnosis related groups (DRGs) payment, and performance evaluations for public hospitals, medical institutions increasingly need HB-HTA. The development of HB-HTA in China can be divided into three phases: An initiation phase (2005-2014), a preliminary exploratory phase (2015-2017), and a rapid development phase (2018-present). HB-HTA has been used to manage medical consumables, medical devices, and medicines, but there are still problems and challenges in terms of concept recognition, the mode of development, and limited professionals and data. To promote and use HB-HTA in developing countries, we have identifies the development paths and recommendations for implementation based on a case study in China, which can be summarized as follows: enhancing the top-level design of HB-HTA, formulating HB-HTA guidelines, further promoting the main ideas of HB-HTA, concentrating on the training of evaluation personnel, establishing an HB-HTA network and paying attention to the flexibility of HB-HTA in the application process, and multi- stakeholder participation.

Prognostic, Diagnostic, and Clinicopathological Significance of Circular RNAs in Pancreatic Cancer: A Systematic Review and Meta-Analysis.

Pancreatic cancer (PC) is a highly aggressive malignant tumor with a high mortality rate. It is urgent to find optimal molecular targets for the early diagnosis and treatment of PC. Here, we aimed to systematically analyze the prognostic, diagnostic, and clinicopathological significance of circular RNAs (circRNAs) in PC. Relevant studies were screened through PubMed, Web of Science, and other databases. The prognostic value of PC-associated circRNAs was assessed using the composite hazard ratio (HR), the diagnostic performance was assessed using the area under the summary receiver operator characteristic (SROC) curve (AUC), and the correlation with clinicopathological characteristics using the composite odds ratio (OR) was explored. In our study, 48 studies were included: 34 for prognosis, 11 for diagnosis, and 30 for correlation with clinicopathological characteristics. For prognosis, upregulated circRNAs were associated with poorer overall survival (OS) (HR = 2.02) and disease-free survival/progression-free survival (HR = 1.84) while downregulated circRNAs were associated with longer OS (HR = 0.55). Notably, the combination of circRNAs, including hsa_circ_0064288, hsa_circ_0000234, hsa_circ_0004680, hsa_circ_0071036, hsa_circ_0000677, and hsa_circ_0001460, was associated with worse OS (HR = 2.35). For diagnosis, the AUC was 0.83, and the pooled sensitivity and specificity were 0.79 and 0.73, respectively. For clinicopathologic characteristics, upregulated circRNAs were associated with poorer tumor differentiation, more nerve and vascular invasion, higher T stage, lymphatic metastasis, distant metastasis, advanced TNM stage, and higher preoperative CA19-9 level. In contrast, downregulated circRNAs were negatively associated with PC differentiation and lymphatic metastasis. Overall, our results showed that circRNAs are closely related to the prognosis and clinicopathological characteristics of PC patients and could be utilized for early diagnosis; thus, they are promising biomarkers for clinical application in PC.

Willingness to Pay for One Additional Quality Adjusted Life Year: A Population Based Survey from China.

OBJECTIVE: The aim of this study was to estimate the population's willingness to pay (WTP) for an additional quality-adjusted life-year (QALY) in China. METHODS: The WTP for an additional QALY (WTP/Q) was estimated using a contingent valuation survey with quota sampling and snowball sampling, using a pre-designed questionnaire with 18 hypothetical scenarios. The change in health state was depicted by the EQ-5D-5L. The questionnaires were completed by telephone and face-to-face interviews. Two-part regression models were used to test validity and how different factors affect WTP/Q. RESULTS: A total of 2008 people participated in this survey and provided 3265 WTP responses for further analysis. The average WTP/Q for the entire sample is 113,120 Renminbi (RMB) (USD 16,884), which is 1.75 times the gross domestic product (GDP) per capita. For the quality-of-life improvement scenarios, the mean WTP/Q is RMB 78,907 (USD 11,777, 1.22 times GDP per capita), which is significantly lower than the life extension scenarios (RMB 177,761, USD 26,531, 2.76 times GDP per capita). Age was found to be negatively related to positive WTP. Educational level was positively related to the probability of reporting positive WTP and the level of WTP/Q. Although the EQ-5D-5L utility scores of respondents did not prove to be statistically significant determinants of WTP/Q, the two dimensions of EQ-5D-5L, pain/discomfort and anxiety/depression, had an impact on WTP/Q. In addition, WTP/Q was higher when the health outcome had a 50% probability of occurring than when the health outcome was 100% certain. WTP/Q was higher when a lower health gain was presented to the respondent. CONCLUSION: This study provides empirical evidence of the monetary value of an additional QALY from a sample of the Chinese population. In addition, a higher threshold for end-of-life therapies should be considered.

Integrin ß1 in Pancreatic Cancer: Expressions, Functions, and Clinical Implications.

Pancreatic cancer (PC) is characterized by rapid progression and a high mortality rate. The current treatment is still based on surgical treatment, supplemented by radiotherapy and chemotherapy, and new methods of combining immune and molecular biological treatments are being explored. Despite this, the survival rate of PC patients is still very disappointing. Therefore, clarifying the molecular mechanism of PC pathogenesis and developing precisely targeted drugs are key to improving PC prognosis. As the most common ß subunit of the integrin family, integrin ß1 has been proved to be closely related to the vascular invasion, distant metastasis, and survival of PC patients, and treatment targeting integrin ß1 in PC has gained initial success in animal models. In this review, we summarize the various signaling pathways by which integrins are involved in PC, focusing on the roles of integrin ß1 in the malignant behaviors of PC. Additionally, recent studies regarding the feasibility of integrin ß1 as a diagnostic and prognostic biomarker in PC are also discussed. Finally, we present the progress of several integrin ß1-based clinical trials to highlight the potential of integrin ß1 as a target for personalized therapy in PC.

α7 nicotinic acetylcholine receptor agonist GTS-21 attenuates DSS-induced intestinal colitis by improving intestinal mucosal barrier function.

BACKGROUND AND AIMS: Cholinergic output, which could modulate innate immune responses through stimulation of α7 nicotinic acetylcholine receptor (α7nAChR), might be a target to minimize tissue damage in autoimmune disease. GTS-21, a selective α7nAChR agonist, has previously demonstrated to inhibit synovium inflammation in rheumatoid arthritis. In this study, we investigated the effect of GTS-21 on dextran sulfate sodium (DSS)-induced colitis model and its potential mechanism. METHODS: Male BABL/c mice (n = 32) were randomly divided into four groups: normal control group, DSS-induced colitis group, GTS-21 treatment with or without α7nAChR antagonist α-BGT treatment group. Disease activity index (DAI), histological activity index (HAI) and colonic macroscopic damage were evaluated. Fluorescein isothiocyanate (FITC)-dextran assay was applied to measure intestinal permeability. The expressions of tight junction (TJ) proteins and NF-κB associated proteins were detected by Western blot. RESULTS: GTS-21 could decrease DAI scores, HAI scores, intestinal permeability and reduce the intestinal bacterial translocation in DSS-induced colitis group, whereas α7nAChR antagonist α-BGT could impair this protective influence. The expressions of TJ proteins were increased with administration of GTS-21 both in vivo and in vitro. Furthermore, GTS-21 also inhibited the NF-қB activation in intestinal epithelial cells and colitis model, while α-BGT reversed the inhibitory effect. CONCLUSION: The α7nAChR agonist GTS-21 attenuated DSS-induced colitis through increasing expressions of TJ proteins in colon tissues and improved intestinal barrier function, which might be due to  modulating NF-қB activation in intestinal epithelial cells.

Long Non-Coding RNAs in Pancreatic Cancer: Biologic Functions, Mechanisms, and Clinical Significance.

Despite tremendous efforts devoted to research in pancreatic cancer (PC), the mechanism underlying the tumorigenesis and progression of PC is still not completely clear. Additionally, ideal biomarkers and satisfactory therapeutic strategies for clinical application in PC are still lacking. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) might participate in the pathogenesis of diverse cancers, including PC. The abnormal expression of lncRNAs in PC is considered a vital factor during tumorigenesis that affects tumor cell proliferation, migration, invasion, apoptosis, angiogenesis, and drug resistance. With this review of relevant articles published in recent years, we aimed to summarize the biogenesis mechanism, classifications, and modes of action of lncRNAs and to review the functions and mechanisms of lncRNAs in PC. Additionally, the clinical significance of lncRNAs in PC was discussed. Finally, we pointed out the questions remaining from recent studies and anticipated that further investigations would address these gaps in knowledge in this field.

Aryl hydrocarbon receptor activation ameliorates experimental colitis by modulating the tolerogenic dendritic and regulatory T cell formation.

BACKGROUND: Intestinal immune dysfunction is involved in the onset of Crohn's disease (CD). Dendritic cells (DCs), antigen-presenting cells, play a key role in the maintenance of intestinal immune homeostasis. The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor widely expressed in various immune cells, including DCs. Although AhR plays an important role in immune tolerance, its role in the DCs is unclear. The purpose of this study was to investigate whether the activation of AhR can induce tolerogenic DCs (tolDCs) and the differentiation of regulatory T (Treg) cells, as well as ameliorate experimental colitis. RESULTS: AhR activation in the DCs resulted in a lower expression of surface markers such as CD80, CD83, CD86, and pro-inflammatory cytokine production, and higher anti-inflammatory production (IL-1ß, IL-23, and IL-12) compared to the control DCs. The surface dendrites in DCs were significantly reduced following AhR activation by 6-formylindolo [3,2-b]carbazole (FICZ). Such DCs with FICZ-mediated activation of AhR, namely tolDCs, promoted Treg cell differentiation. Adoptive transfer of tolDCs to a TNBS-induced colitis mouse model significantly alleviated the severity of inflammation by improving the colon length and decreasing the disease activity index (DAI) and histopathological score. Moreover, the transferred tolDCs decreased the frequency of Th17 cells and increased the frequency of Treg cells in the spleen and mesenteric lymph nodes (MLNs) in murine colitis models. CONCLUSIONS: Activation of AhR in the DCs could induce tolDCs, and the transplantation of tolDCs may help in relieving intestinal inflammation and maintaining the Th17/Treg differentiation balance. Thus, our data suggest that AhR may be a potential therapeutic target for CD.

Intestinal Ultrasound for Differentiating Fibrotic or Inflammatory Stenosis in Crohn's Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Intestinal ultrasound [IUS] has been increasingly reported to distinguish inflammatory or fibrotic intestinal stenosis in Crohn's disease [CD] patients. However, the diagnostic value is unclear. This systematic review and meta-analysis aimed to assess the diagnostic role of different modes of IUS parameters. METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Library from inception to August 2021. Regarding effect sizes, weighted mean differences [WMDs] or standardised mean differences [SMDs] were used. We pooled data using a random-effects or fixed-effects model according to heterogeneity. The diagnostic accuracy of IUS for distinguishing fibrosis was pooled. RESULTS: A total of 19 studies were retained for qualitative analysis, and 14 were included in the meta-analysis [with 511 total subjects and 635 bowel segments]. In patients with fibrotic stenosis, the pooled WMDs for bowel wall thickness were 1.30 mm (95% confidence interval [CI]: 0.69-1.91) thicker than in patients with inflammatory stenosis, and the pooled SMDs for strain value and strain ratio were 0.80 [95% CI: 0.41-1.20] and 1.08 [95% CI: 0.55-1.60] harder than in patients with inflammatory stenosis, respectively. The percentage of maximal enhancement of fibrotic stenosis was lower than that of inflammatory stenosis [WMD -10.03; 95% CI: -17.91- -2.16]. The diagnostic accuracy of IUS was not performed because only a few studies provided relevant diagnostic indicators, and these studies used different modes and parameters. CONCLUSIONS: IUS currently is inaccurate to differentiate fibrotic or inflammatory stenosis in CD patients, and more studies assessing the significance of each parameter and its cut-off value in different modes of IUS are needed to be conducted in the future.

A systematic review and meta-regression of studies eliciting willingness-to-pay per quality-adjusted life year in the general population.

OBJECTIVES: From the demand-side perspective, the monetary value of one additional quality-adjusted life year (QALY) is estimated as willingness-to-pay per QALY (WTPQ). This study aims to summarize the methods and contexts of elicitation of willingness-to-pay per quality-adjusted life year (WTPQ) in the general population and to investigate the heterogeneity of WTPQ estimates. METHODS: Meta-regression analysis was conducted using Comprehensive Meta-Analysis Software. Sensitivity analyses were undertaken by replacing the lowest and highest 5% and 2.5% of WTPQ by percentiles. RESULTS: 33 studies with 102 WTPQ estimates were included. The overall mean and median WTPQ estimates are $1,280,002 and $44,072, respectively. The meta-regressions demonstrated that types of health gain (quality of life or life length) and certainty of health outcomes are statistically significant factors. Furthermore, compared with online interviews, face-to-face interviews tend to yield lower WTPQ. Moreover, the declining trend of QALY gains and positive effect with statistical significance of the sample age were also noticed. CONCLUSION: For valid and representative values of WTPQ, future researchers should therefore take into consideration various scenarios and investigate both health gain with certainty and uncertainty, health gain from both life length and quality of life, and different size of QALY gains.

Elevated Levels of IL-27 Are Associated with Disease Activity in Patients with Crohn's Disease.

Immune disorders play an important role in the pathogenesis of Crohn's disease (CD). Notably, the increased immune response of Th1 cells and related cytokines is associated with the onset of CD. IL-27 is a newly discovered IL-12-related cytokine, but its expression and clinical significance in CD patients are still controversial. This study is aimed at evaluating the serum levels of IL-27 in CD patients and analyzing their clinical significance. The results indicated that serum levels of IL-27 in CD patients were significantly higher than those in control subjects (median (interquartile range (IQR)): 110.0 (95.0, 145.0) vs. 85.0 (80.0, 95.0) pg/ml, P < 0.001). Furthermore, the IL-27 levels significantly increased in CD patients at the active stage compared with CD patients in remission (CDR) (127.5 (100.0, 150.0) vs. 90 (80.0, 110.0) pg/ml, P < 0.001). However, there was no difference in IL-27 levels between CDR and control subjects. The levels of IL-27 were positively correlated with Crohn's disease activity index (CDAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin (FC), and Simple Endoscopic Score for Crohn's Disease (SES-CD) and negatively correlated with hemoglobin (Hb) and serum albumin (ALB). IL-27 combined with CRP favored the prediction of CD activity (area under the curve (AUC): 0.88). Additionally, the proportions of Th17 and Th1 cells in peripheral blood were higher in CD patients than in control subjects. Active CD patients exhibited significantly higher proportions of Th17 and Th1 cells than those in remission. Moreover, correlation analysis indicated that the serum levels of IL-27 were positively associated with the frequency of Th17 cells in CD patients (r = 0.519, P = 0.013) but not associated with the frequency of Th1 cells in CD patients. IL-27 is positively associated with multiple inflammation indicators and may exert a proinflammatory profile by regulating Th17 cell differentiation in the development of Crohn's disease. In the future, IL-27 combined with CRP is expected to become an important biological marker of CD activity.

Fecal microbiota profiling in irritable bowel syndrome and inflammatory bowel disease patients with irritable bowel syndrome-type symptoms.

BACKGROUND: The intestinal microbiota is thought to be involved in the occurrence of inflammatory bowel disease in remission with irritable bowel syndrome (IBS)-type symptoms, but the specific distinct profile of these bacteria remains unclear. This cross-sectional study aims to investigate the fecal microbiota profiling in patients with these diseases. METHODS: Fecal samples from 97 subjects, including Crohn's disease patients in remission with IBS-type symptoms (CDR-IBS+) or without IBS-type symptoms (CDR-IBS-), ulcerative colitis patients in remission with IBS-type symptoms (UCR-IBS+) or without IBS-type symptoms (UCR-IBS-), IBS patients and healthy controls, were collected and applied 16S ribosomal DNA (rDNA) gene sequencing. The V4 hypervariable regions of 16S rDNA gene were amplified and sequenced by the Illumina MiSeq platform. The differences in the sample diversity index in groups were analyzed with R software. RESULTS: The richness of the intestinal microbiota in the CDR-IBS group was markedly lower than those in the control and IBS groups based on the analysis of observed species and the Chao index (P < 0.05). The observed species index in the CDR-IBS+ group was higher than that in the CDR-IBS- group (median index: 254.8 vs 203, P = 0.036). No difference was found in alpha diversity between UCR patients with IBS-type symptoms and those without related symptoms. At the genus level, the number of Faecalibacterium in CDR patients with IBS-type symptoms increased significantly, while Fusobacterium decreased versus those without such symptoms (mean relative abundance of Faecalibacterium: 20.35% vs 5.18%, P < 0.05; Fusobacterium: 1.51% vs 5.2%, P < 0.05). However, compared with the UCR-IBS- group, the number of Faecalibacterium in the UCR-IBS+ group decreased, while the number of Streptococcus increased, but there was no significant difference in the genus structure. The abundance and composition of the microbiota of IBS patients were not distinct from those of healthy controls. CONCLUSIONS: The IBS-type symptoms in CD patients in remission may be related to an increase in Faecalibacterium and a decrease in Fusobacterium. The IBS-type symptoms in UC patients in remission cannot be explained by changes in the abundance and structure of the intestinal microbiota.

Faecalibacterium prausnitzii Attenuates DSS-Induced Colitis by Inhibiting the Colonization and Pathogenicity of Candida albicans.

SCOPE: Intestinal commensal microbiota interactions play critical roles in the inflammatory bowel disease (IBD) development. Candida albicans (CA) can aggravate intestinal inflammation; however, whether Faecalibacterium prausnitzii (FP) can antagonize CA is unknown. METHODS AND RESULTS: CA are co-cultured with bacteria (FP and Escherichia coli (EC)), bacterial supernatant, and bacterial medium, respectively. Then, the CA hyphae-specific genes' expression and CA cells' morphology are investigated. The Nod-like receptor pyrin-containing protein 6 (NLRP6) inflammasome, inflammatory cytokines, and antimicrobial peptides (AMPs) production are evaluated in intestinal epithelial cells pre-treated with bacteria, bacterial med, and bacterial supernatant and exposed without or with CA. Both bacteria significantly prohibit CA numbers, while only FP and FP supernatant prohibit the transformation and virulence factors (extracellular phospholipase, secreted aspartyl proteinase, and hemolysin) secretion of CA in a co-culture system compared with media controls. Further, FP and FP supernatant promote the production of the NLRP6 inflammasome, interleukin (IL)-1ß, IL-18, and antibacterial peptides (ß-defensin (BD)-2 and BD-3) and inhibit in vitro and in vivo CA growth and pathogenicity, and alleviate DSS-colitis in mice, while EC do not show the similar effect. CONCLUSION: FP improve intestinal inflammation by inhibiting CA reproduction, colonization, and pathogenicity and inducing AMP secretion in the gut. This study uncovers new relationships between intestinal microbes and fungi in IBD patients.

Comparing the monetary value of a quality-adjusted life year from the payment card and the open-ended format.

BACKGROUND: The payment card (PC) format and the open-ended (OE) format are common methods in eliciting willingness-to-pay (WTP) of one additional quality-adjusted life year (QALY). The aim of this research is to compare these two formats in eliciting the monetary value of a QALY. METHODS: A contingent valuation survey was carried out using a pre-designed questionnaire with various hypothetical scenarios. The difference between the PC and the OE formats was evaluated by a two-sample equality test. Furthermore, generalized linear models were carried out to control observed heterogeneity and to test theoretical validity. RESULTS: In total, 461 individuals were involved, among whom 235 (51%) answered the PC question, while 226 (49%) answered the OE question. Excluding zero response, the mean WTP values of these two formats for different scenarios varied dramatically, which was from 13,278 to 280,177 RMB for the PC, 18,119 to 620,913 RMB for the OE. The OE format tended to elicit lower values for less serious condition and higher values for more serious condition. However, equality test of mean and median demonstrated insignificant difference of these two formats for all scenarios. For both OE and PC format, most variables were found to have significant effect on the value of WTP/QALY. Moreover, joint estimation indicated a statistically significant positive effect on the OE results. Further analysis demonstrated that the imbalanced zero response distribution caused the main difference of these two formats. CONCLUSIONS: This research indicated insignificantly different WTP/QALY estimates of the PC format and OE format with the grouped data whereas significantly higher estimates of the OE format from the pooled data. These two formats were found to be valid. More research about the difference and the validity of various WTP eliciting methods would be recommended for a robust estimation of WTP/QALY.

Characterization of fungal and bacterial dysbiosis in young adult Chinese patients with Crohn's disease.

Intestinal microbiota dysbiosis has been described in inflammatory bowel disease (IBD), but data from China are limited. In this study, we performed molecular analysis of the fecal microbial community from 20 healthy Chinese subjects and 25 patients with Crohn's disease (CD), and evaluated associations with bacterial and fungal compositions. Decreased richness and diversity of bacterial composition was observed in the CD group compared with healthy (H) subjects. Significant structural differences in bacterial (but not fungal) composition among healthy controls and CD patients were found. A reduction in Firmicutes and Actinobacteria abundance, and overrepresentation of Proteobacteria were observed in the CD patients compared with the H group. The Escherichia-Shigella genus was overrepresented in the CD group, whereas Faecalibacterium, Gemmiger, Bifidobacterium, Romboutsia, Ruminococcus, Roseburia, and Fusicatenibacter abundance were decreased in the CD group compared with H subjects. Differences in fungal microbiota between the H and CD groups were observed at the genus rather than at the phylum level. The Candida genus was overrepresented in the CD (active disease) group compared with the H group, whereas no difference between CD (remission) and H groups was observed. Aspergillus, unclassified_Sordariomycetes, and Penicillium genera had greater representation in the H subjects compared with the CD group. Bacterial and fungal intra- and inter-kingdom correlations were observed between the H and CD groups. Therefore, fecal bacterial and fungal microbiome communities differed considerably between H and CD patients, and between Chinese and Western populations. The role of gut microbiota in homeostasis and in gastrointestinal disorders should be investigated further.

A head-to-head comparison of EQ-5D-5 L and SF-6D in Chinese patients with low back pain.

BACKGROUND: The comparative performance of the 3-level EuroQol 5-dimension and Short Form 6-dimension (SF-6D) has been investigated in patients with low back pain (LBP). The aim of this study was to explore the performance including agreement, convergent validity as well as known-groups validity of the 5-level EuroQol 5-dimension (EQ-5D-5 L) and SF-6D in Chinese patients with LBP. METHODS: Individuals with LBP were recruited from a large tertiary hospital in China. All subjects were interviewed using a standardized questionnaire including the EQ-5D-5 L, 36-item Short Form Health Survey (SF-36), the Oswestry questionnaire and socio-demographic questions from June 2017 to October 2017. Agreement was evaluated by intra-class correlation coefficients (ICCs) and Bland-Altman plots. Spearman's rank correlation coefficients were applied to assess convergent validity. For known-groups validity, the Mann-Whitney U test or Kruskal-Wallis H test were used, effect size (ES) and relative efficiency (RE) were also reported. The efficiency of detecting clinically relevant differences was measured by receiver operating characteristic (ROC) curves between pre-specified groups based on Oswestry disability index (ODI), ES and RE statistics were also reported. RESULTS: Two hundred seventy-two LBP patients (age 38.1, 38% female) took part in the study. Agreement between the EQ-5D-5 L and the SF-6D was good (ICC 0.661) but with systematic discrepancy in the Bland-Altman plots. In terms of convergent validity, most priori assumptions were more related to EQ-5D-5 L than SF-6D, but MCS derived from SF-36 was more associated with SF-6D. EQ-5D-5 L demonstrated better performance for most groups except location and general health grouped by the general assessment of health item from SF-36. Furthermore, when we applied ODI as external indicator of health status, the area under the ROC curve for EQ-5D-5 L was larger than that for the SF-6D (0.892, 95% CI 0.853 to 0.931 versus 0.822, 95% CI 0.771 to 0.873), the effect size was 0.63 for EQ-5D-5 L and 0.44 for SF-6D, and it was proved that EQ-5D-5 L was 42% more efficient than SF-6D at detecting differences measured by ODI. CONCLUSIONS: Both EQ-5D-5 L and SF-6D are valid measures for LBP patients. Even though these two measures had good agreement, they cannot be used interchangeably. The EQ-5D-5 L was superior to the SF-6D in Chinese low back pain patients in this research, with stronger correlation to ODI and better known-groups validity. Further study needs to evaluate other factors, such as responsiveness and reliability.

China issues the National Essential Medicines List (2018 edition): Background, differences from previous editions, and potential issues.

On October 25, 2018, the National Health Commission of China issued the National Essential Medicines List (2018 edition) [NEML (2018)]. The NEML (2018) contains 685 drugs, which consist of 417 chemicals and biological products and 268 Chinese patent medicines. Compared to the 2012 version of the NEML, a total number of 165 drugs were added, representing an increase of 31.7%. The biggest increase (90.9%) is in Chinese patent medicines for surgical use. The NEML (2018) set up the category of pediatric medications for the first time, and 11 cancer drugs were added. The NEML (2018) is characterized by: "basic" to "comprehensive" coverage, it includes both Chinese and Western medicines, it now includes pediatric drugs, and more cancer drugs have been added. There are several issues with the new NEML such as the link between the essential medicines system and the medical insurance system and establishment of firm support for implementation.

An investigation of the PM2.5 and NO2 concentrations and their human health impacts in the metro subway system of Suzhou, China.

This study measured the particle concentrations with an aerodynamic diameter smaller than 2.5 µm (PM2.5), nitrogen dioxide (NO2), and relative humidity (RH) at five metro subway stations in Suzhou's subway system (Lines 1 and 2). The real-time monitoring campaign was conducted from March 30th to April 10th and August 4th to August 21st, 2015. The monitoring practice was carried out during rush (7:00-9:00 AM and 17:00-19:00 PM) and regular hours (other times) at the ground and underground levels under different weather conditions with a purpose of obtaining representative data. The monitored results show that the concentrations of PM2.5 in the train carriages were lower than the concentrations at the underground platforms during both spring and summer. The mean PM2.5 concentrations at all the underground platforms in all the sub-stations monitored were significantly higher than those at the ground level. The human health impact was calculated to be 6300 annual DALYs (or 375 deaths) due to exposure to the subway system in Suzhou according to the UNEP-SETAC toxicity (USEtox) model. Linear regression models were applied to evaluate the relationships between the PM2.5, NO2 concentrations, and RH. We found that a 10% increment in RH from the current average level of 50-60% can lead to a 9.8 µg m-3 concentration decrease in PM2.5. This further results in the total human health impact being reduced to 2451 DALYs (150-4753 DALYs), representing a 20% decrease (1.2-38%).