Composite patch with negative Poisson's ratio mimicking cardiac mechanical properties: Design, experiment and simulation.

Developing patches that effectively merge intrinsic deformation characteristics of cardiac with superior tunable mechanical properties remains a crucial biomedical pursuit. Currently used traditional block-shaped or mesh patches, typically incorporating a positive Poisson's ratio, often fall short of matching the deformation characteristics of cardiac tissue satisfactorily, thus often diminishing their repairing capability. By introducing auxeticity into the cardiac patches, this study is trying to present a beneficial approach to address these shortcomings of the traditional patches. The patches, featuring the auxetic effect, offer unparalleled conformity to the cardiac complex mechanical challenges. Initially, scaffolds demonstrating the auxetic effect were designed by merging chiral rotation and concave angle units, followed by integrating scaffolds with a composite hydrogel through thermally triggering, ensuring excellent biocompatibility closely mirroring heart tissue. Tensile tests revealed that auxetic patches possessed superior elasticity and strain capacity exceeding cardiac tissue's physiological activity. Notably, Model III showed an equivalent modulus ratio and Poisson's ratio closely toward cardiac tissue, underscoring its outstanding mechanical potential as cardiac patches. Cyclic tensile loading tests demonstrated that Model III withstood continuous heartbeats, showcasing outstanding cyclic loading and recovery capabilities. Numerical simulations further elucidated the deformation and failure mechanisms of these patches, leading to an exploration of influence on mechanical properties with alternative design parameters, which enabled the customization of mechanical strength and Poisson's ratio. Therefore, this research presents substantial potential for designing cardiac auxetic patches that can emulate the deformation properties of cardiac tissue and possess adjustable mechanical parameters.

Hydrogels composite optimized for low resistance and loading-unloading hysteresis for flexible biosensors.

With the advancement of wearable and implantable medical devices, hydrogel flexible bioelectronic devices have attracted significant interest due to exhibiting tissue-like mechanical compliance, biocompatibility, and low electrical resistance. In this study, the development and comprehensive performance evaluation of poly(acrylic acid)/ N,N'-bis(acryloyl) cystamine/ 1-butyl-3-ethenylimidazol-1-ium:bromide (PAA/NB/IL) hydrogels designed for flexible sensor applications are introduced. Engineered through a combination of physical and chemical cross-linking strategies, these hydrogels exhibit strong mechanical properties, high biocompatibility, and effective sensing capabilities. At 95 % strain, the compressive modulus of PAA/NB/IL 100 reach up to 3.66 MPa, with the loading-unloading process showing no significant hysteresis loop, indicating strong mechanical stability and elasticity. An increase in the IL content was observed to enlarge the porosity of the hydrogels, thereby influencing their swelling behavior and sensing functionality. Biocompatibility assessments revealed that the hemolysis rate was below 5 %, ensuring their suitability for biomedical applications. Upon implantation in rats, a minimal acute inflammatory response was observed, comparable to that of the biocompatibility control poly(ethylene glycol) diacrylate (PEGDA). These results suggest that PAA/NB/IL hydrogels hold promise as biomaterials for biosensors, offering a balance of mechanical integrity, physiological compatibility, and sensing sensitivity, thereby facilitating advanced healthcare monitoring solutions.

Degradable biomedical elastomers: paving the future of tissue repair and regenerative medicine.

Degradable biomedical elastomers (DBE), characterized by controlled biodegradability, excellent biocompatibility, tailored elasticity, and favorable network design and processability, have become indispensable in tissue repair. This review critically examines the recent advances of biodegradable elastomers for tissue repair, focusing mainly on degradation mechanisms and evaluation, synthesis and crosslinking methods, microstructure design, processing techniques, and tissue repair applications. The review explores the material composition and cross-linking methods of elastomers used in tissue repair, addressing chemistry-related challenges and structural design considerations. In addition, this review focuses on the processing methods of two- and three-dimensional structures of elastomers, and systematically discusses the contribution of processing methods such as solvent casting, electrostatic spinning, and three-/four-dimensional printing of DBE. Furthermore, we describe recent advances in tissue repair using DBE, and include advances achieved in regenerating different tissues, including nerves, tendons, muscle, cardiac, and bone, highlighting their efficacy and versatility. The review concludes by discussing the current challenges in material selection, biodegradation, bioactivation, and manufacturing in tissue repair, and suggests future research directions. This concise yet comprehensive analysis aims to provide valuable insights and technical guidance for advances in DBE for tissue engineering.

Insomnia and creativity in Chinese adolescents: mediation through need for cognition.

BACKGROUND: Creativity is an essential cognitive ability that plays a crucial role in advanced thinking. While previous research has demonstrated the impact of insomnia on cognitive function, its effects on creativity in Chinese adolescents remain unclear. This study explored the relationship between insomnia (specifically, daytime and nighttime disturbances) and creativity in adolescents. Additionally, it examined the potential mediating effect of the need for cognition on this relationship. METHODS: Questionnaires were administered to 302 adolescents to measure their creativity, need for cognition, and insomnia levels using the Williams Creative Tendencies Scale, Need for Cognition Scale, and Bergen Insomnia Scale, respectively. Regression analysis was conducted to examine the direct impact of insomnia on creativity. Furthermore, a mediation model was constructed to investigate the role of the need for cognition in mediating the relationship between insomnia and creativity. RESULTS: The findings of the present study indicated that insomnia had a direct impact on the creativity of adolescents, demonstrating a time-of-day effect. Daytime disturbances were found to have a positive correlation with overall creativity and imagination, whereas no significant direct effect was found between nighttime disturbances and creativity. Further analysis revealed that insomnia, specifically daytime disturbances, might influence creativity by affecting the individual's need for cognition. However, no similar indirect effects were observed for the relationship between nighttime disturbances and creativity. CONCLUSIONS: Our findings indicate that adolescents might experience improved creativity as a result of daytime disruptions, and the level of need for cognition could play a crucial role in understanding the link between insomnia and creativity in adolescents.

Survival analysis and clinicopathological features of patients with stage IA lung adenocarcinoma.

Background: With the development of medical technology and change of life habits, early-stage lung adenocarcinoma (LUAD) has become more common. This study aimed to systematically analyzed clinicopathological factors associated to the overall survival (OS) of patients with Stage IA LUAD. Methods: A total of 5942 Stage IA LUAD patients were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier methods and log-rank tests were used to compare the differences in OS. A nomogram constructed based on the Cox regression was evaluated by Concordance index (C index), calibration curve, decision curve analysis (DCA) and area under curve (AUC). And 136 patients were recruited from Shandong Province Hospital for external validation. Results: Cox analysis regression indicated that 12 factors, such as Diagnosis to Treatment Interval (DTI) and Income Level, were independent prognostic factors and were included to establish the nomogram. The C-index of our novel model was 0.702, 0.724 and 0.872 in the training, internal and external validation cohorts, respectively. The 3-year and 5-year survival AUCs and calibration curves showed excellent agreement in each cohort. Some new factors in the SEER database, including DTI and Income Level, were firstly confirmed as independent prognostic factors of Stage IA LUAD patients. The distribution of these factors in the T1a, T1b, and T1c subgroups differed and had different effects on survival. Conclusion: We summarized 12 factors that affect prognosis and constructed a nomogram to predict OS of Stage IA LUAD patients who underwent operation. For the first time, new SEER database parameters, including DTI and Income Level, were proved to be survival-related.

Identifying the critical oncogenic mechanism of LDHA based on a prognostic model of T-cell synthetic drivers.

BACKGROUND: Despite its early success, immunotherapy focused on removing T-cell inhibition does not achieve the desired effect in most patients. New strategies that target antigen-driven T-cell activation are needed to improve immunotherapy outcomes. However, a comprehensive analysis of synthetic drivers of T-cells is greatly lacking in lung adenocarcinoma (LUAD) and other types of tumors. METHODS: We comprehensively evaluated the patterns of LUAD patients based on T -cell synthetic drivers by unsupervised clustering analysis. A risk model was constructed using Lasso Cox regression analysis. The predicted survival and immunotherapy efficacy of the model was validated by independent cohorts. Finally, single-cell sequencing analysis, and a series of in vitro experiments were conducted to explore the role of lactate dehydrogenase A (LDHA) in the malignant progression of LUAD. RESULTS: Patients in the high-risk group were characterized by survival disadvantage, a "cold" immune phenotype, and by not having benefitted from immunotherapy. LDHA was shown to promote LUAD cell proliferation, cell cycle, invasion, and migration. Secondly, we found that LDHA induced NF-κB pathway activation, tyrosine kinase inhibitor resistance and immunosuppressant microenvironment. Finally, LDHA was found to be highly expressed in fibroblasts, which may be involved in promoting TKI resistance and mediating the immune escape. CONCLUSION: This study revealed that the T-cell synthetic driver-associated prognostic model developed herein significantly predicted prognosis and immunotherapy efficacy in LUAD. We further investigated the role of LDHA in the malignant phenotype of tumor cells and tumor microenvironment remodeling, providing a promising and novel therapeutic strategy for LUAD.

Cezanne promoted autophagy through PIK3C3 stabilization and PIK3C2A transcription in lung adenocarcinoma.

Osimertinib is a promising approved third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for treating patients with lung adenocarcinoma (LUAD) harboring EGFR-activating mutations, however, almost all patients develop resistance to Osimertinib eventually limiting the long-term efficacy. Autophagy is a vital cellular recycling process promoting Osimertinib resistance. Identifying accurate and efficient autophagy-regulatory factors is of great significance in reducing Osimertinib resistance. This study identified Cezanne, a member of the ovarian tumor protease (OTU)-deubiquitinating family, as an autophagy regulator. Cezanne was highly expressed in Osimertinib-resistant cells, and Cezanne overexpression promoted Osimertinib resistance, while chloroquine (CQ), an autophagy inhibitor, reverted this process. In the Cezanne-overexpressing cells, autophagy was activated even in the absence of autophagy inducers rapamycin and Earle's Balanced Salt Solution (EBSS). Further study showed that Cezanne stabilized PIK3C3 by deubiquitinating K48-linked ubiquitination at Lysine 322. Surprisingly, as a compensatory mechanism of PI3P generation, PIK3C2A was shown to be upregulated by Cezanne by promoting its transcription in a POLR2A-dependent way. Based on these results, Cezanne also accelerates EGFR recycling which may explain the mechanism mediating Cezanne expression and Osimertinib resistance. In conclusion, this study establishes a new model connecting Cezanne, autophagy, and Osimertinib resistance, opening new avenues to explore the effect of Cezanne and autophagy in LUAD.

CD70 is a therapeutic target upregulated in EMT-associated EGFR tyrosine kinase inhibitor resistance.

Effective therapeutic strategies are needed for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations that acquire resistance to EGFR tyrosine kinase inhibitors (TKIs) mediated by epithelial-to-mesenchymal transition (EMT). We investigate cell surface proteins that could be targeted by antibody-based or adoptive cell therapy approaches and identify CD70 as being highly upregulated in EMT-associated resistance. Moreover, CD70 upregulation is an early event in the evolution of resistance and occurs in drug-tolerant persister cells (DTPCs). CD70 promotes cell survival and invasiveness, and stimulation of CD70 triggers signal transduction pathways known to be re-activated with acquired TKI resistance. Anti-CD70 antibody drug conjugates (ADCs) and CD70-targeting chimeric antigen receptor (CAR) T cell and CAR NK cells show potent activity against EGFR TKI-resistant cells and DTPCs. These results identify CD70 as a therapeutic target for EGFR mutant tumors with acquired EGFR TKI resistance that merits clinical investigation.

IL6 Mediates Suppression of T- and NK-cell Function in EMT-associated TKI-resistant EGFR-mutant NSCLC.

PURPOSE: Patients with advanced non-small cell lung cancer (NSCLC) harboring activating EGFR mutations are initially responsive to tyrosine kinase inhibitors (TKI). However, therapeutic resistance eventually emerges, often via secondary EGFR mutations or EGFR-independent mechanisms such as epithelial-to-mesenchymal transition. Treatment options after EGFR-TKI resistance are limited as anti-PD-1/PD-L1 inhibitors typically display minimal benefit. Given that IL6 is associated with worse outcomes in patients with NSCLC, we investigate whether IL6 in part contributes to this immunosuppressed phenotype. EXPERIMENTAL DESIGN: We utilized a syngeneic genetically engineered mouse model (GEMM) of EGFR-mutant NSCLC to investigate the effects of IL6 on the tumor microenvironment and the combined efficacy of IL6 inhibition and anti-PD-1 therapy. Corresponding in vitro studies used EGFR-mutant human cell lines and clinical specimens. RESULTS: We identified that EGFR-mutant tumors which have oncogene-independent acquired resistance to EGFR-TKIs were more mesenchymal and had markedly enhanced IL6 secretion. In EGFR-mutant GEMMs, IL6 depletion enhanced activation of infiltrating natural killer (NK)- and T-cell subpopulations and decreased immunosuppressive regulatory T and Th17 cell populations. Inhibition of IL6 increased NK- and T cell-mediated killing of human osimertinib-resistant EGFR-mutant NSCLC tumor cells in cell culture. IL6 blockade sensitized EGFR-mutant GEMM tumors to PD-1 inhibitors through an increase in tumor-infiltrating IFNγ+ CD8+ T cells. CONCLUSIONS: These data indicate that IL6 is upregulated in EGFR-mutant NSCLC tumors with acquired EGFR-TKI resistance and suppressed T- and NK-cell function. IL6 blockade enhanced antitumor immunity and efficacy of anti-PD-1 therapy warranting future clinical combinatorial investigations.

Magnetic compression anastomosis for sigmoid stenosis treatment: A case report.

BACKGROUND: Endoscopic balloon dilation is a minimally invasive treatment for colorectal stenosis. Magnetic compression anastomosis can be applied against gastrointestinal anastomosis. When combined with endoscopy, it offers a unique approach to the recanalization of colorectal stenosis. CASE SUMMARY: We have reported here the case of a 53-year-old female patient who underwent a descending colostomy due to sigmoid obstruction. Postoperative fistula restoration was not possible in her due to sigmoid stenosis. Accordingly, endoscopic-assisted magnetic compression anastomosis for sigmoid stenosis was performed, and the sigmoid stenosis was recanalized 15 d after the surgery. Subsequently, a reduction colostomy was successfully performed after 10 d. CONCLUSION: This case report proposes a novel minimally invasive treatment approach for colorectal stenosis.

AZD4547 and the Alleviation of Hepatoma Cell Sorafenib Resistance via the Promotion of Autophagy.

BACKGROUND: This study is part of a larger research effort to explore the molecular mechanism of hepatocellular carcinoma, reduce drug resistance and seek new targets. OBJECTIVE: The objective of this study is to investigate the effect and mechanism of fibroblast growth factor receptor inhibitor AZD4547 on Sorafenib-resistant hepatoma cells. METHODS: First, we constructed a Sorafenib-resistant hepatoma cell line Huh7R. Different groups of Huh7R cells were treated with Sorafenib, AZD4547, Sorafenib combined with AZD4547, and normal saline. The cell viability was detected by Cell Counting Kit-8. Then Fibroblast growth factor receptor and Toll-like receptor 4 were detected by Western blot, as well as the LC3 II/I, Beclin1, and P62. In addition, we used the autophagy inhibitor 3-methyladenine to identify the mechanism of AZD4547 combined with Sorafenib for inducing Sorafenib-resistant hepatoma cell death. RESULTS: We find that AZD4547 combined with Sorafenib significantly inhibited the viability of Sorafenib-resistant hepatoma cell Huh7R. As for its mechanism, AZD4547 was able to inhibit fibroblast growth factor receptor activity, promote autophagy and regulate immunity. AZD4547 increased LC3 II/I, Beclin1, and Toll-like receptor 4 proteins, and decreased P62 protein level in Huh7R cells significantly when given in combination with sorafenib. Furthermore, 3-methyladenine inhibited autophagy and reversed the killing effect of the combination of AZD4547 and Sorafenib on Huh7R cells. CONCLUSION: The inhibition of fibroblast growth factor receptor activity by AZD4547 can significantly enhance autophagy and immune response, as well as promote the death of Sorafenib-resistant hepatoma cells.

Effect of intestinal microbiota transplantation on cerebral ischemia reperfusion injury in aged mice via inhibition of IL-17.

OBJECTIVES: This study investigates the effects and mechanisms of intestinal microbiota transplantation on cerebral ischemia reperfusion injury in aged mice. METHODS: We constructed a middle cerebral artery occlusion model after fecal microbiota transplantation from young C57 mice to aged C57 mice for 30 consecutive days via enema. The neurological deficit score, cerebral infarction volume, fecal flora composition, and IL-17 levels in the colon, brain, and serum were evaluated in young mice, aged mice, and aged mice that received fecal microbiota transplantation. Moreover, we administered rIL-17A through caudal vein injection to verify its effect on cerebral ischemia reperfusion injury in aged mice. RESULTS: We find that aged mice exhibited larger cerebral infarction volume and more severe neurological deficit than young mice after middle cerebral artery occlusion. Bacteroidetes increased and firmicutes decreased significantly in the feces of aged mice after microbiota transplantation. Furthermore, the transplanted mice showed improved neurological function and reduced infarction volume after middle cerebral artery occlusion compared with the control aged mice. We also find that the neuroprotective effect of the microbiota transplantation was reversed by pre-treatment of rIL-17A. CONCLUSION: In summary, intestinal microbiota transplantation can alleviate cerebral ischemia reperfusion injury in aged mice by restoring their microbiota environment and inhibiting IL-17 in the gut, serum, and brain tissue.

Circ_0008039 supports breast cancer cell proliferation, migration, invasion, and glycolysis by regulating the miR-140-3p/SKA2 axis.

Circular RNAs (circRNAs) have been shown to modulate gene expression and participate in the development of multiple malignancies. The purpose of this study was to investigate the role of circ_0008039 in breast cancer (BC). The expression of circ_0008039, miR-140-3p, and spindle and kinetochore-associated protein 2 (SKA2) was detected by qRT-PCR. Cell viability, colony formation, migration, and invasion were evaluated using methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, colony formation assay, and transwell assay, respectively. Glucose consumption and lactate production were measured using commercial kits. Protein levels of hexokinase II (HK2) and SKA2 were determined by western blot. The interaction between miR-140-3p and circ_0008039 or SKA2 was verified by dual-luciferase reporter assay. Finally, a mouse xenograft model was established to investigate the roles of circ_0008039 in BC in vivo. We found that circ_0008039 and SKA2 were upregulated in BC tissues and cells, while miR-140-3p was downregulated. Knockdown of circ_0008039 suppressed BC cell proliferation, migration, invasion, and glycolysis. Moreover, miR-140-3p could bind to circ_0008039 and its inhibition reversed the inhibitory effect of circ_0008039 interference on proliferation, migration, invasion, and glycolysis in BC cells. SKA2 was verified as a direct target of miR-140-3p and its overexpression partially inhibited the suppressive effect of miR-140-3p restoration in BC cells. Additionally, circ_0008039 positively regulated SKA2 expression by sponging miR-140-3p. Consistently, silencing circ_0008039 restrained tumor growth via increasing miR-140-3p and decreasing SKA2. In conclusion, circ_0008039 downregulation suppressed BC cell proliferation, migration, invasion, and glycolysis partially through regulating the miR-140-3p/SKA2 axis, providing an important theoretical basis for treatment of BC.

Cancer-Associated Fibroblasts-Derived Exosomes Suppress Immune Cell Function in Breast Cancer via the miR-92/PD-L1 Pathway.

Cancer-associated fibroblasts (CAFs) are an essential component in the tumor microenvironment and have been reported to contribute to tumor progression through many mechanisms; however, the detailed mechanism underlying the immune-suppression effect of CAFs is not clearly defined. In this study, human breast cancer-derived CAFs were cultured, and CAF-derived exosomes in a culture medium were isolated. Using a miRNA profiles assay, we identify a significantly higher level of microRNA-92 isolated in CAFs exosomes. After treatment by CAF-derived exosomes, breast cancer cells express higher programmed cell death receptor ligand 1 (PD-L1), accompanied with increased miR-92 expression. Increased PD-L1 expression, which was induced by CAF-derived exosomes, significantly promotes apoptosis and impaired proliferation of T cells. The underlying mechanism of this effect was studied, proliferation and migration of breast cancer cells were increased after the transfection of miR-92, LATS2 was recognized as a target gene of miR-92, and further confirmed by a luciferase assay. Immunoprecipitation showed that LATS2 can interact with YAP1, chromatin immunoprecipitation confirmed that after nuclear translocation YAP1 could bind to the enhancer region of PD-L1 to promotes transcription activity. Furthermore, the animal study confirmed that CAFs significantly promoted tumor progression and impaired the function of tumor-infiltrated immune cells in vivo. Our data revealed a novel mechanism that can induce immune suppression in the tumor microenvironment.

CircUBE2D2 (hsa_circ_0005728) promotes cell proliferation, metastasis and chemoresistance in triple-negative breast cancer by regulating miR-512-3p/CDCA3 axis.

BACKGROUND: Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer with a bad prognosis. Chemotherapy is still the standard of care for TNBC treatment. Circular RNAs (CircRNAs) have been recently discovered to be closely involved in the initiation and development of human cancers. Herein, we focus our attention on the functions and underlying mechanisms of circUBE2D2 in TNBC progression and chemoresistance. METHODS: The expression of circUBE2D2, miR-512-3p, and cell division cycle associated 3 (CDCA3) mRNA were determined by qRT-PCR. CCK-8, colony formation, transwell and flow cytometry assays were performed to detect cell proliferation, migration, invasion and apoptosis. Western blot assay was utilized to measure the protein level of CDCA3. RNA pull-down, luciferase reporter and RIP experiments were employed to examine the possible regulatory mechanism of circUBE2D2. RESULTS: CircUBE2D2 expression was elevated in TNBC tissues and cells. TNBC patients with high circUBE2D2 expression are inclined to present advanced TNM stage, lymph node metastasis and adverse prognosis. Knockdown of circUBE2D2 repressed cell proliferation, migration and invasion in vitro, and impeded tumor growth in vivo. Moreover, silencing of circUBE2D2 reduced doxorubicin resistance of TNBC cells. In-depth mechanism analysis revealed that circUBE2D2 served as a miRNA sponge to protect CDCA3 from the attack of miR-512-3p. Additionally, the tumor-suppressive effect induced by circUBE2D2 depletion was greatly impaired upon miR512-3p down-regulation or CDCA3 overexpression. Also, depletion of circUBE2D2 decreased the resistance to doxorubicin through regulating miR-512-3p/CDCA3 axis. CONCLUSION: CircUBE2D2 promoted TNBC progression and doxorubicin resistance through acting as a sponge of miR-512-3p to up-regulate CDCA3 expression. Targeting circUBE2D2 combine with doxorubicin might be exploited as a novel therapy for TNBC.

The Application of Mobile Telehealth System to Facilitate Patient Information Presentation and Case Discussion.

Background: Most secondary transmission of COVID-19 is occurring in a hospital setting. To decrease person-to-person contact, health care providers have built many isolation wards. However, out-of-hospital professionals cannot access patient information, which has greatly reduced the efficiency of treatment; it is inconvenient for health care professionals to issue a case discussion with professionals from other wards. This article mainly introduces a mobile telehealth system (MTS) applied to facilitate patient information presentation and case discussion. Materials and Methods: The MTS searches patient information, which is stored in hospital intranet, and uses five modules to display patient information. By a request/response module and a real-time interaction module, we successfully conducted case discussions. In addition, we took measures in three areas to prevent patient information leakage. Results: The system uses mobile collaboration technology to present patient information and support case discussion. MTS was officially launched for 37 days, during which it has been used 3,061 times. Conclusions: The building of the MTS not only provides convenience and benefit for health care professionals, but also reduces person-to-person contact.

High-resolution Anorectal Manometry in the Diagnosis of Functional Defecation Disorder in Patients With Functional Constipation: A Retrospective Cohort Study.

BACKGROUND/AIMS: High-resolution anorectal manometry (HRAM) has been considered a first-line diagnostic tool for functional defecation disorder. However, clinical studies on HRAM used in constipation patients are very limited and few studies have reported the characteristics of anorectal pressure in Chinese patients. The aim of this study is to investigate the characteristics of motility data in a cohort of Chinese patients with functional constipation. METHODS: A total of 82 consecutive patients with functional constipation who underwent a standardized HRAM were retrospectively enrolled in this study. The functional defecation disorder was classified into Rao's types. RESULTS: The mean age of 82 patients was 51 years (range, 16-83 years). Indications for anorectal manometry were functional constipation for all patients. The mean resting pressure was 69.2 ± 21.2 mmHg (range, 24.5-126.9 mmHg). The mean maximum squeezing pressure was 198.4 ± 75.6 mmHg (range, 54.2-476.9 mmHg). The mean length of the anal high pressure zone was 3.4 ± 1.0 cm (range, 0.6-4.9 cm). Sixty (73.2%) patients were diagnosed as functional defecation disorder. In attempted defecation, type I was most common (n = 24), followed by type II (n = 12), type III (n = 11), and type IV (n = 13) that were present on HRAM according to Rao's classification. In all 60 patients with functional defecation disorder, 37 were women and 23 were men. Men were significantly more likely than women to have functional defecation disorder (92.0% vs 64.9%, P = 0.014). CONCLUSION: HRAM could be used as a test for the diagnosis of functional defecation disorder and functional defecation disorder is common in Chinese patients with functional constipation.

Design and Implementation of a Message-Based Regional Telemedicine System to Achieve High Availability and Scalability.

BACKGROUND: Different levels of telemedicine systems have been built across China. To share high-quality medical resources and conduct centralized management of telemedicine systems, a regional telemedicine system (RTS) (such as a provincial level system) has been developed to integrate with small-scale telemedicine systems. Although the established systems offer integration services, they are tightly coupled systems, and not easily integrated with new systems. Meanwhile, with the increasing of input/output, it is difficult for them to run with high scalability, considering the cost of architecture redesign and further development. This article presents the design and implementation of regional integration system through a study in Henan, China, mainly aimed to integrate with heterogeneous small-scale telemedicine systems and provide high efficiency. METHODS: A provincial telemedicine system and some city-level telemedicine systems have already been established. The provincial system has been built to act as a regional integration system to connect city-level systems. Adopting message-based technology, the provincial system achieves high availability and high scalability, respectively, through LevelDB + ZooKeeper and multicast. RESULTS: The system achieved the centralized management of established telemedicine systems without restructuring their framework, improving high availability of RTS when one ActiveMQ service node in a group failed, and it did not negatively influence normal business logic when adding a new service node. At the same time, two "Master" state ActiveMQ service nodes provided services simultaneously, which enable the RTS to achieve high scalability. CONCLUSIONS: The message-based regional integration system enriched the RTS with high availability, easy extensibility, and provided a convenient way to integrate new small-scale telemedicine systems.

Beneficial effects of Rifaximin in post-infectious irritable bowel syndrome mouse model beyond gut microbiota.

BACKGROUND AND AIMS: Rifaximin is a minimally absorbed antibiotic, which has shown efficacy in irritable bowel syndrome (IBS) patients. However, the mechanism on how it effects in IBS is still incompletely defined. In this study, Trichinella spiralis-infected post-infectious (PI) IBS mouse model was used, to assess the action of rifaximin on visceral hypersensitivity, barrier function, gut inflammation, and microbiota. METHODS: Post-infectious IBS model was established by T. spiralis infection in mice. Rifaximin were administered to PI-IBS mice for seven consecutive days. The abdominal withdrawal reflex and threshold of colorectal distention were employed to evaluate visceral sensitivity. Smooth muscle contractile response was recorded in the organ bath. Intestinal permeability was measured by Ussing chamber. Expression of tight junction protein and cytokines were measured by Western blotting. Ilumina miseq platform was used to analyze bacterial 16S ribosomal RNA. RESULTS: Post-infectious IBS mice treated with rifaximin exhibited decreased abdominal withdrawal reflex score, increased threshold, reduced contractile response, and intestinal permeability. Rifaximin also suppressed the expression of interleukin-12 and interleukin-17 and promoted the expression of the major tight junction protein occludin. Furthermore, rifaximin did not change the composition and diversity, and the study reavealed that rifaximin had a tiny effect on the relative abundance of Lactobacillus and Bifidobacterium in this PI-IBS model. CONCLUSIONS: Rifaximin alleviated visceral hypersensitivity, recovered intestinal barrier function, and inhibited low-grade inflammation in colon and ileum of PI-IBS mouse model. Moreover, rifaximin exerts anti-inflammatory effects with only a minimal effect on the overall composition and diversity of the gut microbiota in this model.

Activation of corticotropin-releasing factor receptor 1 aggravates dextran sodium sulphate-induced colitis in mice by promoting M1 macrophage polarization.

The corticotropin-releasing factor (CRF) family is involved in modulating gastrointestinal motility, sensitivity and inflammation. CRF signalling exerts an important role in inflammatory bowel disease (IBD), predominantly by activating CRF receptors. The aim of the present study was to investigate the function of CRF receptor 1 (CRF­R1) in the development of mucosal inflammation induced by dextran sulphate sodium (DSS) and the underlying mechanism. Consecutive administration of CRF or CP154526 was used to activate or block the CRF­R1 in DSS­treated mice. Colonic inflammation was evaluated by determining the Disease Activity Index (DAI) and histology score. CRF­R1 expression was proportional to the DAI, the histology score and the number of macrophages. Activation of CRF­R1 aggravated mucosal inflammation by activating nuclear factor (NF)­κB and subsequently increasing the expression levels of tumour necrosis factor (TNF)­α and interleukin (IL)­6. Inhibition of CRF­R1 decreased the expression level of CRF­R1, macrophage infiltration, NF­κB activation, and TNF­α and IL­6 expression levels, ultimately alleviating the mucosal inflammation. Thus, CRF­R1 expression was proportional to the severity of DSS­induced colitis. Activation of CRF­R1 increased the DAI and histological scores of the colons from DSS­treated mice by promoting M1 macrophage polarization, demonstrated as increased NF­κB activation, and TNF­α and IL­6 release. These results provide evidence of the pro­inflammatory role of CRF­R1 in a DSS­induced ulcerative colitis (UC) model and a possible underlying mechanism, which may facilitate the elucidation of potential treatment approaches for UC.