The aim of this study was to investigate lymphocyte subsets, especially natural killer (NK) cells, in patients with systemic sclerosis (SSc) and evaluate the diagnostic value of NK cells in secondary pulmonary arterial hypertension (PAH). A total of 115 SSc patients and 100 age- and sex-matched health controls (HCs) were enrolled in this study. Flow cytometry was employed to quantify NK cells, while the association between NK cells and disease activity as well as PAH was investigated to further elucidate its diagnostic potential. The absolute count of NK (CD3-CD56+) cells significantly decreased in SSc patients. There was a negative correlation between the mRSS score and the injury index. The levels of cytokine exhibited significant elevation among SSc patients. Conversely, SSc-PAH patients demonstrated significantly elevated levels of CRP, UA, and BNP. Additionally, there was a significant reduction in the absolute level of NK cells. ROC curve analysis revealed that the optimal cut-off point for NK cells was 185 cells/µL, while for BNP it was 70.50 pg/mL and for UA it was 323.00 µmol/L. Our study revealed a significant inverse correlation between peripheral blood NK cell levels and the incidence of complicated PAH in patients with SSc.

ObjectiveAs the relationship between urine glyphosate and arthritis in adults in general is still unclear, the study set out to investigate it.MethodsA total of 1,689 people volunteered in the National Health and Nutrition Examination Surveys (US NHANES). Utilizing a multivariate logistic regression model to explore the association between urine glyphosate concentrations (both continuous with categorical) and the risks of developing arthritis, as well as the risks of various types of arthritis. Non-linear correlations have been investigated using restricted cubic spline and smooth curve fitting. We also conducted additional subgroup analyses using categorical defining features.ResultsPatients with arthritis had urine glyphosate levels of 0.4 ng/mL, while non-arthritic individuals had levels of 0.3 ng/mL (p < 0.05). After adjusting for confounding variables, multivariate logistic regression continuous and categorical models demonstrated a significant positive association between elevated urinary glyphosate levels and arthritis risk [1.2 (1.0, 1.4)]. This association was observed in the osteoarthritis (OA) subgroup, with an odds ratio of 1.3 (95% CI: 1.1, 1.6), but was not found in the rheumatoid arthritis (RA) or other arthritis subgroups. Smooth curve fitting and RCS regression analyses further elucidate that urine glyphosate levels exhibit a dose-dependent relationship with the risks of both arthritis and OA, adhering to a linear trend (with a p-value for nonlinearity exceeding 0.05). Subsequent subgroup studies showed that in certain groups of people, the positive relationship between urine glyphosate and arthritis remained significant.ConclusionIncreased exposure to urine glyphosate may be associated with an elevated risk of arthritis, particularly in the subgroup of osteoarthritis.

PURPOSE:Sarcopenia is common among individuals afflicted with gastric cancer (GC), and can culminate in unfavorable prognoses. Nevertheless, the efficacy of surgical interventions in GC patients with sarcopenia remains ambiguous. This study compared the prognostic value of laparoscopic and open radical gastrectomy in GC patients with sarcopenia. METHODS:GC patients with preoperative sarcopenia who underwent radical gastrectomy were enrolled in our study. The patients' outcomes were stratified based on the surgical approach. After correcting for bias in clinical characteristics using propensity score matching, the prognoses of two groups were compared, and independent risk factors for postoperative complications, overall survival (OS) and disease-free survival (DFS) were analyzed. RESULTS:Our study included a total of 136 individuals after propensity score matching, with a postoperative complication rate of 39.0 %. Compared with patients who underwent open gastrectomy, those who opted for laparoscopic gastrectomy exhibited a lower incidence of surgical complications (13.2 % vs 35.3 %, P = 0.003) and better prognoses. By conducting a comprehensive analysis of statistical results, it had been determined that laparoscopic surgery was identified as an independent protective factor for surgical complications (OR = 0.244(0.098-0.607); P = 0.004), OS (HR = 0.522(0.0.297-0.919); P = 0.024), and DFS (HR = 0.459(0.234-0.902); P = 0.024). CONCLUSIONS:Laparoscopic gastrectomy achieves a better long-term prognosis and significantly reduces the incidence of postoperative surgical complications for GC patients with sarcopenia.

Accurate, sensitive, and in situ visualization of aberrant expression level of low‐abundant biomolecules is crucial for early colorectal cancer (CRC) detection ahead of tumor morphology change. However, the clinical used colonoscopy and biopsy methods are invasive and lack of sensitivity at early‐stage of cancerization. Here, an amplified sensing strategy is developed in the second near‐infrared long‐wavelength subregion (NIR‐II‐L, 1500–1900 nm) by integrating DNAzyme‐triggered signal amplification technology and lanthanide‐dye hybrid system. In the early‐stage of CRC, the overexpressed biomarker microRNA‐21 initiates the NIR‐II‐L luminescence ratiometric signal amplification of the CRCsensor. The high sensitivity with a limit of detection (LOD) of 1.26 p m allows non‐invasive visualization of orthotopic colorectal cancerization via rectal administration, which achieves early and accurate in situ diagnosis at 2 weeks ahead of the in vitro histological results. This innovative approach offers a promising tool for early diagnosis and long‐term monitoring of carcinogenesis progression, with potential applications in other cancer‐related biomarkers.

Disrupted gastrointestinal (GI) motility is highly prevalent in patients with inflammatory bowel disease (IBD), but its potential causative role remains unknown. Herein, the role and the mechanism of impaired GI motility in colitis pathogenesis are investigated. Increased colonic mucosal inflammation is found in patients with chronic constipation (CC). Mice with GI dysmotility induced by genetic mutation or chemical insult exhibit increased susceptibility to colitis, dependent on the gut microbiota. GI dysmotility markedly decreases the abundance of Lactobacillus animlalis and increases the abundance of Akkermansia muciniphila. The reduction in L. animlalis, leads to the accumulation of linoleic acid due to compromised conversion to conjugated linoleic acid. The accumulation of linoleic acid inhibits Treg cell differentiation and increases colitis susceptibility via inducing macrophage infiltration and proinflammatory cytokine expression in macrophage. Lactobacillus and A. muciniphila abnormalities are also observed in CC and IBD patients, and mice receiving fecal microbiota from CC patients displayed an increased susceptibility to colitis. These findings suggest that GI dysmotility predisposes host to colitis development by modulating the composition of microbiota and facilitating linoleic acid accumulation. Targeted modulation of microbiota and linoleic acid metabolism may be promising to protect patients with motility disorder from intestinal inflammation.

BackgroundThe significant impact of digital health emerged prominently during the COVID-19 pandemic. Despite this, there is a paucity of bibliometric analyses focusing on technologies within the field of digital health patents. Patents offer a wealth of insights into technologies, commercial prospects, and competitive landscapes, often undisclosed in other publications. Given the rapid evolution of the digital health industry, safeguarding algorithms, software, and advanced surgical devices through patent systems is imperative. The patent system simultaneously acts as a valuable repository of technological knowledge, accessible to researchers. This accessibility facilitates the enhancement of existing technologies and the advancement of medical equipment, ultimately contributing to public health improvement and meeting public demands. ObjectiveThe primary objective of this study is to gain a more profound understanding of technology hotspots and development trends within the field of digital health. MethodsUsing a bibliometric analysis methodology, we assessed the global technological output reflected in patents on digital health published between 2017 and 2021. Using Citespace5.1R8 and Excel 2016, we conducted bibliometric visualization and comparative analyses of key metrics, including national contributions, institutional affiliations, inventor profiles, and technology topics. ResultsA total of 15,763 digital health patents were identified as published between 2017 and 2021. The China National Intellectual Property Administration secured the top position with 7253 published patents, whereas Koninklijke Philips emerged as the leading institution with 329 patents. Notably, Assaf Govari emerged as the most prolific inventor. Technology hot spots encompassed categories such as “Medical Equipment and Information Systems,” “Image Analysis,” and “Electrical Diagnosis,” classified by Derwent Manual Code. A patent related to the technique of receiving and transmitting data through microchips garnered the highest citation, attributed to the patentee Covidien LP. ConclusionsThe trajectory of digital health patents has been growing since 2017, primarily propelled by China, the United States, and Japan. Applications in health interventions and enhancements in surgical devices represent the predominant scenarios for digital health technology. Algorithms emerged as the pivotal technologies protected by patents, whereas techniques related to data transfer, storage, and exchange in the digital health domain are anticipated to be focal points in forthcoming basic research.

The association between ITGB7 expression and survival, CMS types, and stages of CRC.

Acute liver injury (ALI) is a severe liver disease that is characterized by sudden and massive hepatocyte necrosis and deterioration of liver functions. Oxidative stress is increasingly recognized as a key factor in the induction and progression of ALI. Scavenging excessive reactive oxygen species (ROS) with antioxidants has become a promising therapeutic option, but intrinsically hepatocyte-targeting antioxidants with excellent bioavailability and biocompatibility are yet to be developed. Herein, self-assembling nanoparticles (NPs) composed of amphiphilic polymers are introduced to encapsulate organic Selenium compound L-Se-methylselenocysteine (SeMC) and form SeMC NPs, which protect the viabilities and functions of cultured hepatocytes in drug- or chemical-induced acute hepatotoxicity models via efficient ROS removal. After further functionalization with the hepatocyte-targeting ligand glycyrrhetinic acid (GA), the resultant GA-SeMC NPs exhibit enhanced hepatocyte uptake and liver accumulation. In mouse models of ALI induced by acetaminophen (APAP) or carbon tetrachloride (CCl4), treatment with GA-SeMC NPs significantly decrease the levels of hepatic lipid peroxidation, tissue vacuolization and serum liver transaminases, while prominently increase that of endogenous antioxidant enzymes. Our study therefore presents a liver-targeting drug delivery strategy for the prevention and treatment of hepatic diseases.

β7 blockade decreased the number of migrated CD3+ T cells towards CRC-organoids.

The detailed molecular mechanism between type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC) is still uncertain. Bone morphogenetic protein 4 (BMP4) dysregulation is implicated in T2DM and CRC, respectively. This study aims to investigate whether BMP4 can mediate the interaction of CRC with T2DM. We firstly explored the expression of BMP4 in The Cancer Genome Altas (TCGA) databases and CRC patients with or without DM from the Shanghai Tenth People’s Hospital. The diabetic model of CRC cell lines in vitro and the mice model in vivo were developed to explore the BMP4 expression during CRC with or without diabetes. Further inhibition of BMP4 to observe its effects on CRC. Also, glucagon-like peptide-1 receptor agonist (GLP-1RA) was used to verify the underlying mechanism of hypoglycemic drugs on CRC via BMP4. BMP4 expression was upregulated in CRC patients, and significantly higher in CRC patients with diabetes (P < 0.05). High glucose-induced insulin resistance (IR)-CRC cells and diabetic mice with metastasis model of CRC had increased BMP4 expression, activated BMP4-Smad1/5/8 pathway, and improved proliferative and metastatic ability mediated by epithelial-mesenchymal transition (EMT). And, treated CRC cells with exogenously BMP inhibitor-Noggin or transfected with lentivirus (sh-BMP4) could block the upregulated metastatic ability of CRC cells induced by IR. Meanwhile, GLP-1R was downregulated by high glucose-induced IR while unregulated by BMP4 inhibitor noggin, and treated GLP-1RA could suppress the proliferation of CRC cells induced by IR through downregulated BMP4. BMP4 increased by high glucose promoted the EMT of CRC. The mechanism of the BMP4/Smad pathway was related to the susceptible metastasis of high glucose-induced IR-CRC. The commonly used hypoglycemic drug, GLP-1RA, inhibited the growth and promoted the apoptosis of CRC through the downregulation of BMP4. The result of our study suggested that BMP4 might serve as a therapeutic target in CRC patients with diabetes.

Background Healthcare workers' relationship with industry is not merely an agent mediating between consumer and vendor, but they are also inventors of the interventions they exist to deliver. Driven by the background of the digital health era, scientific research and technological (Sci-tech) innovation in the medical field are becoming more and more closely integrated. However, scholars shed little light on Sci-tech relevance to evaluate the innovation performance of healthcare organizations, a distinctive feature of healthcare organizations' innovation in the digital health era. Methods Academic publications and patents are the manifestations of scientific research outputs and technological innovation outcomes, respectively. The study extracted data from publications and patents of 159 hospitals in China to evaluate their innovation performance. A total of 18 indicators were constructed, four of which were based on text similarity match and represented the Sci-tech relevance. We then applied factor analyses, analytical hierarchy process, and logistic regression to construct an evaluation model. We also examined the relationship between hospitals' innovation performance and their geographical locations. Finally, we implemented a mediation analysis to show the influence of digital health on hospital innovation performance. Results A total of 16 indicators were involved, four of which represented the Sci-tech including the number of articles matched per patent (NAMP), the number of patents matched per article (NPMA), the proportion of highly matched patents (HMP), and the proportion of highly matched articles (HMA). Indicators of HMP ( r = 0.52, P = 2.40 × 10 −12 ), NAMP ( r = 0.52, P = 2.54 × 10 −12 ), and NPMA ( r = 0.51, P = 5.53 × 10 −12 ) showed a strong positive correlation with hospital innovation performance score. The evaluation model in this study was different from other Chinese existing hospital ranking systems. The regional innovation performance index (RIP) of healthcare organizations is highly correlated with per capita disposable income ( r = 0.58) and regional GDP ( r = 0.60). There was a positive correlation between digital health innovation performance scores and overall hospital innovation performance scores ( r = 0.20). In addition, the hospitals' digital health innovation performance affected the hospital's overall innovation score with the mediation of Sci-tech relevance indicators (NPMA and HMA). The hospitals' digital health innovation performance score showed a significant correlation with the number of healthcare workers ( r = 0.44). Conclusion This study constructed an assessment model with four invented indicators focusing on Sci-tech relevance to provide a novel tool for researchers to evaluate the innovation performance of healthcare organizations in the digital health era. The regions with high RIP were concentrated on the eastern coastal areas with a higher level of economic development. Therefore, the promotion of scientific and technological innovation policies could be carried out in advance in areas with better economic development. The innovations in the digital health field by healthcare workers enhance the Sci-tech relevance in hospitals and boost their innovation performance. The development of digital health in hospitals depends on the input of medical personnel.

Differentially expressed gene and gene ontology analysis.

Abstract Background: Rheumatoid arthritis (RA) is a chronic autoimmune joint disease characterized by persistent synovitis and systemic inflammation of the joints. Cell therapy, a cellular drug delivery therapy based on the control of immune dysregulation, inflammatory cytokine production, and overall systemic inflammation, is expected to reverse the process of joint destruction when applied to RA. Based on this, the field of cell therapy applied to RA treatment has been gaining attention in recent years and many results have been achieved. Bibliometric analysis can provide insight into the development of a field. This study aims to provide an overview of the knowledge structure and research hotspots of cell therapy in RA through bibliometrics. Method: The Web of Science Core Collection (WoSCC) database was used to search the literature on cellular therapies related to RA between 2003 and 2022. VOSviewers, CiteSpace, and the R package "bibliometrics" were used to perform the bibliometric analysis. Results: This article includes 8822 articles from 107 countries, mainly from China and the United States. Fluctuating growth in the number of articles published on cell therapy applied to RA. The University of Amsterdam, Harvard University, Karolinska Institutet, and Stanford University are the main research institutions. The journal Arthritis research & therapy is the most popular journal in the field, and the journal Annals of rheumatic diseases is the most frequently cited. 41982 authors have published in this field, including more collaborative publications; Tak, paul p, Emery, paul, Doerner, Thomas, Isaacs, john d, Tanaka, and Yoshida have published several papers, while Arnett Fc is the author of most frequently cited paper. The University of Amsterdam has been extensively involved in the publication of papers on this topic. Swedish and Korean scientists have published fewer relevant papers as corresponding authors, but have been extensively involved in the investigation of this topic. Studying the mechanisms of various factors (e.g. immune cells, immune molecules, cytokines, and inflammatory responses) in the occurrence and development of RA and studying the therapeutic strategies of cellular therapies for the future precision treatment of RA are the two main topics in this research area. "T cells", "bone marrow (BM) transplantation", "mesenchymal cells", and "monoclonal antibodies" are the emerging research top keywords of the hot spots. Conclusion: This article is the first bibliometric study that comprehensively summarizes the research trends and their developments in the application of cell therapy to the treatment of RA. The content includes recent research results and hot directions in the field, providing reference information for scholars studying cell therapy and RA.

The expression pattern of α4β7 and αEβ7 in tumor infiltrating immune cells in WT mice bearing MC38 orthotopic tumor.

Tumor tissue ITGB7 expression level represents the CD8+ T and B cell infiltration level, and the ITGB7 expression level on CD8+ T cells.

The correlation between ITGB7 expression and the expression of genes that are related to immunotherapy.

Immune cell infiltration in tumor and adjacent normal tissues from CRC patients.

Background: Colorectal cancer (CRC) was one of the most widely diagnosed cancers in the United States in 2021. CRC patients may experience significant psychological stress and are susceptible to depression and anxiety. Previous studies have shown that cognitive behavioral therapy (CBT) can reduce fatigue and improve quality of life among breast cancer patients. However, as a non-pharmaceutical treatment, it remains unclear whether CBT improves chemotherapy-induced side effects and immune function in CRC patients. In this study, we will conduct a randomized controlled trial (RCT) among CRC patients undergoing chemotherapy to determine whether CBT can reduce the side effects of chemotherapy and improve the immune function of CRC patients. Methods: The study will be a single-center RCT. CRC patients undergoing chemotherapy will receive either eight sessions of group-based CBT (every 2-3 weeks) or usual care (usual oncology care). Each participant will undergo assessments at baseline (T0), immediately post-intervention (T1), 3 months postintervention (T2), and 6 months post-intervention (T3). The primary outcome will include chemotherapyinduced side effects in CRC patients. The secondary outcome will be immune function (measured by levels of inflammatory cytokines). Other outcomes will include the levels of tumor markers, assessments of psychological status (perception of stress, depression and anxiety, self-efficacy, sleep quality, quality of life, social support condition, and cognitive function), and necessary laboratory examinations (biochemical index and blood cell counts) among CRC patients undergoing chemotherapy. Discussion: Our study will provide clinical evidence regarding whether CBT should be generalized in clinical treatment and the extent to which CBT reduces chemotherapy- induced side effects for CRC patients.

Glypican-1 (GPC1) is a glycosylated protein recognized as a promising biomarker for cancer. Nonetheless, there have been few systematic studies on GPC1 in colon adenocarcinoma (COAD). We conducted bioinformatic analysis based on The Cancer Genome Atlas (TCGA) and used clinical samples to verify that GPC1 is overexpressed in colon adenocarcinoma. Kaplan-Meier analysis showed that higher GPC1 expression was associated with poor overall survival (OS). The Cox regression model further showed that GPC1 expression is an independent negative prognostic factor for COAD. Gene set enrichment analysis demonstrated that multiple oncogenic signaling pathways were differentially enriched in GPC1 high- versus low-expressing COAD tumors, including DNA methylation, G2/M damage checkpoint, and telomere dysfunction. We observed a positive correlation between GPC1 expression and immune cell infiltration, such as regulatory T cells (Tregs), macrophages, and mast cells, and immunohistochemistry of 50 COAD tissues revealed that GPC1 expression was positively associated with Treg enrichment. Our results provide a promising candidate gene to predict the prognosis of COAD and new insights into tumor immunity. Further research is required to validate these results.