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Purpose: This study aimed to summarize and analyze the clinical data of intestinal tuberculosis (ITB) in order to provide guidance for accurate diagnosis and treatment of ITB. Methods: This study consecutively included patients with ITB who were admitted to our hospital from 2008 to 2021 and retrospectively analyzed their clinical features. Results: Forty-six patients were included. The most common clinical symptom was weight loss (67.4%). Seventy percent of 20 patients were positive for tuberculin skin test; 57.1% of 14 patients were positive for mycobacterium tuberculosis specific cellular immune response test, while 84.6% of 26 patients were positive for tuberculosis infection T cell spot test. By chest computed tomography (CT) examination, 25% and 5.6% of 36 patients were diagnosed with active pulmonary tuberculosis and with inactive pulmonary tuberculosis, respectively. By abdominal CT examination, the most common sign was abdominal lymph node enlargement (43.2%). Forty-two patients underwent colonoscopy, and the most common endoscopic manifestation was ileocecal ulcer (59.5%), followed by colonic ulcer (35.7%) and ileocecal valve deformity (26.2%). ITB most frequently involved the terminal ileum/ileocecal region (76.1%). Granulomatous inflammation with multinucleated giant cells and caseous necrosis was found via endoscopic biopsies, the ultrasound-guided percutaneous biopsy of enlarged mesentery lymph nodes, and surgical interventions. The acid-fast bacilli were discovered in 53.1% of 32 samples. Twenty-one cases highly suspected of ITB were confirmed after responding to empiric anti-tuberculosis therapy. Conclusions: It was necessary to comprehensively analyze clinical features to make an accurate diagnosis of ITB and aid in distinguishing ITB from diseases such as Crohn's disease and malignant tumors. [ABSTRACT FROM AUTHOR]

Apoptosis disorder is generally regarded as an important mechanism of carcinogenesis. Inducement of tumor cell apoptosis can be an effectual way to treat cancer. Bcl-2-associated athanogene 1 (Bag-1) is a positive regulator of Bcl-2 which is an anti-apoptotic gene. Bag-1 is highly expressed in colorectal cancer, which plays a critical role in promoting metastasis, poor prognosis, especially in anti-apoptotic function, and is perhaps a valuable gene target for colorectal cancer therapy. Recently, we applied a novel non-viral gene carrier, magnetic gold nanoparticle, and mediated plasmid pGPH1/GFP/Neo-Bag-1-homo-825 silencing Bag-1 gene for treating colorectal cancer in vivo and in vitro. By mediating with magnetic gold nanoparticle, siRNA plasmid was successfully transfected into cell. In 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, magnetic gold nanoparticle had no significant cytotoxicity and by which delivered RNA plasmid inhibited cell viability significantly ( P < 0.05). Downregulation of Bag-1 promoted cell apoptosis (∼47.0 %) in vitro and significantly decreased tumor growth when the cells were injected into nude mice. Based on the studies in vivo, the relative expression of Bag-1 was 0.165 ± 0.072 at mRNA level and ∼60 % at protein level. In further study, C-myc and β-catenin, mainly molecules of Wnt/β-catenin pathway, were decreased notably when Bag-1 were silenced in nanoparticle plasmid complex-transfected Balb c/nude tumor xenograft. In conclusion, Bag-1 is confirmed an anti-apoptosis gene that functioned in colorectal cancer, and the mechanism of Bag-1 gene causing colorectal cancer may be related to Wnt/β-catenin signaling pathway abnormality and suggested that magnetic gold nanoparticle-delivered siRNA plasmid silencing Bag-1 is an effective gene therapy method for colorectal cancer. [ABSTRACT FROM AUTHOR]

The present study aimed to characterize the gut microbiota and serum metabolome changes associated with sleep deprivation (SD) as well as to explore the potential benefits of multi-probiotic supplementation in alleviating SD-related mental health disorders. Rats were subjected to 7 days of SD, followed by 14 days of multi-probiotics or saline administration. Open-field tests were conducted at baseline, end of SD (day 7), and after 14 days of saline or multi-probiotic gavage (day 21). Metagenomic sequencing was conducted on fecal samples, and serum metabolites were measured by untargeted liquid chromatography tandem-mass spectrometry. At day 7, anxiety-like behaviors, including significant decreases in total movement distance ( P = 0.0002) and staying time in the central zone ( P = 0.021), were observed. In addition, increased levels of lipopolysaccharide (LPS; P = 0.028) and decreased levels of uridine ( P = 0.018) and tryptophan ( P = 0.01) were detected in rats after 7 days of SD. After SD, the richness of the gut bacterial community increased, and the levels of Akkermansia muciniphila , Muribaculum intestinale , and Bacteroides caecimuris decreased. The changes in the host metabolism and gut microbiota composition were strongly associated with the anxiety-like behaviors caused by SD. In addition, multi-probiotic supplementation for 14 days modestly improved the anxiety-like behaviors in SD rats but significantly reduced the serum level of LPS ( P = 0.045). In conclusion, SD induces changes in the gut microbiota and serum metabolites, which may contribute to the development of chronic inflammatory responses and affect the gut-brain axis, causing anxiety-like behaviors. Probiotic supplementation significantly reduces serum LPS, which may alleviate the influence of chronic inflammation., Importance: The disturbance in the gut microbiome and serum metabolome induced by SD may be involved in anxiety-like behaviors. Probiotic supplementation decreases serum levels of LPS, but this reduction may be insufficient for alleviating SD-induced anxiety-like behaviors., Competing Interests: The authors declare no conflict of interest.

Objective: This study aimed to construct prognostic models to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with primary gastrointestinal melanoma (PGIM)., Design: An observational and retrospective study., Setting: Data were obtained from the Surveillance, Epidemiology and End Results (SEER) programme database, encompassing a broad geographical and demographic spectrum of patients across the USA., Participants: A total of 991 patients diagnosed with PGIM were included in this study., Methods: A total of 991 patients with PGIM were selected from the SEER database. They were further divided into a training cohort and a validation cohort. Independent prognostic factors were identified by Cox regression analysis. Two prognostic models were constructed based on the results of multivariable Cox regression analysis. The concordance index (C-index) and area under the time-dependent receiver operating characteristic curve (time-dependent AUC) were used to evaluate the discriminative ability. Calibration curves were plotted to evaluate the agreement between the probability as predicted by the models and the actual probability. Risk stratification was developed given the model., Results: By the multivariable Cox regression analysis, we identified four independent risk factors (age, stage, lymph node density and surgery) for OS, and three independent risk factors (stage, lymph node density and surgery) for CSS, which were used to construct prognostic models. C-index, time-dependent AUC, calibration curves and Kaplan-Meier curves of risk stratification indicated that these two models had good discriminative ability, predictive ability as well as clinical value., Conclusions: The prognostic models of OS and CSS had satisfactory accuracy and were of clinical value in evaluating the prognosis of patients with PGIM., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Immune checkpoint inhibitors (ICIs) have become a promising therapeutic strategy for malignant tumors, improving patient prognosis, along with a spectrum of immune-related adverse events (irAEs), including gastrointestinal toxicity, ICI-related colitis (IRC), and diarrhea. The gut microbiota has been suggested as an important regulator in the pathogenesis of IRC, and microbiota modulations like probiotics and fecal microbiota transplantation have been explored to treat the disease. This review discusses the interaction between the gut microbiota and IRC, focusing on the potential pathogenic mechanisms and promising interventions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Zhang, Meng and Pan.)

Objective: This study aimed to observe the cell growth status and multidirectional differentiation ability in a 3D-bioprinted tissue model of self-assembled nanopeptides and human adipose-derived mesenchymal stem cells (Ad-MSCs). Methods: Primary Ad-MSCs were isolated, cultured, and identified by flow cytometry. Tissue models were printed via 3D bioprinting technology using a "biological ink" consisting of a mixed solution of self-assembled nanopeptides and Ad-MSCs. Ad-MSCs were induced into osteogenic, adipogenic, and endothelial differentiation and compared with the control groups by staining. Results: The nanopeptide fiber was 10-30 nm in diameter and 200-500 nm in length under the atomic-force microscope. It had the characteristics of nano-scale materials. Flow cytometry showed that the isolated and cultured cells were positive for CD29 (98.51%), CD90 (97.87%), and CD166 (98.32%) but did not express CD31 (1.58%), CD34 (2.42%), CD45 (2.95%), or human leukocyte antigen (HLA)-DR (0.53%), consistent with the immunophenotype of Ad-MSCs. Then, a tissue model was printed using the biological ink, followed by induction of differentiation of Ad-MSCs within the tissue model. Alizarin red S staining showed the formation of calcium nodules in the osteogenesis induction experimental group, and oil red O stained lipid droplets in Ad-MSCs in the adipogenesis induction experimental group, whereas the two control groups were not stained. Conclusion: Ad-MSCs from primary cultures have the characteristics of stem cells. Self-assembled nanopeptide hydrogel is a good tissue engineering material that can serve as an extracellular matrix. Ad-MSCs in the 3D-printed tissue model using a biological ink consisting of a mixed solution of self-assembled nanopeptides and Ad-MSCs grew well and still had strong differentiation ability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhou, Tian, Yi, Fan, Shao, Wu and Sun.)

Recently, a deletion in the human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) gene cluster has been associated with a modest increased risk of breast cancer, but studies yielded inconsistent results. Therefore we performed a meta-analysis to derive a more precise conclusion. Six studies including 18241 subjects were identified by searching PubMed and Embase databases from inception to April 2016. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were evaluated under allele contrast, dominant, recessive, homozygous, and heterozygous models. All the analyses suggested a correlation of APOBEC3 deletion with increased breast cancer risk (D vs I: OR = 1.29, 95% CI = 1.23-1.36; D/D+I/D vs I/I: OR = 1.34, 95% CI = 1.26-1.43; D/D vs I/D+ I/I: OR = 1.51, 95% CI = 1.36-1.68; D/D vs I/I: OR = 1.75, 95% CI= 1.56-1.95; I/D vs I/I: OR = 1.28, 95% CI = 1.19-1.36). Stratified analysis by ethnicity showed that the relationship is stronger and more stable in Asians. In summary, our current work indicated that APOBEC3 copy number variations might have a good screening accuracy for breast cancer.

Apoptosis disorder is generally regarded as an important mechanism of carcinogenesis. Inducement of tumor cell apoptosis can be an effectual way to treat cancer. Bcl-2-associated athanogene 1 (Bag-1) is a positive regulator of Bcl-2 which is an anti-apoptotic gene. Bag-1 is highly expressed in colorectal cancer, which plays a critical role in promoting metastasis, poor prognosis, especially in anti-apoptotic function, and is perhaps a valuable gene target for colorectal cancer therapy. Recently, we applied a novel non-viral gene carrier, magnetic gold nanoparticle, and mediated plasmid pGPH1/GFP/Neo-Bag-1-homo-825 silencing Bag-1 gene for treating colorectal cancer in vivo and in vitro. By mediating with magnetic gold nanoparticle, siRNA plasmid was successfully transfected into cell. In 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, magnetic gold nanoparticle had no significant cytotoxicity and by which delivered RNA plasmid inhibited cell viability significantly (P < 0.05). Downregulation of Bag-1 promoted cell apoptosis (∼47.0 %) in vitro and significantly decreased tumor growth when the cells were injected into nude mice. Based on the studies in vivo, the relative expression of Bag-1 was 0.165 ± 0.072 at mRNA level and ∼60 % at protein level. In further study, C-myc and β-catenin, mainly molecules of Wnt/β-catenin pathway, were decreased notably when Bag-1 were silenced in nanoparticle plasmid complex-transfected Balb c/nude tumor xenograft. In conclusion, Bag-1 is confirmed an anti-apoptosis gene that functioned in colorectal cancer, and the mechanism of Bag-1 gene causing colorectal cancer may be related to Wnt/β-catenin signaling pathway abnormality and suggested that magnetic gold nanoparticle-delivered siRNA plasmid silencing Bag-1 is an effective gene therapy method for colorectal cancer.

Bcl-2-associated athanogene 1 (Bag-1) is a positive regulator of Bcl-2 which is an anti-apoptotic gene. Bag-1 was very slightly expressed in normal tissues, but often highly expressed in many tumor tissues, particularly in colon cancer, which can promote metastasis, poor prognosis and anti-apoptotic function of colon cancer. We prepared and evaluated magnetic gold nanoparticle/Bag-1 siRNA recombinant plasmid complex, a gene therapy system, which can transfect cells efficiently, for both therapeutic effect and safety in vitro mainly by electrophoretic mobility shift assays, flow cytometric analyses, cell viability assays, western blot analyses and RT-PCR (real-time) assays. Magnetic gold nanoparticle/Bag-1 siRNA recombinant plasmid complex was successfully transfected into LoVo colon cancer cells and the exogenous gene was expressed in the cells. Flow cytometric results showed apoptosis rate was significantly increased. In MTT assays, magnetic gold nanoparticles revealed lower cytotoxicity than Lipofectamine 2000 transfection reagents (P<0.05). Both in western blot analyses and RT-PCR assays, magnetic gold nanoparticle/Bag-1 siRNA recombinant plasmid complex transfected cells demonstrated expression of Bag-1 mRNA (P<0.05) and protein (P<0.05) was decreased. In further study, c-myc and β-catenin which are main molecules of Wnt/β‑catenin pathway were decreased when Bag-1 were silenced in nanoparticle plasmid complex transfected LoVo cells. These results suggest that magnetic gold nanoparticle mediated siRNA silencing Bag-1 is an effective gene therapy method for colon cancer.