The structure of intestinal tissue is complex. In vitro simulation of intestinal structure and function is important for studying intestinal development and diseases. Recently, organoids have been successfully constructed and they have come to play an important role in biomedical research. Organoids are miniaturized three-dimensional (3D) organs, derived from stem cells, which mimic the structure, cell types, and physiological functions of an organ, making them robust models for biomedical research. Intestinal organoids are 3D micro-organs derived from intestinal stem cells or pluripotent stem cells that can successfully simulate the complex structure and function of the intestine, thereby providing a valuable platform for intestinal development and disease research. In this article, we review the latest progress in the construction and application of intestinal organoids.
Organoids/cytology* ; Intestines/physiology* ; Humans ; Animals ; Pluripotent Stem Cells

Purpose::Vibrio vulnificus ( V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. Methods::An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. Results::In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival ( p = 0.014), reduced the serum creatinine ( p = 0.002), urea nitrogen ( p = 0.030), aspartate aminotransferase ( p = 0.029), and alanine aminotransferase ( p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1β: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1β, IL-6, TNF-α in liver (IL-1β: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1β: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid ( p = 0.225), liver ( p = 0.186), or kidney ( p = 0.637). Conclusion::Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.

AIM To evaluate the quality of Beidougen Formula Granules.METHODS Fifteen batches of standard decoctions and three batches of formula granules were prepared,after which paste rate and contents,transfer rates of magnoflorine,daurisoline,dauricine were determined.HPLC specific chromatograms were established,and cluster analysis was adopted in chemical pattern recognition.RESULTS For three batches of formula granules,the paste rates were 15.1%-16.6%,the contents of magnoflorine,daurisoline,dauricine were 18.93-19.39,9.42-9.60,6.79-6.85 mg/g with the transfer rates of 34.42%-35.25%,43.81%-44.65%,27.27%-27.51%from decoction pieces to formula granules,respectively,and there were seven characteristic peaks in the specific chromatograms with the similarities of more than 0.95,which demonstrated good consistence with those of standard decoctions and accorded with related limit requirements.Fifteen batches of standard decoctions were clustered into two types,and the medicinal materials produced from Jilin,Hebei,Shangdong could be used for the preparation of formula granules.CONCLUSION This reasonable and reliable method can provide references for the quality control and clinical application of Beidougen Formula Granules.

Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective:To investigate the impact of ionizing radiation(IR)on the structure and function of the testis and pro-vide some strategies for the prevention and treatment of IR-induced damage(IRD).Methods:Using radiation dose simulation,se-men analysis,hormone testing,electron microscopy and single-cell transcriptome sequencing,we assessed and analyzed a case of IRD.We established a mouse model of IRD to validate the results of single-cell sequencing,and investigated the specific biological mecha-nisms of IRD and potential strategies for its intervention.Results:IR at 1-2 Gy significantly reduced sperm concentration and mo-tility,which gradually recovered after 12 months but the percentage of morphologically normal sperm remained low.It also caused im-balanced levels of various steroid hormones,decreased testosterone and dehydroepiandrosterone sulfate,increased progesterone,prolac-tin,luteinizing hormone,and follicle-stimulating hormone.Electron microscopy revealed damages to the testis structure,including loss of germ cells,atrophy of the seminiferous tubules,nuclear membrane depression of the spermatocytes,mitochondrial atrophy and de-formation,and reduction of mitochondrial cristae.Single-cell sequencing indicated significant changes in the function of the Leydig cells and macrophages and disrupted lipid-related metabolic pathways after IRD.Administration of L-carnitine to the mouse model im-proved lipid metabolism disorders and partially alleviated IRD to the germ cells.Conclusion:Ionizing radiation can cause disorders of testicular spermatogenesis and sexual hormones and inhibit lipid metabolism pathways in Leydig cells and macrophages.Improving lipid metabolism can alleviate IRD to germ cells.

DNMT3A encodes a DNA methyltransferase involved in development, cell differentiation, and gene transcription, which is mutated and aberrant-expressed in cancers. Here, we revealed that loss of DNMT3A promotes malignant phenotypes in lung cancer. Based on the epigenetic inhibitor library synthetic lethal screening, we found that small-molecule HDAC6 inhibitors selectively killed DNMT3A-defective NSCLC cells. Knockdown of HDAC6 by siRNAs reduced cell growth and induced apoptosis in DNMT3A-defective NSCLC cells. However, sensitive cells became resistant when DNMT3A was rescued. Furthermore, the selectivity to HDAC6 inhibition was recapitulated in mice, where an HDAC6 inhibitor retarded tumor growth established from DNMT3A-defective but not DNMT3A parental NSCLC cells. Mechanistically, DNMT3A loss resulted in the upregulation of HDAC6 through decreasing its promoter CpG methylation and enhancing transcription factor RUNX1 binding. Notably, our results indicated that HIF-1 pathway was activated in DNMT3A-defective cells whereas inactivated by HDAC6 inhibition. Knockout of HIF-1 contributed to the elimination of synthetic lethality between DNMT3A and HDAC6. Interestingly, HIF-1 pathway inhibitors could mimic the selective efficacy of HDAC6 inhibition in DNMT3A-defective cells. These results demonstrated HDAC6 as a HIF-1-dependent vulnerability of DNMT3A-defective cancers. Together, our findings identify HDAC6 as a potential HIF-1-dependent therapeutic target for the treatment of DNMT3A-defective cancers like NSCLC.

OBJECTIVE: To compare the efficacy of percutaneous compression plate and cannulated compression screw in the treatment of displaced femoral neck fractures in young and middle-aged patients. METHODS: From January 2015 to July 2020, 68 young and middle-aged patients with displaced femoral neck fracture were retrospectively analyzed. Among them, 31 cases were fixed by percutaneous compression plate (PCCP), and 37 cases were fixed by cannulated compression screw (CCS). General data such as gender, age, cause of injury, comorbidities, fracture classification and cause of injury of two groups were collected. The operation time, intraoperative blood loss, hospital stay, full weight bearing time, fracture healing time, visual analogue scale(VAS), Harris hip score and complications were compared between two groups. RESULTS: Patients in both groups were followed up for more than 2 years. There were no significant differences in operation time, intraoperative blood loss, fracture reduction quality, hospital stay and VAS between two groups. The fracture healing time in PCCP group was significantly shorter than that in CCS group (t=-4.404, P=0.000). The complete weight bearing time of PCCP group was significantly shorter than that of CCS group (t=-9.011, P=0.000). Harris score of hip joint in PCCP group was better than that in CCS group 2 years after operation (P=0.002). Complications occurred in 3 cases (9.68%) in PCCP group, while 11 cases (29.72%) in CCS group, with a statistically significant difference (P=0.042). CONCLUSION Both PCCP and CCS can be used for the treatment of displaced femoral neck fractures in young and middle-aged people. Compared with CCS, PCCP fixation can achieve shorter fracture healing time and create conditions for early full weight bearing. PCCP results in higher hip score and lower complications.
Middle Aged ; Humans ; Treatment Outcome ; Blood Loss, Surgical ; Retrospective Studies ; Fracture Fixation, Internal/methods* ; Femoral Neck Fractures/surgery* ; Bone Screws

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

In order to investigate the molecular mechanism of silk/threonine protein kinase (STK)-mediated blue light response in the algal Chlamydomonas reinhardtii, phenotype identification and transcriptome analysis were conducted for C. reinhardtii STK mutant strain crstk11 (with an AphvIII box reverse insertion in stk11 gene coding region) under blue light stress. Phenotypic examination showed that under normal light (white light), there was a slight difference in growth and pigment contents between the wild-type strain CC5325 and the mutant strain crstk11. Blue light inhibited the growth and chlorophyll synthesis in crstk11 cells, but significantly promoted the accumulation of carotenoids in crstk11. Transcriptome analysis showed that 860 differential expression genes (DEG) (559 up-regulated and 301 down-regulated) were detected in mutant (STK4) vs. wild type (WT4) upon treatment under high intensity blue light for 4 days. After being treated under high intensity blue light for 8 days, a total of 1 088 DEGs (468 upregulated and 620 downregulated) were obtained in STK8 vs. WT8. KEGG enrichment analysis revealed that compared to CC5325, the crstk11 blue light responsive genes were mainly involved in catalytic activity of intracellular photosynthesis, carbon metabolism, and pigment synthesis. Among them, upregulated genes included psaA, psaB, and psaC, psbA, psbB, psbC, psbD, psbH, and L, petA, petB, and petD, as well as genes encoding ATP synthase α, β and c subunits. Downregulated genes included petF and petJ. The present study uncovered that the protein kinase CrSTK11 of C. reinhardtii may participate in the blue light response of algal cells by mediating photosynthesis as well as pigment and carbon metabolism, providing new knowledge for in-depth analysis of the mechanism of light stress resistance in the algae.
Chlamydomonas reinhardtii/genetics* ; Photosynthesis/genetics* ; Plants/metabolism* ; Protein Kinases ; Threonine/metabolism* ; Carbon/metabolism* ; Serine/metabolism*

In the current international situation, there is the possibility of nuclear war and nuclear terrorism. The nuclear and radiological emergency in the event of an accident should be enhanced. The World Health Organization (WHO) issued a publication on January 27, 2023, updating the list of drugs recommended for stockpiling in response to radiation and nuclear emergencies, which was the first update since 2007. The list of recommended drug stocks in the publication includes drugs to prevent or reduce the effects of radiation, as well as drugs used to treat injuries after exposure. Based on the list of drugs, this article reviews the emergency response to nuclear and radiological accidents, the general situation of emergency drug stockpiles, drug reserves in some countries, and current considerations, with a view to providing references for emergency medical rescue in nuclear and radiological accidents in China.