Objective:To investigate the effect of fecal microbiota transplantation(FMT)on unilateral ureteral obstruction(UUO)-induced renal fibrosis in mice.Methods:Male C57BL/6J mice were randomly divided into the control group,UUO group,UUO+FMT group and myeloid-derived suppressor cells(MDSCs)transfer group.The latter 3 groups were constructed renal fibrosis models by UUO,the UUO+FMT group received FMT from control mice after UUO surgery,and the MDSCs transfer group underwent splenectomy and intravenous injection of MDSCs from the peripheral blood of the UUO+FMT group.Renal tissue specimens were collected at 14 d after UUO for HE and Masson staining.TNF-α and IL-10 expression levels were detected by real-time fluorescence quantitative PCR(qRT-PCR),Western blot and immunofluorescence staining.Results:HE staining showed that the renal tissue structure of the control group was normal.The UUO group showed significant dilatation of renal tubules accompanied by obvious inflammatory cell infiltration.However,the renal lesions in the UUO+FMT group and MDSCs transfer group were significantly improved compared with those in the UUO group.Masson staining showed that the positive area of collagen deposition significantly increased in the UUO group compared with the control group,while the positive area of collagen deposition decreased in the UUO+FMT group and MDSCs transfer group compared with the UUO group.The results of qRT-PCR,Western blot and immunofluorescence showed that the expression levels of TNF-α and IL-10 were elevated in renal tissues of the UUO group compared with the control group.Compared with the UUO group,the expression level of TNF-α decreased while IL-10 increased in the UUO+FMT group and MDSCs transfer group.Conclusions:FMT reduces the expression of TNF-α and increase the expression of IL-10 in the kidney of UUO mice,and alleviates renal fibrosis.FMT may exert a nephroprotective effect by regulating MDSCs.

Background and purpose:Human epidermal growth factor receptor 2(HER2)serves as one of the paramount drivers of breast cancer metastasis,with roughly 20%-30%of breast cancer patients exhibiting high expression of HER2.The expression level of HER2 is regulatable at multiple molecular levels and determines the metastatic potential of breast cancer cells;however,the manner in which HER2 expression is modulated at the mRNA level remains ambiguous.Circ-0007766 is a circRNA originated from the coding gene ERBB2 for HER2,and whether circ-0007766 can regulate HER2 expression via the ceRNA mechanism has not been reported.This study aimed to analyze whether circ-0007766 acts as a miR-1972 sponge to promote breast cancer cell migration and invasion via upregulation of HER2 expression.Methods:In this study,a high-throughput circRNA chip was employed to screen for circRNAs that exhibited highly specific expression in HER2-positive breast cancer cells.RNA fluorescence in situ hybridization(FISH)was utilized to detect the subcellular localization of circ-0007766.The BaseScope experiment was conducted to analyze the expression level of circ-0007766 in breast cancer tissues and its clinical diagnostic significance.Breast cancer cell models with overexpression and knockdown of circ-0007766 were constructed by transfecting cloning plasmids and siRNA in vitro.The effect of circ-0007766 on the migration and invasion of breast cancer cells was assessed using transwell migration and invasion experiments,and the migration and invasion abilities of MDA-MB-231 and SK-BR-3 cells were measured.Additionally,it was evaluated whether circ-0007766 could promote the migration and invasion of breast cancer cells through miR-1972.A dual luciferase reporter gene assay was used to verify whether circ-0007766 could regulate HER2 expression by binding to miR-1972.The direct interaction between circ-0007766 and miR-1972 was further verified through the RAP experiment.RIP detection was performed in MDA-MB-231 cells,and the relative 3'UTR of HER2 mRNA was measured by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR).Western blot was used to detect the protein expressions.Results:Circ-0007766 was conspicuously highly expressed in HER2-positive breast cancer cells and distributed in both the cytoplasm and nucleus of cells,with the preponderance being in the cytoplasm.The expression level of circ-0007766 was strikingly higher in breast cancer tissues than in para-cancerous tissues.The expression of circ-0007766 was significantly elevated in HER2-positive breast cancer samples compared with HER2-negative samples.The overexpression(knockdown)of circ-0007766 in HER2-negative breast cancer cells(in HER2-positive breast cancer cells)was capable of promoting(inhibiting)the migration and invasion of breast cancer cells.Circ-0007766 directly bound to miR-1972,which inhibited breast cancer cell migration and invasion,thereby forming an endogenous competitive RNA(ceRNA)regulatory network and impeding the downregulation of HER2 mRNA and protein expression mediated by miR-1972.Circ-0007766 could potentiate the inhibitory effect of miR-1972 on HER2-mediated breast cancer cell migration and invasion that was negatively regulated by miR-1972.CircRNAs sequestered miRNAs to function as ceRNAs,thereby regulating gene expression at both the transcriptional and translational levels.Finally,we discovered that the expressions of circ-0007766 and HER2 were positively correlated in breast cancer cell and tissue samples,while the expression levels of miR-1972 and HER2 were negatively correlated.Circ-0007766 could specifically target miR-1972 to hinder its regulatory effect on HER2 expression.Conclusion:This study discovers that circ-0007766 facilitates the migration and invasion of breast cancer cells via the miR-1972/HER2 signal axis,offering a novel biomarker and potential therapeutic target for patients with metastatic HER2-positive breast cancer.

Three novel sesquiterpenoid heterodimers,designated as auckcostusolides A-C(1-3),were isolated from Aucklandia costus leaves.The structures of compounds 1-3 were elucidated through comprehensive spectroscopic analysis,with their absolute configurations established using a combination of X-ray single-crystal diffraction and electronic circular dichroism(ECD)calculations.Notably,compounds 1 and 2,despite sharing identical planar structures derived from two identical sesquiterpenoids,exhibited oppos-ite configurations at C-11 and C-8'.This configurational difference can be attributed to distinct Diels-Alder cycloaddition processes between the sesquiterpenoid monomers.Additionally,the cytotoxic effects of compounds 1-3 were evaluated against colorectal can-cer HCT116 cells,fibrosarcoma HT1080 cells,and hepatocellular carcinoma HepG2 cells.Compounds 1-3 induced cell death was characterized by endoplasmic reticulum(ER)swelling and cytoplasmic vacuolization,typical morphological changes associated with paraptosis.Mechanistic studies revealed that compounds 1 and 3 triggered paraptosis-like cell death through the accumulation of react-ive oxygen species(ROS),activation of ER stress,and stimulation of the MAPK signaling pathway.

OBJECTIVE: To investigate the regulatory effects of miR-30e-5p on biological behaviors of colorectal cancer cells and the role of PTEN/CXCL12 axis in mediating these effects. METHODS: Bioinformatic analysis was performed to explore the differential expression of miR-30e-5p between colorectal cancer tissues and normal tissues. RT-qPCR was used to detect the differential expression of miR-30e-5p in intestinal epithelial cells and colorectal cancer cells. Bioinformatics and dual luciferase assay were used to predict and validate the targeting relationship between miR-30e-5p and PTEN. Human and murine colorectal cancer cell lines were transfected with miR-30e-5p mimics, miR-30e-5p inhibitor, miR-30e-5p mimics+LV-PTEN, or miR-30e-5p inhibitor + si-PTEN. The changes in biological behaviors of the cells were detected using plate clone formation assay, CCK-8 assay, flow cytometry, scratch healing and Transwell assays. PTEN and CXCL12 expressions in the cancer cells were detected by Western blotting. The effects of miR-30e-5p inhibitor on colorectal carcinogenesis and development were observed in nude mice. RESULTS: Bioinformatic analysis showed that miR-30e-5p expression was significantly elevated in colorectal cancer tissues compared with the adjacent tissue (P < 0.01). Higher miR-30e-5p expression was detected in colorectal cancer cell lines than in intestinal epithelial cells (P < 0.01). Dual luciferase assay confirmed the targeting relationship between miR-30e-5p and PTEN (P < 0.05). Transfection with miR-30e-5p mimics significantly enhanced proliferation and metastasis and inhibited apoptosis of the colorectal cancer cells (P < 0.05), and co-transfection with LV-PTEN obviously reversed these changes (P < 0.05). MiR-30e-5p mimics significantly inhibited PTEN expression and enhanced CXCL12 expression in the cancer cells (P < 0.01), and miR-30e-5p inhibitor produced the opposite effect. Transfection with miR-30e-5p inhibitor caused cell cycle arrest in the cancer cells, which was reversed by co-transfection with si-PTEN (P < 0.05). In the in vivo experiments, the colorectal cancer cells transfected with miR-30e-5p inhibitor showed significantly lowered tumorigenesis. CONCLUSION Overexpression of miR-30e-5p promotes the malignant behaviors of colorectal cancer cells by downregulating PTEN to activate the CXCL12 axis.
Humans ; Animals ; Mice ; MicroRNAs/metabolism* ; Cell Line, Tumor ; Cell Proliferation/physiology* ; Mice, Nude ; Cell Movement/physiology* ; Colorectal Neoplasms/pathology* ; Luciferases/metabolism* ; Gene Expression Regulation, Neoplastic ; PTEN Phosphohydrolase/metabolism* ; Chemokine CXCL12/metabolism*

Although somatic cells can be reprogrammed to pluripotent stem cells (PSCs) with pure chemicals, authentic pluripotency of chemically induced pluripotent stem cells (CiPSCs) has never been achieved through tetraploid complementation assay. Spontaneous reprogramming of spermatogonial stem cells (SSCs) was another non-transgenic way to obtain PSCs, but this process lacks mechanistic explanation. Here, we reconstructed the trajectory of mouse SSC reprogramming and developed a five-chemical combination, boosting the reprogramming efficiency by nearly 80- to 100-folds. More importantly, chemical induced germline-derived PSCs (5C-gPSCs), but not gPSCs and chemical induced pluripotent stem cells, had authentic pluripotency, as determined by tetraploid complementation. Mechanistically, SSCs traversed through an inverted pathway of in vivo germ cell development, exhibiting the expression signatures and DNA methylation dynamics from spermatogonia to primordial germ cells and further to epiblasts. Besides, SSC-specific imprinting control regions switched from biallelic methylated states to monoallelic methylated states by imprinting demethylation and then re-methylation on one of the two alleles in 5C-gPSCs, which was apparently distinct with the imprinting reprogramming in vivo as DNA methylation simultaneously occurred on both alleles. Our work sheds light on the unique regulatory network underpinning SSC reprogramming, providing insights to understand generic mechanisms for cell-fate decision and epigenetic-related disorders in regenerative medicine.
Male ; Mice ; Animals ; Cellular Reprogramming/genetics* ; Tetraploidy ; Pluripotent Stem Cells/metabolism* ; Induced Pluripotent Stem Cells/metabolism* ; DNA Methylation ; Spermatogonia/metabolism* ; Germ Cells/metabolism*

Objective:To develop the Nurse Managers Negative Leadership Behavior Scale and test its reliability and validity.Methods:This study is a cross-sectional study. The Nurse Managers Negative Leadership Behavior Scale item pool was formed through literature review and semi-structured interviews. A total of 28 nursing management experts from Hubei Province, Beijing, Guangdong Province and other places were selected for expert consultation to form the first draft of the scale. The scale was further revised through pre-experiment and item analysis. In May 2022, 300 nurses from the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were selected by convenient sampling for a questionnaire survey to test the reliability and validity of the scale. A total of 300 questionnaires were distributed, and 265 valid questionnaires were recovered, with an effective recovery rate of 88.33%. One week after the survey, 20 nurses were randomly selected to re-issue the questionnaire for the retest reliability test of the scale.Results:Totally, 19 experts completed two rounds of expert consultation, with expert authority coefficient of 0.880, Kendall harmony coefficient of 0.160 and 0.130 ( P<0.05) . Exploratory factor analysis extracted six factors, including neglect of needs, personal attack, right satisfaction, unpredictable behavior, slack work and improper supervision, and the cumulative variance interpretation rate was 75.125%. The confirmatory factor analysis showed that the model fitted well and the factor structure was stable. The Nurse Managers Negative Leadership Behavior Scale included six dimensions and 36 items. The total Cronbach's α coefficient of the scale was 0.880, the split-half reliability coefficient was 0.895, and the retest reliability coefficient was 0.876. The content validity index of the scale was 0.930, and the content validity index of each item was 0.800 to 1.000. Conclusions:The Nurse Managers Negative Leadership Behavior Scale has good reliability and validity, and can be used to evaluate the negative leadership behavior of head nurses in China.

Objective:To analyze the current development status, research hot-spots and development trends of county-level Chinese hospitals in China.Methods:By retrieving the papers of county-level Traditional Chinese Medicine (TCM) hospitals in China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodicals Full-text Database (VIP), Wanfang and China Biomedical Database (SinoMed ) with CiteSpace 5.5.R2 software to draw maps of the author, institution and keyword and make analysis.Results:A total of 598 papers are included in this study, and the trend of publications shows an upward trend and then a downward trend. Researchers conduct research in the form of forming research teams. The research institutions are mainly medical colleges and scientific research institutions. The most frequently showed keyword is "medical reform". The keyword knowledge map shows that the research content mainly involves medical reform, problem analysis and countermeasures, economic operation efficiency, TCM service capability, data envelopment analysis and so on.Conclusions:The county-level TCM hospitals generally show sound development trend in China. The research trend is dominated by county-level TCM hospitals. Scale development has been transformed into the study of hospital operation efficiency. County-level TCM hospitals need to start from their own actual conditions, strengthen cooperation in the form of teams and strengthen academic cooperation among institutions, so as to realize the basic TCM services for ordinary people.

Objective:To investigate the clinicopathological features and computed tomography (CT) findings of tracheal glomus tumor (GT) in order to improve the understanding and diagnosis of tracheal GT.Methods:The clinical and CT imaging data of 2 patients with tracheal GT diagnosed in the First Affiliated Hospital of Zhengzhou University were analyzed retrospectively. The image characteristics based on previous reports were analyzed.Results:The clinical manifestations of trachea GT were dyspnea, chest tightness, hemoptysis, etc., which were easy to be misdiagnosed. The CT manifestations were spherical or nodular protrusions in the trachea cavity, with uneven edges, which can be lobulated. Cystic changes can be seen in the focus. After enhancement, it showed progressive filling and obvious enhancement, without deep infiltration and distant metastasis.Conclusions:Chest CT can accurately localize tracheal GT, provide its morphological size, blood supply, growth characteristics and other characteristics, accurately display the overall morphology of the lesion, and provide some help for the development of the surgical plan, and its definitive diagnosis still relies on pathological examination.

During the traumatic brain injury (TBI), improved expression of circulatory miR-21 serves as a diagnostic feature. Low levels of exosome-miR-21 in the brain can effectively improve neuroinflammation and blood-brain barrier (BBB) permeability, reduce nerve apoptosis, restore neural function and ameliorate TBI. We evaluated the role of macrophage derived exosomes-miR-21 (M-Exos-miR-21) in disrupting BBB, deteriorating TBI, and Rg1 interventions. IL-1

Objective:To examine the correlation factors of acute appendicitis associated with appendiceal neoplasms.Methods:Consecutive 712 patients with acute appendicitis who treated at Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University from January 2002 to December 2016 were analyzed retrospectively. There were 314 females and 398 males, aging (42.5±16.2) years (range: 14 to 94 years). Among the 712 cases, 36 patients were diagnosed with acute appendicitis associated with appendiceal neoplasms, the other 676 patients had no appendiceal neoplasm. The patients ′ clinical baseline characteristics and clinical parameters were compared between the two groups. The correlation factors of acute appendicitis associated with appendiceal neoplasms were evaluated by using the univariate (χ 2 test or t test) and multivariate Logistic regression analysis. The area under curve of receiver operating characteristic curves was utilized to evaluate the discriminatory power of the predictive models. Results:According to the univariate analysis, gender, age, body mass index, the duration of chronic right low abdominal pains≥3 months, the frequency of recurrently acute right lower abdominal pain≥2, the frequency of acute right lower abdominal pain, past history of diabetes, hypertension or coronary heart disease, the level of neutrophils and leukocytes preoperatively, stercolith and periappendiceal effusion, and modified Alvarado score were positively correlated with appendiceal neoplasms (all P<0.05). Then four variables were incorporated into the model eventually by multivariate Logistic regression analysis, which were as follows: age (increased per decade) ( OR=2.23, 95% CI: 1.68 to 2.95, P<0.01), gender (female) ( OR=4.21, 95% CI: 1.74 to 10.19, P=0.001), the duration of chronic right low abdominal pains (more than 3 months) ( OR=2.53, 95% CI: 1.01 to 3.37, P=0.048), and modified Alvarado score (decreased per 1 score) ( OR=2.54, 95% CI: 1.87 to 3.34, P<0.01). The area of curve was 0.93 (95% CI: 0.88 to 0.97), which indicated that the model exhibits an excellent ability to discriminate between appendiceal neoplasms and acute appendicitis. Conclusions:The older age, female, the duration of chronic right low abdominal pains, and lower modified Alvarado score are independent correlation factors for acute appendicitis associated with appendiceal neoplasms. Clinicians should be alert for the above clinical characteristics and choose optimal treatment for acute appendicitis associated with appendiceal neoplasms.