Objective To explore the difference in gut microbiota composition between patients with obstructive sleep apnea(OSA)and healthy individuals and the role of gut microbiota in the pathogenesis of OSA.Methods Thirty-nine patients with OSA admitted to our hospital between May and December,2022 and 20 healthy individuals were enrolled in this study.Stool samples were collected from all the participants for analysis of microbiome composition using 16S rRNA high-throughput sequencing analysis.The alpha diversity,beta diversity,and species difference were determined between the two groups and marker species analysis and metabolic pathway function prediction analysis were performed.Results The species diversity(Shannon and Simpson)indexes,richness(observed species)and evenness(Pielou)of gut microbiota were significantly lower in OSA patients than in the healthy individuals(P<0.05).The OSA patients had also a significantly lowered community diversity(P<0.05)with different gut microbial communities from those of the healthy individuals shown by increased relative abundance of potentially pathogenic bacteria such as Pseudomonas and Monocytogenes(P<0.05).LEfSe analysis showed that the abundance of 23 species of gut microbiota differed significantly between the two groups and the OSA patients had significant increases in the abundance of Pseudomonas,Meganomonas,and Fusobacterium(P<0.05).The differential marker flora affected host homeostasis.Random Forest and ROC curve analyses confirmed that Pseudomonas could be used as important biomarkers for a differential diagnosis.Metabolic pathway function prediction analysis showed that biosynthesis function had the greatest contribution to maintaining gut microbiota homeostasis,and Pseudomonas affected the occurrence and progression of OSA by participating in aromatic bioamine degradation and ketogluconic acid metabolic pathway.Conclusion OSA patients have obvious gut microbiota disturbances,and Pseudomonas may affect the development of OSA by participating in substance metabolism to serve as the potential target gut bacteria for OSA treatment.

Objective:To explore the causal relationship between gut microbiota and lung function (FEV1/FVC) using two-sample Mendelian randomization method; To explore its application in the TCM field.Methods:This was a Mendelian randomization study. The GWAS data of gut microbiota from the MiBioGen consortium study and the GWAS data of lung function (FEV1/FVC) published by IEU OpenGWAS in the public database were used, and instrumental variables were extracted according to prespecified thresholds. The inverse variance weighted method (IVW) was mainly used for analysis. The results were evaluated according to the effect indicator β value and 95% CI. When the IVW method was statistically significant, further sensitivity analysis was performed. Leave-one-out test, heterogeneity test, horizontal gene pleiotropy test and MR-Egger regression intercept analysis were used to verify the stability and reliability of the results. Results:A total of 10 causal relationships between gut microbiota and lung function (FEV1/FVC) were determined using the IVW method: family. BacteroidalesS24.7group ( β=-0.029, P=0.015), family. ClostridialesvadinBB60group ( β=-0.028, P=0.040), family. Streptococcaceae ( β=-0.056, P=0.042), genus. LachnospiraceaeFCS020group ( β=0.025, P=0.029), genus. Lactococcus ( β=-0.024, P=0.038), genus. Peptococcus ( β=0.025, P=0.049), genus. RuminococcaceaeUCG011 ( β=-0.030, P=0.038), genus. Ruminococcus2 ( β=0.028, P=0.033), genus. Terrisporobacter ( β=-0.030, P=0.018), phylum. Cyanobacteria ( β=0.027, P=0.039). Leave-one-out analysis showed that the results were stable, and the effects of heterogeneity and horizontal gene pleiotropy on causal effect estimation could be removed. Conclusion:The gut microbiota may play a role in the changes of lung function, which to a certain extent confirms the TCM theory of "exterior-interior relationship between the lung and large intestine", and can provide certain reference for the research direction of TCM.

Objective:To construct a new thrombus risk assessment model and evaluate its predictive ability for venous thromboembolism(VTE)in the patients with malignant tumors,and to provide the basis for the early predition of the malignant tumor patients with high risk for VTE.Methods:A total of 128 untreated malignant tumor patients were included,of which 40 were diagnosed with VTE within 2 months of malignant tumor diagnosis and categorized as VTE group.A total of 88 patients who did not develop VTE were categorized as non-VTE group.The clinical risk factors and laboratory indicators of the patients in two groups were compared and analyzed;the types of thrombotic events of the patients were analyzed;the diagnostic values of thrombin-antithrombin-complex(TAT),α2-plasmin inhibitor-plasmin complex(PIC),D-dimer(D-dimer),and fibrin degradation products(FDP)in malignant tumors complicated by VTE were assessed using receiver operating characteristic(ROC)curve analysis;Multivariate Logistic regression analysis was used to analyze the correlations of the clinical risk factors and biomarkers with the malignant tumors complicated with VTE.A new thrombus risk assessment model was constructed,consisting of TAT≥0.70 μg·L-1,poor differentiation,and cardiovascular risk factors.The predictive probability of the model for malignant tumors complicated by VTE was evaluated based on the significance,goodness of fit,calibration curve,and C value of the model.The clinical application value of the new thrombus risk assessment model,COMPASS-CAT risk score(CRS),and Khorana risk score(KRS)in assessing malignant tumor patients complicated by VTE was compared using the C value and decision curve analysis(DCA).Results:The plasma levels of TAT(P＜0.001),PIC(P＜0.001),D-dimer(P＜0.05),and FDP(P＜0.01)of the patients in VTE group were higher than those in non-VTE group.Compared with the patients without cardiovascular risk factors,poor differentiation,and lymphatic metastasis,the malignant tumor patients with cardiovascular risk factors(P＜0.001),poor differentiation(P＜0.001),and lymphatic metastasis(P＜0.05)were more likely to develop VTE.Most VTE events(65％)were isolated deep vein thromboembolism(DVT).The ROC curve analysis showed that the area under the curve(AUC),sensitivity,and specificity of TAT and PIC were higher than those of D-dimer and FDP.TAT≥0.70 μg·L-1(P＜0.05),poor differentiation(P＜0.01),and cardiovascular risk factors(P＜0.01)were the independent risk factors for VTE in the malignant tumor patients.A new thrombus risk assessment model consisting of TAT≥0.70 μg·L-1,poor differentiation,and cardiovascular risk factors was constructed.The new risk assessment model had a high goodness of fit(P=0.805)and good predictive ability during internal validation(x2=75.266,P＜0.001).The ROC curve analysis results showed that the C values for the new thrombus risk prediction model,CRS,and KRS were 0.908,0.676,and 0.541,respectively.The DCA curve analysis results showed that the new thrombus risk assessment model had a higher net benefit rate compared with CRS and KRS.Conclusion:TAT and PIC have greater diagnostic efficiency than D-dimer in the early prediction of the malignant tumor patients with high-risk VTE.For the patients included in this study,the new thrombus risk assessment model,constructed from TAT≥0.70 μg·L-1,poor differentiation,and cardiovascular risk factors,has superior diagnostic efficiency and clinical predictive value compared with CRS and KRS.

Objective To explore the difference in gut microbiota composition between patients with obstructive sleep apnea(OSA)and healthy individuals and the role of gut microbiota in the pathogenesis of OSA.Methods Thirty-nine patients with OSA admitted to our hospital between May and December,2022 and 20 healthy individuals were enrolled in this study.Stool samples were collected from all the participants for analysis of microbiome composition using 16S rRNA high-throughput sequencing analysis.The alpha diversity,beta diversity,and species difference were determined between the two groups and marker species analysis and metabolic pathway function prediction analysis were performed.Results The species diversity(Shannon and Simpson)indexes,richness(observed species)and evenness(Pielou)of gut microbiota were significantly lower in OSA patients than in the healthy individuals(P<0.05).The OSA patients had also a significantly lowered community diversity(P<0.05)with different gut microbial communities from those of the healthy individuals shown by increased relative abundance of potentially pathogenic bacteria such as Pseudomonas and Monocytogenes(P<0.05).LEfSe analysis showed that the abundance of 23 species of gut microbiota differed significantly between the two groups and the OSA patients had significant increases in the abundance of Pseudomonas,Meganomonas,and Fusobacterium(P<0.05).The differential marker flora affected host homeostasis.Random Forest and ROC curve analyses confirmed that Pseudomonas could be used as important biomarkers for a differential diagnosis.Metabolic pathway function prediction analysis showed that biosynthesis function had the greatest contribution to maintaining gut microbiota homeostasis,and Pseudomonas affected the occurrence and progression of OSA by participating in aromatic bioamine degradation and ketogluconic acid metabolic pathway.Conclusion OSA patients have obvious gut microbiota disturbances,and Pseudomonas may affect the development of OSA by participating in substance metabolism to serve as the potential target gut bacteria for OSA treatment.

Tooth germ injury can lead to abnormal tooth development and even tooth loss, affecting various aspects of the stomatognathic system including form, function, and appearance. However, the research about tooth germ injury model on cellular and molecule mechanism of tooth germ repair is still very limited. Therefore, it is of great importance for the prevention and treatment of tooth germ injury to study the important mechanism of tooth germ repair by a tooth germ injury model. Here, we constructed a Tg(dlx2b:Dendra2-NTR) transgenic line that labeled tooth germ specifically. Taking advantage of the NTR/Mtz system, the dlx2b⁺ tooth germ cells were depleted by Mtz effectively. The process of tooth germ repair was evaluated by antibody staining, in situ hybridization, EdU staining and alizarin red staining. The severely injured tooth germ was repaired in several days after Mtz treatment was stopped. In the early stage of tooth germ repair, the expression of phosphorylated 4E-BP1 was increased, indicating that mTORC1 is activated. Inhibition of mTORC1 signaling in vitro or knockdown of mTORC1 signaling in vivo could inhibit the repair of injured tooth germ. Normally, mouse incisors were repaired after damage, but inhibition/promotion of mTORC1 signaling inhibited/promoted this repair progress. Overall, we are the first to construct a stable and repeatable repair model of severe tooth germ injury, and our results reveal that mTORC1 signaling plays a crucial role during tooth germ repair, providing a potential target for clinical treatment of tooth germ injury.
Animals ; Mice ; Mechanistic Target of Rapamycin Complex 1/pharmacology* ; Signal Transduction ; Tooth/metabolism* ; Tooth Germ/metabolism* ; Odontogenesis

Objective:To investigate the regulatory effect of miR-26a in radiation-induced heart disease (RIHD) mice.Methods:C57/BL6 mice were used to establish RIHD models. The cardiac function, fibrosis, the expression levels of collagen 1 (COL1) and connective tissue growth factor (CTGF), and miR-26a were detected in RIHD mice. Whether CTGF was the target gene of miR-26a was verified by dual luciferase kit. Moreover, cardiac fibroblasts were transfected with miR-26a up and miR-26a down lentivirus vectors to construct the miR-26a overexpression and underexpression cell models. The expression of CTGF, proliferation, and apoptosis of cardiac fibroblasts were detected.Results:In the RIHD mice, heart function was decreased, myocardial fibrosis was remodeled, the expression levels of COL1 and CTGF were up-regulated, and the expression level of miR-26a was down-regulated. Dual luciferase reporter assay confirmed that CTGF was the target gene regulated by miR-26a. Overexpression of miR-26a could inhibit the expression of CTGF, suppress the proliferation of cardiac fibroblasts, promote cell apoptosis and secrete collagen. Underexpression of miR-26a yielded the opposite results.Conclusion:MiR-26a affects the function of cardiac fibroblasts by targeting CTGF and probably mediates the process of radiation-induced myocardial fibrosis, which may become a new regulatory target of RIHD.

Objective:To explore the work experience of nurses in Thoracic Surgery Department during independent working, so as to provide a reference for organizational management, education and training.Methods:From September 2020 to July 2021, 27 Thoracic Surgery Department nurses of 3 hospitals in Beijing, Shanghai and Guangzhou were selected for the in-depth interview. Colaizzi 7-step analysis was used for data analysis.Results:A total of 4 themes were extracted, namely stress, role adaptation, support sources, expectations for management and training. The stress theme included anxiety and fears about new phases of work, stress of communication and other stresses. The theme of role adaptation involved improving theoretical and practical abilities, being affirmed by patients, trusted by colleagues, and becoming mature in mind. The theme of support sources consisted of team support and family support. The theme of expectations for management and training composed of strengthening organizational support and flexible education and training before independent working.Conclusions:Negative emotions such as tension and anxiety are common in Thoracic Surgery Department nurses in the early stage of independent working. Thoracic Surgery Department nurses experience the satisfaction of self-realization after adapting to their role. Team and family support play an important role during the role transition. In the future, organizational management should be strengthened, education and training should be diversified, and a core competence evaluation system for Thoracic Surgery Department nurses should be established to promote the smooth transition of Thoracic Surgery Department nurses to work independently.

Objective:To investigate the radiosensitizing effect of Ta 4C 3-PVP nanosheets on the tumor of 4T1 murine triple-negative breast cancer cells planted in mice. Methods:4T1 tumor-bearing mice model was established by subcutaneous injection of 4T1 cells into the right flank of the female BALB/c mice. The mice were divided into four groups uniformly according to their tumor size: blank control group, Ta 4C 3-PVP group, ionizing radiation (IR) group and Ta 4C 3-PVP plus IR group. A single dose of 8 Gy X-ray local irradiation was given to xenograft tumor at 24 h after tail intravenous injection of Ta 4C 3-PVP (20 mg/kg). The xenograft tumor volume and weight, the pathological changes of tumor tissue, the expression of tumor proliferative marker Ki-67 protein, and the formation of γ-H2AX foci [a DNA double-strand breaks (DSBs) molecular marker] were detected. Tumor growth curve was established, and enhancement factor (EF) and tumor inhibition rate were calculated. Results:Compared with the blank control group, tumor growth was significantly inhibited ( t=5.41, 9.59, P < 0.05) and tumor weight was markedly decreased ( t=2.67, 4.40, P < 0.05) in both IR group and Ta 4C 3-PVP plus IR group at day 16 after IR. The EF in Ta 4C 3-PVP plus IR group was 1.57, and tumor inhibition rate in Ta 4C 3-PVP plus IR group were about 64%, which was much higher than that of IR group alone(42%). Immunohistochemistry and immunofluorescence histochemistry assays showed that the expression of Ki-67 protein was obviously decreased and the amount of γ-H2AX foci was significantly increased in both IR group and Ta 4C 3-PVP plus IR group in comparison with the blank control group ( t=5.73, 8.02, 2.97, 9.86, P < 0.05). Moreover, the inhibition of Ki-67 protein expression and the increase of γ-H2AX foci were much higher in Ta 4C 3-PVP plus IR group than that in IR group ( t=4.75, 4.42, P < 0.05). Conclusions:Ta 4C 3-PVP nanosheets could enhance radiosensitivity of xenograft tumor in 4T1 tumor-bearing mice through increasing the IR-induced DNA DSBs.

Objective:To investigate the regulatory role of microRNA in radiation-induced heart disease (RIHD) in mice and provide a new strategy for its treatment.Methods:Based on the Gene Expression Omnibus database (GSE147241), which includes normal heart tissue and irradiation heart tissue, we conducted bioinformatics research and analysis to determine the differentially-expressed genes. Then, thirty male C57/BL6 mice were randomly divided into the control group, irradiation group and miR-133a overexpression intervention group. The heart received single dose of X-ray 20 Gy in the irradiation group and miR-133a overexpression intervention group, but not in the control group, and then fed for 16 weeks. Cardiac function was assessed by echocardiography. Myocardial fibrosis was detected by Masson staining. The expression levels of miR-133a, CTGF, COL-1 and COL-3 mRNA were detected by qRT-PCR. The expression levels of CTGF, COL-1 and COL-3 proteins were detected by western blot.Results:miR-133a was the differentially-expressed gene between the irradiation and control groups. Overexpression of miR-133a could mitigate the decrease in cardiac function and increase in myocardial collagen content ( P<0.01). Meantime, overexpression of miR-133a could down-regulate the expression levels of CTGF, COL-1, COL-3 mRNA and protein ( P<0.01). Conclusions:Radiation increases the synthesis of collagen and leads to myocardial fibrosis remodeling. Overexpression of miR-133a can alleviate the radiation-induced myocardial fibrosis.

Small proteins specifically refer to proteins consisting of less than 100 amino acids translated from small open reading frames (sORFs), which were usually missed in previous genome annotation. The significance of small proteins has been revealed in current years, along with the discovery of their diverse functions. However, systematic annotation of small proteins is still insufficient. SmProt was specially developed to provide valuable information on small proteins for scientific community. Here we present the update of SmProt, which emphasizes reliability of translated sORFs, genetic variants in translated sORFs, disease-specific sORF translation events or sequences, and remarkably increased data volume. More components such as non-ATG translation initiation, function, and new sources are also included. SmProt incorporated 638,958 unique small proteins curated from 3,165,229 primary records, which were computationally predicted from 419 ribosome profiling (Ribo-seq) datasets or collected from literature and other sources from 370 cell lines or tissues in 8 species (Homo sapiens, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Danio rerio, Saccharomyces cere-visiae, Caenorhabditis elegans, and Escherichia coli). In addition, small protein families identified from human micro-biomes were also collected. All datasets in SmProt are free to access, and available for browse, search, and bulk downloads at http://bigdata.ibp.ac.cn/SmProt/.