ObjectiveTo explore the sequential effects of hypoxic exercising on miR-27/PPARγ and lipid metabolism target gene and protein expression levels in the obesity rats’ liver. Methods13-week-old male diet-induced obesity rats were randomly divided into three groups (n＝10): normal oxygen concentration quiet group (N), hypoxia quiet group (H), hypoxic exercise group (HE). Exercise training on the horizontal animal treadmill for 1 h/d, 5 d/week for a total of 4 week, and the intensity of horizontal treadmill training was 20 m/min (hypoxic concentration was 13.6%). Comparison of the weights of perirenal fat and epididymal fat in rats across different groups and calculation of Lee’s index based on body weight and body length of rats in each group were done. And the serum concentrations of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) levels were detected. RT-PCR and Western Blot were used to detect the levels of miR-27, PPARγ, CYP7A1 and CD36. ResultsHypoxic exercise decreased the expression levels of miR-27 in the obese rats’ liver, however, the expression level of PPARγ was gradually increased. The expression levels of miR-27 in HE group were significantly lower than N group (P<0.05). The expression levels of PPARγ mRNA in N group were significantly lower than H group (P<0.05), especially lower than HE group (P<0.01). The protein expression of PPARγ protein in N group was significantly lower than that other groups (P<0.01). The expression of lipid metabolism-related genes and proteins increased in the obese rats’ liver. The expression of CYP7A1 mRNA in N group was significantly lower than H group (P<0.05), especially lower than HE group (P<0.01). The expression of CYP7A1 protein in the obese rats’ liver in N group was extremely lower than H group and HE group (P<0.01). The protein expression of CD36 in N group was significantly lower than that in HE group (P<0.05). Hypoxia exercise improved the related physiological and biochemical indexes of lipid metabolism disorder. The perirenal fat weight of obese rats in HE group was extremely lower than N group and H group (P<0.01), and the perirenal fat weight in N group was significantly higher than H group (P<0.05). The epididymal fat weight in N group was significantly higher than H group (P<0.05), and extremely higher than HE group (P<0.01). The Lee’s index in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of TC in obese rats in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of TG in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of LDL-C in N group was extremely higher than HE group (P<0.01). The serum concentration of HDL-C in N group was extremely lower than H group (P<0.01). ConclusionHypoxia and hypoxia exercise may negatively regulate the levels of PPARγ by inhibiting miR-27 in the obese rats’ liver, thereby affecting the expression of downstream target genes CYP7A1 and CD36, and promoting cholesterol, fatty acid oxidation and HDL-C transport in the liver, and ultimately the lipid levels in obese rats were improved. The effect of hypoxia exercise on improving blood lipid is better than simple hypoxia intervention.

Antimicrobial resistance (AMR) is a growing public health crisis that requires innovative solutions. Emerging multidrug resistant (MDR) Salmonella typhimurium has raised concern for its effect on pathogenic infection and mortality in humans caused by enteric diseases. To combat these MDR Salmonella typhimurium pathogens, highly effective and broad-spectrum antibiotics such as flufenicol (FFC) need to be evaluated for their potent antibacterial activity against Salmonella typhimurium. However, the low solubility and low oral bioavailability of flufenicol need to be addressed to better combat AMR. In this work, we develop a novel nano-formulation, flufenicol nano-micelles (FTPPM), which are based on d-α-tocopherol polyethylene glycol 1,000 succinate (TPGS)/poloxamer 188 (P188), for the targeted treatment of biofilms formed by drug-resistant Salmonella typhimurium in the intestine. Herein, FTPPM were prepared via a thin film hydration method. The preparation process for the mixed micelles is simple and convenient compared with other existing nanodrug delivery systems, which can further decrease production costs. The optimized FTPPM demonstrated outstanding stability and sustained release. An evaluation of the in vivo anti-drug-resistant Salmonella typhimurium efficacy demonstrated that FTPPM showed a stronger efficacy (68.17 %) than did florfenicol-loaded TPGS polymer micelles (FTPM), flufenicol active pharmaceutical ingredients (FFC-API), and flufenicol commercially available medicine (FFC-CAM), and also exhibited outstanding biocompatibility. Notably, FTPPM also inhibited drug-resistant Salmonella typhimurium from forming biofilms. More importantly, FTPPM effectively restored intestinal flora disorders induced by drug-resistant Salmonella typhimurium in mice. In summary, FTPPM significantly improved the solubility and oral bioavailability of florfenicol, enhancing its efficacy against drug-resistant Salmonella typhimurium both in vitro and in vivo. FTPPM represent a promising drug-resistant Salmonella typhimurium treatment for curbing bacterial resistance via oral administration.

Antimicrobial resistance(AMR)is a growing public health crisis that requires innovative solutions.Emerging multidrug resistant(MDR)Salmonella typhimurium has raised concern for its effect on path-ogenic infection and mortality in humans caused by enteric diseases.To combat these MDR Salmonella typhimurium pathogens,highly effective and broad-spectrum antibiotics such as flufenicol(FFC)need to be evaluated for their potent antibacterial activity against Salmonella typhimurium.However,the low solubility and low oral bioavailability of flufenicol need to be addressed to better combat AMR.In this work,we develop a novel nano-formulation,flufenicol nano-micelles(FTPPM),which are based on D-α-tocopherol polyethylene glycol 1,000 succinate(TPGS)/poloxamer 188(P188),for the targeted treatment of biofilms formed by drug-resistant Salmonella typhimurium in the intestine.Herein,FTPPM were prepared via a thin film hydration method.The preparation process for the mixed micelles is simple and convenient compared with other existing nanodrug delivery systems,which can further decrease pro-duction costs.The optimized FTPPM demonstrated outstanding stability and sustained release.An evaluation of the in vivo anti-drug-resistant Salmonella typhimurium efficacy demonstrated that FTPPM showed a stronger efficacy(68.17％)than did florfenicol-loaded TPGS polymer micelles(FTPM),flufenicol active pharmaceutical ingredients(FFC-API),and flufenicol commercially available medicine(FFC-CAM),and also exhibited outstanding biocompatibility.Notably,FTPPM also inhibited drug-resistant Salmonella typhimurium from forming biofilms.More importantly,FTPPM effectively restored intestinal flora dis-orders induced by drug-resistant Salmonella typhimurium in mice.In summary,FTPPM significantly improved the solubility and oral bioavailability of florfenicol,enhancing its efficacy against drug-resistant Salmonella typhimurium both in vitro and in vivo.FTPPM represent a promising drug-resistant Salmonella typhimurium treatment for curbing bacterial resistance via oral administration.

Primary hyperparathyroidism is a disease with a large potential population. Some cases of primary hyperparathyroidism are non-primary, preventable and curable at early stage, requiring long-term follow-up after surgery. Therefore, all-round and full-cycle management are necessary for primary hyperparathyroidism, which involves an enhancing focus on etiological prevention, early detection, prompt diagnosis, timely intervention, multi-disciplinary standardized diagnosis and treatment, and postoperative scientific management. Meanwhile, implementing a "12+5+1" multidisciplinary joint diagnosis and treatment model, along with a two-way referral model, to achieve the transition from a disease-oriented diagnostic and treatment model to a patient-oriented, all-round and full-cycle interdisciplinary management model. This management can reduce the incidence and recurrence rate of primary hyperparathyroidism, and related osteoporosis or osteopenia, fractures, nephrolithiasis, metastatic vascular calcification, and systemic abnormal migratory calcium deposits, improve the overall quality of life and prognosis of patients.

Objective To investigate the value of serum hepatitis B virus(HBV)RNA for predicting hepatitis B virus e antigen(HBeAg)clearance and seroconversion after nucleoside(acid)analogs(NAs)treatment in patients with chronic hepatitis B(CHB).Methods Serum samples were collected from 178 CHB patients who received NAs monotherapy in Weihai Hospital affiliated to Shandong University of Traditional Chinese Medicine from February 12,2017 to February 21,2019.Serum HBV RNA levels were analyzed by real-time fluorescence-based quantitative PCR at baseline and after NAs treatment.Results The patients with HBeAg clearance and seroconversion showed significantly lower serum HBV RNA levels at baseline,6 months and 12 months of treatment compared with those without HBeAg clearance and seroconversion(P＜0.001).During follow-up,the patients with lower baseline HBV RNA levels had higher rate of cumulative HBeAg clearance(Log Rank x2=11.282,P=0.001)or seroconversion(Log Rank x2=10.739,P=0.001)than the patients with higher baseline HBV RNA levels.Cox regression model analysis indicated that serum HBV RNA levels at baseline,6 months and 12 months of treatment were an independent predictor for HBeAg clearance and seroconversion in CHB patients(P＜0.05).The area under the ROC curve(AUC)of baseline serum HBV RNA level was 0.808(95％CI:0.743-0.872)for predicting HBeAg clearance and 0.824(95％CI:0.763-0.885)for predicting seroconversion.The AUC of HBV RNA level at 6 months of treatment was 0.830(95％CI:0.765-0.894)for predicting HBeAg clearance and 0.732(95％CI:0.657-0.808)for predicting seroconversion.The AUC of HBV RNA level at 12 months of treatment was 0.737(95％CI:0.641-0.833)for predicting HBeAg clearance and 0.757(95％CI:0.671-0.842)for predicting seroconversion.The AUC of baseline HBV RNA level combined with HBV RNA decline at 6 months of treatment was 0.856(95％CI:0.795-0.917)for predicting HBeAg clearance and 0.864(95％CI:0.802-0.926)for predicting seroconversion.The AUC of baseline HBV RNA level combined with HBV RNA decline at 12 months of treatment was 0.881(95％CI:0.826-0.936)for predicting HBeAg clearance and 0.848(95％CI:0.784-0.911)for predicting seroconversion.Conclusions Serum HBV RNA levels have high predictive value for HBeAg clearance and seroconversion after NAs therapy in CHB patients,suggesting that HBV RNA levels are helpful for identifying non-responders and informing combination therapy.

Objective:To analyze the distribution and drug resistance of pathogens of bacterial bloodstream infection in patients with hematological diseases in the Department of Hematology of Tianjin Medical University General Hospital, and to provide etiological data for clinical empirical anti-infection treatment.Methods:A retrospective analysis was conducted on the general clinical information, pathogenic bacteria and drug susceptibility test results of patients with hematological diseases diagnosed with bacterial bloodstream infection by menstrual blood culture in our center from January 2016 to December 2022.Results:Patients included 498 inpatients, with a total of 639 bacterial strains. Among the patients, 86.9% patients had malignancies, and 76.7% had agranulocytosis. Symptoms of concurrent infections, including those of the respiratory tract, oral mucosa, skin and soft tissues, and abdominal sources were observed in 68.3% patients. Gram-negative bacteria (G -) accounted for 79.0% of the isolated bacteria, and gram-positive bacteria (G +) accounted for 21.0%. The top five isolated pathogens were Klebsiella pneumoniae (22.5%), Escherichia coli (20.8%), Pseudomonas aeruginosa (15.0%), Enterococcus faecium (5.5%), and Stenotrophomonas maltophilum (5.0%). Escherichia coli exhibited a decreasing trend of resistance to quinolones, cephalosporins, and carbapenems. Klebsiella pneumoniae exhibited increasing rates of resistance to quinolones and cephalosporins between 2016 and 2018, but the rated decreased after 2019. The resistance rate to carbapenems exhibited by Pseudomonas aeruginosa was approximately 20%. Carbapenem-resistant strains of Pseudomonas aeruginosa strains were first detected in 2017, with a peak resistance rate of 35.7%, detected in 2019. A 60.0% resistance rate to methicillin was observed in methicillin-resistant coagulase-negative staphylococci (MRCNS), and one case of linezolid-resistant MRCNS was detected. Conclusions:Pathogenic bacteria of bacterial bloodstream infections were widely distributed in our center, and precautions are warranted against carbapenem resistant P. aeruginosa and Klebsiella pneumoniae.

Objective To clarify the anti-inflammatory quality markers(Q-markers)of Salvia plebeia and determine their contents,so as to provide a reference for the quality control of Salvia plebeia.Methods The main components of Salvia plebeia were characterized by high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS).According to the fragmentation information of the secondary mass spectrometry and the literature data,the analysis and identification were carried out.Further,the active components with high oral bioavailability(OB)and in line with the five principles of drug-like(DL)were screened from the identified chemical components through the SwissADME platform.The SwissTargetPrediction database was used to find and predict the component targets of Salvia plebeia.Disease targets were screened through online Mendelian Inheritance in Man(OMIM),GeneCards database,etc.String11.5 database and Cytoscape3.7.2 software were used to construct the PPI network and screen core targets.Gene Ontology(GO)annotation and KEGG pathway enrichment analysis were performed using DAVID6.8,and the enriched pathways were verified by experiments to clarify their mechanism of action.Reverse traceability was used to analyze the potential pharmacodynamic material basis of key pathways,experimental verification was carried out,and high-performance liquid chromatography(HPLC)content determination method was established.Results 36 main components were identified,including flavonoids and terpenoids.Further screening of 190 active ingredients and disease intersection targets;through network topology screening,18 core targets were obtained;enrichment analysis showed that the primary pathways involved in the anti-inflammatory effect of Salvia plebeia include:NF-κB signaling pathway,PI3K-Akt signaling pathway and TNF signaling pathway.Four related components including homoplantaginin,hispidulin,luteolin and isorhamnetin were obtained by reverse traceability of the NF-κB signaling pathway.Molecular docking demonstrated excellent docking activities of the 4 components to PTGS2 with the binding energies of-9.5,-9.7,-9.4,and-9.4 kcal·mol-1,respectively.According to the measurability of quality markers,it was determined that homoplantaginin and hispidulin could be used as anti-inflammatory quality markers of Salvia plebeia.Western Blot results showed that homoplantaginin and hispidulin could significantly reduce the expression of COX-2 and NF-κB p-p65(P<0.05,P<0.01).Conclusion The anti-inflammatory quality markers of Salvia plebeia are homoplantaginin and hispidulin,which can exert anti-inflammatory effects through the NF-κB pathway.

Gut dysbiosis,a well-known risk factor to triggers the progression of Alzheimer's disease(AD),is strongly associated with metabolic disturbance.Trimethylamine N-oxide(TMAO),produced in the dietary choline metabolism,has been found to accelerate neurodegeneration in AD pathology.In this study,the cognitive function and gut microbiota of TgCRND8(Tg)mice of different ages were evaluated by Morris water maze task(MWMT)and 16S rRNA sequencing,respectively.Young pseudo germ-free(PGF)Tg mice that received faecal microbiota transplants from aged Tg mice and wild-type(WT)mice were selected to determine the role of the gut microbiota in the process of neuropathology.Excessive choline treatment for Tg mice was used to investigate the role of abnormal choline metabolism on the cognitive functions.Our results showed that gut dysbiosis,neuroinflammation response,Aβ deposition,tau hyper-phosphorylation,TMAO overproduction and cyclin-dependent kinase 5(CDK5)/transcription 3(STAT3)activation occurred in Tg mice age-dependently.Disordered microbiota of aged Tg mice accelerated AD pathology in young Tg mice,with the activation of CDK5/STAT3 signaling in the brains.On the contrary,faecal microbiota transplantation from WT mice alleviated the cognitive deficits,attenuated neuro-inflammation,Aβ deposition,tau hyperphosphorylation,TMAO overproduction and suppressed CDK5/STAT3 pathway activation in Tg mice.Moreover,excessive choline treatment was also shown to aggravate the cognitive deficits,Aβ deposition,neuroinflammation and CDK5/STAT3 pathway activation.These findings provide a novel insight into the interaction between gut dysbiosis and AD progression,clarifying the important roles of gut microbiota-derived substances such as TMAO in AD neuropathology.

To understand the current status of emergency nurses’ patient safety attitude cognition and its influencing factors, 746 emergency nurses from 34 hospitals were investigated with the revised Chinese version of the safety attitude questionnaire. The results showed that the total mean score of patient safety attitude of emergency nurses was (3.98±0.40) points, which was above the middle level. Among them, the mean scores of team cooperation, safety atmosphere, management perception, work satisfaction, working condition, and stress perception were (4.14±0.85) points, (3.85±0.81) points, (3.90±0.81) points, (3.91±0.85) points, (3.86±1.06) points, and (3.89±0.59) points, respectively. Multiple linear regression analysis showed that length of service and grade of hospital were the influencing factors of emergency nurses’ patient safety attitude (P<0.05). It is suggested that the managers should incorporate patient safety culture into the training and management of emergency nurses, especially strengthen the safety culture education for junior nurses; the secondary hospital should also focus on enhancing team cooperation training for emergency nurses and improving the working environment of them, so as to reduce unsafe behaviors in nursing work and ensure patients’ safety.

BACKGROUND: Long non-coding RNA colon cancer-associated transcript 1 (CCAT1) is involved in transforming multiple cancers into malignant cancer types. Previous studies underlining the mechanisms of the functions of CCAT1 primarily focused on its decoy for miRNAs (micro RNAs). However, the regulatory mechanism of CCAT1-protein interaction associated with tumor metastasis is still largely unknown. The present study aimed to identify proteome-wide CCAT1 partners and explored the CCAT1-protein interaction mediated tumor metastasis. METHODS: CCAT1-proteins complexes were purified and identified using RNA antisense purification coupled with the mass spectrometry (RAP-MS) method. The database for annotation, visualization, and integrated discovery and database for eukaryotic RNA binding proteins (EuRBPDB) websites were used to bioinformatic analyzing CCAT1 binding proteins. RNA pull-down and RNA immunoprecipitation were used to validate CCAT1-Vimentin interaction. Transwell assay was used to evaluate the migration and invasion abilities of HeLa cells. RESULTS: RAP-MS method worked well by culturing cells with nucleoside analog 4-thiouridine, and cross-linking was performed using 365 nm wavelength ultraviolet. There were 631 proteins identified, out of which about 60% were RNA binding proteins recorded by the EuRBPDB database. Vimentin was one of the CCAT1 binding proteins and participated in the tumor metastasis pathway. Knocked down vimetin ( VIM ) and rescued the downregulation by overexpressing CCAT1 demonstrated that CCAT1 could enhance tumor migration and invasion abilities by stabilizing Vimentin protein. CONCLUSION CCAT1 may bind with and stabilize Vimentin protein, thus enhancing cancer cell migration and invasion abilities.
Humans ; HeLa Cells ; RNA, Long Noncoding/metabolism* ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Vimentin/metabolism* ; MicroRNAs/metabolism* ; Colonic Neoplasms/genetics* ; RNA-Binding Proteins/metabolism* ; Gene Expression Regulation, Neoplastic/genetics* ; Cell Movement/genetics*