ObjectiveTo observe the therapeutic effect of BD-77 by nebulized inhalation on animal models of various respiratory viral infections and investigate the mechanism of broad-spectrum antiviral action of BD-77 using proteomics. MethodThe influenza virus H1N1/FM1 experiment used ICR mice and divided them into a normal group， model group， Tamiflu group， and BD-77 groups of 75 and 37.5 g·L^-1 for inhalation of 20 min and 25 min. Human coronavirus 229E and OC43 experiment divided the BALB/c mice into a normal group， model group， chloroquine phosphate group， and BD-77 groups of 75， 37.5， 18.75， and 9.375 g·L^-1， with 10 mice in each group. Influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection-induced pneumonia models were used to detect mouse lung index， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the viral load in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect related inflammatory factors in lung tissue， and proteomics analysis was performed on the lung tissue of OC43-infected mice. ResultCompared with that in the normal group， the lung index of mice in each infection group was significantly increased （P<0.01）， and viral nucleic acid could be detected in the lung tissue of mice infected with human coronaviruses 229E and OC43. The levels of interleukin-6 （IL-6）， IL-10， and tumor necrosis factor-α （TNF-α） in the lung tissue of mice infected with human coronavirus 229E were all significantly increased （P<0.01）. BD-77 could significantly reduce the lung index of mice infected with influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 （P<0.05， P<0.01）， cut down the viral load in the lungs of mice infected with human coronaviruses 229E and OC43 （P<0.01）， and lower the contents of IL-6， IL-10， and TNF-α in the lung tissue of mice infected with human coronavirus 229E （P<0.01）. Proteomics analysis of the lung tissue of OC43-infected mice showed that BD-77 regulated the AMPK signaling pathway， TNF signaling pathway， NOD-like signaling pathway， IL-17 signaling pathway， Forkhead box protein O （FoxO） signaling pathway， transforming growth factor-β （TGF-β） signaling pathway， and other signaling pathways. ConclusionNebulized inhalation of BD-77 is effective in treating pneumonia caused by influenza virus H1N1/FM1 and human coronaviruses 229E and OC43 infection in mice and may exert its antiviral effects by regulating the balance of cellular metabolism， enhancing the immune function of the host， and attenuating inflammatory responses.

ObjectiveTo study the potential quality marker （Q-marker） of Tinosporae Radix associated with efficacy of "relieving sore throat" based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS）， multivariate statistical analysis （MSA）， and network pharmacology. MethodUPLC-Q-TOF-MS was used to identify the main chemical components in 18 batches of Tinosporae Radix. On this basis， principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） were employed to screen out the main marker components that caused differences between groups. Moreover， network pharmacology technology was applied to predict the potential "sore throat-relieving" components， and the molecular docking between the common components resulting from MSA and network pharmacology and the core targets was carried out to verify the marker components. ResultA total of 17 compounds， including alkaloids， diterpenoid lactones， and sterols， were identified by UPLC-Q-TOF-MS. Five main differential components were found by MSA： Columbamine， jatrorrhizine， palmatine， menisperine， and columbin. Network pharmacology analysis yielded six compounds： tetrahydropalmatine， palmatine， menisperine， fibleucin， neoechinulin A， and columbin which were selected as potential "sore throat-relieving" components of Tinosporae Radix. They may relieve sore throat by acting on interleukin-6， epidermal growth factor receptor， prostaglandin G/H synthase 2， matrix metalloproteinase-9， proto-oncogene tyrosine-protein kinase Src and other targets， and regulating Hepatitis B， influenza A， human T-cell virus infection， human cytomegalovirus infection， coronavirus disease-2019， and other signaling pathways. The common active components in Tinosporae Radix resulting from MSA and network pharmacology analysis were palmatine， menisperine， and columbin， which had high binding affinity with six core targets and can be used as the Q-marker components of Tinosporae Radix in "relieving sore throat". ConclusionThis study predicts the "sore throat-relieving" Q-marker of Tinosporae Radix， which lays a basis for developing the quality standard of Tinosporae Radix based on the efficacy and improving the quality evaluation system of the medicinal.

Objective:To explore the relationship between urinary exosomal microRNA (exo-miR) - 155 in patients with type 2 diabetes mellitus (T2DM) and the onset and severity of diabetic kidney disease (DKD).Methods:From January to May 2019, 5 patients with T2DM normoalbuminuria and 5 patients with type 2 DKD were recruited from the Department of Endocrinology and Metabolism of Chongming Hospital of Shanghai Health Medical College as a microRNA screening cohort. Urine samples were collected to extract urinary exosomes, and the urine exo-miR spectrum was detected and analyzed using the miRCURY LNA array. From June 2019 to October 2022, 351 patients with T2DM who met the enrollment criteria and were matched by age and sex were included in the validation cohort in the Department of Endocrinology and Metabolism of the hospital. Patients were divided into 3 groups according to urinary albumin/creatinine ratio (UACR): normoalbuminuria group (UACR<30 mg/g, n=143), microalbuminuria group (30 mg/g≤UACR≤300 mg/g, n=171) and macroalbuminuria group (UACR>300 mg/g, n=37). According to DKD diagnostic guidelines, microalbuminuria group and macroalbuminuria group were classified into DKD group. Real-time fluorescence quantitative PCR was used to detect the expression level of exo-miR-155 in urine. Results:The results of transmission electron microscopy, nanoparticle tracking analysis, and Western blotting showed that the extraction of exosome vesicles was successful. In the screening cohort, according to the screening criteria of P<0.05 and fold changes (FC)>1.5, 226 differentially expressed miRNAs were identified from the urinary exosomes of the DKD group compared to the T2DM group. Among them, miR-155 ranged highest (FC=32.75, P<0.001). In the validation cohort, compared with the normoalbuminuria group [0.76 (0.55, 0.95)], the macroalbuminuria group [1.84 (1.18, 2.42)] had the most significant increase in urinary exo-miR-155 level ( Z=-7.411, P<0.001), followed by the microalbuminuria group [0.86 (0.69, 1.25)] ( Z=-4.092, P<0.001), and the urinary exo-miR-155 level in the macroalbuminuria group was significantly higher than that in the microalbuminuria group ( Z=-5.841, P<0.001). The correlation analysis showed that urinary exo-miR-155 level was positively correlated with UACR ( r s=0.329, P<0.001) and negatively correlated with estimated glomerular filtration rate ( r s=-0.249, P=0.015). The results of receiver operating characteristic curve analysis showed that the area under the curve of urinary exo-miR-155 level predicted DKD progression in T2DM patients was 0.892 (95% CI 0.859-0.925), corresponding cutoff value was 0.982, and the sensitivity and specificity were 71.9% and 87.7%, respectively. Multivariate logistic regression analysis showed that urinary exo-miR-155≥0.982 was an independent risk factor for progression to DKD in T2DM patients ( OR=3.310, 95% CI 1.981-5.530, P<0.001). Conclusion:The expression level of urinary exo-miR-155 is increased in T2DM patients with microalbuminuria and macroalbuminuria, which is related to the degree of albuminuria, and can be used as a predictive marker to identify potential DKD.

Objective:To explore the accuracy of determination of the pathogen in children with lower respiratory infection according to sputum properties and the selection of corresponding antibiotics.To analyze the relationship between children's age, length of hospital stays and sputum culture positive rate.Methods:From March 2015 to November 2016, 300 children with lower respiratory infection in the Seventh Affiliated Hospital of Guangxi Medical University were selected.The isolated sputums through the nasal cavity were cultured, the sputum properties and antibiotics used at the beginning and 3-4 days later(after sputum culture) were recorded.Results:The sputum culture showed that 110 of 300 cases with lower respiratory infection were positive.Main pathogens were streptococcus pneumoniae, E.coli, staphylococcus aureus, klebsiella pneumoniae subspecies.Compared with the children with positive sputum culture, for white phlegm sputum and yellow phlegm sputum, the children with sputum culture negative had higher accuracy of antibiotic use(white phlegm sputum: 64.4%, yellow phlegm sputum: 57.1%), the difference was statistically significant (χ 2=36.04, P<0.01). The bacteria positive rate and multiple resistance rate had no statistically significant differences in length of treatment time prior to admission(all P>0.05). However, the bacteria positive rate (hospital stay ≤7 d: 24.7%, hospital stay>7 d: 48.1%, χ 2=17.66) and multiple resistance rate (hospital stay≤7 d: 13.9%, hospital stay>7 d: 35.1%; χ 2=5.40) had statistically significant differences in the length of hospitalization(all P<0.05). The bacteria positive rates in different age groups were as follows: 1-6 months: 48.1%, >6-36 months: 28.3%, >36 months: 25.0%.Compared with the two others, the positive rate of 1-6 months was higher and had statistically significant difference (χ 2=13.64, P<0.05). Conclusion:Accuracy of antibiotics use has a certain relationship with sputum color or properties and the result of sputum culture, for white phlegm sputum and yellow phlegm sputum, the accuracy of antibiotics use is higher.Once identified pathogen, sensitive antibiotics should be adopted.Probably, bacteria positive rate and multiple resistance rate have a certain relationship with the length of hospital stay and age.

Objective To summarize the clinical characteristics,imaging characteristics,treatment and progno-sis of unilateral pulmonary vein atresia (UPVA)in children and to improve the clinician′ s understanding of this disease. Methods The clinical data of 4 cases of UPVA from January 2014 to December 2016 in Department of Cardiology,Guangzhou Women and Children′s Medical Center were retrospectively analyzed,and 50 cases from reviews of PubMed,OVID and Elsevier in the international medical literature database and 4 cases in Wanfang database for the domestic report were reviewed. The clinical characteristics,diagnosis,treatment and prognosis of total of 58 cases were analyzed. Results Four patients,with an average age of 1. 8 years (1. 5 - 2. 7 years),showing congenital UPVA in 3 patients and secondary UPVA in 1 patient. There was 1 case of left upper pulmonary vein atresia,2 cases of left pulmo-nary vein atresia and 1 case of right pulmonary vein atresia. Three cases showed recurrent hemoptysis and recurrent cough occurred in 1 case. Three cases were complicated with congenital heart disease. There was one case underwent bronchial artery embolization,1 case received pulmonary vein left atrium connection,and 2 cases received conservative treatment. All patients had been followed up for 1 - 3 years so far. The patient receiving pulmonary vein left atrium had been completely cured,and the patient receiving bronchial artery embolization showed no occurrence of hemoptysis but still showed recurrent cough hemoptysis. The patient with secondary UPVA had no obvious clinical symptoms,the other 1 case who rejected operation and received conservative treatment still had recurrent pulmonary infection,intermittent hemoptysis. The average age of 54 cases(40 cases with age ≤18 years old)from the literature reports was 13. 76 years (8 days - 43 years)in which 52 cases were diagnosed as congenital UPVA,while 2 cases were secondary UPVA. Twenty - seven cases were right pulmonary vein atresia,22 cases were left pulmonary vein atresia,and 5 cases were other types. There were 94. 4％(51 / 54 cases)of the patients having recurrent cough,pulmonary infection,92. 6％(50 /54 cases)of the patients with exertional dyspnea and polypnea,68. 5％(37 / 54 cases)of the patients with hemoptysis and hematemesis. There were 50. 0％(27 / 54 cases)of UPVA patients who were complicated with heart malformation. Different degrees of pulmonary hypertension were observed in 75. 9％(41 / 54 cases)of children,and 35. 2％(19 / 54 cases)of patients had pulmonary lymphatic dilatation. Pulmonary resection was performed in 25 cases,pulmonary vein left atrium connection was performed in 11 cases,bronchial artery embolization was performed in 7 cases,and conserva-tive treatment was performed in 11 cases. After operation,most of the patients had good prognosis without obvious clini-cal symptoms or mild symptoms. Conclusions In clinical practice,if unexplained hemoptysis,recurrent lower respira-tory tract infection,pulmonary consolidation,pulmonary dysplasia or pulmonary hypertension present,the possibility of UPVA should be considered. Early diagnosis and early bronchial artery embolization,reconstruction of the pulmonary vein and atrial connection and repair of the defect of heart,can improve the symptoms or cure the children and reduce the morta-lity significantly.

Objective To investigate the diagnostic value of the partial least square discriminant analysis (PLS-DA) model based on seven serum cytokines for children patients with mycoplasma pneumonia,the 7 cytokines includ interleukin-2 (IL-2),IL-4,IL-6,IL-8,IL-10,tumor necrosis factor alpha (TNF-α) and interferonγ(IFN-γ).Methods Serum levels of cytokines were measured by the double antibody sandwich method of ELI-SA in 140 patients with pneumoniae infection and 135 normal healthy controls,and data was analyzed with the receiver operation characteristic (ROC) curve and the PLS-DA.Results The area under the ROC curve (AUC) of serum IL-10 and IFN-γfor the diagnosis of MPP was 0.84 (95％ CL:0.79 ～ 0.89).The sensitivity of IL-10 and IFN-γ for the diagnosis of MPP was 91.4％ and 82.1％,with the specificity was 77.0％ and 82.2％,respectively.The diagnostic accuracy of the PLS-DA model based on seven serum cytokines for children MPP and the controls was 90.0％ and 88.15％,and the prediction accuracy was 86.4％ and 87.4％,respectively.Conclusion Seven serum cytokines based on PLS-DA model was helpful for the diagnosis of children patients with MPP.

Objective:To explore the protective effect of the water-soluble total flavonoids from Isodon lophanthoides var.gerardia-nus (Benth.) H.Hara on LO2 cells damage.Methods:The cytotoxicity was evaluated by MTT cell viability determination to confirm the concentration range .Hepatocyte damage model was established by H 2 O2 treatment.After the oxidative stress hepatocyte was coin-cubated with WSTF at different concentrations for various times , the protective effect of WSTF on H 2 O2-induced hepatocyte damage was evaluated by MTT cell viability determination and the content determination of ALT , AST and MDA in cell supernatant .The inhibition of WSTF against H 2 O2-induced LO2 cells apoptosis was evaluated by the quantitative determination of Rhodamine 123 fluorescence and intracellular ROS.Results:The LO2 cells injured by 0.3 mmol· L-1 H2 O2 treatment for 4 h were used as the hepatocyte damage model.The concentration range of WSTF was 0.0312-0.125 mg· ml-1.WSTF could inhibit H2O2-induced injury in LO2 cells and obviously reduce ALT, AST and MDA.Moreover, WSTF could reverse mitochondrial membrane potential depolarization and decrease the amount of intracellular ROS .Conclusion:WSTF exhibits notable protective and curative effects on hepatocyte damage in vitro.

Circulating DNA is defined as a kind of extracellular DNA that exists in plasma,cerebrospinal fluid and synovial fluid.The concentration of circulating DNA of cancer patients is significantly higher than that in healthy people.The genetic and epigenetic alterations of circulating cell-free nucleic acids are relevant to cancer development and progression,for example,gene mutation,DNA methylation and microsatellite instability and so on.The quantitative and qualitative detection of circulating DNA shows promising potential value in cancer screening,diagnosis,disease monitoring treatment and prognosis.

Objective To analyze the effect of clinical pathway of nursing on health education in patients undergoing tonsil-lectomy.Methods Participants included 180 patients undergoing tonsillectomy in our hospital from September 2012 to September 2013 were randomly divided into the clinical pathway of nursing group ( experimental group) and the traditional nursing group ( control group) with 90 cases in each group.The sleep quality, heart rate, blood pressure, body weight, hemorrhage, health education com-pliance rate and nursing service satisfaction were recorded and compared between the two groups.Results The sleep quality, health education compliance rate and nursing service satisfaction in the experimental group was better than that in the control group;The inci-dence of heart rate speed up, blood pressure increase, loss weight, the standard rate of health education, hemorrhage and the satisfac-tion of nursing quality was lower than that in the control group.There was statistical significance in the difference between the two groups (p<0.05).Conclusion Health education with the clinical pathway of nursing can improve the quality of nursing, promote the rehabilitation and increase the nursing service satisfaction .

Purpose The diagnosis, treatment and prognosis of benign and malignant biliary stricture are significantly different. This study aims to evaluate the quantitative analysis of biliary structures using magnetic resonance cholangiopancreatography (MRCP) combined with dynamic contrast enhanced CT (DCE-CT).Materials and Methods The quantitative parameters of MRCP and DCE-CT imaging data from 27 patients with benign biliary stricture (benign group) and 30 patients with malignant biliary stricture (malignant group) were retrospectively analyzed. The wall thickness, stricture length and diameter, proximal ductal dilatation and degree of enhancement in two groups were compared, and its correlation was analyzed to evaluate the accuracy of MRCP and DCE-CT.Results There were significant differences in wall thickness [(3.2±2.0) mmvs (2.1±0.6) mm], stricture length [(15.8±8.1) mmvs (9.5±6.5) mm] and diameter [0 mmvs (2.0±0.9) mm], proximal ductal dilatation and the degree of enhancement [(12.7±3.6) mmvs (9.3±2.7) mm] between the two groups (t=2.825, 3.270, 4.025,P<0.001;Z=-3.909,P<0.001). Multivariable stepwise regression analysis showed that the wall thickness and diameter, and the CT HU in portal venous and equilibrium phases combined with CT plain scanning were significant predictors of malignant biliary strictures (t=-6.424-2.309,P<0.05). The sensitivity, specificity, inter-modality agreement and Youden index of MRCP and DCE-CT in diagnosing 57 patients with biliary stricture were 96.67%, 100.00%, 98.25% and 0.97, respectively; with statistical significance in predicting benign and malignant biliary stricture (AUC=0.994,P<0.001).Conclusion Using MRCP and DCE-CT, the wall thickness and diameter of the stricture, and the difference in CT HU in portal venous and equilibrium phases combined with CT plain scanning are valuable in differential diagnosis of benign and malignant biliary stricture.