Projection micro stereolithography three-dimensional(3D)printing method was proposed in this study to fabricate complex microchannels of combined cross-sections.By using 3D printing and polydimethylsiloxane(PDMS)replication methods,two inertial microfluidic chips of three-step and five-step cross-sections were fabricated,and the dimension precisions of the microchannels were controlled within 20 μm.Using the microfluidic chips,the movements of two fluorescent polystyrene particles with diameters of 10 and 6 μm in the stepped channels were investigated.In addition,numerical simulations were applied to demonstrate the inertial focusing mechanisms of particles in the channels.It was found that 10-μm particles had three equilibrium positions in the three-step channel,which located at the inner walls of the three steps,respectively,and most particles focused at the inner step.The 6-μm particles also had three equilibrium positions in the three-step channel.However,the particles migrated to the middle and the outer steps under high flow rates.In the five-step channel,when the flow rate was increased gradually,10-μm particles had a single and two equilibrium positions,respectively,and the particles migrated towards the inner channel wall under high flow rates.In comparison to 10-μm particles,6-μm particles had two stable equilibrium positions in the five-step channel at all flow rate range.It could be concluded that the quantity,shape and strength of the secondary flow vortex could be altered by changing structure of the combined cross-section,thus the equilibrium positions and quantities of the focusing particles could be also regulated.The research outcome might provide new insights for precise cell inertial manipulation and promote the application and development of inertial microfluidic technology in biomedical and other fields.

Objective To study the mechanism of Sanhuang Decotion in the treatment of ulcerative colitis(UC)under Candida albicans colonization in mice based on Dectin-1-Syk-CARD9 signaling pathway.Methods Mice model of UC with fungal colonization were established with dextran sodium sulfate free drinking and C.albicans intragastric administration.Mice were divided into normal control group,model group,sulfasalazine group,fluconazole group,and Sanhuang Decotion low-and high-dosage groups,and receive corresponding drug interventions.General state of mice were observed,and the disease activity index(DAI)score of mice were calculated.The load of C.albicans in intestine was detected,the length of the colon was measured,and pathological scoring of the colon tissue was performed.The ultrastructural changes of colon epithelium were observed under transmission electron microscopy.The contents of TNF-α,IL-6 and IL-12 in serum and colon tissues were detected by ELISA.The mRNA and protein expression of Dectin-1,Syk,CARD9,NF-κBp65 and inflammation factors in intestinal epithelial cells and colon tissues were detected by qPCR,Western blot and immunohistochemistry.Results Compared with the normal control group,the model group mice showed reduced activity,decreased food intake,accompanied by loose stools,significantly increased DAI score,increased load of C.albicans in the intestine,shortened colon length,and increased histopathological score,with widening of gap between colon epithelial cells,cytoplasmic dissolution,mitochondrial swelling;TNF-α,IL-6 and IL-12 in serum and colon tissue increased,the expressions of Dectin-1 and CARD9 mRNA and protein in colon epithelial cells increased,p-Syk,p-NF-κBp65,CARD9,TNF-α,IL-1β,IL-6 protein expression in colon tissue increased(P<0.01,P<0.05).Compared with the model group,the Sanhuang Decotion high-dosage group mice showed a significant decrease in DAI score,decreased intestinal C.albicans load,increased colon length,decreased histopathological score,more complete and orderly arrangement of microvilli in colon epithelial cells,mild mitochondrial swelling,TNF-α,IL-6 and IL-12 in serum and colon tissue decreased,and the mRNA and protein expression of Dectin-1 and CARD9 in colon tissue increased,the expression of p-Syk,p-NF-κBp65,CARD9,TNF-α,IL-1β,IL-6 protein in colon tissue decreased(P<0.01,P<0.05).Conclusion Sanhuang Decotion may exert an anti C.albicans colonization UC effect by inhibiting the Dectin-1-Syk-CARD9 signaling pathway and reducing the release of inflammatory factors.

GNPS-based mass spectrum-molecular networks is an effective strategy for rapidly identifying known natural products and discovering novel structures. The chemical diversity of azaphilones from the fermentation extracts of Talaromyces sp. HK1-18 was studied by molecular network technique. Three linear tricyclic azaphilones, sequoiamonacins A-C (2a, 2b, 1), were isolated by silica gel column chromatography and high performance liquid chromatography from the extracts of the fungal strain of HK1-18, and their structures were identified by nuclear magnetic resonance and high-resolution mass spectrometry. Guided by the mass spectra of sequoiamonacins A-C (2a, 2b, 1), the cluster of sequoiamonacinoid analogues was discovered from the full molecular networking of HK1-18. By analyzing the MS/MS fragments of each parent ion in this cluster, 7 azaphilones (3-9) included 6 new ones (4-9) were predicted successfully. Then the MS/MS cracking regularity of this type of azaphilones was revealed. Compound 1 showed anti-inflammatory activity, which can inhibit the production of interleukin-1α (IL-1α) in lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7, with an inhibitory rate of 29% at the concentration of 12.5 μg·mL^-1.

Objective To investigate the antioxidant activity of bamboo stem extracts and the therapeutic effect of bamboo stem water extract on oxidative inflammation induced by tert butyl hydroperoxide (t-BHP) in human colon adenocarcinoma cells (Caco-2). Methods In this study, ABTS, DPPH, and FRAP assays were used to determine the extracellular antioxidant activity of petroleum ether extract, ethyl acetate extract, n-butanol extract, 95% ethanol extract, and distilled water extract from bamboo stems. The human intestinal Caco-2 cell line was used as the model cell, and t-BHP was selected as the oxidative stress modeling agent. The CCK-8 assay was used to detect cell viability and the optimal oxidative damage concentration of t-BHP. The content of MDA, 8-OHdG, TNF-α and IL-1β were detected to assess antioxidant stress effect. Results The five extracts of bamboo all had certain antioxidant activity, among which the water extract of bamboo stem had the best comprehensive antioxidant activity with high cell viability in Caco-2 cells. The optimal modeling concentration of t-BHP was 200 μMol/L. The water extract of bamboo stem significantly reduced the content of oxidative stress related biomarkers and inflammatory factors in Caco-2 cells induced by t-BHP. Conclusion The stem extracts of bamboo in Xianning City have strong in vitro antioxidant activity. Among them, the water extract of bamboo stem has a protective effect on t-BHP induced oxidative damage in Caco-2 cells, suggesting that the water extract possesses a potential to be developed as new antioxidant products for clinical prevention and treatment of oxidative damage related diseases.

Objective To observe the efficacy of dapagliflozin tablets combination with sacubitril/valsartan sodium tablets in the treatment of patients with heart failure(HF)after acute myocardial infarction(AMI)intervention.Methods Patients with HF after AMI intervention were randomly divided into control group and treatment group.The control group was given conventional anti-heart failure therapy+sacubitril/valsartan sodium tablets(50 mg for the first time,then gradually increased to 200 mg each time,twice a day),and the treatment group was additionally treated with dapagliflozin(10 mg every time,once a day)on the basis of the control group,and the course of treatment was 6 months.The two groups were compared in terms of clinical efficacy,cardiac function[left ventricular ejection fraction(LVEF),left ventricular remodeling index(LVRI),6-minute walking distance(6MWD)],heart failure markers[brain natriuretic peptide(BNP),N-terminal pro-brain natriuretic peptide(NT-proBNP),troponin(Tn)],and serum related biochemical indicators[soluble human stromelysin-2(ST2),angiotensin 2(AT-Ⅱ),soluble intercellular adhesion molecule-1(sICAM-1)],incidence rates of major adverse cardiovascular events(MACE)during follow-up and adverse drug reactions during treatment.Results Six cases dropped out during treatment,and finally 46 cases were included in control group and treatment group,respectively.After treatment,the effective rates of treatment in treatment group(91.30％)was significantly higher than that in control group(76.09％,P＜0.05).After treatment,the LVEF values in control group and treatment group were(51.38±4.82)％and(54.43±4.63)％;LVRI values were(1.47±0.15)and(1.35±0.17)g·mL-1;6MWD values were(390.53±40.32)and(362.61±38.51)m;the BNP levels were(28.34±2.47)and(26.51±2.16)pmol·L-1;NT-proBNP levels were(262.61±53.18)and(227.68±46.73)ng·L-1;sICAM-1 levels were(84.61±7.14)μg·L-1 and(74.68±7.08)μg·L1,and there were statistical differences between both groups(all P＜0.05).During follow-up,the incidence rate of MACE in treatment group(6.52％)was significantly lower than that in control group(21.74％,P＜0.05).The main adverse drug reactions in the two groups were renal dysfunction,hypotension,urogenital infection and hyperkalemia,but there was no significant difference in the incidence of adverse reactions between treatment group(13.04％)and control group(10.87％,P＞0.05).Conclusion Dapagliflozin tablets combined with sacubitril/valsartan sodium tablets can significantly improve cardiac function and related indicators and reduce the incidence of MACE in patients with HF after AMI intervention.

Objective To investigate the effects of total flavones from Oxytropis falcata Bunge on hepatic fibrosis(HF)induced by carbon tetrachloride and liver transforming growth factor(TGF-β)/Smad signaling pathway.Methods Forty-eight male rats were randomly divided into normal group(intraperitoneal injection of peanut oil,intragastric administration of 0.9％NaCl),model group(intraperitoneal injection of 40％CC14 peanut oil solution induced HF model,intragastric administration of 0.9％NaCl),positive control group(modeling,intragastric administration of 0.2 mg·kg-1 of colchicine),experimental-L,-M,-H groups(modeling,intragastric administration of 100,200 and 400 mg·kg-1 of total flavonoid extract of Oxytropis falcata Bunge),8 individuals in each group,for 4 consecutive weeks.The histopathological changes were observed by hematoxylin-eosin and Masson staining.Serum liver function and liver fibrosis were measured;erum inflammatory factors were detected;fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to determine gene expression in liver.Results The pathological injury of liver tissue in the model group was serious,and a large number of inflammatory factors and collagen fibers were accumulated,while the rest of the treatment groups had different degrees of remission.In normal group,model group,positive control group,experimental-L,-M,-H groups,glutamic-pyruvic transaminase levels were(49.28±12.44),(5 885.42±948.37),(4 454.60±489.27),(4 650.47±843.53),(3 761.75±887.30)and(3 544.90±1 066.75)μg·L-1;glutamic-oxaloacetic transaminase levels were(186.90±46.89),(5 936.23±793.81),(3 971.37±780.28),(4 360.30±863.35),(3 943.10±439.47)and(3 971.38±631.08)μg·L-1;hyaluronic acid levels were(45.08±17.16),(104.32±36.06),(66.83±20.09),(70.30±21.07),(60.00±9.68)and(59.02±10.73)μg·L-1;laminin levels were(23.13±3.89),(60.85±13.66),(35.67±9.92),(39.98±9.39),(36.55±12.21)and(34.68±24.83)μg·L-1;type Ⅲ procollagen level were(24.98±5.34),(82.58±30.14),(40.70±16.14),(51.08±23.21),(43.60±12.48)and(44.20±11.66)p±g·L-1;interleukin(IL)-1β levels were(37.63±1.24),(46.10±3.23),(39.22±2.36),(41.33±0.93),(40.25±2.04)and(39.18±2.23)pg·mL-1;tumor necrosis factor-α levels were(314.58±20.56),(383.71±16.97),(349.00±7.93),(348.88±25.11),(325.75±27.84)and(335.07±21.33)pg·mL-1;TGF-β1 mRNA expression of relative quantity respectively were 1.00±0.00,60.99±15.70,9.61±1.59,7.37±1.09,6.41±0.64,6.87±1.09;Smad7 mRNA relative expression were 1.00±0.00,0.34±0.05,0.21±0.03,0.35±0.02,0.38±0.02,0.42±0.03.The above indexes in the model group were compared with the normal group,and the above indexes in the experimental-M,-H groups were compared with the model group,and the differences were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion Total flavonoids of Oxytropis falcata Bunge have protective effects on CC14-induced liver fibrosis in rats,and the mechanism may be related to the regulation of TGF-β/Smad pathway.

Objective To investigate the risk factors of in-hospital mortality and establish a risk prediction model for patients receiving venoarterial extracorporeal membrane oxygenation(VA-ECMO).Methods We retrospectively collected the data of 302 patients receiving VA-ECMO in ICU of 3 hospitals in Guangdong Province between January,2015 and January,2022 using a convenience sampling method.The patients were divided into a derivation cohort(201 cases)and a validation cohort(101 cases).Univariate and multivariate logistic regression analyses were used to analyze the risk factors for in-hospital death of these patients,based on which a risk prediction model was established in the form of a nomogram.The receiver operator characteristic(ROC)curve,calibration curve and clinical decision curve were used to evaluate the discrimination ability,calibration and clinical validity of this model.Results The in-hospital mortality risk prediction model was established based the risk factors including hypertension(OR=3.694,95%CI:1.582-8.621),continuous renal replacement therapy(OR=9.661,95%CI:4.103-22.745),elevated Na2+ level(OR=1.048,95%CI:1.003-1.095)and increased hemoglobin level(OR=0.987,95%CI:0.977-0.998).In the derivation cohort,the area under the ROC curve(AUC)of this model was 0.829(95%CI:0.770-0.889),greater than those of the 4 single factors(all AUC<0.800),APACHE Ⅱ Score(AUC=0.777,95%CI:0.714-0.840)and the SOFA Score(AUC=0.721,95%CI:0.647-0.796).The results of internal validation showed that the AUC of the model was 0.774(95%CI:0.679-0.869),and the goodness of fit test showed a good fitting of this model(χ2=4.629,P>0.05).Conclusion The risk prediction model for in-hospital mortality of patients on VA-ECMO has good differentiation,calibration and clinical effectiveness and outperforms the commonly used disease severity scoring system,and thus can be used for assessing disease severity and prognostic risk level in critically ill patients.

The main chemical components of Allii Macrostemonis Bulbus and components in serum were analyzed and identified rapidly and precisely by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)technique in this study.The compounds were identified based on the relative molecular mass,fragmentation ions,and retention time of chromatographic peaks.A total of 36 kinds of chemical components were identified from Allii Macrostemonis Bulbus,including 28 kinds of saponins,3 kinds of amino acids,2 kinds of flavonoids,one kind of organosulfur compound,one kind of nucleoside,and one kind of hormone-lipid compound.In addition,8 kinds of compounds of Allii Macrostemonis Bulbus were identified from the serum.Based on the intersection compounds of which detected in serum and screened out by TCMSP platform database,by using targeted network pharmacology and molecular docking technology,a"drug-component-target-pathway"association network was constructed.Naringenin,quercetin,macrostemonoside E and 25(R)-26-O-β-D-glucopyranosyl-22-hydroxy-5β-furostan-3-O-β-D-glucopyranosyl(1→2)-β-D-glucopyranoside were screened as the main active constituents of Allii Macrostemonis Bulbus in the treatment of hyperlipidemia.In addition,adenosine 5′-monophosphate-activated protein kinase(AMPK),tumor necrosis factor(TNF),vascular endothelial growth factor A(VEGFA)and matrix metallopeptidase 9(MMP9)were the key action targets for Allii Macrostemonis Bulbus in the treatment of hyperlipidemia.Molecular docking was performed using the main pharmacodynamic components and key action targets.The results indicated that all the four active components showed strongly bound to AMPK.This suggested that the regulation of lipid metabolism might be the key mechanism of Allii Macrostemonis Bulbus in antihyperlipidemic effect.This study provided a data reference for the research on the pharmacodynamic components of Allii Macrostemonis Bulbus,and provided a basis for the improvement of quality standard of Allii Macrostemonis Bulbus.

Objective:To analyze the epidemiological and clinical characteristics of respiratory syncytial virus (RSV) infection in children in Jiangsu Province from 2014 to 2023.Methods:The acute respiratory infection cases in children aged 0-14 years were selected from outpatient/emergency or inpatient departments in 2 surveillance sentinel hospitals, respectively, in Nanjing, Suzhou and Taizhou of Jiangsu from 1 July 2014 to 31 December 2023, and RSV nucleic acid test was conducted and the intensity of the RSV infection was accessed by WHO influenza epidemiological threshold method, and case information and clinical data were collected. χ2 test was used to compare the differences between groups, and the Bonferroni method was used for pairwise comparisons between groups. Results:In 4 946 cases of acute respiratory infections, the RSV positive rate was 8.21% (406/4 946), and the age M( Q1, Q3) of the cases was 1 (0, 3) years. The RSV positive rate was 10.92% (258/2 362) during 2014-2019 and 6.06% (118/1 948) during 2019-2023, the difference was significant ( χ2=31.74, P<0.001). RSV infection mainly occurred from October to March during 2014-2019, with the incidence peak in December and moderate or higher intensity. The seasonality of RSV infection was not obvious during 2019-2023, with low intensity. The RSV positive rate was highest in children in age group 0- years (17.85%, 151/846), and the positive rate declined gradually with age ( χ2=184.51, P<0.001). The RSV positive rate was higher in inpatient cases (9.84%, 244/2 480) than in outpatient/emergency cases (6.57%, 162/2 466) ( χ2=17.54, P<0.001). In the 155 RSV infection cases with complete clinical data, the clinical symptoms mainly included cough (99.35%, 154/155), fever (55.48%, 86/155), and shortness of breath (45.16%, 70/155). In the cases aged <6 months, the proportion of those with fever was low, but the proportion of those with shortness of breath, transferred to intensive care units, and receiving oxygen therapy were higher (all P<0.05). Children aged <6 months and those with underlying diseases were more likely to have severe RSV infection (all P<0.05). Conclusions:RSV infection in children in Jiangsu Province showed seasonal prevalence in winter from 2014 to 2019. Since 2020, the seasonal characteristics of the epidemic have changed, the epidemic period has been dispersed and the epidemic intensity has decreased. Infants <1 year old were at high risk for RSV infection, and those <6 months old and with underlying diseases might have severe infection.

Objective To investigate the risk factors of in-hospital mortality and establish a risk prediction model for patients receiving venoarterial extracorporeal membrane oxygenation(VA-ECMO).Methods We retrospectively collected the data of 302 patients receiving VA-ECMO in ICU of 3 hospitals in Guangdong Province between January,2015 and January,2022 using a convenience sampling method.The patients were divided into a derivation cohort(201 cases)and a validation cohort(101 cases).Univariate and multivariate logistic regression analyses were used to analyze the risk factors for in-hospital death of these patients,based on which a risk prediction model was established in the form of a nomogram.The receiver operator characteristic(ROC)curve,calibration curve and clinical decision curve were used to evaluate the discrimination ability,calibration and clinical validity of this model.Results The in-hospital mortality risk prediction model was established based the risk factors including hypertension(OR=3.694,95%CI:1.582-8.621),continuous renal replacement therapy(OR=9.661,95%CI:4.103-22.745),elevated Na2+ level(OR=1.048,95%CI:1.003-1.095)and increased hemoglobin level(OR=0.987,95%CI:0.977-0.998).In the derivation cohort,the area under the ROC curve(AUC)of this model was 0.829(95%CI:0.770-0.889),greater than those of the 4 single factors(all AUC<0.800),APACHE Ⅱ Score(AUC=0.777,95%CI:0.714-0.840)and the SOFA Score(AUC=0.721,95%CI:0.647-0.796).The results of internal validation showed that the AUC of the model was 0.774(95%CI:0.679-0.869),and the goodness of fit test showed a good fitting of this model(χ2=4.629,P>0.05).Conclusion The risk prediction model for in-hospital mortality of patients on VA-ECMO has good differentiation,calibration and clinical effectiveness and outperforms the commonly used disease severity scoring system,and thus can be used for assessing disease severity and prognostic risk level in critically ill patients.