Background::Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid ( GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods::We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 ( E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results::GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions::GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

Aim To investigate the effects of Cartham-us tinctorius L.extract(CTLE)on oxidative stress,lipid metabolism,and apoptosis levels of mice with al-cohol-induced liver injury and its mechanism of action.Methods The mouse model of alcohol-associated liver disease was established by chronic alcohol feeding and acute alcohol gavage.Mice were randomly divided into four groups.During the modeling period,the state changes of mice were observed every day,and their weight was recorded.At the end of modeling,blood and liver tissues were collected from each group of mice.The blood of mice was analyzed biochemically,and HE staining and Oil Red O staining were used to evaluate further the degree of pathological damage in the liver of mice.Quantitative real-time PCR(qPCR)and Western blot were applied to detect the mRNA and protein expression levels of p-PI3K,PI3K,p-Akt,Akt,p-mTOR,mTOR,p-FoxO1,FoxO1,p-FoxO3a,FoxO3a,p-FoxO4,FoxO4,BCL and BAX factors.Results Compared to the model group,the CTLE administration group showed improved hepatic patho-logical injury and reduced lipid deposition.The bio-chemical indexes in serum and liver,such as ALT,AST,TG,TC,and MDA levels were reduced,while GSH and SOD levels increased.Regulating the PI3K/Akt/FoxO pathway resulted in increased production of SOD,which reduced damage and apoptosis caused by reactive oxygen species(ROS).Conclusions CTLE can exert anti-oxidative stress and anti-apoptotic effects through the PI3K/Akt/FoxO pathway and attenuates alcoholic liver injury in mice,providing new ideas for the treatment of alcoholic liver disease and the develop-ment of related drugs.

Aim To investigate the protective effect of Jujing formula on retina of mice with dry age-related macular degeneration(AMD).Methods The mouse model of dry AMD was induced by intraperitoneal in-jection of sodium iodate,and the prognosis was given to the Jujing formula.Retinal thickness was detected by optical coherence tomography(OCT),the retinal morphological changes were observed by hematoxylin-eosin(HE)staining,and the apoptosis of retinal cells was detected by in situ terminal transferase labeling(TUNEL)staining.Combination of tumor necrosis fac-tor-α(TNF-α),interleukin-6(IL-6)and interleukin-1β(IL-1 β)in eyeballs and serum,superoxide dis-mutase(SOD),glutathione(GSH)and malondialde-hyde(MDA)were evaluated to assess the protective effects of Jujing formula on retinal injury in mice with dry AMD.Results The results of OCT,HE and TUNEL staining showed that Jujing formula significant-ly improved the retinal injury induced by sodium iodate in mice with dry AMD,increased the retinal thickness(P＜0.05),reduced the apoptosis of retinal cells(P＜0.01),and increased the levels of GSH,IL-6 and SOD activity in eyeballs and serum(P＜0.01).The levels of TNF-α,IL-6,IL-1β and MDA were reduced(P＜0.01).Conclusions Jujing formula has certain therapeutic effects on retinal injury in dry AMD,which may be related to inhibiting inflammatory response and enhancing antioxidant capacity.

Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]

Analyzing polysorbate 20(PS20)composition and the impact of each component on stability and safety is crucial due to formulation variations and individual tolerance.The similar structures and polarities of PS20 components make accurate separation,identification,and quantification challenging.In this work,a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography(HPLC)with charged aerosol detection(CAD)to separate 18 key components with multiple esters.The separated components were characterized by ultra-high-performance liquid chro-matography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS)with an identical gradient as the HPLC-CAD analysis.The polysorbate compound database and library were expanded over 7-time compared to the commercial database.The method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process relationship.UHPLC-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different sources.The method observed the impact of 4 degradation conditions on peak components,identifying stable components and their tendencies to change.HPLC-CAD and UHPLC-Q-TOF-MS results provided insights into fingerprint differences,distinguishing quasi products.

Objective To explore the effectiveness of different intervention strategies in response to outbreaks of emerging highly pathogenic respiratory infectious diseases(RIDs)in mega-city in China,and provide decision-ma-king basis for effective response to emerging RIDs.Methods A susceptible-exposed-infectious-recovered(SEIR)transmission dynamics model was constructed,referencing to and combining the pathogenicity and infectivity para-meters of previous emerging RIDs.The outbreak of emerging highly pathogenic RIDs with low,moderate,and high infectivity in a mega-city with a population of 10 million in China was simulated,the development of the epidemic within 100 days after implementing different combinations of non-pharmaceutical interventions(NPIs)in response to the outbreak was compared.Results When highly pathogenic RIDs outbreak occurred,and if its infectivity was low(R0 was about 1.5),it was unnecessary to adopt strict NPIs to control epidemic.If its infectivity was moderate(R0 was about 6),different intensities of NPIs were needed based on its existing infection scale.When the initial num-ber of infected cases was 50,moderate-intensity NPIs could keep the infection and death at a low level within 100 days,and the required bed number in hospital for cases could be kept below the national average reserve level.But when the scale of infection exceeded 100 cases,high-intensity NPIs were needed to control the development of the epidemic.In the case of extremely strong infectivity(R0 was about 10),regardless of the scale of infection,only immediate high-intensity NPIs could control the epidemic,infection and death scale.Conclusion In case of out-breaks of highly pathogenic RIDs,adopting appropriate NPIs as early as possible based on their epidemiological characteristics and infection scale is necessary to minimize the harm to the population.

Peak picking is one of the essential steps in non-targeted metabolomics data preprocessing based on liquid chromatography-mass spectrometry.Among various peak-picking algorithms,centWave algorithm based on continuous wavelet transform has been widely adopted in high-resolution mass spectrometry.In this study,the optimization effects of two centWave parameter optimization algorithms,IPO and centWave Sweep,were compared.Two datasets including metabolite standards and urine were used for comprehensive evaluation of these two algorithms with respect to three indicators:good peak shape ratio,reliable peak ratio,and repeatable peak ratio.To quickly and accurately distinguish good and bad peak shapes,three ensemble learning algorithms,random forest,adaboost and gradient boosting decision tree,were selected to establish a model for distinguishing chromatographic peak shape.Finally,according to the accuracy and F1 score,random forest was selected to establish a discrimination model(Accuracy 93.5%,F1 score 0.938).Compared with recommended parameters of XCMS Online,the proportion of reliable peaks and the proportion of repeatable peaks of two parameter optimization algorithms were improved in different datasets.However,when it came to the proportion of peaks with good shape,there was no significant difference between the optimized parameters and the parameters recommended by XCMS Online in different datasets.Furthermore,all three parameter settings resulted in relatively low proportions of peaks with good shape.The results indicated that the current parameter optimization algorithm was unable to improve the proportion of peaks with good shape.An excessive number of bad shape peaks could not only decrease the statistical power of analysis but also generate false positive results.Therefore,it was critical to perform additional confirmation of potential markers in the practical application of metabolomics researches.

Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10^-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.

Rapid epidemiological screening for tuberculosis (TB) usually uses tuberculin pure protein derivative (PPD) skin test, which has limitations such as low specificity and high side effects. ESAT-6 and CFP-10 are secreted proteins of Mycobacterium tuberculosis, but the related genes are missing from Bacillus Calmette-Guerin (BCG). In this study, the fusion protein ESAT6-CFP10 (EC) was expressed and purified, and prepared into chitosan nanoparticles (EC-NPs), which were loaded into the microneedle patch and carried out the preliminary test of tuberculosis skin test. The drug loading capacity of MNP-EC-NPs (microneedle patch, MNP) can reach 0.03 μg per needle and 1.92 μg per patch. The shelf life of MNP-EC-NPs can reach 6 months at room temperature, and it can effectively penetrate the epidermis. Volunteer skin test results showed that MNP-EC-NPs can effectively distinguish between BCG vaccinators, and can effectively show positive reaction in the skin of tuberculosis patients without significant side effects. The experiment was approved by the Ethics Committee of Wuhan Pulmonary Hospital [2022 (2)]. In this study, a TB skin test method was established, using ESAT6-CFP10 fusion protein instead of PPD, and using soluble microneedle dosage form, which improved the specificity of TB skin test diagnosis and provided a new technical scheme for TB epidemic screening.

Cordycepin (Cpn), a natural active compound derived from the traditional Chinese medicine Cordyceps sinensis, has antifibrotic, antioxidant, and anti-inflammatory effects, but the impact of Cpn on pulmonary fibrosis and the downstream molecular mechanism remain unclear. In this study, A549 cells were induced by transforming growth factor β1 (TGFβ1) in vitro, the viability of A549 cells was evaluated by CCK-8 assay; and migration of A549 cells were detected by wound healing assay, invasion of A549 cells were detected by transwell assay. Molecular docking and molecular dynamics simulations were used to predict the interaction of histone deacetylase 7 (HDAC7) with vimentin and the association of Cpn with HDAC7. The pulmonary fibrosis model of mice was established by bleomycin in vivo to investigate the effect of Cpn on pathological changes of lung tissue. The impact of Cpn and molecular mechanism on pulmonary fibrosis were studied by Western blot assay, cell transfection assay, immunoprecipitation assay, immunofluorescence assay, immunohistochemistry and real-time quantitative PCR (RT-qPCR). All animal experiments were approved by the Shanghai Children's Medical Center Experimental Animal Ethics Committee (grant No. SCMC-LAWEC-2022-017). Results showed that Cpn had no toxic effect on A549 cells even at the concentration of 100 μmol·L^-1. Cpn inhibited migration and invasion of A549 cells and reduced deposition of collagen, the degree of lung inflammation and fibrosis in mice; in vivo and in vitro models, Cpn significantly reversed mRNA and protein expressions of epithelial-mesenchymal transition (EMT) and lung fibrosis markers collagen I, α-smooth muscle actin (α-SMA), N-cadherin, vimentin and E-cadherin and HDAC7. Deficiency of HDAC7 suppressed TGFβ1-induced EMT and expression of collagen I; vimentin interacted with HDAC7; and molecular docking experiment revealed that Cpn was interrelated with HDAC7. In conclusion, Cpn can target HDAC7 to mediate EMT and exert its anti-fibrotic effect, the inhibition of EMT and the improvement of pulmonary fibrosis provide a new idea and choice for the development of anti-pulmonary fibrosis drug.