BACKGROUND:A novel aggregation induced luminescence fluorescence probe based on the mechanism of intramolecular motility restriction can be used for the detection of disease markers,tumor diagnosis,and bacterial imaging recognition.OBJECTIVE:To prepare a near-infrared Ⅱ nanoprobe called FA-DSPE-PEG-AIE@NPs based on aggregation-induced luminescence,and to explore its potential of targeted fluorescence imaging and photothermal therapy for prostate cancer.METHODS:Lecithin,polyethylene glycol phospholipids,folate polyethylene glycol phospholipids,and aggregation induced luminescent molecule 2TT-oC26B were used as raw materials.The folate-targeted nanoprobe FA-DSPE-PEG-AIE@NPs were prepared by nanoprecipitation method,and basic characterization of the nanoprobe was detected.PC3 human prostate cancer cells and human umbilical vein endothelial cells were selected as experimental objects.The cytotoxicity and phototoxicity of FA-DSPE-PEG-AIE@NPs were detected.PC3 human prostate cancer cells were selected as the experimental objects.Flow cytometry and calcein/propidium iodide staining were used to assess the efficacy of photothermal therapy.PC3 human prostate cancer cells were injected subcutaneously into the abdomen of BALB/C nude mice to establish a tumor model,and nanoprobes FA-DSPE-PEG-AIE@NPs were injected into the tail vein.The mice were immediately subjected to near-infraced Ⅱ fluorescence imaging.12 hours later,the tumor was irradiated by laser for 5 minutes,and the photothermal treatment effect was observed within 14 days.RESULTS AND CONCLUSION:(1)The nanoprobes FA-DSPE-PEG-AIE@NPs with a mean diameter of(171.0±0.3)nm showed a well-defined spherical morphology.The nanoprobe had a wide absorption spectrum and tail emission extending to the near-infrared Ⅱ which emitted a bright near-infrared Ⅱ fluorescence signal under laser irradiation.(2)The nanoprobes FA-DSPE-PEG-AIE@NPs had low cytotoxicity and high phototoxicity.The results of flow cytometry and calcein/propidium iodide staining showed that nanoprobes FA-DSPE-PEG-AIE@NPs had an obvious photothermal killing effect on human prostate cancer cells.(3)The nanoprobes FA-DSPE-PEG-AIE@NPs successfully achieved near-infrared Ⅱ fluorescence imaging of mouse blood vessels and the maximum enrichment time of the tumor was 12 hours.The vessel widths of the hind leg and single blood vessels of abdomen were estimated to be 0.63 mm and 0.42 mm.The tumor volume of mice was significantly smaller after 14 days of treatment.(4)The results show that nanoprobes FA-DSPE-PEG-AIE@NPs can achieve near-infrared Ⅱ fluorescence imaging and photothermal therapy of prostate cancer effectively,which may provide a new method for early diagnosis and combined treatment of prostate cancer.

Objective This study aimed to evaluate the clinical effect of hyaluronic acid(HA)scaffold combined with adipose-derived stem cells(ADSCs)in chronic wound healing of lower limbs and explore its applica-tion potential in promoting chronic wound healing.Methods A total of 50 patients were included in this study.They were divided into study and control groups according to the random number table method.There were 25 cases in each of the two groups of patients.HA and ADSCs were mixed in a 1:1 ratio and evenly injected into the wound base and the subcutaneous tissue around the wound at a rate of 0.1 ml/cm3.In the control group,ADSCs were only injected into the wound base and subcutaneous tissue around the wound.The infection rate,treatment satisfaction,wound healing rate,visual analogue score(VAS),and wound quantitative score were compared between the two groups at 7 days,14 days,and 28 days.Results The infection rate in the study group was lower than that in the control group,and the difference was statistically significant(P<0.05).Moreover,at 14 days and 28 days after treatment,the wound healing rate in the study group was higher than that in the control group,and the difference was statistically significant(P<0.05).On the 7th,14th,and 28th days after treatment,the VAS scores and the wound quantitative scores were lower than those in the control group,and the difference was statisti-cally significant(P<0.05).Furthermore,the treatment satisfaction rate in the research group(92％)was higher than that in the control group(80％).Conclusion HA scaffold combined with ADSCs could promote the healing of chronic wounds in lower limbs,reduce infection rate,and relieve wound pain,which provides a new idea for the treatment of chronic wounds.

BACKGROUND:A novel aggregation induced luminescence fluorescence probe based on the mechanism of intramolecular motility restriction can be used for the detection of disease markers,tumor diagnosis,and bacterial imaging recognition.OBJECTIVE:To prepare a near-infrared Ⅱ nanoprobe called FA-DSPE-PEG-AIE@NPs based on aggregation-induced luminescence,and to explore its potential of targeted fluorescence imaging and photothermal therapy for prostate cancer.METHODS:Lecithin,polyethylene glycol phospholipids,folate polyethylene glycol phospholipids,and aggregation induced luminescent molecule 2TT-oC26B were used as raw materials.The folate-targeted nanoprobe FA-DSPE-PEG-AIE@NPs were prepared by nanoprecipitation method,and basic characterization of the nanoprobe was detected.PC3 human prostate cancer cells and human umbilical vein endothelial cells were selected as experimental objects.The cytotoxicity and phototoxicity of FA-DSPE-PEG-AIE@NPs were detected.PC3 human prostate cancer cells were selected as the experimental objects.Flow cytometry and calcein/propidium iodide staining were used to assess the efficacy of photothermal therapy.PC3 human prostate cancer cells were injected subcutaneously into the abdomen of BALB/C nude mice to establish a tumor model,and nanoprobes FA-DSPE-PEG-AIE@NPs were injected into the tail vein.The mice were immediately subjected to near-infraced Ⅱ fluorescence imaging.12 hours later,the tumor was irradiated by laser for 5 minutes,and the photothermal treatment effect was observed within 14 days.RESULTS AND CONCLUSION:(1)The nanoprobes FA-DSPE-PEG-AIE@NPs with a mean diameter of(171.0±0.3)nm showed a well-defined spherical morphology.The nanoprobe had a wide absorption spectrum and tail emission extending to the near-infrared Ⅱ which emitted a bright near-infrared Ⅱ fluorescence signal under laser irradiation.(2)The nanoprobes FA-DSPE-PEG-AIE@NPs had low cytotoxicity and high phototoxicity.The results of flow cytometry and calcein/propidium iodide staining showed that nanoprobes FA-DSPE-PEG-AIE@NPs had an obvious photothermal killing effect on human prostate cancer cells.(3)The nanoprobes FA-DSPE-PEG-AIE@NPs successfully achieved near-infrared Ⅱ fluorescence imaging of mouse blood vessels and the maximum enrichment time of the tumor was 12 hours.The vessel widths of the hind leg and single blood vessels of abdomen were estimated to be 0.63 mm and 0.42 mm.The tumor volume of mice was significantly smaller after 14 days of treatment.(4)The results show that nanoprobes FA-DSPE-PEG-AIE@NPs can achieve near-infrared Ⅱ fluorescence imaging and photothermal therapy of prostate cancer effectively,which may provide a new method for early diagnosis and combined treatment of prostate cancer.

Background::Computer-aided detection (CAD) software has been introduced to automatically interpret digital chest X-rays. This study aimed to evaluate the performance of CAD software (JF CXR-1 v3.0, which was developed by a domestic Hi-tech enterprise) in tuberculosis (TB) case finding in China.Methods::In 2019, we conducted an internal evaluation of the performance of JF CXR-1 v3.0 by reading standard images annotated by a panel of experts. In 2020, using the reading results of chest X-rays by a panel of experts as the reference standard, we conducted an on-site prospective study to evaluate the performance of JF CXR-1 v3.0 and local radiologists in TB case finding in 13 township health centers in Zhongmu County, Henan Province.Results::Internal assessment results based on 277 standard images showed that JF CXR-1 v3.0 had a sensitivity of 85.94% (95% confidence interval [CI]: 77.42%, 94.45%) and a specificity of 74.65% (95% CI: 68.81%, 80.49%) to distinguish active TB from other imaging conditions. In the on-site evaluation phase, images from 3705 outpatients who underwent chest X-ray detection were read by JF CXR-1 v3.0 and local radiologists in parallel. The imaging diagnosis of local radiologists for active TB had a sensitivity of 32.89% (95% CI: 22.33%, 43.46%) and a specificity of 99.28% (95% CI: 99.01%, 99.56%), while JF CXR-1 v3.0 showed a significantly higher sensitivity of 92.11% (95% CI: 86.04%, 98.17%) ( p < 0.05) and maintained high specificity at 94.54% (95% CI: 93.81%, 95.28%). Conclusions::CAD software could play a positive role in improving the TB case finding capability of township health centers.

This study systematically investigated the molecular mechanisms underlying the involvement of mesoderm development-associated genes in melanoma progression through integrated bioinformatics analy-sis and experimental validation.Utilizing the GSVA(gene set variation analysis)algorithm to perform enrichment analysis of 7 752 biological functions in 406 skin cutaneous melanoma(SKCM)cases,we i-dentified for the first time the significant activation of mesoderm development pathways during SKCM pathogenesis.Four core regulatory genes(SMAD4,NODAL,BMPR1A,and ZFP36L1)were screened using LASSO-COX regression analysis and a prognostic risk-scoring system was established.Gene Ontolo-gy(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses revealed predomi-nant enrichment of these genes in mRNA metabolic processes and TGF-β signaling pathways.Experimen-tal validation through Quantitative Polymerase Chain Reaction(qPCR),Western blotting,and immuno-histochemistry(IHC)demonstrated that:(1)Downregulation of SMAD4 and BMPR1A in tumor tissues was significantly correlated with poor prognosis(P＜0.05);(2)NODAL promoted tumor invasion and metastasis by regulating epithelial-mesenchymal transition(EMT);(3)High ZFP36L1 expression was associated with enhanced chemotherapy sensitivity.Further analyses revealed significant correlations be-tween core gene expression levels and tumor immune infiltration characteristics as well as immune check-point molecules.By integrating multi-omics analysis with experimental validation,this study elucidates the critical roles of mesoderm development-associated genes in SKCM progression,particularly clarifying the molecular mechanisms through which SMAD4/NODAL/BMPR1A/ZFP36L1 influence tumor biologi-cal behaviors via immune microenvironment regulation and EMT processes.These findings provide novel theoretical foundations for molecular subtyping and targeted therapy in melanoma.

This study systematically investigated the molecular mechanisms underlying the involvement of mesoderm development-associated genes in melanoma progression through integrated bioinformatics analy-sis and experimental validation.Utilizing the GSVA(gene set variation analysis)algorithm to perform enrichment analysis of 7 752 biological functions in 406 skin cutaneous melanoma(SKCM)cases,we i-dentified for the first time the significant activation of mesoderm development pathways during SKCM pathogenesis.Four core regulatory genes(SMAD4,NODAL,BMPR1A,and ZFP36L1)were screened using LASSO-COX regression analysis and a prognostic risk-scoring system was established.Gene Ontolo-gy(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses revealed predomi-nant enrichment of these genes in mRNA metabolic processes and TGF-β signaling pathways.Experimen-tal validation through Quantitative Polymerase Chain Reaction(qPCR),Western blotting,and immuno-histochemistry(IHC)demonstrated that:(1)Downregulation of SMAD4 and BMPR1A in tumor tissues was significantly correlated with poor prognosis(P＜0.05);(2)NODAL promoted tumor invasion and metastasis by regulating epithelial-mesenchymal transition(EMT);(3)High ZFP36L1 expression was associated with enhanced chemotherapy sensitivity.Further analyses revealed significant correlations be-tween core gene expression levels and tumor immune infiltration characteristics as well as immune check-point molecules.By integrating multi-omics analysis with experimental validation,this study elucidates the critical roles of mesoderm development-associated genes in SKCM progression,particularly clarifying the molecular mechanisms through which SMAD4/NODAL/BMPR1A/ZFP36L1 influence tumor biologi-cal behaviors via immune microenvironment regulation and EMT processes.These findings provide novel theoretical foundations for molecular subtyping and targeted therapy in melanoma.

Objective To investigate the intervention effects and mechanism of Danggui Shaoyao power on spontaneous abortion rats.Methods A total of 60 first-day pregnant rats were randomly divided into normal group,model group,dydrogesterone group and Danggui Shaoyao power low,middle,and high dose groups,with 10 rats in each group.The low,middle,and high dose groups were given Danggui Shaoyao power 5.175 g·kg-1,10.35 g·kg-1,20.7 g·kg-1,respectively,from 1 to 12 days of gestation,and the dydrogesterone group was given dydrogesterone tablet solution 2 mg·kg-1 once a day.On the 13th day of gestation,rats model of spontaneous abortion was established by intragastric administration of 5 mg·kg-1 of mifepristone tablet solution except for the normal group.Serum levels of GnRH,FSH,LH,E2 were measured,and abortion rates and uterine coefficients were calculated.The pathological changes of pregnant uterus were observed by haematoxylin-eosin(HE)staining.The differential proteins in rats pregnant uterus were detected by Label-Free shotgun proteomic technique,and the PPI,Gene Ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways analysis of the differential proteins were analyzed.Immunohistochemistry was used to verify the expression levels of differential proteins.Results Compared with normal group,the serum levels of GnRH,FSH,LH,E2 and uterine coefficients were decreased,and the abortion rates were increased in model group(P<0.05).There were abortion lesions of spontaneous abortion in model group.Compared with model group,the serum levels of GnRH,FSH,LH,E2 and uterine coefficients were increased(P<0.05),and the abortion rates were decreased(P<0.05)in dydrogesterone group and Danggui Shaoyao power low,middle,and high dose groups.Proteomic results showed that a total of 550 proteins were quantified in this study.PPI analysis showed that a total of 159 proteins interacted with other proteins as hubs;the results of GO and KEGG enrichment analysis showed that the intervention effect of Danggui Shaoyao power on spontaneous abortion is related to the focal adhesion pathway,and involved upregulation of Akt2,Col6a1,Col6a2 and downregulation of Pten.Immunohistochemistry results showed that compared with normal group,the expression level of Akt2,Col6a1 and Col6a2 were decreased(P<0.05),and the expression level of Pten was increased(P<0.05)in model group.Compared with model group,the expression level of Akt2,Col6a1 and Col6a2 were increased(P<0.05),and the expression level of Pten was decreased(P<0.05)in dydrogesterone group and Danggui Shaoyao power low,middle,and high dose groups.Conclusions Danggui Shaoyao power has the intervention effect on spontaneous abortion,and its mechanism may be related to by demoting the protein expressions of Pten,and promoting the protein expressions of Akt2,Col6a1 and Col6a2.

Background::Computer-aided detection (CAD) software has been introduced to automatically interpret digital chest X-rays. This study aimed to evaluate the performance of CAD software (JF CXR-1 v3.0, which was developed by a domestic Hi-tech enterprise) in tuberculosis (TB) case finding in China.Methods::In 2019, we conducted an internal evaluation of the performance of JF CXR-1 v3.0 by reading standard images annotated by a panel of experts. In 2020, using the reading results of chest X-rays by a panel of experts as the reference standard, we conducted an on-site prospective study to evaluate the performance of JF CXR-1 v3.0 and local radiologists in TB case finding in 13 township health centers in Zhongmu County, Henan Province.Results::Internal assessment results based on 277 standard images showed that JF CXR-1 v3.0 had a sensitivity of 85.94% (95% confidence interval [CI]: 77.42%, 94.45%) and a specificity of 74.65% (95% CI: 68.81%, 80.49%) to distinguish active TB from other imaging conditions. In the on-site evaluation phase, images from 3705 outpatients who underwent chest X-ray detection were read by JF CXR-1 v3.0 and local radiologists in parallel. The imaging diagnosis of local radiologists for active TB had a sensitivity of 32.89% (95% CI: 22.33%, 43.46%) and a specificity of 99.28% (95% CI: 99.01%, 99.56%), while JF CXR-1 v3.0 showed a significantly higher sensitivity of 92.11% (95% CI: 86.04%, 98.17%) ( p < 0.05) and maintained high specificity at 94.54% (95% CI: 93.81%, 95.28%). Conclusions::CAD software could play a positive role in improving the TB case finding capability of township health centers.

Objective This study aimed to evaluate the clinical effect of hyaluronic acid(HA)scaffold combined with adipose-derived stem cells(ADSCs)in chronic wound healing of lower limbs and explore its applica-tion potential in promoting chronic wound healing.Methods A total of 50 patients were included in this study.They were divided into study and control groups according to the random number table method.There were 25 cases in each of the two groups of patients.HA and ADSCs were mixed in a 1:1 ratio and evenly injected into the wound base and the subcutaneous tissue around the wound at a rate of 0.1 ml/cm3.In the control group,ADSCs were only injected into the wound base and subcutaneous tissue around the wound.The infection rate,treatment satisfaction,wound healing rate,visual analogue score(VAS),and wound quantitative score were compared between the two groups at 7 days,14 days,and 28 days.Results The infection rate in the study group was lower than that in the control group,and the difference was statistically significant(P<0.05).Moreover,at 14 days and 28 days after treatment,the wound healing rate in the study group was higher than that in the control group,and the difference was statistically significant(P<0.05).On the 7th,14th,and 28th days after treatment,the VAS scores and the wound quantitative scores were lower than those in the control group,and the difference was statisti-cally significant(P<0.05).Furthermore,the treatment satisfaction rate in the research group(92％)was higher than that in the control group(80％).Conclusion HA scaffold combined with ADSCs could promote the healing of chronic wounds in lower limbs,reduce infection rate,and relieve wound pain,which provides a new idea for the treatment of chronic wounds.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.