This study investigated the prevalence and potential mechanisms of gentamicin heterore-sistance in Streptococcus isolates from dairy cows.In this study,A total of 39 Streptococcus isola-ted from raw milk were collected,and the minimum inhibitory concentration(MIC)of gentamicin and other drugs on the isolates was determined by micro broth dilution method,and the K-B paper diffusion method,colony analysis profile(PAP),and resistance stability test were used to investigate the heteroresistance characteristics of Streptococcus,and the mechanism of heteroresis-tance was analyzed based on whole genome sequencing and resequencing.Seven suspected heterore-sistance strains were identified by K-B paper diffusion method,accounting for 17.95％(7/39)of the total number of suspected strains.PAP confirmed that the MIC to MNIC ratio of L147,L108 and L174 was greater than 8,and the frequency of resistant subgroups ranged from 1.38×10-5 to 8.18 × 10-5,which was greater than 1 × 10-7,confirming that they were heteroresistance strains.Resistance stability tests revealed that the resistant subpopulations of all three strains were not stably inherited.Whole-genome sequencing revealed mutations in the ribosomal target genes of aminoglycoside antibiotics,rsmA,rsmB and rsmE,compared with the reference genome,which may lead to heteroresistance to gentamicin in Streptococcus.The occurrence of heteroresistance of Streptococcus to gentamicin is high in dairy sources,so more attention should be paid to the occur-rence of heteroresistance when using gentamicin for clinical treatment.

Liver fibrosis is a key histologic marker of long-term outcome in chronic liver disease. Non-invasive tests (NITs) have been shown to have predictive value, but the superiority of "dynamic" versus "static" assessment remains controversial. This article systematically reviews the latest evidence to elucidate the association between longitudinal changes in NITs and hepatic adverse events and assess the incremental contribution of dynamic monitoring to the model. Additionally, it reveals that the dynamic monitoring of NITs is truly superior to single evaluation, but the evidence is limited and the heterogeneity is significant. Dynamic modeling approaches for NITs require a shift from traditional parameter estimation to time-series machine learning. Future studies should make breakthroughs in disease stratification, modeling method innovation, data quality improvement, and prediction ability assessment so as to promote the transition of NITs from "static risk label" to "dynamic individualized engine," which can truly serve clinical decision-making.

This study was aimed at exploring the prevalence and drug sensitivity of Gordonia strains isolated from sputum samples in Henan Province,to provide data to aid in the prevention and treatment of Gordonia infection.A combination of 16S rDNA and sec A1 gene sequencing was used to identify the isolated strains,and susceptibility to16 drugs was determined with the broth microdilution method.A total of 21 strains were identified through 16S rDNA gene and sec A1 gene sequencing,including five strains of Gordonia broncians,eight strains of Gordonia paraphernivans,seven strains of Gordonia sputi,and one strain of Gordonia aichiensis.Drug sensi-tivity testing showed high Gordonia sensitivity to drugs such as ceftriaxone,linezolid,doxycycline,amoxicillin/clavulanic acid,mino-cycline,cefotaxime,trimethoprim/sulfamethoxazole,imipenem,tobramycin,and clarithromycin.The sensitivity rates of the isolated strains were 90.48%(19/21),100%(21/21),90.48%(19/21),90.48%(19/21),95.24%(20/21),90.48%(19/21),90.48%(19/21),90.48%(19/21),and 95.24%(20/21),respectively.Gordonia showed high resistance to rifampicin and cefepime,with rates of 28.57%(6/21)and 19.05%(4/21),respectively.Meanwhile,the resistance varied among bacterial strains.The resistance rate of G.sputi to rifampicin reached 71.43%(5/7),whereas that of G.parapffinivoras to cefepime was 37.5%(3/8).The main species of Gordo-nia isolated from sputum samples of patients in Henan Province were G.bronchialis,G.paraffinivoras,G.sputi,and G.aichiensis.Drug sensitivity tests indicated that drugs including amoxicillin/clavulanic acid,ceftriaxone,cefotaxime,tobramycin,clarithromycin,mi-nocycline,trimethoprim/sulfamethoxazole,linezolid,and doxycycline had good antibacterial effects against Gordonia.

This study was aimed at exploring the prevalence and drug sensitivity of Gordonia strains isolated from sputum samples in Henan Province,to provide data to aid in the prevention and treatment of Gordonia infection.A combination of 16S rDNA and sec A1 gene sequencing was used to identify the isolated strains,and susceptibility to16 drugs was determined with the broth microdilution method.A total of 21 strains were identified through 16S rDNA gene and sec A1 gene sequencing,including five strains of Gordonia broncians,eight strains of Gordonia paraphernivans,seven strains of Gordonia sputi,and one strain of Gordonia aichiensis.Drug sensi-tivity testing showed high Gordonia sensitivity to drugs such as ceftriaxone,linezolid,doxycycline,amoxicillin/clavulanic acid,mino-cycline,cefotaxime,trimethoprim/sulfamethoxazole,imipenem,tobramycin,and clarithromycin.The sensitivity rates of the isolated strains were 90.48%(19/21),100%(21/21),90.48%(19/21),90.48%(19/21),95.24%(20/21),90.48%(19/21),90.48%(19/21),90.48%(19/21),and 95.24%(20/21),respectively.Gordonia showed high resistance to rifampicin and cefepime,with rates of 28.57%(6/21)and 19.05%(4/21),respectively.Meanwhile,the resistance varied among bacterial strains.The resistance rate of G.sputi to rifampicin reached 71.43%(5/7),whereas that of G.parapffinivoras to cefepime was 37.5%(3/8).The main species of Gordo-nia isolated from sputum samples of patients in Henan Province were G.bronchialis,G.paraffinivoras,G.sputi,and G.aichiensis.Drug sensitivity tests indicated that drugs including amoxicillin/clavulanic acid,ceftriaxone,cefotaxime,tobramycin,clarithromycin,mi-nocycline,trimethoprim/sulfamethoxazole,linezolid,and doxycycline had good antibacterial effects against Gordonia.

This study investigated the prevalence and potential mechanisms of gentamicin heterore-sistance in Streptococcus isolates from dairy cows.In this study,A total of 39 Streptococcus isola-ted from raw milk were collected,and the minimum inhibitory concentration(MIC)of gentamicin and other drugs on the isolates was determined by micro broth dilution method,and the K-B paper diffusion method,colony analysis profile(PAP),and resistance stability test were used to investigate the heteroresistance characteristics of Streptococcus,and the mechanism of heteroresis-tance was analyzed based on whole genome sequencing and resequencing.Seven suspected heterore-sistance strains were identified by K-B paper diffusion method,accounting for 17.95％(7/39)of the total number of suspected strains.PAP confirmed that the MIC to MNIC ratio of L147,L108 and L174 was greater than 8,and the frequency of resistant subgroups ranged from 1.38×10-5 to 8.18 × 10-5,which was greater than 1 × 10-7,confirming that they were heteroresistance strains.Resistance stability tests revealed that the resistant subpopulations of all three strains were not stably inherited.Whole-genome sequencing revealed mutations in the ribosomal target genes of aminoglycoside antibiotics,rsmA,rsmB and rsmE,compared with the reference genome,which may lead to heteroresistance to gentamicin in Streptococcus.The occurrence of heteroresistance of Streptococcus to gentamicin is high in dairy sources,so more attention should be paid to the occur-rence of heteroresistance when using gentamicin for clinical treatment.

Liver fibrosis is a key histologic marker of long-term outcome in chronic liver disease. Non-invasive tests (NITs) have been shown to have predictive value, but the superiority of "dynamic" versus "static" assessment remains controversial. This article systematically reviews the latest evidence to elucidate the association between longitudinal changes in NITs and hepatic adverse events and assess the incremental contribution of dynamic monitoring to the model. Additionally, it reveals that the dynamic monitoring of NITs is truly superior to single evaluation, but the evidence is limited and the heterogeneity is significant. Dynamic modeling approaches for NITs require a shift from traditional parameter estimation to time-series machine learning. Future studies should make breakthroughs in disease stratification, modeling method innovation, data quality improvement, and prediction ability assessment so as to promote the transition of NITs from "static risk label" to "dynamic individualized engine," which can truly serve clinical decision-making.

The aqueous two-phase system (ATPS) is an all-aqueous system fabricated from two immiscible aqueous phases. It is spontaneously assembled through physical liquid-liquid phase separation (LLPS) and can create suitable templates like the multicompartment of the intracellular environment. Delicate structures containing multiple compartments make it possible to endow materials with advanced functions. Due to the properties of ATPSs, ATPS-based drug delivery systems exhibit excellent biocompatibility, extraordinary loading efficiency, and intelligently controlled content release, which are particularly advantageous for delivering drugs in vivo. Therefore, we will systematically review and evaluate ATPSs as an ideal drug delivery system. Based on the basic mechanisms and influencing factors in forming ATPSs, the transformation of ATPSs into valuable biomaterials is described. Afterward, we concentrate on the most recent cutting-edge research on ATPS-based delivery systems. Finally, the potential for further collaborations between ATPS-based drug-carrying biomaterials and disease diagnosis and treatment is also explored.

Objective To explore the effect of microRNA-613 (miR-613)/Wee1 axis on the radiosensitivity of colorectal cancer cells.Methods A total of 20 patients with radiosensitive colorectal cancer and 20 patients with radioresistance were selected from Yan'an Hospital Affiliated to Kunming Medical University from November 2016 to May 2017.Human colorectal cancer cell lines LoVo and HCT116 were selected and the radioresistant cell lines LoVo/R and HCT116/R were established for subsequent experiments.Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the expression of miR-613 and Wee1 in colorectal cancer tissues and cell lines.The radioresistant cells were transfected by miR-613 mimic,and non-transfected cells were used as control group.The effects of miR-613 overexpression on the proliferation,invasion and cell cycle of radiation resistance of colorectal cancer cells at different radiation doses were evaluated by CCK-8 assay,Transwell assay and Western blotting,respectively.Furthermore,dual-luciferase reporter gene assay was used to verify whether Wee1 was a target gene of miR-613.si-Wee1 was transfected into radioresistant cells of colorectal cancer,or co-transfected with si-Wee1 and miR-613 inhibitor,and non-transfected cells were used as control group.The effects of miR-613/Wee1 axis on cell proliferation,invasion and cell cycle were detected by CCK-8,Transwell and Western blotting at different radiation doses.Results The expression of miR-613 was downregulated in the radiation resistance group of patients (1.54 ± 0.25 vs.2.64 ± 0.45;t =3.140,P =0.009) and radiation resistance cell lines (LoVo/R vs.LoVo:1.03 ± 0.12 vs.3.05 ± 0.15;t =8.944,P =0.006;HCT116/R vs.HCT116:1.01 ±0.11 vs.2.85 ±0.16;t =8.050,P =0.008).Overexpression of miR-613 was significantly inhibited the proliferation (LoVo/R:t6 Gy =6.018,P =0.013;HCT116/R:t6Gy =5.634,P =0.015) and invasion (LoVo/R:45.00 ± 8.95 vs.180.15 ± 6.95,t6 Gy =11.93,P =0.003;HCT116/R:49.97 ±6.21 vs.170.20 ±7.03,t6 Gy =12.82,P =0.006) of LoVo/R and HCT116/R cells and decreased the expression levels of G2-M phase cell cycle correlated proteins (CDK1 and cyclin B).Moreover,dual-luciferase reporter gene assay confirmed that Wee1 was a target of miR-613.Mechanistically,overexpression of miR-613 promoted the radiosensitivity of LoVo/R and HCT116/R cells through inhibiting cell proliferation (compared with si-Wee1 group,co-transfected with si-Wee1 and miR-613 inhibitor,and control group,LoVo/R:F8 Gy =40.742,P =0.007;HCT116/R:F8 Gy =28.958,P =0.011),invasion (LoVo/R:F8 Gy =55.413,P =0.004;HCT116/R:F8 Gy =65.634,P =0.003) and arresting cell at G2-M phase via downregulating Wee1.Conclusion miR-613/Wee1 axis plays a certain role in regulating the radiation resistance of colorectal cancer cells,overexpression of miR-613 may reverse the radiation resistance of colorectal cancer cells.

Objective To investigate the genotype of M.tuberculosis in He'nan Province.Methods A total of 668 M.tuberculosis clinical strains collected in difference regions of He'nan Province during 2015 were genotyped by two standard methods,including classical 24-locus mycobacterium interspersed repetitive unit variable-number tandem-repeat (MIRU-VNTR) typing and spoligotyping.Results The 668 isolates were divided into 11 clusters and 35 patterns by spoligotyping.Among the 558 Beijing strains,546 were typical Beijing strains and the other 12 were atypical Beijing strains.Among the 110 non-Beijing strains,eight were new strains and the remaining 102 non-Beijing strains were divided into 10 families.There were 76 isolates belonging to T family,including 59 of T1 families,7 of T2 families,and 10 of T3 families.The 668 strains were divided into 550 gene patterns by standard 24-locus VNTR,including 508 un-clustered patterns and 160 clustered into 42 clusters.The largest cluster contained 21 strains,the other clusters contained 2-20 strains.Conclusion Beijing strain is still the most prevalent M.tuberculosis in He'nan Province.

Objective To investigate the glomerular microvascular injury and repair in patients with IgA nephropathy (IgAN) as well as its relationship with intermedin (IMD).Methods Eighty cases of renal tissue taken from patients first diagnosed as IgAN in Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University and 15 cases of normal renal tissue were detected by the expression of glomerular IMD,CD31,and VE-cadherin through immunohistochemical method.ELISA method was used to detect VEGF and IMD of plasm from 31 normal subjects and 36 cases chosen from the IgAN patients.Their changes and internal relationship were analyzed according to Lee's and chronic kidney disease (CKD) classification.Results (1) Compared with the control group the expressions of CD31,IMD,and VE-cadherin in IgAN patients were statistically significant (P ＜0.01).Compared with the control group the levels of IMD and VEGF in plasma of IgAN patients in early stage of CKD group and late stage of CKD group were statistically significant (P ＜ 0.01).(2)Correlation analysis:the expression of glomerular CD31 and Lee's classification were negatively correlated (r=-0.232,P ＜ 0.05);glomerular IMD was negatively correlated with Lee's classification (r=-0.241,P＜0.05),while positively correlated with glomerular VE-cadherin (r=0.417,P＜ 0.01).VEGF in plasma of IgAN patients was positive correlated with CKD classification,BUN (r=0.458,0.409,P＜0.05),and negatively correlated with serum ALB (r=-0.532,P＜0.01).Conclusion Microvascular injury exists in patients with IgAN.The expression of VE-cadherin and IMD are positively correlated,suggesting that IMD may be involved in the progression of vascular protection and angiogenesis in IgAN.The contents of IMD and VEGF in plasma of IgAN patients increase,indicating that they may play a role in the progression of IgAN.