Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.

Objective:To investigate the clinical distribution characteristics changes in antimicrobial resistance, and carbapenemase resistance genes of Klebsiella pneumoniae isolated from children in Chongqing region during the period of January 2019 to December 2024, providing a basis for the rational use of antibiotics and the prevention and control of nosocomial infections.Methods:An observational study was conducted to retrospectively analyze 5 020 Klebsiella pneumoniae (KP) isolates detected in four hospitals of the Southwest Pediatric Laboratory Specialty Alliance. Antimicrobial susceptibility testing was performed by the minimum inhibitory concentration method combined with the disk diffusion method. Results were interpreted according to the 2024 Clinical and Laboratory Standards Institute (CLSI) standards. Carbapenemase resistance genes were detected by polymerase chain reaction (PCR) combined with Sanger sequencing. WHONET 5.6 was used for resistance analysis and SPSS 19.0 for statistical analysis. The chi-square test was used to assess trends in resistance rates, ESBL detection rates, and resistance rates of different CRKP carbapenemase genotypes from 2019 to 2024. Statistical significance was confirmed if the two-tailed P-value was <0.05. Results:A total of 5 020 strains were isolated, with a detection rate of 5.1% (5 020/99 063). The majority were from sputum (59.2%, 2 970/5 020), followed by pus (17.1%, 857), urine (9.7%, 487), venous blood (6.5%, 326), secretions (2.6%, 130), and other specimens (5.0%, 250).The lowest resistance rate was to amikacin (3.8%), followed by levofloxacin (10.9%), imipenem (19.1%), and meropenem (19.9%). Resistance rates to cefoperazone/sulbactam ( χ2=9.982 0, P=0.001 6), piperacillin/tazobactam ( χ2=10.110 0, P=0.001 5), ceftazidime ( χ2=3.849 0, P=0.049 8), cefotaxime ( χ2=7.605 0, P=0.005 8), cefepime ( χ2=13.510 0, P=0.000 2), aztreonam ( χ2=6.457 0, P=0.011 1), imipenem ( χ2=4.672 0, P=0.030 7), and levofloxacin ( χ2=7.555 0, P=0.006 0) showed an annual increasing trend. The main carbapenemase genes were blaNDM-5 (42.2%, 127/301), blaNDM-1 (33.9%, 102/301), and blaKPC-2 (17.3%, 52/301). Patients with KPC-2-producing strains (median age, 240 days) were older than those with NDM-1/NDM-5-producing strains (median age, 40 days) ( χ2=22.620 0, P<0.000 1). In neonatal wards, the detection rate of NDM-KP was higher than that of KPC-KP (64.6%, 148/229 vs. 26.9%, 14/52, χ2=24.680 0, P<0.000 1), whereas in ICUs, it was lower (6.1%, 14/229 vs. 26.9%, 14/52, χ2=20.450 0, P<0.000 1). Conclusion:In Chongqing region, the isolation rate of K. pneumoniae from sputum was the highest with most cases from neonatal wards. Resistance to carbapenems showed an upward trend. BlaNDM-5 was the predominant genotype in pediatric CRKP. Patients with KPC-KP were older than those with NDM-KP. NDM-KP predominated in neonatal wards, while KPC-KP predominated in ICUs, with KPC-KP showing higher antimicrobial resistance.

Objective To analyzing the correlation between serum microRNA(miRNA,miR)-128-3p,miRNA(miR)-126 expression and Gensini score in patients with coronary artery disease.Methods A retrospective study was conducted on 60 patients with coronary artery disease who were treated in the Department of Cardiology,Harrison International Peace Hospital from June 2020 to 2022.They were selected as the observation group,and another 60 patients with non-coronary artery disease who were treated in the hospital during the same period were selected as the control group.Serum miR-128-3p,miR-126 and Gensini scores were measured and compared between the two groups,and compared the serum miR-128-3p,miR-126 and Gensini scores of patients with single,double,and multiple vessel lesions in the observation group.According to the stenosis rate of coronary arteries,they were divided into I degree,II degree,III degree and IV degree groups.The serum miR-128-3p,miR-126 and Gensini scores were compared among different stenosis grading groups.According to the Gensini score,patients were divided into mild and severe lesion groups.According to the Gensini score,patients were divided into mild and severe lesion groups.The serum miR-128-3p and miR-126 levels were compared between the mild and severe lesion groups.Pearson analysis determined the correlation between serum miR-128-3p and miR-126 levels and Gensini score.Receiver operating characteristic curve(ROC)was plotted,and the area under curve(AUC)was calculated to analyze the predictive efficacy of the combined detection of serum miR-128-3p and miR-126 levels for coronary artery disease.Logistic regression analysis of influencing factors of coronary artery disease.Results Compared with the control group,the observation group showed an increase in serum miR-128-3p(4.28±0.52 vs 2.61±0.36)and Gensini score(31.29±5.62 score vs 6.16±1.04 score),observation group showed a decrease in serum miR-126,with statistically significant differences(t=21.678,34.058,11.002,all P<0.05).Compared with the double vessel disease and single vessel disease groups,the serum miR-128-3p and Gensini score in the multi vessel disease group increased(t=4.945,7.171;6.795,11.686),the serum miR-126 decreased(t=3.104,5.033),and the differences were statistically significant(all P<0.05).Compared with the I～II group,the serum miR-128-3p and Gensini score in the III～IV group increased significantly(t=5.590,12.961),the serum miR-126 decreased significantly(t=6.021),with statistical significance differences(all P<0.05).Compared with the mild lesion group,the serum miR-128-3p level increased in the severe lesion group(t=4.056),the serum miR-126 level decreased(t=4.806),and the differences were statistically significant differences(all P<0.05).There was a positive correlation between serum miR-128-3p and Gensini score(r=0.404,P<0.05),and a negative correlation between serum miR-126 and Gensini score(r=-0.393,P<0.05).The AUC of combined detection of serum miR-128-3p and miR-126 was higher than that of single detection,and the differences were statistically significant(Z=2.768,2.152,all P<0.05).The differences in smoking,triglycerides(TG),uric acid(UA),fibrinogen(FIB)between the observation group and the control group were statistically significant(t/χ2=4.231～28.732,all P<0.05).Conclusion Patients with coronary artery disease have high expression of serum miR-128-3p and low expression of serum miR-126,which is correlated with Gensini score.The combined detection of serum miR-128-3p and miR-126 can improve the predictive efficiency of coronary artery disease,and the occurrence of coronary artery disease is related to multiple factors,which should be given clinical attention.

Objective:To investigate the clinical distribution characteristics changes in antimicrobial resistance, and carbapenemase resistance genes of Klebsiella pneumoniae isolated from children in Chongqing region during the period of January 2019 to December 2024, providing a basis for the rational use of antibiotics and the prevention and control of nosocomial infections.Methods:An observational study was conducted to retrospectively analyze 5 020 Klebsiella pneumoniae (KP) isolates detected in four hospitals of the Southwest Pediatric Laboratory Specialty Alliance. Antimicrobial susceptibility testing was performed by the minimum inhibitory concentration method combined with the disk diffusion method. Results were interpreted according to the 2024 Clinical and Laboratory Standards Institute (CLSI) standards. Carbapenemase resistance genes were detected by polymerase chain reaction (PCR) combined with Sanger sequencing. WHONET 5.6 was used for resistance analysis and SPSS 19.0 for statistical analysis. The chi-square test was used to assess trends in resistance rates, ESBL detection rates, and resistance rates of different CRKP carbapenemase genotypes from 2019 to 2024. Statistical significance was confirmed if the two-tailed P-value was <0.05. Results:A total of 5 020 strains were isolated, with a detection rate of 5.1% (5 020/99 063). The majority were from sputum (59.2%, 2 970/5 020), followed by pus (17.1%, 857), urine (9.7%, 487), venous blood (6.5%, 326), secretions (2.6%, 130), and other specimens (5.0%, 250).The lowest resistance rate was to amikacin (3.8%), followed by levofloxacin (10.9%), imipenem (19.1%), and meropenem (19.9%). Resistance rates to cefoperazone/sulbactam ( χ2=9.982 0, P=0.001 6), piperacillin/tazobactam ( χ2=10.110 0, P=0.001 5), ceftazidime ( χ2=3.849 0, P=0.049 8), cefotaxime ( χ2=7.605 0, P=0.005 8), cefepime ( χ2=13.510 0, P=0.000 2), aztreonam ( χ2=6.457 0, P=0.011 1), imipenem ( χ2=4.672 0, P=0.030 7), and levofloxacin ( χ2=7.555 0, P=0.006 0) showed an annual increasing trend. The main carbapenemase genes were blaNDM-5 (42.2%, 127/301), blaNDM-1 (33.9%, 102/301), and blaKPC-2 (17.3%, 52/301). Patients with KPC-2-producing strains (median age, 240 days) were older than those with NDM-1/NDM-5-producing strains (median age, 40 days) ( χ2=22.620 0, P<0.000 1). In neonatal wards, the detection rate of NDM-KP was higher than that of KPC-KP (64.6%, 148/229 vs. 26.9%, 14/52, χ2=24.680 0, P<0.000 1), whereas in ICUs, it was lower (6.1%, 14/229 vs. 26.9%, 14/52, χ2=20.450 0, P<0.000 1). Conclusion:In Chongqing region, the isolation rate of K. pneumoniae from sputum was the highest with most cases from neonatal wards. Resistance to carbapenems showed an upward trend. BlaNDM-5 was the predominant genotype in pediatric CRKP. Patients with KPC-KP were older than those with NDM-KP. NDM-KP predominated in neonatal wards, while KPC-KP predominated in ICUs, with KPC-KP showing higher antimicrobial resistance.

Objective To analyzing the correlation between serum microRNA(miRNA,miR)-128-3p,miRNA(miR)-126 expression and Gensini score in patients with coronary artery disease.Methods A retrospective study was conducted on 60 patients with coronary artery disease who were treated in the Department of Cardiology,Harrison International Peace Hospital from June 2020 to 2022.They were selected as the observation group,and another 60 patients with non-coronary artery disease who were treated in the hospital during the same period were selected as the control group.Serum miR-128-3p,miR-126 and Gensini scores were measured and compared between the two groups,and compared the serum miR-128-3p,miR-126 and Gensini scores of patients with single,double,and multiple vessel lesions in the observation group.According to the stenosis rate of coronary arteries,they were divided into I degree,II degree,III degree and IV degree groups.The serum miR-128-3p,miR-126 and Gensini scores were compared among different stenosis grading groups.According to the Gensini score,patients were divided into mild and severe lesion groups.According to the Gensini score,patients were divided into mild and severe lesion groups.The serum miR-128-3p and miR-126 levels were compared between the mild and severe lesion groups.Pearson analysis determined the correlation between serum miR-128-3p and miR-126 levels and Gensini score.Receiver operating characteristic curve(ROC)was plotted,and the area under curve(AUC)was calculated to analyze the predictive efficacy of the combined detection of serum miR-128-3p and miR-126 levels for coronary artery disease.Logistic regression analysis of influencing factors of coronary artery disease.Results Compared with the control group,the observation group showed an increase in serum miR-128-3p(4.28±0.52 vs 2.61±0.36)and Gensini score(31.29±5.62 score vs 6.16±1.04 score),observation group showed a decrease in serum miR-126,with statistically significant differences(t=21.678,34.058,11.002,all P<0.05).Compared with the double vessel disease and single vessel disease groups,the serum miR-128-3p and Gensini score in the multi vessel disease group increased(t=4.945,7.171;6.795,11.686),the serum miR-126 decreased(t=3.104,5.033),and the differences were statistically significant(all P<0.05).Compared with the I～II group,the serum miR-128-3p and Gensini score in the III～IV group increased significantly(t=5.590,12.961),the serum miR-126 decreased significantly(t=6.021),with statistical significance differences(all P<0.05).Compared with the mild lesion group,the serum miR-128-3p level increased in the severe lesion group(t=4.056),the serum miR-126 level decreased(t=4.806),and the differences were statistically significant differences(all P<0.05).There was a positive correlation between serum miR-128-3p and Gensini score(r=0.404,P<0.05),and a negative correlation between serum miR-126 and Gensini score(r=-0.393,P<0.05).The AUC of combined detection of serum miR-128-3p and miR-126 was higher than that of single detection,and the differences were statistically significant(Z=2.768,2.152,all P<0.05).The differences in smoking,triglycerides(TG),uric acid(UA),fibrinogen(FIB)between the observation group and the control group were statistically significant(t/χ2=4.231～28.732,all P<0.05).Conclusion Patients with coronary artery disease have high expression of serum miR-128-3p and low expression of serum miR-126,which is correlated with Gensini score.The combined detection of serum miR-128-3p and miR-126 can improve the predictive efficiency of coronary artery disease,and the occurrence of coronary artery disease is related to multiple factors,which should be given clinical attention.

Objective To investigate the efficacy and influencing factors of allo-HSCT in the treatment of MDS patients with ASXL1+.Methods The second-generation sequencing technique was used to detect 22 gene mutations in 247 newly diagnosed MDS patients in our hospital.The patients were divided into chemotherapy group and transplant group according to treatment style.The differences of OS and PFS between the two groups were compared,and the influencing factors of prognosis of transplant patients were analyzed.Results ASXL1+ was detected in 75 patients(30.36%),with a median mutation ratio of 42.93(18.10,58.39)%,10 received supportive treatment,43 received demethylation therapy or demethylation combined with pre-excitation therapy,and 22 received allo-HSCT.2-year PFS rate and OS rate of transplantation group were significantly higher than that of chemotherapy group(P<0.05).The 2-year OS rate in the low ASXL1 mutation load group(VAF≤42.93%)was significantly higher than that in the high ASXL1 mutation load group(VAF>42.93%)(P<0.05).In the context of allo-HSCT in patients with ASXL1+,2-year OS and PFS rates were significantly reduced in patients with RUNX1+ or ASXL1+(P<0.05);Multivariate analysis showed that high mutation load of ASXL1 or U2AF1+ were independent risk factors for OS in transplant patient(P<0.05).U2AF1+ were the risk factors for PFS(P<0.05).Conclusion allo-HSCT significantly improved the prognosis of patients with ASXL1+ MDS.High ASXL1 mutation load or U2AF1+ were independent risk factors affecting the outcome of allo-HSCT.

Objective: The expression of spectrin beta chain, brain1(SPTBN1) were measured in nasopharyngeal carcinoma (NPC) cell lines, as well as tissues and serums of NPC cases and normal controls. The clinical value of SPTBN1 expression for NPC diagnosis were assessed along with the antibody levels of early antigen-IgA(EA-IgA) and viral capsid antigen-IgA(VCA-IgA). Methods: A total of 71 nasopharynx tissue specimens and 130 serum from both NPC cases and matched health controls were collected from December 2016 to December 2018. In logistic regression the levels of SPTBN1, EA-IgA, VCA-IgA were identified and included in an integrative risk prediction model. Discriminatory accuracy was measured by generation of receiver operator curves and estimation of area under the curve (AUC). Results: The SPTBN1 concentration in cell lines from NP69, 6-10B to 5-8F showed a decreasing trend (H=50.205, P<0.05). The SPTBN1 expression level in serums were significantly lower [73(42, 142)] compared to controls, while EA-IgA and VCA-IgA levels [3.42(1.29, 5.19),3.55(1.95, 5.01)]were higher in NPC serum samples (H_SPTBN1=24.105, H_EA-IgA=52.398, H_VCA-IgA=70.426, P<0.01). The findings were confirmed in tissues that the positive SPTBN1 rate were significantly lower in cases (86.7%) as compared to controls (43.9%, χ²=13.443, P<0.001). In the risk prediction model for NPC diagnosis, the AUC of SPTBN1 alone and the integrated regression model were 0.794 and 0.987, respectively (Z=4.900,P<0.01). Conclusions The lower expression of SPTBN1 was a potential marker in NPC diagnosis. The combined analysis of SPTBN1, EA-IgA and VCA-IgA may improve the sensitivity and specificity in NPC diagnosis.

Objective To observe the changes of glycocholic acid (CG) and evaluate the diagnostic value of CG combined with total bile acid (TBA) and leucine aminopeptidase (LAP) in various liver diseases.Methods From October 2016 to March 2017,210 serum samples of healthy people,asymptomatic hepatitis B virus (HBV) infected,hepatitis,biliary obstruction,hepatocirrhosis and primary hepatocellular carcinoma patients were collected.CG and LAP were detected by corresponding kits,and liver function,coagulation function and other indicators of patients were collected and analyzed statistically.Results The serum level of CG were elevated in the 4 liver disease groups and differed statistically from the normal group or the asymptomatic HBV infected group.CG level was positively correlated with LAP (r =0.380,P ＜ 0.01).In liver function indexes,CG was correlated with total bilirubin (TB),direct bilirubin (DB),TBA and alkaline phosphatase (AKP).At the same time,CG was correlated with fibrinogen(Fib),thrombin time(TT).LAP and TBA were introduced into regression equation Y =-0.835 + 0.157X1 +0.312X2 (X1:LAP,X2:TBA,R2 =0.685) as final variables in multivariate linear regression to analyse the influencing factors of CG.Receiver operator characteristic (ROC) curve analysis showed that CG had the strongest ability to diagnose liver diseases in combination with LAP.Conclusions The change of CG level is of great significance in all kinds of liver diseases.The combination of LAP has the strongest ability to diagnose liver diseases.

Objective To investigate the expression level of nucleobindin-2 (NUCB2/Nesfatin-1) in nasopharyngeal carcinoma (NPC) patients, other patients with head and neck cancer, rhinitis patients, and healthy subjects in the serum, and evaluate the clinical application value of NUCB2/Nesfatin-1 combined with three items of Epstein-Barr (EB) virus (EA-IgA;VCA-IgA;Rta-IgG) in NPC diagnosis.Methods From Xiangya Hospital of Central South University during January 2017 to June 2017, nasopharyngeal carcinoma patients, other patients with head and neck cancer, rhinitis patients, and healthy subjects samples were 140 cases, respectively.The corresponding kits were used to detect nesfatin-1, EA-IgA, VCA-IgA, and Rta-IgG.Results The serum level of nesfatin-1 in NPC patients was the highest, and the difference was statistically significant compared to other groups.The serum levels of EA-IgA, VCA-IgA, and Rta-IgG were the highest in NPC patients, and were significantly different from those in other groups.Nesfatin-1 was significantly correlated with VCA-IgA and Rta-IgG.There was no significant correlation between nesfatin-1, EA-IgA and NPC staging;Multiple linear regression analysis was used to analyze the influencing factors of nesfatin-1, and the regression equation was Y =208.029 + 17.96X1 + 146.702X2 + 398.879X3 (X1:age;X2:VCA-IgA;X3:Rta-IgG;R2 =0.236).Receiver operating characteristic (ROC) curve analysis showed that nesfatin-I combined with VCA-IgA and Rta-IgG had the best efficiency in the diagnosis of NPC.In single index evaluation, nesfatin-1 has the lowest specificity, but the highest sensitivity.Conclusions The sensitivity of nesfatin-1 for NPC diagnosis is polar altitude, it can make up for the deficiency of EA-IgA, VCA-IgA, and Rta-IgG in diagnosing NPC.The combination of VCA-IgA and Rta-IgG can greatly improve the ability of diagnosing NPC.