Objective:To evaluate the efficacy and safety of blinatumomab in adult patients with relapsed/refractory(R/R)or measurable residual disease(MRD)positive B-cell acute lymphoblastic leukemia(B-ALL)in the real world.Methods:The clinical data of 30 B-ALL patients received at least 1 course of blinatumomab therapy in the Chinese PLA General Hospital from January 1st,2021 to December 31st,2023 were retrospectively analyzed,including pre-treatment baseline clinical feature,post-treatment complete response(CR),CR with partial hematologic recovery(CRh),CR with incomplete hematologic recovery(CRi),complete MRD response rate,MRD response rate(MRD＜10-4),overall survival(OS),and disease-free survival(DFS),as well as drug-related adverse reactions.Results:Among 5 patients who were not assessed 4 were MRD negative and 1 did not receive bone marrow biopsy.In the R/R B-ALL group(13 cases),11 patients achieved CR/CRh/CRi and 10 patients achieved complete MRD response.In MRD+group(12 cases),9 patients achieved overall MRD response and 7 patients achieved complete MRD response.The median follow-up time was 8.4(95％CI:6.3-10.4)months.The median OS was 15.5(95％CI:0.7-30.3)months in the R/R group,while not reached in the MRD+group.The median DFS of the two groups were not reached.Drug-related adverse reactions occurred in 22 patients,and pyrexia was the most common(13 cases).Grade ≥3 adverse reactions occurred in 15 patients,and neutropenia was the most common(9 cases).Cytokine release syndrome occurred in 6 patients,including 5 cases with grade 1 and 1 case with grade 3.No patients interrupted therapy or died due to drug-related adverse reactions.Conclusion:Blinatumomab is effective in the treatment of R/R or continuous MRD+B-ALL with acceptable adverse reactions.

Aim To observe the effect of lipopolysac-charide(LPS)induced supernatant of BV-2 cells on the inflammatory response and apoptosis of HT22 neu-rons.Methods After the concentration and time of LPS were determined by CCK-8 method,BV-2 cells were cultured with medium without LPS and medium containing LPS,the morphological changes of BV-2 microglia were observed by inverted microscope,and the CD86/CD206 ratio of BV-2 microglia was detected by immunofluorescence.Subsequently,BV-2 cell cul-ture supernatants were isolated and added to HT22 neuronal culture to observe the effect on the inflamma-tory response of HT22 neurons.The proliferation of HT22 neurons was detected by CCK-8 method and EdU method.The structural changes of HT22 neurons were observed under the microscope and examined by urani-um-lead staining.The levels of cytokines interleukin-1β(IL-1β),interleukin-10(IL-10),nuclear factor kappa-B(NF-κB)and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent as-say(Elisa).Neuronal apoptosis was detected by the TUNEL method.The protein expressions of Bax,Bcl-2 and inflammatory factors were detected by Western blot.Results After induction with 1 mg·L-1 LPS,BV-2 cells exhibited increased cell body size,thicker protrusions on both side,and some cells showed de-formed protrusions,the CD86/CD206 ratio in BV-2 cells decreased,promoting the transformation of BV-2 cells from M2 type to M1 type.After treating with the culture supernatant of BV-2 cells,HT22 neuronal cell activity and proliferation were reduced,axons short-ened,and the number of cells decreased.Neuronal cell bodies were enlarged and some cells were de-formed,with damaged cell membranes,round cell nu-clei but displaced nucleoli from the normal position,swollen mitochondria with vacuoles,reduced internal ridge structures,and increased levels of inflammatory factors NF-κB,IL-1 β,and TNF-α(P＜0.05 or P＜0.01),while the anti-inflammatory factor IL-10 de-creased(P＜0.05),protein expression of the pro-apoptotic indicator Bax increased(P＜0.01),and the protein expression of the anti-apoptotic indicator Bcl-2 decreased(P＜0.05).Conclusion After induction of BV-2 cell polarization by LPS,the supernatant could inhibit HT22 neuronal cell viability,upregulate inflam-matory factor expression and promote apoptosis.

Aim To study whether intravenous injec-tion of miR-129-3p mimetic(agomir)can resist bone loss caused by hind limb disuse,and to provide new i-deas for preventing bone loss in microgravity environ-ment.Methods Forty-eight C57BL/6J male mice were randomly divided into the control group(CON),tail suspension model group(TS),tail suspension+miR-129-3p agomir administration group(miRNA)and tail suspension+miR-129-3p negative sequence agomir control group(NC).The miRNA group was given 4 mg·kg-1 miR-129-3p agomir by intravenous injection into the medial canthus twice a week.The NC agomir group were consistent with those in the miR-129-3p agomir group,and the CON and TS groups were given only equal volumes of normal saline.After four weeks,all mice were sacrificed and samples were collected.Micro-CT scan of femur,three-point femur bending test,serum bone metabolism index detection,oxidative stress index detection and osteogenesis-related protein expression analysis in bone tissue were per-formed.Results After four weeks,the number of tra-becular bone in the TS group was significantly re-duced,and Tb.BMD,Tb.Th,Tb.N,Tb.BS/TV and Tb.BV/TV were significantly lower than those in the CON group(P＜0.01).While Tb.Sp TS group was significantly higher than the CON group(P＜0.05),the maximum load and flexural strength of the femur significantly decreased(P＜0.01),the content of ser-um bone formation index PINP was significantly lower than that of the CON group(P＜0.01),and the con-tent of bone resorption index CTX-I was significantly higher than that of the CON group(P＜0.01),the content of serum oxidative damage indexes 8-iso-PGF2α and 8-OHdG significantly increased(P＜0.01),and the expression of osteogenesis-related pro-teins in bone tissue markedly decreased(P＜0.01).However,the increase or decrease of all indexes in miRNA group was significantly lower than that in TS group.Conclusions miR-129-3p mimetic can signifi-cantly reduce bone loss caused by hind limb disuse.This experiment provides a new idea and method for preventing bone loss in microgravity environment.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Aim To observe the effect of lipopolysac-charide(LPS)induced supernatant of BV-2 cells on the inflammatory response and apoptosis of HT22 neu-rons.Methods After the concentration and time of LPS were determined by CCK-8 method,BV-2 cells were cultured with medium without LPS and medium containing LPS,the morphological changes of BV-2 microglia were observed by inverted microscope,and the CD86/CD206 ratio of BV-2 microglia was detected by immunofluorescence.Subsequently,BV-2 cell cul-ture supernatants were isolated and added to HT22 neuronal culture to observe the effect on the inflamma-tory response of HT22 neurons.The proliferation of HT22 neurons was detected by CCK-8 method and EdU method.The structural changes of HT22 neurons were observed under the microscope and examined by urani-um-lead staining.The levels of cytokines interleukin-1β(IL-1β),interleukin-10(IL-10),nuclear factor kappa-B(NF-κB)and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent as-say(Elisa).Neuronal apoptosis was detected by the TUNEL method.The protein expressions of Bax,Bcl-2 and inflammatory factors were detected by Western blot.Results After induction with 1 mg·L-1 LPS,BV-2 cells exhibited increased cell body size,thicker protrusions on both side,and some cells showed de-formed protrusions,the CD86/CD206 ratio in BV-2 cells decreased,promoting the transformation of BV-2 cells from M2 type to M1 type.After treating with the culture supernatant of BV-2 cells,HT22 neuronal cell activity and proliferation were reduced,axons short-ened,and the number of cells decreased.Neuronal cell bodies were enlarged and some cells were de-formed,with damaged cell membranes,round cell nu-clei but displaced nucleoli from the normal position,swollen mitochondria with vacuoles,reduced internal ridge structures,and increased levels of inflammatory factors NF-κB,IL-1 β,and TNF-α(P＜0.05 or P＜0.01),while the anti-inflammatory factor IL-10 de-creased(P＜0.05),protein expression of the pro-apoptotic indicator Bax increased(P＜0.01),and the protein expression of the anti-apoptotic indicator Bcl-2 decreased(P＜0.05).Conclusion After induction of BV-2 cell polarization by LPS,the supernatant could inhibit HT22 neuronal cell viability,upregulate inflam-matory factor expression and promote apoptosis.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective:Near-infrared(NIR)spectroscopy technology faces the problem of insufficient model generalization due to individual differences in non-invasive blood glucose testing,in order to solve this problem,to improve data utilization,and to build predictive models with stronger generalization ability,this study introduces a transfer learning method to study the NIR spectroscopy non-invasive glucose testing.Methods:Migration learning is a machine learning technique that aims to improve task performance in the target domain by transferring knowledge from the source domain to the target domain.In this study,we used community population data as the source domain and student population data as the target domain to improve the performance of the noninvasive glucose detection model on the target domain.In order to verify the effectiveness of migration learning,this study compares the performance of the model before and after migration learning.Results:the model's performance on the noninvasive glucose detection task is significantly improved by the migration learning strategy,and the MAPE and MAE of the migrated model decreases by 52.5460％and 6.0805％,respectively,and the RMSE and MSE decreases by 10.7215％and 12.1135％.Conclusions:This study demonstrates the promising application of transfer learning in the field of non-invasive blood glucose detection,which is expected to realize portable and continuous blood glucose monitoring in the future by migrating the features that are difficult to access in the source domain but are related to blood glucose values to the target domain,which will greatly improve the quality of life of diabetic patients.Advances in noninvasive glucose testing technology will not only reduce patients' pain,but also provide a more convenient means of glucose monitoring,which will provide strong support for diabetes management.

Objective:Near-infrared(NIR)spectroscopy technology faces the problem of insufficient model generalization due to individual differences in non-invasive blood glucose testing,in order to solve this problem,to improve data utilization,and to build predictive models with stronger generalization ability,this study introduces a transfer learning method to study the NIR spectroscopy non-invasive glucose testing.Methods:Migration learning is a machine learning technique that aims to improve task performance in the target domain by transferring knowledge from the source domain to the target domain.In this study,we used community population data as the source domain and student population data as the target domain to improve the performance of the noninvasive glucose detection model on the target domain.In order to verify the effectiveness of migration learning,this study compares the performance of the model before and after migration learning.Results:the model's performance on the noninvasive glucose detection task is significantly improved by the migration learning strategy,and the MAPE and MAE of the migrated model decreases by 52.5460％and 6.0805％,respectively,and the RMSE and MSE decreases by 10.7215％and 12.1135％.Conclusions:This study demonstrates the promising application of transfer learning in the field of non-invasive blood glucose detection,which is expected to realize portable and continuous blood glucose monitoring in the future by migrating the features that are difficult to access in the source domain but are related to blood glucose values to the target domain,which will greatly improve the quality of life of diabetic patients.Advances in noninvasive glucose testing technology will not only reduce patients' pain,but also provide a more convenient means of glucose monitoring,which will provide strong support for diabetes management.

Objective:To evaluate the efficacy and safety of blinatumomab in adult patients with relapsed/refractory(R/R)or measurable residual disease(MRD)positive B-cell acute lymphoblastic leukemia(B-ALL)in the real world.Methods:The clinical data of 30 B-ALL patients received at least 1 course of blinatumomab therapy in the Chinese PLA General Hospital from January 1st,2021 to December 31st,2023 were retrospectively analyzed,including pre-treatment baseline clinical feature,post-treatment complete response(CR),CR with partial hematologic recovery(CRh),CR with incomplete hematologic recovery(CRi),complete MRD response rate,MRD response rate(MRD＜10-4),overall survival(OS),and disease-free survival(DFS),as well as drug-related adverse reactions.Results:Among 5 patients who were not assessed 4 were MRD negative and 1 did not receive bone marrow biopsy.In the R/R B-ALL group(13 cases),11 patients achieved CR/CRh/CRi and 10 patients achieved complete MRD response.In MRD+group(12 cases),9 patients achieved overall MRD response and 7 patients achieved complete MRD response.The median follow-up time was 8.4(95％CI:6.3-10.4)months.The median OS was 15.5(95％CI:0.7-30.3)months in the R/R group,while not reached in the MRD+group.The median DFS of the two groups were not reached.Drug-related adverse reactions occurred in 22 patients,and pyrexia was the most common(13 cases).Grade ≥3 adverse reactions occurred in 15 patients,and neutropenia was the most common(9 cases).Cytokine release syndrome occurred in 6 patients,including 5 cases with grade 1 and 1 case with grade 3.No patients interrupted therapy or died due to drug-related adverse reactions.Conclusion:Blinatumomab is effective in the treatment of R/R or continuous MRD+B-ALL with acceptable adverse reactions.

Breast cancer(BRCA)remains one of the leading causes of cancer-related deaths worldwide due to its high rates of metastasis and recurrence,making it crucial to explore its underlying molecular mechanisms.Our previous study demonstrated that miR-326 inhibits BRCA progression by targeting EPH receptor B3(EPHB3).This study further explores the molecular mechanism by which long non-coding RNAs(LncRNAs)regulates BRCA progression via the competing endogenous RNA(ceRNA)mecha-nism,in which it competes with EPHB3 for miR-326 binding.Bioinformatics analysis identified LncRNA Small Nucleolar RNA Host Gene 12(SNHG12)as a potential miR-326-binding molecule.SNHG12 was found to be significantly upregulated in BRCA tissues,exhibiting a negative correlation trend with miR-326 and a positive correlation trend with EPHB3,suggesting its potential involvement in the ceRNA regu-latory network.Nuclear-cytoplasmic fractionation assays revealed cytoplasmic localization of SNHG12,while dual-luciferase reporter assays confirmed its direct binding to miR-326.Functional experiments demonstrated that SNHG12 knockdown significantly suppressed BRCA cell proliferation,invasion,and migration,while miR-326 inhibition reversed these effects.Furthermore,miRNA pulldown assay re-vealed significant enrichment of SNHG12 and EPHB3 in the miR-326 pulldown products,indicating di-rect binding between them.Western blotting and rescue experiments revealed that SNHG12 upregulates EPHB3 expression by sponging miR-326,thereby promoting the malignant behaviors of BRCA cells.Col-lectively,this study revealed that LncRNA SNHG12 promotes BRCA progression by regulating the miR-326/EPHB3 axis through a ceRNA mechanism.The SNHG12/miR-326/EPHB3 pathway may represent a promising target for the molecular diagnosis and targeted therapy of BRCA.