Objective:Non-targeted metabolomics based on ultra-performance liquid chromatography mass spectrometry(UPLC-MS)platform was used to study the metabolic characteristics of multiple myeloma(MM)patients,and explore potential new metabolic mechanisms affecting the occurrence and development of MM.Methods:The study enrolled 42 MM patients,including 21 newly diagnosed(ND)patients and 21 relapsed patients(RP),and 21 age-sex matched healthy controls(HC)as subjects.UPLC-MS analysis platform was used to detect small molecule metabolites in serum of the subjects.Principal component analysis(PCA),orthogonal partial least-squared discriminant analysis(OPLS-DA)and 200 random permutations were used to analyze the differences of metabolic profiles among groups.Identification of differential metabolites was completed in the Human Metabolome Database(HMDB)and abnormal metabolic pathway analysis was performed using the KEGG database.Results:The metabolic profiles of MM patients and healthy controls were significantly separated in both PCA and OPLS-DA models,while the metabolic profiles of newly diagnosed and relapsed MM patients were significantly separated only in OPLS-DA model.In ND vs HC,RP vs HC and RP vs ND cohorts,19,24 and 18 differential metabolites were identified respectively,mainly sphingolipids,glycerophospholipids and fatty acyl amino acids.The metabolic pathway abnormalities in newly diagnosed and relapsed MM patients were mainly manifested in sphingolipid metabolism and glycerophospholipid metabolism compared to healthy controls.Compared with newly diagnosed MM patients,relapsed MM patients were mainly manifested in sphingolipid metabolism and ether-lipid metabolism.Conclusion:The metabolic profiles of MM patients are significantly different from those of healthy people.Relapsed MM patients and newly diagnosed MM patients have similar metabolic profiles,but there are still some differences.Glycerophospholipid metabolism,sphingolipid meta-bolism and ether-lipid metabolism may play important biological roles in the occurrence and development of MM.

Objective To explore the effectiveness of the peripheral arterial calcification scoring system(PACSS)based on computed tomography angiography(CTA)in assessing renal function in patients with peripheral arterial disease(PAD).Methods The clinical data,CTA imaging data,and laboratory results from PAD patients who underwent lower limb artery CTA examination were retrospectively collected.The PACSS was utilized to score the calcification in both lower limb arteries.Participants were categorized into three groups based on their estimated glomerular filtration rate(eGFR)(normal group:eGFR≥90 mL/min;mild renal dysfunction group:eGFR 60-89 mL/min,and moderate to severe renal dysfunction group:eGFR＜60 mL/min).The demographic data,clinical symptoms,and comorbidities among the three groups were compared by analysis of variance(ANOVA).The Spearman correlation coefficient was employed to evaluate the relationship between eGFR,cystatin C,and PACSS score.Results The age(P＜0.001)and PACSS score(P＜0.05)of patients with renal dysfunction were significantly higher than those of patients with normal renal function.However,there were no significant differences in gender,prevalence of diabetes,hypertension,or severe limb ischemia.Spearman correlation analysis showed that eGFR was negatively correlated with PACSS score(r=-0.18 in the right lower limb,P=0.037,r=-0.24 in the left lower limb,P=0.006).In contrast,cystatin C was positively correlated with PACSS score(r=0.26 in the right lower limb,P＜0.001,r=0.22 in the left lower limb,P=0.002).Conclusion The PACSS score of lower limb artery in PAD patients is corre-lated with the severity of renal dysfunction.This finding may facilitate early warning and clinical intervention for PAD patients with renal dysfunction.

Purpose To explore whether tryptanthrin(TRYP)can inhibit the malignant behavioral ability of glio-ma cells,and to elucidate the specific mechanism of its action.Methods MTT assay was performed to detect the effect of TRYP on the proliferation of glioma cells;Transwell assay was performed to detect the effect of TRYP on the migration and invasion of glioma cells;AnnexinV-FITC/PI apoptosis assay was performed to detect the effect of TRYP on the apoptosis of glioma cells;PI/RNase cell cycle assay was performed to detect the effect of TRYP on the cell cycle distribution of glioma cells;Western blot assay was performed to detect the effect of TRYP on the protein expressions of p-ERK and c-Myc in glioma cells.The effect of TRYP on the proliferation of glioma cells in vivo was verified by con-structing a subcutaneous transplantation tumor model in nude mice,and the effect of TRYP on the apoptotic ability of cells in the transplantation tumor was detected by TUNEL assay.Immunohistochemistry was used to detect the effect of TRYP on the expression of Ki67,BRAF,c-Myc,and p-ERK proteins in transplanted tumor tissues.Results MTT assay showed that TRYP could effectively inhibit the proliferation of glioma cells(P＜0.001).Transwell assay showed that TRYP could inhibit the invasion and migration of glioma cells(P＜0.001).AnnexinV-FITC/PI cell apoptosis as-say showed that TRYP could promote the apoptosis of glioma cells(P＜0.001).The results of PI/RNase cell cycle as-say showed that TRYP was able to promote the G2 phase block of glioma cells(P＜0.001).Western blot results showed that the expression levels of c-Myc and p-ERK proteins in the glioma cells were significantly reduced after TR-YP treatment(P＜0.001).The results of subcutaneous transplantation tumor model in nude mice showed that TRYP could effectively inhibit the growth rate(P＜0.01)and weight(P＜0.05)of transplanted tumor.TUNEL assay showed that TRYP could promote the apoptosis of tumor cells in transplanted tumor(P＜0.001).Immunohistochemis-try results showed that TRYP could effectively inhibit the protein expression of Ki67(P＜0.01),BRAF,c-Myc,and p-ERK(P＜0.001).Conclusion TRYP can inhibit the proliferation,invasion,and migration ability of glioma cells,promote apoptosis of glioma cells,and block the cell cycle of glioma cells.TRYP may inhibit the malignant pro-gression of glioma cells by suppressing the protein expression of BRAF,c-Myc and p-ERK1/2 in the MAPK/ERK sig-naling pathway.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective:To investigate the effect of microRNA-363-5p targeted binding to THBS3 on angiotensin Ⅱ-induced apoptosis in cardiomyocytes and its molecular mechanism.Methods:A human-derived cardiomyocyte cell line(AC16)was used to establish an in vitro cardiomyocyte apoptosis model with angiotensin Ⅱ(AngⅡ),and a dual luciferase reporter assay was performed to detect the relationship between miR-363-5p and THBS3;apoptosis rate was detected by flow cytometry,and real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was performed to detect the relative expression of microR-363-5p,ATF-6mRNA,THBS3mRNA expression;Western Blot to detect the relative expression of caspase-12,caspase-3,GRP78,Bax,Bcl-2.Results:(1)Compared with the control group,the relative expression level of miR-363-5p in AngⅡ group was significantly decreased.(2)Compared with Mir-inhibitor-NC and Mir-mimics-NC groups,the apoptosis rate of miR-inhibitor and miR-mimics groups was significantly increased and decreased,the relative expression level of Bax protein was significantly increased and decreased,and the relative expression level of Bcl-2 was decreased and increased.(3)miR-363-5p targeted binding to THBS3.(4)Compared with the THBS3-OENC group,the relative expression of Bax and caspase-3 proteins was significantly higher,the relative expression of Bcl-2 protein was significantly lower,and the apoptosis rate was higher in the THBS3-OE group.(5)Compared with the negative control group,the relative expression of Bax and caspase-3 proteins in the miR-mimcs+THBS3-OE group was significantly higher,the relative expression of Bcl-2 protein was significantly lower,the apoptosis rate was significantly higher,and the cell viability was significantly lower.(6)Compared with the miR-inhibitor group,the relative expression of GRP78 and caspase-12 was decreased in the miR-inhibitor-4-PBA group,and the apoptosis rate was significantly reduced.(7)Compared with the negative control group,the apoptosis rate was elevated in the ATF-6-OE group,and the relative expression of caspase-12 was significantly increased.(8)Compared with the negative control group,miR-inhibitor+ATF-6 siRNA group showed decreased apoptosis rate and decreased relative expression of caspase-12.Conclusions:MicroRNA-363-5p is able to target binding to THBS3 to regulate myocardial apoptosis,a process that may be mediated through the endoplasmic reticulum stress ATF-6 pathway.

Purpose To explore whether tryptanthrin(TRYP)can inhibit the malignant behavioral ability of glio-ma cells,and to elucidate the specific mechanism of its action.Methods MTT assay was performed to detect the effect of TRYP on the proliferation of glioma cells;Transwell assay was performed to detect the effect of TRYP on the migration and invasion of glioma cells;AnnexinV-FITC/PI apoptosis assay was performed to detect the effect of TRYP on the apoptosis of glioma cells;PI/RNase cell cycle assay was performed to detect the effect of TRYP on the cell cycle distribution of glioma cells;Western blot assay was performed to detect the effect of TRYP on the protein expressions of p-ERK and c-Myc in glioma cells.The effect of TRYP on the proliferation of glioma cells in vivo was verified by con-structing a subcutaneous transplantation tumor model in nude mice,and the effect of TRYP on the apoptotic ability of cells in the transplantation tumor was detected by TUNEL assay.Immunohistochemistry was used to detect the effect of TRYP on the expression of Ki67,BRAF,c-Myc,and p-ERK proteins in transplanted tumor tissues.Results MTT assay showed that TRYP could effectively inhibit the proliferation of glioma cells(P＜0.001).Transwell assay showed that TRYP could inhibit the invasion and migration of glioma cells(P＜0.001).AnnexinV-FITC/PI cell apoptosis as-say showed that TRYP could promote the apoptosis of glioma cells(P＜0.001).The results of PI/RNase cell cycle as-say showed that TRYP was able to promote the G2 phase block of glioma cells(P＜0.001).Western blot results showed that the expression levels of c-Myc and p-ERK proteins in the glioma cells were significantly reduced after TR-YP treatment(P＜0.001).The results of subcutaneous transplantation tumor model in nude mice showed that TRYP could effectively inhibit the growth rate(P＜0.01)and weight(P＜0.05)of transplanted tumor.TUNEL assay showed that TRYP could promote the apoptosis of tumor cells in transplanted tumor(P＜0.001).Immunohistochemis-try results showed that TRYP could effectively inhibit the protein expression of Ki67(P＜0.01),BRAF,c-Myc,and p-ERK(P＜0.001).Conclusion TRYP can inhibit the proliferation,invasion,and migration ability of glioma cells,promote apoptosis of glioma cells,and block the cell cycle of glioma cells.TRYP may inhibit the malignant pro-gression of glioma cells by suppressing the protein expression of BRAF,c-Myc and p-ERK1/2 in the MAPK/ERK sig-naling pathway.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective:To investigate the effect of microRNA-363-5p targeted binding to THBS3 on angiotensin Ⅱ-induced apoptosis in cardiomyocytes and its molecular mechanism.Methods:A human-derived cardiomyocyte cell line(AC16)was used to establish an in vitro cardiomyocyte apoptosis model with angiotensin Ⅱ(AngⅡ),and a dual luciferase reporter assay was performed to detect the relationship between miR-363-5p and THBS3;apoptosis rate was detected by flow cytometry,and real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was performed to detect the relative expression of microR-363-5p,ATF-6mRNA,THBS3mRNA expression;Western Blot to detect the relative expression of caspase-12,caspase-3,GRP78,Bax,Bcl-2.Results:(1)Compared with the control group,the relative expression level of miR-363-5p in AngⅡ group was significantly decreased.(2)Compared with Mir-inhibitor-NC and Mir-mimics-NC groups,the apoptosis rate of miR-inhibitor and miR-mimics groups was significantly increased and decreased,the relative expression level of Bax protein was significantly increased and decreased,and the relative expression level of Bcl-2 was decreased and increased.(3)miR-363-5p targeted binding to THBS3.(4)Compared with the THBS3-OENC group,the relative expression of Bax and caspase-3 proteins was significantly higher,the relative expression of Bcl-2 protein was significantly lower,and the apoptosis rate was higher in the THBS3-OE group.(5)Compared with the negative control group,the relative expression of Bax and caspase-3 proteins in the miR-mimcs+THBS3-OE group was significantly higher,the relative expression of Bcl-2 protein was significantly lower,the apoptosis rate was significantly higher,and the cell viability was significantly lower.(6)Compared with the miR-inhibitor group,the relative expression of GRP78 and caspase-12 was decreased in the miR-inhibitor-4-PBA group,and the apoptosis rate was significantly reduced.(7)Compared with the negative control group,the apoptosis rate was elevated in the ATF-6-OE group,and the relative expression of caspase-12 was significantly increased.(8)Compared with the negative control group,miR-inhibitor+ATF-6 siRNA group showed decreased apoptosis rate and decreased relative expression of caspase-12.Conclusions:MicroRNA-363-5p is able to target binding to THBS3 to regulate myocardial apoptosis,a process that may be mediated through the endoplasmic reticulum stress ATF-6 pathway.