Cardiovascular diseases are the leading cause of mortality, posing a significant threat to human health due to the high incidence rate. Atherosclerosis, a chronic inflammatory disease, serves as the primary pathological basis for most such conditions. The incidence of atherosclerosis continues to rise, but its pathogenesis has not been fully elucidated. As an important member of the small GTPase superfamily, Ras-association proximate 1 (Rap1) is an important molecular switch involved in the regulation of multiple physiological functions including cell differentiation, proliferation, and adhesion. Rap1 achieves the utility of the molecular switch by cycling between Rap1-GTP and Rap1-GDP. Rap1 may influence the occurrence and development of atherosclerosis in a cell-specific manner. This article summarizes the potential role and mechanism of Rap1 in the progression of atherosclerosis in different cells, aiming to provide new therapeutic targets and strategies for clinical intervention.
Humans ; Atherosclerosis/metabolism* ; rap1 GTP-Binding Proteins/physiology* ; Animals ; Cell Differentiation ; Cell Adhesion ; Cell Proliferation

Objective:To explore the differences in the standardized z-score amplitude of low-frequency fluctuations (zALFFs) across different brain regions between children with global developmental delay (GDD) and healthy children (HC) using functional near-infrared spectroscopy (fNIRS), and correlating zALFF values with the subjects′ Gesell Developmental Scale (GDS) scores.Methods:Thirty-one children aged 2-4 years with GDD and 29 HC of the same age were studied. fNIRS was used to record both groups′ brain activity in response to natural stimuli and to measure any changes in oxygenated hemoglobin (HbO) levels in cerebral blood flow. zALFF values were calculated and the values of 44 channels were compared between the two groups. The correlations between zALFF values and GDS scores were computed.Results:The zALFF values of the children with GDD were significantly lower than those of the HC in the right frontal pole (channel 10) and the right pre-motor and supplementary motor areas (channel 43). In contrast, the zALFF values in the left pre-motor and supplementary motor areas (channels 24 and 26) were significantly higher in the children with GDD compared to the HC. Spearman ranked correlation analysis revealed that the zALFF values in the right pre-motor and supplementary motor areas (channel 43) were positively correlated with socialization scores on the GDS ( r=0.37, P≤0.05). Conclusions:The delays in cognitive and motor development in children with GDD may be associated with functional abnormalities in the right frontal polar region and the bilateral premotor and supplementary motor areas. zALFF values from the right premotor and supplementary motor areas are positively correlated with social skills.

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.

Objective To investigate the application value of full-length lower extremity CT scans performed at different noise index(NI)in terms of image quality and radiation dose for robot-assisted total knee arthroplasty(RTKA).Methods Eighty patients who underwent RTKA were selected and randomly divided into four groups based on different NI:NI=8,NI=18,NI=28,and NI=38.Subjective scores were assigned to the full-length lower extremity CT images and the three-dimensional skeletal models generated by volume rendering(VR)post-processing.Objective evaluations were performed using three indicators:dose length product(DLP),volume CT dose index(CTDIvol),and hip-knee-ankle angle(HKA).The application value of full-length lower extremity CT scans in RTKA was analyzed.Results(1)As the NI value increased,the subjective scores of thin-slice images decreased.Images with NI between 8 and 18 met the imaging diagnostic standards,while those with NI higher than 18 were unacceptable.(2)As the NI value increased,all VR skeletal models met the acceptance criteria for RTKA.(3)As the NI value increased,DLP and CTDIvol gradually decreased,with statistically significant differences(P<0.05),However,in the comparison between the NI=28 and NI=38 groups,the difference was not statistically significant(P>0.05).Conclusion Performing full-length lower extremity CT scans with an NI of 28 not only meets the preoperative planning requirements for RTKA but also minimizes the radiation dose.

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.

Objective To investigate the application value of full-length lower extremity CT scans performed at different noise index(NI)in terms of image quality and radiation dose for robot-assisted total knee arthroplasty(RTKA).Methods Eighty patients who underwent RTKA were selected and randomly divided into four groups based on different NI:NI=8,NI=18,NI=28,and NI=38.Subjective scores were assigned to the full-length lower extremity CT images and the three-dimensional skeletal models generated by volume rendering(VR)post-processing.Objective evaluations were performed using three indicators:dose length product(DLP),volume CT dose index(CTDIvol),and hip-knee-ankle angle(HKA).The application value of full-length lower extremity CT scans in RTKA was analyzed.Results(1)As the NI value increased,the subjective scores of thin-slice images decreased.Images with NI between 8 and 18 met the imaging diagnostic standards,while those with NI higher than 18 were unacceptable.(2)As the NI value increased,all VR skeletal models met the acceptance criteria for RTKA.(3)As the NI value increased,DLP and CTDIvol gradually decreased,with statistically significant differences(P<0.05),However,in the comparison between the NI=28 and NI=38 groups,the difference was not statistically significant(P>0.05).Conclusion Performing full-length lower extremity CT scans with an NI of 28 not only meets the preoperative planning requirements for RTKA but also minimizes the radiation dose.

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.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.