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 explore the potential mechanism of metformin on ATP-binding cassette transport A1(ABCA1)expression.Methods J774A.1 macrophages were treated with metformin and cycloheximide,and ABCA1 expression was determined by Western blot.His-tagged ABCA1 and HA-tagged Ub plasmids were co-transferred into HEK293 cells and stimulated with metformin.Co-immunoprecipitation(Co-IP)was used to test the binding ability of ABCA1 and ubiquitin.Candidate E3 ubiquitin-protein ligases(CE3)of ABCA1 were identified through Co-IP-based pro-teomics.The MIB1 plasmid was constructed and transferred into HEK293 cells,and Western blot was used to determine the effect of metformin and MIB1 on ABCA1 expression.Results Metformin increased the expression of ABCA1 in J774A.1 cells(P<0.01),and inhibited ABCA1 degradation(P<0.05).Metformin disrupted the binding of ABCA1 to ubiquitin(P<0.05).The proteins regulated by metformin in ABCA1 expression were primarily enriched in pathways re-lated to cell development,inflammation and immune defense.Metformin may upregulate ABCA1 protein expression via MIB1(P<0.05).Conclusion Metformin inhibits the degradation of ABCA1 by blocking the ubiquitin-proteasome system(UPS),and MIB1 might act as a candidate E3 ubiquitin-protein ligase(CE3)for ABCA1.

The academic thought of Professor GAO Shuzhong on acupuncture and moxibustion is investigated systematically and summarized as 5 aspects: establishing GAO 's theory and methodological method of "siguan santong" (four gates and three opens); structuring the theory of "yinyang, qi movement, ascending and descending" pivoted at the umbilicus; deepening the laws of "stereo-layered holographic correspondence in the human body"; proposing "the method of bi-location" of acupoint systems based on meridian and collateral theories; developing the characteristic differentiation theory of acupuncture and moxibustion. These summaries reflect the unique perspective and distinctive features of Professor GAO Shuzhong on the theory of acupuncture and moxibustion, and his clinical thinking; and bring the practical significance for the discipline and academic development of acupuncture and moxibustion.
Moxibustion/history* ; Humans ; China ; Acupuncture/education* ; Acupuncture Therapy/history* ; History, 20th Century

OBJECTIVE: To explore the possible mechanism by which the "Zhibian" (BL54) toward "Shuidao" (ST28) acupuncture improves ovarian function in mice with poor ovarian response (POR) by observing its effect on gut microbiota. METHODS: A total of 35 SPF-grade C57BL/6 female mice were screened for normal estrous cycles using vaginal smears, and 30 mice were selected. Ten mice were assigned to the blank group, while the remaining mice were used to establish the POR model by intragastric administration of tripterygium wilfordii suspension. The successfully modeled mice were randomly divided into a model group and an acupuncture group, with 10 mice in each group. After modeling, the acupuncture group received the "Zhibian" (BL54) toward "Shuidao" (ST28) acupuncture method once daily for 20 minutes per session. Ovulation induction began the day after the intervention, and samples were collected after ovulation induction. Vaginal cytology was used to observe estrous cycle changes, and the number of oocytes obtained, ovarian wet weight, and ovarian index were recorded. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH) were detected using ELISA. HE staining was used to observe ovarian histology. Gut microbiota was analyzed using 16S rRNA gene sequencing technology. Western blot was used to detect the relative protein expression levels of Occludin and zonula occludens-1 (ZO-1) in colonic tissue. Correlation analysis was conducted among serum hormone indexes, the number of oocytes obtained, ovarian index and gut microbiota. RESULTS: Compared with the blank group, the model group showed a higher estrous cycle disorder rate (P<0.01), increased serum FSH and LH levels, and a higher LH/FSH ratio (P<0.01), while the number of oocytes obtained, ovarian wet weight, ovarian index, and serum E2 and AMH levels were significantly reduced (P<0.01). Compared with the model group, the acupuncture group showed a lower estrous cycle disorder rate (P<0.01), decreased serum FSH and LH levels, and a lower LH/FSH ratio (P<0.01), along with an increased number of oocytes obtained, higher ovarian wet weight, ovarian index, and elevated serum AMH and E2 levels (P<0.01, P<0.05). The blank group had a large number of well-developed primordial follicles, with abundant and closely arranged follicles at various stages. In the model group, there was a significant increase in the number of atretic follicles, a reduction in the number of follicles at various stages, and loosely arranged ovarian tissue. Compared with the blank group, the model group showed a significant decrease in the number of normal follicles (P<0.01) and an increase in the number of atretic follicles (P<0.01). The acupuncture group showed a reduction in atretic follicles and an increase in the number of follicles at various stages compared with the model group, with a significant increase in normal follicles (P<0.01) and a decrease in atretic follicles (P<0.01). Compared with the blank group, the model group exhibited reduced gut microbiota diversity and richness, with significantly lower Chao1 and Shannon indices (P<0.01), and a greater clustering distance from the blank group. The model group also showed an increase in the relative abundance of Firmicutes_D, Verrucomicrobiota, Paramuribaculum, Dubosiella, and Muribaculum (P<0.01, P<0.05), while the relative abundance of Firmicutes_A and the relative protein expression of Occludin and ZO-1 in colonic tissue were decreased (P<0.01). Compared with the model group, the acupuncture group showed improved gut microbiota diversity and richness, with increased Chao1 and Shannon indices (P<0.05), and a clustering distance closer to the blank group. The acupuncture group exhibited reduced relative abundance of Firmicutes_D, Verrucomicrobiota, and Muribaculum (P<0.05, P<0.01), while the relative abundance of Firmicutes_A and the relative protein expression of Occludin and ZO-1 were significantly increased (P<0.01, P<0.05). Correlation analysis indicated a relationship between gut microbiota and serum hormone indicators, as well as the ovarian index. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis showed that the metabolic pathways of the intersecting species were related to amino acid biosynthesis and nucleotide metabolism. CONCLUSION The "Zhibian" (BL54) toward "Shuidao" (ST28) acupuncture method improves ovarian function in POR mice, and its mechanism may be related to regulating gut microbiota structure and maintaining intestinal barrier homeostasis.
Animals ; Female ; Gastrointestinal Microbiome ; Mice ; Acupuncture Therapy ; Mice, Inbred C57BL ; Humans ; Ovary/physiopathology* ; Acupuncture Points ; Follicle Stimulating Hormone/metabolism* ; Luteinizing Hormone/metabolism* ; Estrous Cycle ; Anti-Mullerian Hormone/blood*

Aim To explore the potential mechanism of metformin on ATP-binding cassette transport A1(ABCA1)expression.Methods J774A.1 macrophages were treated with metformin and cycloheximide,and ABCA1 expression was determined by Western blot.His-tagged ABCA1 and HA-tagged Ub plasmids were co-transferred into HEK293 cells and stimulated with metformin.Co-immunoprecipitation(Co-IP)was used to test the binding ability of ABCA1 and ubiquitin.Candidate E3 ubiquitin-protein ligases(CE3)of ABCA1 were identified through Co-IP-based pro-teomics.The MIB1 plasmid was constructed and transferred into HEK293 cells,and Western blot was used to determine the effect of metformin and MIB1 on ABCA1 expression.Results Metformin increased the expression of ABCA1 in J774A.1 cells(P<0.01),and inhibited ABCA1 degradation(P<0.05).Metformin disrupted the binding of ABCA1 to ubiquitin(P<0.05).The proteins regulated by metformin in ABCA1 expression were primarily enriched in pathways re-lated to cell development,inflammation and immune defense.Metformin may upregulate ABCA1 protein expression via MIB1(P<0.05).Conclusion Metformin inhibits the degradation of ABCA1 by blocking the ubiquitin-proteasome system(UPS),and MIB1 might act as a candidate E3 ubiquitin-protein ligase(CE3)for ABCA1.

Objective:To investigate the effect of luteolin on angiotensin Ⅱ (Ang Ⅱ)-induced cardiomyocyte hypertrophy in H9c2 cells and to reveal its potential mechanism.Methods:After H9c2 cells were cultured, they were divided into 0, 1, 2 and 4 μmol/L luteolin groups according to different cell treatment conditions. H9c2 cells were stimulated by Ang II to establish a cardiomyocyte hypertrophy model, which was divided into control group, Ang II group and luteolin+Ang II group. Cell survival rates were assessed by cell counting kit-8 assay. The degrees of cell hypertrophy were assessed by phalloidin staining assay. The levels of cellular oxidative stress were assessed by the 2′,7′-dichlorodihydrofluorescein diacetate fluorescent probe assay and thiobarbituric acid assay. The expression of apoptotic protein B-cell lymphoma-2 associated X protein (Bax), cleaved cysteine aspartic acid specific protease-3 (cleaved Caspase-3) and nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway proteins were assessed by Western blotting. The datas were analyzed by t test and one-way analysis of variance. Results:The survival rates of H9c2 cells in the 0, 1, 2, and 4 μmol/L luteolin group were 97.31%, 95.65%, 94.64%, and 93.27%, respectively. The degree of hypertrophy and the fluorescence intensity of H9c2 cells in Ang Ⅱ group were higher than those in the control group. The degree of hypertrophy and the fluorescence intensity of H9c2 cells in the luteolin+Ang Ⅱ group were lower than those in the Ang Ⅱ group. Compared with the control group, the survival rate of H9c2 cells in Ang Ⅱ group was decreased (96.26% vs 51.68%, P<0.01), the level of malondialdehyde was increased [(1.00±0.08) nmol/mg vs (3.27±0.31) nmol/mg, P<0.01], and the relative expression levels of Bax (0.79±0.04 vs 1.55±0.09, P<0.01), cleaved Caspase-3 (0.11±0.02 vs 1.00±0.04, P<0.01), Nrf2 (0.77±0.04 vs 0.95±0.03, P<0.05), and HO-1 (0.12±0.04 vs 0.41±0.05, P<0.01) were all increased. Compared with Ang Ⅱ group, the survival rate of H9c2 cells in the luteolin+Ang Ⅱ group (81.52%) was increased ( P<0.01), the level of malondialdehyde [(1.73±0.21) nmol/mg] was decreased ( P<0.01), the relative expression levels of Bax (1.25±0.05) and cleaved Caspase-3 (0.48±0.07) were decreased ( P<0.05, 0.01), Nrf2 (1.24±0.13) and HO-1 (0.82±0.03) were increased (both P<0.01). Conclusions:Luteolin effectively inhibits Ang Ⅱ-induced cardiomyocyte hypertrophy through the Nrf2/HO-1 pathway and has potential therapeutic value.

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.

Artificial intelligence has been a huge success and contributes to the workplace. In the digital era, the amount of data in clinical practice is increasing, which requires healthcare workers to integrate and interpret the various information generated during clinical work. With the help of artificial intelligence techniques, especially machine learning techniques, researchers in cardiovascular medicine have developed a variety of predictive models to improve the efficiency of clinical work and treatment outcomes. The types of machine learning models were introduced, and the current prediction models of cardiovascular diseases using machine learning technology were summarized. The purpose of this paper is to facilitate accurate diagnosis of cardiovascular diseases and to provide a clearer direction for future development of cardiovascular disease prediction models using machine learning techniques.

Objective To investigate the clinical manifestations,endoscopic,histopathological and im-munofluorescence IgA detection characteristics in children patients with Henoch-Schonlein purpura (HSP) with gastrointestinal tract symptoms as initial symptoms.Methods The clinical data of 29 children admitted to this hospital from April 2018 to December 2019 with gastrointestinal symptoms as the first manifestation and initially diagnosed with HSP were retrospectively analyzed.The clinical manifestations,laboratory and imageological examination results,endoscopic and histopatological examination results,immunofluoresence IgA detection results,treatment regimen and outcome were analyzed.Results The clinical manifestations were mainly abdominal pain,vomiting,hematochezia,rash,joint swelling and pain,testicular swelling pain,etc.Hemoglobin was decreased (<110 g/L) in 3 cases (10.34%),the eosinophilic cells count was increased (>0.6×109/L) in 1 case and serum total IgE was increased in 8 cases (27.58%).The food specificity IgE was positive in 4 cases (13.79%),including crab,nut,soybean and mugwort 1 case each (3.45%).Twenty-two cases conducted the abdominal imageological examination,in which there were 5 cases of abdominal cavity hydrops,4 cases (13.79%) of pelvic cavity hydrops and 15 cases of intestinal wall edema and thickness.The endoscopic manifestations were mucosal hyperemia and edema in 29 cases (100.00%),erosion in 24 cases (82.76%),mucosal roughness in 10 cases (34.48%),ulceration in 8 cases (27.59%),and punctated bleeding in 6 cases.The main manifestations of mucosal pathology were mucosal inflammation with IgA deposition in 10 cases (34.48%).Immunofluorescence IgA detection was positive in 10 cases (34.48%).Conclusion When abdominal HSP is highly suspected,the endoscopic examination could be performed as soon as possible to evaluate the degree of mucosal lesions and perfect the immunofluorescence IgA detection to further identify the disease cause

A composite nystagmus classification framework enhanced by dual attention mechanism is proposed to address the problem that the existing researches only identify whether nystagmus occurs in a horizontal,vertical,or axial direction,but fail to consider the issue of composite nystagmus composed of multiple directions with various intensities in clinical practice.A spatiotemporal concentration algorithm for nystagmus videos is presented,and it combines convolutional neural networks and Hough transform to remove interference from invalid frames and regions and to improve the quality of nystagmus videos.Then,a dense optical flow algorithm is used to extract the optical flow field of eye movement.Finally,a composite nystagmus classification network based on dual attention mechanism enhancement is constructed.An improved efficient channel attention module is used to effectively obtain the direction and intensity of nystagmus in different channels of the optical flow map;and a temporal attention module is added at the end of the bidirectional long short-term memory network to achieve significant expression of classification results based on different temporal features.On the nystagmus dataset provided by the cooperating hospital,the proposed method has an accuracy rate of 83.17%for composite nystagmus classification,and achieved accuracy rates of 91.03%,89.74%,and 86.05%for individual horizontal,vertical,and axial nystagmus classifications.The proposed method realizes the intelligent classification of composite nystagmus and is valuable in clinic.