Objective To understand the clinical characteristics of patients with Streptococcus anginosus group(SAG)pulmonary abscess and resistance of SAG.Methods 67 patients with pulmonary abscess admitted to a hos-pital from January 2018 to May 2022 were retrospectively analyzed,clinical data of patients with SAG pulmonary abscess were analyzed,and the minimum inhibitory concentration of antimicrobial agents to 18 SAG strains was de-tected by microbroth dilution method,the carriage of resistance genes and virulence genes of SAG were detected by high-throughput sequencing technology.Results Among 67 patients with pulmonary abscess,SAG accounted for 29.9％(20/67),out of which 2 were excluded due to bacterial inactivation,and 18 patients were included for fur-ther studies.18 patients with SAG pulmonary abscess were all community acquired,with an average age of(60.9±9.1)years.There were 13(72.2％)male patients,most patients(94.4％)complicated chronic pulmonary disease,with cough(94.4％)and expectoration(88.9％)as the initial symptoms,some patients(44.4％)had chest pain,and more than half(61.1％)didn't have fever.The proportion of neutrophils,erythrocyte sedimentation rate,and C-reactive protein were mostly elevated,while procalcitonin was normal.The resistance rate of 18 SAG strains to erythromycin,clindamycin,and tetracycline was＞65％,out of which 14 strains carried resistance gene ermB,13 strains carried resistance gene tetM,and 1 strain carried both resistance gene msrD and mefA.18 SAG strains were detected virulence gene psaA,out of which 3 strains were detected virulence gene nan A.Conclusion SAG is an im-portant pathogen that causes pulmonary abscess,and the patients'complications are mainly chronic pulmonary di-seases,with non-specific clinical manifestations;Most strains carry ermB and tetM genes,mediating resistance to macrolides,lincosamides,and tetracyclines.

Objective:To investigate endothelial cell heterogeneity in diabetic cardiomyopathy (DCM) and identify potential therapeutic targets of dapagliflozin in cardiac vascular endothelial cells.Methods:ePharmaLib reverse virtual screening was performed on 15 148 protein crystals to identified the binding interactions between human-derived proteins and dapagliflozin. Subsequently, single-cell RNA sequencing data (PRJNA1069235) from wild-type mice (control group) and db/db mice (DCM group) were integrated, then dimensionality reduction and clustering analysis were performed to identify endothelial cell subpopulations in the heart tissue of DCM mice, followed by functional annotation. Cell-cell communication analysis was explored to investigate fibroblast-endothelial cell interactions. The Agilent Mouse ceRNA Microarray chip was used to perform transcriptomic analysis of heart tissue from mice fed a high-fat diet and treated with dapagliflozin. Intersection analysis of reverse virtual screening results, single-cell RNA sequencing results and chip analysis data was performed to identify common differentially expressed genes. In vitro, human umbilical vein endothelial cells were divided into blank control group, tumor necrosis factor-α (TNF-α) group (TNF-α 10 mg/L), dapagliflozin low concentration group (TNF-α 10 mg/L+dagliazin 2 μmol/L), dapagliflozin medium concentration group (TNF-α 10 mg/L+dagliazin 5 μmol/L) and dapagliflozin high concentration group (TNF-α 10+dagliazin 10 μmol/L). Western blot and real-time reverse transcriptase polymerase chain reaction were used to detect the expression of inflammatory factors and differential genes.Results:ePharmaLib reverse virtual screening identified 168 human-derived proteins with potential binding affinity to dapagliflozin, and single-cell analysis identifiedf 6 types of endothelial cell subpopulations. Compared with the control group, the abundance of capillary endothelial cells was significantly lower in DCM group, while the abundance of microvascular and venous endothelial cells was significantly higher ( P all<0.05). Cell-cell communication analysis showed significant expression of Pgf-Vegfr1 ligand-receptor pair. In addition, 15 differentially expressed genes were identified by intersection analysis of 168 dapagliflozin-binding proteins. Including Bcl2, Baz2b, Nos3, Ephb4, Cdk8, Pparg, Pde2a, Fgfr2, Fto, Stk24, Dlg1, Gsk3b, Pdpk1, Fas and Tnks2. Notably, Baz2b, Pparg, Fto and Gsk3b were differentially expressed in all cell subpopulations. Six differential genes, including Pde7a, Dlg1, Gsk3b, Nampt, Met and Adk, were obtained by the intersection of the chip analysis data with the virtual screening results of dapagliflozin. In vitro, compared to the human umbilical vein endothelial cells of TNF-α group, the expression levels of interleukin-6, interleukin-1β and p-P65 proteins and messenger RNA of Bcl2, Nos3, Cdk8, Pde2a, Dlg1, Pdpk1, Tnks2, Baz2b, Pparg, Fas, Pde7a and Nampt were significantly lower than dapagliflozin high concentration group ( P all<0.05). Conclusions:Dapagliflozin may inhibit endothelial cell inflammatory responses and improve endothelial dysfunction in DCM by regulating key genes such as Dlg1, Bcl2, Nos3, Pde7a and Nampt.

Objective To investigate the effects of Aurora kinase A(AURKA)on the tumor microenvironment of colorectal cancer(CRC)and to predict the active compounds in Chinese herbs that can target AURKA.Methods Based on the transcriptomic data and clinical information from 380 CRC tissues and 51 paracancerous tissues in The Cancer Genome Atlas(TCGA)database,the infiltration of different cells in the tumor tissues was analyzed using xCell and the binding of active compounds of Chinese herbs with AURKA was predicted through molecular docking.Results The expression of AURKA was significantly upregulated in CRC tissues compared with that in paracancerous tissues(P＜0.05),and CRC patients with high AURKA expression had shorter overall survival.Compared with the AURKA low-expression group,the abundance of macrophages,monocytes,and effector memory CD4+and CD8+T cells was significantly downregulated in the AURKA high-expression group(P＜0.05).In addition,the cytotoxicity of T cells was significantly reduced(P＜0.05).Further analysis revealed that AURKA expression was positively correlated with the abundance of myeloid-derived suppressor cells(MDSCs)and the expression levels of their chemokines CXCL2 and CXCL5(P＜0.05).Genes that were differentially expressed between the AURKA high-and low-expression groups were mainly enriched in monocyte migration,chemokine-induced cellular responses,and other related processes.Chinese herbal compounds,including hesperidin,aristololactam A Ⅱ a,anacardic acid,coumestrol,and 17β-estradiol,all showed binding energies to AURKA lower than-1.2 kcal/mol,indicating a certain level of binding stability.Among these Chinese herbal compounds,17β-estradiol exhibited the best binding stability to AURKA-3UOL.Conclusion The high expression of AURKA in CRC tissues suggests a poor clinical prognosis.AURKA can promote the development of a suppressive immune microenvironment in CRC,and 17β-estradiol,an active compound from Chinese herbs,is a potential therapeutic agent targeting AURKA.

Hepatic fibrosis is a chronic pathological condition characterized by hepatic stellate cell activation and excessive deposition of extracellular matrix， which would progress to liver cirrhosis and even hepatocellular carcinoma. Therefore， reversal of hepatic fibrosis is of great importance for improving quality of life and prolonging survival time. Currently， various therapeutic drugs for hepatic fibrosis have entered the stage of clinical trial. This article reviews the research advances in therapeutic drugs for hepatic fibrosis in the recent years， in order to provide insights into the treatment of hepatic fibrosis and future research directions for drugs.

Objective:To investigate the association between blood pressure variability (BPV) and all-cause mortality and cardiovascular events in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), and provide reference for clinical management in CAPD patients.Methods:This retrospective cohort study included patients who received CAPD at Guangdong Provincial People's Hospital between May 1, 2010, and July 31, 2023. Baseline and clinical data of the patients were collected. Coefficient of variation of systolic blood pressure (CVSBP) was used to assess BPV. The patients were divided into CVSBP T1, CVSBP T2 and CVSBP T3 groups based on CVSBP tertiles, and the differences among the three groups were compared. Diastolic blood pressure and mean arterial pressure were used to further assess BPV and sensitivity analysis was conducted. The primary endpoint was the composite outcome of all-cause mortality and cardiovascular events. Kaplan-Meier survival curve and Cox regression analysis were used to analyze the association between CVSBP and the primary endpoint.Results:A total of 358 CAPD patients were included, with age of (43.6±13.3) years, and 197 males (55.0%). The proportion of males, proportion of smoking, baseline blood urea nitrogen, serum creatinine and serum albumin in CVSBP T2 (9.08%≤CVSBP<12.55%, n=120) group and CVSBP T3 (CVSBP≥12.55%, n=119) group were lower than those in CVSBP T1 group (CVSBP<9.08%, n=119), and baseline systolic blood pressure, residual kidney Kt/V and total Kt/V were higher than those in CVSBP T1 group, with statistically significant difference among the three groups (all P<0.05). During follow-up of 37(23, 76) months, 49 patients (13.7%) experienced the composite endpoint events, including 12 patients (3.4%) of all-cause deaths and 42 patients (11.7%) of cardiovascular events. Kaplan-Meier survival analysis showed that the incidence of composite endpoint events in CVSBP T3 group was higher than that in CVSBP T1 group and CVSBP T2 group, but the difference was not statistically significant (Log-rank χ2=3.795, P=0.150). Multivariate Cox regression analysis showed that, after adjusting for age, sex, diabetes, baseline systolic blood pressure, residual renal function, and serum albumin, as a continuous variable, CVSBP was not associated with the risk of composite outcome in CAPD patients ( HR=1.058, 95% CI 0.985?1.135, P=0.122); as a categorical variable, with CVSBP T1 group as reference, CVSBP T2 group and CVSBP T3 group were not associated with the risk of composite outcome ( HR=1.222, 95% CI 0.471?3.167, P=0.681; HR=1.827, 95% CI 0.737?4.530, P=0.193). The sensitivity analysis showed that increased variability of diastolic blood pressure ( HR=1.162, 95% CI 1.063?1.270, P=0.021) and increased variability of mean arterial pressure ( HR=1.114, 95% CI 1.030?1.204, P=0.007) were correlated with higher risk of composite outcome in CPAD patients. Conclusions:Systolic blood pressure variability during follow-up is not associated with risk of composite outcome of all-cause mortality and cardiovascular events in CAPD patients. Increased variability of diastolic blood pressure and increased variability of mean arterial pressure are associated with a higher risk of composite outcome in CPAD patients. Interventions to reduce BPV may be helpful to improve the long-term prognosis of CAPD patients.

Objective:To explore the time variations of the influence of the ultra-high dose rate irradiation (FLASH irradiation, FLASH-IR) and conventional dose rate irradiation (CONV-IR) of electron beams under different doses on the energy metabolism of triple-negative breast cancer cells MDA-MB-231.Methods:The basal metabolism of the MDA-MB-231 cells and normal breast epithelial cells MCF-10A was compared using a Seahorse XF Pro Metabolic Analyzer. Based on an irradiation platform with a thermionic cathode electron accelerator (6 MeV), the MDA-MB-231 cells were exposed to FLASH-IR (106 Gy/s) and CONV-IR (0.1 Gy/s) at 2 and 14 Gy, respectively. Meanwhile, a sham irradiation group was established under identical culture conditions. The mitochondrial metabolism and glycolytic metabolism of the cells at 4, 24, and 48 h post-irradiation were analyzed.Results:Compared to the MCF-10A cells, the MDA-MB-231 cells exhibited a greater reliance on glycolytic metabolism. Compared to those of the sham irradiation group, MDA-MB-231 cells in the 2 Gy CONV-IR group showed up-regulated ATP-linked respiration at 4, 24, and 48 h post-irradiation ( t = 2.69-3.70, P < 0.05). Their glycolytic level and glycolytic capacity were up-regulated only at 4 h post-irradiation and were down-regulated at 48 h ( t = 2.79, -4.44, P < 0.05). In contrast, there was no statistically significant difference in these indicators between the FLASH-IR and CONV-IR groups ( P > 0.05). However, the proton leak of the MDA-MB-231 cells in the FLASH-IR group was relatively down-regulated at 4 h post-irradiation and was significantly up-regulated at 24 h and 48 h post-irradiation compared with the CONV-IR group ( t = -2.45, 3.19, 6.51, P < 0.05). At 14 Gy, the MDA-MB-231 cells in the CONV-IR group showed progressively increased mitochondrial and glycolytic metabolism across all time points ( t = 2.48-12.14, P < 0.05). Notably, compared with the CONV-IR group, the MDA-MB-231 cells in the FLASH-IR group exhibited more significantly up-regulated basal respiration, ATP-linked respiration, and non-mitochondrial oxygen consumption ( t = 2.56-6.51, P < 0.05), as well as a higher glycolytic capacity at 24 h post-irradiation ( t = 2.86, P < 0.05). Conclusions:Low-dose (2 Gy) FLASH-IR induces relatively up-regulated proton leak in breast cancer cells MDA-MB-231 at 24 h post-irradiation. In contrast, under high-dose (14 Gy) FLASH-IR, the MDA-MB-231 cells show more pronounced mitochondrial metabolic stress and a higher demand for energy metabolism.

Objective To investigate the reliability and validity of the Chinese version of speech,spatial and qualities of hearing scale(SSQ).Methods The SSQ was translated into Chinese using the translation and back-translation method.Self-assessment with the scale was conducted for 50 adults with normal hearing and 28 adults with hearing impairment who had bilateral hearing aids fitted.Two weeks after the initial assessment,10 individuals with bilateral hearing aids fitted were randomly selected to be re-assessed using the same scale.The Cronbach's αcoefficients of the scores of each dimension and the total score of the scale was used to evaluate the internal consis-tency of the scale,and the correlation coefficient of the results of the two assessments was used to test the test-retest reliability of the scale.The expert evaluation method was adopted to test the content validity of the scale,and the correlation coefficients of the scores of each dimension and the total score were used to test the construct validity of the scale.The score differences of each item and each dimension between adults with normal hearing and adults with bilateral hearing aids fitted were compared to test the discriminant validity.Results Valid responses were obtained from all 78 participants.① The test-retest reliability coefficients of the total scale and the three dimensions were all greater than 0.750(P＜0.01),indicating excellent test-retest reliability.The Cronbach's α coefficients of the total scale and the three dimensions were all greater than 0.700,suggesting excellent internal consistency.② All four ex-perts indicated that the content of each item in the three dimensions of the SSQ scale was in line with the measure-ment requirements,showing excellent content validity.The correlation coefficients between the scores of the three dimensions and the total scale were between 0.809 and 0.890,indicating a high degree of correlation.There were statistically significant differences in the scores of the three dimensions between the normal group and the group with bilateral hearing aids fitted(P＜0.05),and the overall discriminant validity of the scale was excellent.Conclusion The Chinese version of the SSQ has good reliability and validity,and can be used as a subjective auditory assessment in clinical practice.

Objective:To explore the continuing care needs of primary caregivers for neonates with enterostomy during the discharge transition period, based on Meleis's Transitions Theory.Methods:Totally 17 primary caregivers of neonates with enterostomy who were hospitalized or attending follow-up visits at Shenzhen Children's Hospital from June to December 2022 were selected by purposive sampling. Semi-structured in-depth interviews were conducted, and the data were analyzed using Colaizzi's seven-step phenomenological analysis method.Results:Four themes emerged: the need for caregiving knowledge, guidance on stoma care and operation skills, the demand for diverse forms of continuing care services, and psychological support needs.Conclusions:Primary caregivers for neonates with enterostomy face numerous challenges and needs during the discharge transition period. Essential strategies include providing stoma care training and assessment before discharge, enhancing caregiving capacity, implementing diversified health education to improve caregivers' knowledge accessibility, delivering hybrid (online and offline) multidisciplinary continuing care services, and addressing caregivers' psychological well-being.

Objective:To explore the time variations of the influence of the ultra-high dose rate irradiation (FLASH irradiation, FLASH-IR) and conventional dose rate irradiation (CONV-IR) of electron beams under different doses on the energy metabolism of triple-negative breast cancer cells MDA-MB-231.Methods:The basal metabolism of the MDA-MB-231 cells and normal breast epithelial cells MCF-10A was compared using a Seahorse XF Pro Metabolic Analyzer. Based on an irradiation platform with a thermionic cathode electron accelerator (6 MeV), the MDA-MB-231 cells were exposed to FLASH-IR (106 Gy/s) and CONV-IR (0.1 Gy/s) at 2 and 14 Gy, respectively. Meanwhile, a sham irradiation group was established under identical culture conditions. The mitochondrial metabolism and glycolytic metabolism of the cells at 4, 24, and 48 h post-irradiation were analyzed.Results:Compared to the MCF-10A cells, the MDA-MB-231 cells exhibited a greater reliance on glycolytic metabolism. Compared to those of the sham irradiation group, MDA-MB-231 cells in the 2 Gy CONV-IR group showed up-regulated ATP-linked respiration at 4, 24, and 48 h post-irradiation ( t = 2.69-3.70, P < 0.05). Their glycolytic level and glycolytic capacity were up-regulated only at 4 h post-irradiation and were down-regulated at 48 h ( t = 2.79, -4.44, P < 0.05). In contrast, there was no statistically significant difference in these indicators between the FLASH-IR and CONV-IR groups ( P > 0.05). However, the proton leak of the MDA-MB-231 cells in the FLASH-IR group was relatively down-regulated at 4 h post-irradiation and was significantly up-regulated at 24 h and 48 h post-irradiation compared with the CONV-IR group ( t = -2.45, 3.19, 6.51, P < 0.05). At 14 Gy, the MDA-MB-231 cells in the CONV-IR group showed progressively increased mitochondrial and glycolytic metabolism across all time points ( t = 2.48-12.14, P < 0.05). Notably, compared with the CONV-IR group, the MDA-MB-231 cells in the FLASH-IR group exhibited more significantly up-regulated basal respiration, ATP-linked respiration, and non-mitochondrial oxygen consumption ( t = 2.56-6.51, P < 0.05), as well as a higher glycolytic capacity at 24 h post-irradiation ( t = 2.86, P < 0.05). Conclusions:Low-dose (2 Gy) FLASH-IR induces relatively up-regulated proton leak in breast cancer cells MDA-MB-231 at 24 h post-irradiation. In contrast, under high-dose (14 Gy) FLASH-IR, the MDA-MB-231 cells show more pronounced mitochondrial metabolic stress and a higher demand for energy metabolism.

Objective To understand the clinical characteristics of patients with Streptococcus anginosus group(SAG)pulmonary abscess and resistance of SAG.Methods 67 patients with pulmonary abscess admitted to a hos-pital from January 2018 to May 2022 were retrospectively analyzed,clinical data of patients with SAG pulmonary abscess were analyzed,and the minimum inhibitory concentration of antimicrobial agents to 18 SAG strains was de-tected by microbroth dilution method,the carriage of resistance genes and virulence genes of SAG were detected by high-throughput sequencing technology.Results Among 67 patients with pulmonary abscess,SAG accounted for 29.9％(20/67),out of which 2 were excluded due to bacterial inactivation,and 18 patients were included for fur-ther studies.18 patients with SAG pulmonary abscess were all community acquired,with an average age of(60.9±9.1)years.There were 13(72.2％)male patients,most patients(94.4％)complicated chronic pulmonary disease,with cough(94.4％)and expectoration(88.9％)as the initial symptoms,some patients(44.4％)had chest pain,and more than half(61.1％)didn't have fever.The proportion of neutrophils,erythrocyte sedimentation rate,and C-reactive protein were mostly elevated,while procalcitonin was normal.The resistance rate of 18 SAG strains to erythromycin,clindamycin,and tetracycline was＞65％,out of which 14 strains carried resistance gene ermB,13 strains carried resistance gene tetM,and 1 strain carried both resistance gene msrD and mefA.18 SAG strains were detected virulence gene psaA,out of which 3 strains were detected virulence gene nan A.Conclusion SAG is an im-portant pathogen that causes pulmonary abscess,and the patients'complications are mainly chronic pulmonary di-seases,with non-specific clinical manifestations;Most strains carry ermB and tetM genes,mediating resistance to macrolides,lincosamides,and tetracyclines.