AIM:To investigate the effects of the Qingfei-Jiedu-Huatan formula(QJHF)on damage to the lung vascular endothelial barrier induced by Klebsiella pneumoniae in mice with severe pneumonia,as well as to elucidate its underlying mechanisms.METHODS:Fifty-one C57BL/6J mice were randomly divided into control group(n=6),model group(n=15),QJHF group(n=15),and ceftriaxone sodium(CRO)group(n=15).Severe pneumonia was in-duced in the mice by a single tracheal intubation with 50 μL of 1×1011 CFU/mL Klebsiella pneumoniae on day 0.Six hours after modeling,the mice in QJHF and CRO groups received their respective treatments,while those in control and model groups were administered an equal volume of saline.All mice were sacrificed on day 3 after the end of gavage.Lung histo-pathological changes were assessed using hematoxylin-eosin(HE)staining.Levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in lung tissues were measured by enzyme-linked immunosorbent assay(ELISA).Flow cytometry was used to detect CD11b+Ly6g+cells in bronchoalveolar lavage fluid(BALF).Proteomics and network pharma-cology analyses were conducted to elucidate the mechanisms of drug action.Western blot was conducted to assess the ex-pression levels of vascular endothelial cadherin(VE-cadherin),zonula occludens-1(ZO-1),occludin,vascular endothe-lial growth factor(VEGF),P38 mitogen-activated protein kinase(P38),and phosphorylated P38(p-P38)in lung tis-sues.RESULTS:Treatment with QJHF significantly attenuated the symptoms such as mental status and respiratory dis-tress,reduced mortality,mitigated lung tissue lesions,and decreased levels of IL-6,TNF-α,IL-1β,as well as BALF to-tal protein concentration,total cell count and neutrophil content in a mouse model of severe pneumonia(P＜0.05 or P＜0.01).Additionally,QJHF increased the expression of VE-cadherin,ZO-1 and occludin proteins in lung tissues.Pro-teomic analysis demonstrated that QJHF modulated the expression of 129 proteins in the lung tissues of mice suffering from severe pneumonia.Network pharmacology identified 328 potential targets associated with 14 major bioactive components of QJHF and 1 665 genes related to severe pneumonia,with 125 overlapping genes between the two datasets.The construc-tion of a protein-protein interaction(PPI)network,along with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the regulated proteins and overlapping genes,indicated that QJHF primarily in-fluenced the PI3K-Akt,MAPK and Rap1 signaling pathways,as well as VEGFR.Western blot analysis showed that QJHF significantly inhibited the expression of VEGF and P38 in lung tissues(P＜0.05 or P＜0.01).CONCLUSION:Treatment with QJHF attenuates severe pneumonia in mice,potentially by inhibiting VEGF/P38 signaling to protect the vascular endothelial barrier.

AIM:To investigate the effects of the Qingfei-Jiedu-Huatan formula(QJHF)on damage to the lung vascular endothelial barrier induced by Klebsiella pneumoniae in mice with severe pneumonia,as well as to elucidate its underlying mechanisms.METHODS:Fifty-one C57BL/6J mice were randomly divided into control group(n=6),model group(n=15),QJHF group(n=15),and ceftriaxone sodium(CRO)group(n=15).Severe pneumonia was in-duced in the mice by a single tracheal intubation with 50 μL of 1×1011 CFU/mL Klebsiella pneumoniae on day 0.Six hours after modeling,the mice in QJHF and CRO groups received their respective treatments,while those in control and model groups were administered an equal volume of saline.All mice were sacrificed on day 3 after the end of gavage.Lung histo-pathological changes were assessed using hematoxylin-eosin(HE)staining.Levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in lung tissues were measured by enzyme-linked immunosorbent assay(ELISA).Flow cytometry was used to detect CD11b+Ly6g+cells in bronchoalveolar lavage fluid(BALF).Proteomics and network pharma-cology analyses were conducted to elucidate the mechanisms of drug action.Western blot was conducted to assess the ex-pression levels of vascular endothelial cadherin(VE-cadherin),zonula occludens-1(ZO-1),occludin,vascular endothe-lial growth factor(VEGF),P38 mitogen-activated protein kinase(P38),and phosphorylated P38(p-P38)in lung tis-sues.RESULTS:Treatment with QJHF significantly attenuated the symptoms such as mental status and respiratory dis-tress,reduced mortality,mitigated lung tissue lesions,and decreased levels of IL-6,TNF-α,IL-1β,as well as BALF to-tal protein concentration,total cell count and neutrophil content in a mouse model of severe pneumonia(P＜0.05 or P＜0.01).Additionally,QJHF increased the expression of VE-cadherin,ZO-1 and occludin proteins in lung tissues.Pro-teomic analysis demonstrated that QJHF modulated the expression of 129 proteins in the lung tissues of mice suffering from severe pneumonia.Network pharmacology identified 328 potential targets associated with 14 major bioactive components of QJHF and 1 665 genes related to severe pneumonia,with 125 overlapping genes between the two datasets.The construc-tion of a protein-protein interaction(PPI)network,along with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the regulated proteins and overlapping genes,indicated that QJHF primarily in-fluenced the PI3K-Akt,MAPK and Rap1 signaling pathways,as well as VEGFR.Western blot analysis showed that QJHF significantly inhibited the expression of VEGF and P38 in lung tissues(P＜0.05 or P＜0.01).CONCLUSION:Treatment with QJHF attenuates severe pneumonia in mice,potentially by inhibiting VEGF/P38 signaling to protect the vascular endothelial barrier.

Objective:To investigate the correlation and influencing factors between sarcopenia and cardiac structure and function in elderly inpatients.Methods:A total of 945 elderly patients, aged 60 years and older, were recruited from the Geriatrics Department at Xuanwu Hospital.Sarcopenia was assessed, while cardiac structure and function were evaluated through echocardiography and NT-proBNP measurements.Results:Patients were classified into two groups: a sarcopenia group(n=185, 19.6%)and a non-sarcopenia group(n=760, 80.4%).Compared to the non-sarcopenia group, the sarcopenia group exhibited a reduction in left atrial diameter(LAD), left ventricular end-diastolic diameter(LVEDD), left ventricular mass(LVM), stroke volume(SV), and cardiac output(CO)(all P<0.05).In contrast, NT-proBNP levels were significantly elevated in the sarcopenia group( P<0.001).Multivariate logistic regression analysis identified older age( OR=1.080, P<0.001)and elevated NT-proBNP( OR=1.001, P<0.001)as independent risk factors for sarcopenia.Conversely, higher LAD( OR=0.858, P<0.001)and LVM( OR=0.988, P=0.002)were recognized as independent protective factors.Additionally, NT-proBNP demonstrated a negative correlation with handgrip strength( r=-0.241, P<0.001), gait speed( r=-0.215, P<0.001), SPPB score( r=-0.270, P<0.001), and appendicular skeletal muscle mass(ASM)( r=-0.208, P<0.001), while exhibiting a positive correlation with the 5-time chair stand test( r=0.169, P<0.001).LVM was positively correlated with handgrip strength( r=0.213, P<0.001)and ASM( r=0.456, P<0.001).Furthermore, LAD was positively correlated with handgrip strength( r=0.071, P=0.029)and ASM( r=0.305, P<0.001). Conclusions:Notably, significant differences exist in cardiac structure and function between elderly patients with sarcopenia and those without.Furthermore, indicators related to sarcopenia are correlated with alterations in cardiac structure and function.

AIM:To establish a severe pneumonia mouse model induced by bacterial infection.METHODS:A total of 102 male SPF C57BL/6J mice were randomly divided into a control group and a model group.Klebsiella pneu-moniae was administered via tracheal instillation at a concentration of 5×109 CFU.Mice were euthanized on days 1,2,4,8,and 14 post-infection to assess general condition,body weight,mortality,white blood cell and neutrophil counts,in-flammatory markers,and pathological changes in lung,heart,liver,spleen,kidney,and intestinal tissues.RESULTS:Mice in the model group exhibited symptoms such as dyspnea and huddling from 6 hours to 4 days post-infection,which progressively worsened,accompanied by continuous weight loss(P<0.01).These symptoms gradually resolved between days 5 and 14.Arterial oxygen saturation in the model group dropped to 80.7%from days 1 to 8(P<0.01)but returned to normal from days 9 to 14.A total of 23 model mice died between days 1 and 9,with no deaths thereafter,resulting in a mortality rate of 31.9%(P<0.01).Pathological examination revealed inflammatory cell infiltration,congestion,and ede-ma in lung tissue from days 1 to 2,with continued inflammatory cell infiltration,alveolar structural disorganization from days 4 to 8,and alveolar rupture and fusion by day 14(P<0.05 or P<0.01).Additionally,model mice showed significant increases in neutrophil count,white blood cell count,protein content in bronchoalveolar lavage fluid,total cell count,neutrophil ratio,and levels of inflammatory factors tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in peripheral blood from days 1 to 8(P<0.05 or P<0.01).No significant pathological changes were observed in heart and liver tissues,while spleen,kidney,and intestinal tissues exhibited notable pathological changes:indistinct boundaries be-tween red and white pulp in the spleen,significant congestion and edema around renal glomeruli,renal tubules,and col-lecting ducts,and extensive inflammatory cell infiltration in the colonic mucosa.CONCLUSION:Tracheal instillation of 5×109 CFU Klebsiella pneumoniae induces severe pathological changes in the lungs of mice,offering a robust model for studying the pathogenesis and treatment of severe pneumonia.

The rapid development of digital intelligence technologies is providing a powerful boost to the high-quality development of the healthcare system.Considering the current state of our healthcare services and guided by General Secretary Xi Jinping's insights on new quality productive forces and the directives from Third Plenary Session of Communist Party of China's 20th Central Committee,the high-quality development of the healthcare service system should focus on digital intelligence technologies such as cloud computing,big data,privacy computing,blockchain,Internet of Things(IoT),mobile computing,and AI.The key measures should include the optimization of production factors,services,and governance.Emphasis should be placed on enhancing the efficient and intensive development of the development model,ensuring the high-quality and continuous integration of the supply model,and transitioning to scientific and modern management methods.Herein,we analyzed the"factor optimization—service optimization—governance optimization"development mechanism driven by digital intelligence and proposed corresponding implementation pathways,intending to provide references for establishing a high-quality and efficient healthcare service system with Chinese characteristics.

Objective:To investigate the correlation and influencing factors between sarcopenia and cardiac structure and function in elderly inpatients.Methods:A total of 945 elderly patients, aged 60 years and older, were recruited from the Geriatrics Department at Xuanwu Hospital.Sarcopenia was assessed, while cardiac structure and function were evaluated through echocardiography and NT-proBNP measurements.Results:Patients were classified into two groups: a sarcopenia group(n=185, 19.6%)and a non-sarcopenia group(n=760, 80.4%).Compared to the non-sarcopenia group, the sarcopenia group exhibited a reduction in left atrial diameter(LAD), left ventricular end-diastolic diameter(LVEDD), left ventricular mass(LVM), stroke volume(SV), and cardiac output(CO)(all P<0.05).In contrast, NT-proBNP levels were significantly elevated in the sarcopenia group( P<0.001).Multivariate logistic regression analysis identified older age( OR=1.080, P<0.001)and elevated NT-proBNP( OR=1.001, P<0.001)as independent risk factors for sarcopenia.Conversely, higher LAD( OR=0.858, P<0.001)and LVM( OR=0.988, P=0.002)were recognized as independent protective factors.Additionally, NT-proBNP demonstrated a negative correlation with handgrip strength( r=-0.241, P<0.001), gait speed( r=-0.215, P<0.001), SPPB score( r=-0.270, P<0.001), and appendicular skeletal muscle mass(ASM)( r=-0.208, P<0.001), while exhibiting a positive correlation with the 5-time chair stand test( r=0.169, P<0.001).LVM was positively correlated with handgrip strength( r=0.213, P<0.001)and ASM( r=0.456, P<0.001).Furthermore, LAD was positively correlated with handgrip strength( r=0.071, P=0.029)and ASM( r=0.305, P<0.001). Conclusions:Notably, significant differences exist in cardiac structure and function between elderly patients with sarcopenia and those without.Furthermore, indicators related to sarcopenia are correlated with alterations in cardiac structure and function.

Objective:To evaluate the hemodynamic changes and short-term (one year) outcomes after superficial temporal artery(STA)-middle cerebral artery (MCA) bypass by vascular ultrasonography.Methods:Operation group included a total of 41 hemispheres of 38 patients who underwent STA-MCA bypass for severe stenosis or occlusion of MCA or severe stenosis or occlusion of internal carotid artery(ICA), or Moyamoya disease at Xuanwu Hospital between August 2017 and June 2020. The following examinations were performed in all patients: cranial MRI, CT perfusion imaging, and cerebral angiography. All of the patients were retrospectively followed up for one year postsurgery. Normal group included a total of 40 hemispheres of 20 healthy people who had been examined by vascular ultrasonography of carotid artery and intracranial artery. Inner diameter, peak systolic velocity (PSV), end-diastolic velocity (EDV), mean velocity (MV), resistance index (RI), pulsatility index (PI) and flow of STA, PSV, EDV, MV, PI, RI of external carotid artery (ECA) and PSV, EDV, MV, PI, RI of MCA at 1 week, 6 months and 12 months after STA-MCA bypass of operation group were compared with normal group.Results:①Inner diameter, PSV, MV and flow of STA were increased significantly in operation group at 1 week, 6 and 12 months than normal group (all P<0.05). The flow of STA was decreased significantly from 1 week to 12 months after operation (all P<0.05), but Inner diameter, PSV and MV were only decreased gradually from 1 week to 12 months after operation (all P>0.05). ②STA/ECA PI and RI decreased significantly after operation compared with normal group (all P<0.01). Conclusions:Vascular ultrasonography is a non-invasive examination which can objectively evaluate the extracranial and intracranial hemodynamic changes after STA-MCA bypass, and provide reference effectiveness of the operation. The flow of STA has decreased gradually from 1 week to 12 months after operation to achieve the homeostasis, but it is still higher than normal.STA/ECA PI and RI can be a steady indirect pointer to show the fluency of bypass.

Objective:The unilateral (left) ureteral obstruction (UUO) model was established in mice to explore the changes of renal injury with time and the related mechanisms.Methods:Fifty mice were randomly divided into two groups: sham group and UUO group (UUO model was made by unilateral ureteral ligation). The biochemical indexes, left kidney weight/final weight (LR/BW) and right kidney weight/final weight (RR/BW) of the two groups at different time points were observed, and the left kidney weight/right kidney weight ratio (LR/RR) was calculated. Hematoxylin-eosin (HE), Masson and periodic acid-Schiff (PAS) staining were used to detect the pathological changes of the kidney in mice. Immunofluorescence staining was used to observe the loss of peritubular capillaries (PTC), proliferation of renal parenchymal cells (Ki67 + cells), macrophages (CD68 + markers), infiltration of fibroblasts and expression of Wnt/β-catenin in the kidney of mice. Results:The weight of mice in UUO group decreased rapidly [(18.2±1.1)g vs (22.4±1.2)g] on the third day of modeling, then slowly increased until the 28th day, and significantly decreased [(17.5±0.8)g] on the 60th day; LR/RR and LR/BW increased significantly in the third day, and then decreased gradually; Renal function of mice in UUO group deteriorated significantly on the 60th day [serum creatinine (0.89±0.09)mg/dl, urea nitrogen (41.26±5.65)mg/dl]. In UUO group, renal tubulointerstitial fibrosis and glomerulosclerosis were observed under light microscope in the obstructed kidney; with the passage of time, PTC loss gradually increased; macrophages increased significantly in the left renal parenchyma at first, but began to decrease 28 days later; the number of fibroblasts increased significantly in the first 14 days of the obstructed side (left side) kidney, and then decreased to the normal level; There was no significant difference in the cell number of the non obstructive kidney between UUO group and sham group; The immunofluorescence intensity expression of Wnt/β- catenin of obstructive side (left side) in UUO group was significantly up-regulated in the first 14 days after renal injury, and decreased after 28 days.Conclusions:The development of UUO renal fibrosis involves many changes, including PTC loss, macrophage infiltration, fibroblast activation and expression, but these changes weaken with time.

Objective:To investigate the influence of indoxyl sulfate(IS), a typical protein-bound uremic toxin, on left atrial (LA) functional strains using three-dimensional speckle tracking echocardiography (3DSTE).Methods:From May 2019 to January 2020, 128 individuals were consecutively enrolled, including 37 healthy controls and 91 patients, who received maintenance hemodialysis (MHD) in the blood purification center of Zhongshan Hospital affiliated to Fudan University. Conventional echocardiographic parameters and 3DSTE datas of LA were obtained on interdialytic days.LA reservoir, conduit and contraction strains (LASr, LAScd and LASct) were calculated and compared. IS concentration in plasma was assessed by high-performance liquid chromatography tandem mass spectrometry in the MHD cohort.According to the IS concentration, the MHD group was divided into high and low IS (HI and LI) groups. The LA data were also compared between the two groups and linear regression analysis was used to identify independent impact factors of LA strains.Results:Compared to the control group, MHD group had markedly enlarged LA volumes( P<0.05). With regard to the LA phasic strains, both of LASr and LAScd were decreased( P<0.05), while LASct remained unchanged( P>0.05). Compared to the LI group, LASr, LAScd and LASct of the HI group were significantly decreased(all P<0.05). Correlation analysis showed IS concentration correlated well with LASr( rs=-0.674, P<0.001), LAScd( rs=0.454, P<0.001) and LASct( rs=0.376, P<0.001). After adjustment of age, systolic blood pressure, left ventricular mass index(LVMI), and pulmonary systolic pressure, IS concentration remained independently associated with LASr (β=-0.206, 95% CI=-0.353--0.059, P=0.007). Conclusions:In MHD patients, LA is enlarged, and its reservoir function and conduit function are impaired.LA strains derived from 3DSTE are independently related to the IS concentration in plasma, which can be used for the monitoring and evaluation of IS induced cardiac injury.