ObjectiveTo investigate the inhibitory effect of gingerol， an active component of ginger， on Staphylococcus aureus （S. aureus） infection， and to preliminarily explore its mechanism related to extracellular vesicles （EVs）. MethodsS.aureus infection models were established in human umbilical vein endothelial cell （HUVECs）， Vero E6 cells， and C57BL/6 mice. Experimental groups included control， infection， and gingerol-treated groups. Bacterial load and VE-cadherin protein expression were detected using immunofluorescence and Western blot. EVs were isolated by size exclusion chromatography and characterized by transmission electron microscopy and nanoparticle tracking analysis. miRNA sequencing was performed on EVs. ResultsGingerol treatment significantly reduced the bacterial load in both in vitro and in vivo infection models and upregulated VE-cadherin expression. miRNA sequencing of EVs revealed that S. aureus infection upregulated the expression of hsa-miR-320c， while gingerol treatment reversed this abnormal expression. Bioinformatic analysis further predicted that the target genes of hsa-miR-320c were significantly enriched in cell junction-related pathways. ConclusionGingerol exhibits clear antibacterial and host-protective effects， by regulating hsa-miR-320c in EVs to maintain endothelial barrier integrity.

The comorbidity of depression and cancer represents a significant global public health challenge,severely impacting patients' quality of life and clinical outcomes.This systematic review considers the epidemiological characteristics,clinical implications,and major challenges in current research regarding comorbid depression and cancer,focusing on the role of depression in promoting tumor progression and suppressing immune function via the neuroendocrine-immune regulatory network.We discuss the dynamic changes and interaction mechanisms of depression-related neurotransmitters(such as serotonin and norepinephrine)and stress hormones(such as cortisol)within the tumor microenvironment.We also reveal the molecular mechanisms by which depression regulates malignant biological behaviors such as tumor immune evasion,metastasis,and angiogenesis via activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system.This review also evaluates the application value and limitations of existing animal models for studying the mechanisms underlying the comorbidity of depression and cancer,emphasizing the importance and urgency of developing more precise comorbidity models to uncover the mechanisms and explore management strategies.This review aims to raise awareness of risk prediction,clinical interventions,and basic research on the comorbidity of depression and cancer,to provide a theoretical foundation and new research directions for developing depression-cancer comorbidity models.

The comorbidity of depression and cancer represents a significant global public health challenge,severely impacting patients' quality of life and clinical outcomes.This systematic review considers the epidemiological characteristics,clinical implications,and major challenges in current research regarding comorbid depression and cancer,focusing on the role of depression in promoting tumor progression and suppressing immune function via the neuroendocrine-immune regulatory network.We discuss the dynamic changes and interaction mechanisms of depression-related neurotransmitters(such as serotonin and norepinephrine)and stress hormones(such as cortisol)within the tumor microenvironment.We also reveal the molecular mechanisms by which depression regulates malignant biological behaviors such as tumor immune evasion,metastasis,and angiogenesis via activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system.This review also evaluates the application value and limitations of existing animal models for studying the mechanisms underlying the comorbidity of depression and cancer,emphasizing the importance and urgency of developing more precise comorbidity models to uncover the mechanisms and explore management strategies.This review aims to raise awareness of risk prediction,clinical interventions,and basic research on the comorbidity of depression and cancer,to provide a theoretical foundation and new research directions for developing depression-cancer comorbidity models.

【Objective】 To establish a risk model for predicting spontaneous rupture bleeding of renal angiomyolipoma (RAML) in order to better assess and deal with the risk. 【Methods】 The information of 436 RAML patients diagnosed during Jan.2018 and Dec.2022 was retrospectively analyzed.According to the inclusion and exclusion criteria, 216 patients were included and divided into the rupture bleeding group (n=35) and non-rupture bleeding group (n=181).The factors influencing spontaneous rupture bleeding were identified using univariate and multivariate analysis, and a nomogram was constructed accordingly with R language.The nomogram was evaluated using Calibration curve and area under the receiver operator characteristic curve (AUC). 【Results】 It was found that clinical manifestations, tumor diameter, tumor convexity, tumor blood supply, and tuberous sclerosis complex (TSC) were significantly correlated with rupture bleeding.The Calibration curve fitted well with the nomogram.The AUC was 0.956 (95%CI: 0.856-0.943), indicating that the nomogram had good statistical performance. 【Conclusion】 The model can effectively predict the risk of spontaneous rupture bleeding of renal angiomyolipoma.

OBJECTIVE To explore the mechanism of Cirsium japonicum extract in improving hypercholesterolemia based on metabolomics technology. METHODS The extract of C. japonicum was prepared by macroporous resin adsorption， and its main components were identified by liquid chromatography-tandem mass spectrometry. The experimental mice were randomly divided into control group （n＝6） and modeling group （n＝16）. The hypercholesterolemia model was induced by diet in modeling group； after modeling， the rats of modeling group were divided into model group （n＝8） and C. japonicum extract group （n＝8）. C. japonicum extract group was given C. japonicum extract 400 mg/（kg·d） by gavage （calculated by extract）， and other 2 groups were given constant volume of 0.3% sodium carboxymethyl cellulose solution， for 6 weeks. After medication， the intervention effect of C. japonicum extract was evaluated by the levels of serum total cholesterol （TC）， triglyceride （TG） and the histopathological changes of liver. The mechanism of C. japonicum extract in improving hypercholesterolemia model mice was investigated by metabolomics. RESULTS It was identified that C. japonicum extract contained 12 components， such as 030302005） chlorogenic acid， linarin and pectolinarin. After 6 weeks of intervention， compared with control group， serum level of TC was increased significantly while the level of TG was decreased significantly in model group （P＜0.05）， while a large number of lipid droplets， disorderly arrangement of liver cells and the damaged structure of liver cord were observed in liver tissue. Compared with model group， the serum level of TC was decreased significantly in C. japonicum extract group（P＜0.05）； the lipid droplets in liver tissue were significantly reduced， with liver cells arranged radially and tightly centered around the central vein， and liver cords arranged neatly. The metabolomics study showed that after the intervention of C. japonicum extract， the levels of metabolites were significantly adjusted back， such as ethanolamine， fumaric acid and cholesterol； finally， three metabolism pathways， such as alanine-aspartate-glutamic acid metabolism， arginine biosynthesis， citric acid cycle， were obtained. CONCLUSIONS The main components of C. japonicum extract are phenolic acids and flavonoids， such as chlorogenic acid， linarin， pectolinarin. C. japonicum extract can improve hypercholesterolemia by regulating the contents and distribution of differential metabolites， adjusting alanine-aspartate-glutamic acid metabolism， arginine biosynthesis and citric acid cycle， participating in oxidation-reduction reaction， improving liver lipid accumulation， and playing anti-inflammatory role.

Objective:To investigate the efficacy and safety of encephalo-duro-arterio-synangiosis (EDAS) for intracranial atherosclerotic steno-occlusive disease (ICASD).Methods:Patients with symptomatic ICASD received EDAS treatment in the Department of Neurosurgery, the PLA General Hospital from January 2018 to January 2019 were retrospectively included. The baseline information, perioperative complications, primary endpoint events, and changes in modified Rankin Scale (mRS) scores before and after surgery were collected. The primary endpoint event was any stroke/death that occurred within 30 d after enrollment. The secondary endpoint events were any stroke/death, non-stroke bleeding (subdural or epidural bleeding), and clinical functional improvement after 30 d. The clinical functional improvement was defined as a decrease of ≥1 in the mRS score compared to before surgery.Results:A total of 40 patients were included, including 30 males and 10 females, aged 53.9±8.6 years old. The clinical symptoms were mainly limb weakness and dizziness. One case of ischemic stroke and one case of hemorrhagic stroke occurred during the perioperative period. The primary endpoint event incidence was 2.5%. The patients were followed up for 49.75±2.99 months after surgery. One patient died of cerebral hemorrhage 31 months after surgery, and one patient developed acute ischemic stroke 35 months after surgery. The postoperative mRS scores of 34 patients decreased compared to before surgery, and the clinical function improvement rate was 85%. The mRS score increased in 2 cases after surgery compared to before surgery and 4 cases had no change.Conclusion:EDAS can improve the clinical function of patients with symptomatic ICASD and reduce the incidence of long-term stroke.

Objective    To investigate whether metformin has protective effect on myocardial injury in patients with coronavirus disease 2019 (COVID-19) combined with coronary heart diseases and diabetes. Methods    COVID-19 patients with coronary heart disease and diabetes who were admitted to Tongji Hospital from January 18 to April 25 in 2020 were enrolled. They were divided into a metformin group and a none-metformin group according to whether the metformin was used. The demographic characteristics, clinical symptoms, laboratory parameters, treatment and clinical outcomes of the two groups were analyzed retrospectively. Results    There were 29 patients in the metformin group, 3 patients (12.0%, 3/25) suffered myocardial injury and 1 (3.4%) died of acute respiratory failure complicated by septic shock; 67 patients were in the non-metformin group and 24 (37.5%, 24/64) had myocardial injury but 15 died in hospital among whom 1 died of septic shock complicated by disseminated intravascular coagulation, 1 acute respiratory failure complicated by possible cerebral hemorrhage, 2 acute respiratory failure, 1 fulminant myocarditis, 3 acute myocardial infarction and 7 cardiac arrest. The incidence of myocardial injury (12.0% vs. 37.5%, P=0.019), hospital mortality (3.4% vs. 22.4%, P=0.034) and mortality of cardiovascular events (0.0% vs. 16.4%, P=0.049) in the metformin group were significantly lower than those in the non-metformin group. Multivariate analysis showed that the use of insulins (OR=11.235, P=0.003) was an influencing factor for in-hospital mortality of patients. The use of metformin (OR=0.154, P=0.013) was positively correlated with the myocardial injury. Conclusion    When patients with coronary heart disease and diabetes are infected with COVID-19, metformin can effectively reduce myocardial damage and has a certain effect on reducing hospital mortality. Combined with clinical considerations, it is worthy of popularization.

Objective:To investigate the postnatal grading, surgical intervention and prognosis in fetal hydronephrosis.Methods:The clinical data of 243 children who were prenatally diagnosed with fetal hydronephrosis and first seen at Dalian Children′s Hospital after birth from November 2014 to November 2017 were retrospectively analyzed. All cases were followed up by routine ultrasound after birth and were assessed and graded according to the postnatal urinary tract dilation (UTD) system. The children with clinical indication for surgery underwent surgical treatment (operation group), and the children without clinical indication were closely followed up (non-operation group).Results:Among 243 children, 182 were male and 61 were female; the gestational age at first diagnosis was (27.5±3.2) weeks, and the maternal age was (29 ± 6) years; 212 cases were unilateral, and 31 cases were bilateral. The results of the first ultrasound examination result showed UTD low-risk was in 117 cases, medium-risk in 67 cases, high-risk in 59 cases. All the children were followed up from 14 to 50 months, with a mean of 26.4 months. During the follow-up period, 117 cases with UTD low-risk did not undergo surgical treatment; 62 cases of 67 with UTD medium-risk did not receive operation, and 5 were operated; while operation were performed on 56 cases of 59 with UTD high-risk, and 3 children with stable hydronephrosis were not treated surgically. The non-operation group had 182 cases, and operation group had 61 cases. The UTD high-risk rate and renal pelvis anteroposterior diameter of first ultrasound examination in operation group were significantly higher than those in non-operation group: 91.80% (56/61) vs. 1.65% (3/182) and 1.9 (1.6, 2.4) mm vs. 0.7 (0.3, 1.5) mm, the thickness of renal parenchyma was significantly lower than that in non-operation group: 3.0 (1.3, 4.1) mm vs. 6.0 (5.1, 7.2) mm, and there were statistical differences ( P<0.01 or <0.05). The result of follow-up in operation group showed that the renal pelvis anteroposterior diameter and the ratio of renal pelvis anteroposterior diameter to renal parenchyma thickness 1 year after operation were significantly lower than those before operation: (1.6 ± 0.7) cm vs. (3.5 ± 1.5) cm and 0.3 ± 0.2 vs. 1.1 ± 1.0, the thickness of renal parenchyma and differentiated renal function were significantly higher than those before operation: (5.8 ± 2.4) mm vs. (3.2 ± 3.1) mm and (45.4 ± 1.9)% vs. (39.5 ± 2.3)%, and there were statistical differences ( P<0.05). Conclusions:UTD grading system is required after birth. Children with hydronephrosis in UTD low-risk and most of the UTD medium-risk have relatively satisfactory prognosis. The hydronephrosis children with UTD high-risk should undergo early surgery if progressive worsening appears and decline in differentiated renal function is detected.

Objective To investigate the effect and the mechanism of epithelial-mesenchymal transition (EMT) in renal tubular cells induced by uric acid.Methods Normal rat kidney tubular cell line (NRK-52E) were exposed to different concentrations of uric acid (100,200,400,600,800 μmol/L UA) for 48 hours to induce EMT.Morphological changes of the NRK-52E cells were examined under an inverted phase contrast microscope.The protein expression of E-cadherin,α-SMA,p-Akt and Akt were detected by Western blotting.The distribution of E-cadherin and α-SMA were detected by immunofluorescence.NRK-52E cells were pretreated by different concentrations of LY294002(0,2.5,5,10,15 μmol/L),the inhibitor of PI3K/p-Akt signaling pathway,and then processed by uric acid (400 μmol/L) for 48 hours.Western blotting was used to detect the protein expression of p-Akt and Akt.NRK-52E cells were then divided into four groups:normal group (N),uric acid group (UA),LY294002 group (LY),uric acid with LY294002 group (UA + LY).The protein expression of E-cadherin and α-SMA were detected by Western blotting,the distribution of E-cadherin,α-SMA and p-Akt were detected by immunofluorescence.Results There was abundant cellular expression of E-cadherin in unstimulated renal tubular cells whereas its expression was significantly decreased in uric acidstimulated cells (P ＜ 0.05).In addition,uric acid induced de novo expression of α-SMA in contrast to almost negative staining in untreated cells (P ＜ 0.05).p-Akt were obviously increased in high uric acid group (P ＜ 0.05) and Akt changed not significantly (P ＞ 0.05).NRK-52E cells transformed into elongated fibroblast-like cells from cuboidal clustered epithelial cells.These indicated that uric acid has induced EMT and activated PI3K/p-Akt signaling pathway in NRK-52E cells.However,the above effects of uric acid were abolished when p-Akt was blocked by the PI3K inhibitor (10,15 μmol/L LY294002),indicated that LY294002 has reversed the trend of EMT.Conclusions High uric acid induces phenotypic transition of renal tubular cells probably via activating PI3K/Akt signaling pathway.

Objective To assess the impact of physical training on physiological function of adult renal transplant recipients by meta-analysis and to provide theoretical guidance for clinical practice.Methods Randomized controlled trials of physical training for the treatment of renal transplant recipients until October 2017 were searched in the database of Cochrane library,PubMed,Embase,Web of Science,Wanfang Data and CNKI.Data extracted from the literatures were analyzed with RevMan software (version 5.3).Results A total of 10 studies in 10 manuscripts met the inclusion criteria,and 557 cases were included.Meta-analysis results were as follows.Compared with the control group (routine drug therapy),the level of peak exercise oxygen uptake (peak VO2) was significantly increased in physical training group (routine drug therapy and physical training) (MD=2.40,95％ CI 0.15-4.64,P=0.04).However,there was no statistically significant difference in the change of blood lipid,blood pressure,hemoglobin and serum creatinine between the two groups (all P ＞0.05).Conclusions Physical training can improve cardio respiratory fitness of renal transplant recipients in the early stage,but it has no obvious effect on blood pressure,blood lipid,hemoglobin and blood creatinine.