Objective To explore time-related changes in renal function,renal injury biomarkers,and renal pathology in rats entering a low-pressure and low-oxygen(LPLO)environment simulating moving from the plains to a plateau.Methods Thirty male Sprague-Dawley rats were divided randomly into five groups(n=6 rats per group).Rats in the Control group were placed outside the chamber under normal pressure and oxygen conditions.Rats in the experimental groups were placed in an LPLO chamber to simulate a plateau environment at 5000 m above sea level,and were maintained in the chamber for 3,7,14,and 28 days,respectively.Serum levels of creatinine(CRE),cystatin C(CysC),neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),and interleukin-18(IL-18)were measured as biomarkers of renal injury.Pathological changes in the kidney were observed by hematoxylin and eosin and periodic acid-Schiff staining,with quantitative assessment of the following parameters:average glomerular diameter,peritubular capillary(PTC)density per tubule,tubular injury score,and outer medulla(OM)congestion score.Results NGAL,KIM-1,CysC,and CRE were significantly increased in the experimental compared with the Control group(all P＜0.05).The average glomerulus diameter was significantly reduced in the LPLO 3 d group and significantly increased in the LPLO 14 d group(both P＜0.05).The peritubular capillary(PTC)/tubule ratio was significantly decreased.The renal tubular injury and OM congestion scores were significantly increased(both P＜0.05).Regression analysis showed that PTC/tubule was linearly negatively correlated with the LPLO duration,while CRE,CysC,and pathological indicators(mean glomerular diameter,OM congestion score,renal tubular injury score)were curvilinearly correlated with the duration of LPLO(all P＜0.05).Variables with a curvilinear correlation were analyzed using restricted cubic splines(RCS).Each curve exhibited an inverted-L shape,with inflection points on day 7,indicating that the rate of increase of all indicators was highest within the first 7 days of LPLO,and the rate of increase then slowed from 7 days to 28 days.Conclusions A simulated move from a plains to a plateau environment was associated with significant structural and functional renal damage,but the kidneys then showed a self-adaptive adjustment process towards the plateau environment.

Objectives:To investigate the clinical value of cardiac magnetic resonance imaging(CMR)feature-tracking strain analysis in risk stratification of diabetic heart failure with preserved ejection fraction(HFpEF).Methods:In this retrospective study,a total of 215 patients with diabetic HFpEF who underwent CMR at Chinese Academy of Medical Sciences Fuwai Hospital from January 2012 to December 2018 were included.Myocardial strain parameters were calculated using CMR feature-tracking technology.Patients were followed up by medical records or telephone calls.Composite endpoint event,all-cause death or heart failure hospitalization during follow-up were recorded.Patients were divided into event group and event-free group.Univariable and multivariable Cox proportional hazard regression analyses were performed to determine the risk factors for the outcomes in diabetic HFpEF.The effects of hypertension and obesity on the prognosis of diabetic HFpEF patients and whether they affect the prognostic value of CMR feature-tracking strain analysis were also analyzed.Results:During a follow-up of(7.1±1.8)years,93(43.3%)patients had endpoint events(event group),including 28 all-cause deaths and 65 heart failure hospitalization.Compared with the event-free group(n=122),patients in the event group had significantly lower left ventricular ejection fraction,higher prevalence and extent of late gadolinium enhancement,and significantly reduced global longitudinal strain(GLS),global circumferential strain,global radial strain,and global systolic longitudinal strain rate(all P<0.05).The absolute GLS value was significantly lower in event group than in event-free group,regardless of the presence of hypertension and obesity.Multivariate Cox regression analysis showed that estimated glomerular filtration rate(HR=0.983,95%CI:0.972-0.993,P=0.001),left atrial volume index(HR=1.015,95%CI:1.005-1.026,P=0.004),and GLS(HR=1.142,95%CI:1.060-1.231,P<0.001)were independent risk factors for adverse cardiovascular events in diabetic HFpEF patients.However,adjusted N-terminal pro-brain natriuretic peptide was not an independent prognostic factor.The cut-offvalue of GLS to predict outcome was-14.09%from ROC curve analysis.The Kaplan-Meier curve showed that in patients with and without hypertension and obesity,patients with the GLS>-14.09%had lower event-free survival compared to patients with GLS≤-14.09%(all P<0.05),and the ability of GLS to predict adverse outcomes was not affected by hypertension and obesity.Conclusions:GLS obtained by CMR feature-tracking strain analysis is an independent predictor of adverse outcomes in diabetic HFpEF,and its ability to predict adverse outcomes is independent of hypertension and obesity.

Objectives:To investigate the clinical value of cardiac magnetic resonance imaging(CMR)feature-tracking strain analysis in risk stratification of diabetic heart failure with preserved ejection fraction(HFpEF).Methods:In this retrospective study,a total of 215 patients with diabetic HFpEF who underwent CMR at Chinese Academy of Medical Sciences Fuwai Hospital from January 2012 to December 2018 were included.Myocardial strain parameters were calculated using CMR feature-tracking technology.Patients were followed up by medical records or telephone calls.Composite endpoint event,all-cause death or heart failure hospitalization during follow-up were recorded.Patients were divided into event group and event-free group.Univariable and multivariable Cox proportional hazard regression analyses were performed to determine the risk factors for the outcomes in diabetic HFpEF.The effects of hypertension and obesity on the prognosis of diabetic HFpEF patients and whether they affect the prognostic value of CMR feature-tracking strain analysis were also analyzed.Results:During a follow-up of(7.1±1.8)years,93(43.3%)patients had endpoint events(event group),including 28 all-cause deaths and 65 heart failure hospitalization.Compared with the event-free group(n=122),patients in the event group had significantly lower left ventricular ejection fraction,higher prevalence and extent of late gadolinium enhancement,and significantly reduced global longitudinal strain(GLS),global circumferential strain,global radial strain,and global systolic longitudinal strain rate(all P<0.05).The absolute GLS value was significantly lower in event group than in event-free group,regardless of the presence of hypertension and obesity.Multivariate Cox regression analysis showed that estimated glomerular filtration rate(HR=0.983,95%CI:0.972-0.993,P=0.001),left atrial volume index(HR=1.015,95%CI:1.005-1.026,P=0.004),and GLS(HR=1.142,95%CI:1.060-1.231,P<0.001)were independent risk factors for adverse cardiovascular events in diabetic HFpEF patients.However,adjusted N-terminal pro-brain natriuretic peptide was not an independent prognostic factor.The cut-offvalue of GLS to predict outcome was-14.09%from ROC curve analysis.The Kaplan-Meier curve showed that in patients with and without hypertension and obesity,patients with the GLS>-14.09%had lower event-free survival compared to patients with GLS≤-14.09%(all P<0.05),and the ability of GLS to predict adverse outcomes was not affected by hypertension and obesity.Conclusions:GLS obtained by CMR feature-tracking strain analysis is an independent predictor of adverse outcomes in diabetic HFpEF,and its ability to predict adverse outcomes is independent of hypertension and obesity.

Objective To explore time-related changes in renal function,renal injury biomarkers,and renal pathology in rats entering a low-pressure and low-oxygen(LPLO)environment simulating moving from the plains to a plateau.Methods Thirty male Sprague-Dawley rats were divided randomly into five groups(n=6 rats per group).Rats in the Control group were placed outside the chamber under normal pressure and oxygen conditions.Rats in the experimental groups were placed in an LPLO chamber to simulate a plateau environment at 5000 m above sea level,and were maintained in the chamber for 3,7,14,and 28 days,respectively.Serum levels of creatinine(CRE),cystatin C(CysC),neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),and interleukin-18(IL-18)were measured as biomarkers of renal injury.Pathological changes in the kidney were observed by hematoxylin and eosin and periodic acid-Schiff staining,with quantitative assessment of the following parameters:average glomerular diameter,peritubular capillary(PTC)density per tubule,tubular injury score,and outer medulla(OM)congestion score.Results NGAL,KIM-1,CysC,and CRE were significantly increased in the experimental compared with the Control group(all P＜0.05).The average glomerulus diameter was significantly reduced in the LPLO 3 d group and significantly increased in the LPLO 14 d group(both P＜0.05).The peritubular capillary(PTC)/tubule ratio was significantly decreased.The renal tubular injury and OM congestion scores were significantly increased(both P＜0.05).Regression analysis showed that PTC/tubule was linearly negatively correlated with the LPLO duration,while CRE,CysC,and pathological indicators(mean glomerular diameter,OM congestion score,renal tubular injury score)were curvilinearly correlated with the duration of LPLO(all P＜0.05).Variables with a curvilinear correlation were analyzed using restricted cubic splines(RCS).Each curve exhibited an inverted-L shape,with inflection points on day 7,indicating that the rate of increase of all indicators was highest within the first 7 days of LPLO,and the rate of increase then slowed from 7 days to 28 days.Conclusions A simulated move from a plains to a plateau environment was associated with significant structural and functional renal damage,but the kidneys then showed a self-adaptive adjustment process towards the plateau environment.

Objectives:To analyze the consistency of evaluating left ventricular hemodynamics (HDF) based on single plane and multi plane cine sequences of magnetic resonance mitral valve orifice.Methods:A prospective study was conducted on 48 healthy adults, and two methods were used to measure the mitral valve diameter and calculate HDF parameters. The first method was to measure the diameter of the mitral valve opening in the left ventricular three chamber cine sequence; The second method is to measure the mitral valve diameter using cine sequences of two chamber, three chamber, and four chamber hearts, and then take the average value. Paired t-tests were used to compare the differences in HDF measured by two methods, and Pearson correlation coefficient ( r), intra group correlation coefficient ( ICC), and Bland-Altman analysis were used to test the consistency and reproducibility of the two methods. Results:The root mean square (RMS) of longitudinal HDF calculated using single plane and multi plane mitral valve diameters were [(17.28±4.41)% vs (17.21±4.61)%] ( P=0.379) for the entire cardiac cycle, [(21.45±5.54)% vs (21.49±5.68)%] ( P=0.646) for systolic phase, and [(12.78±4.10)% vs (12.54±4.24)%] ( P=0.106) for diastolic phase, respectively. The difference in the calculation results of HDF parameters related to ventricular function was not statistically significant (all P>0.05), and there was good consistency ( r=0.924-0.996, ICC=0.924-0.995). The two HDF parameters related to atrial function were sensitive to the measurement method of mitral valve orifice diameter [RMS of longitudinal HDF during active atrial emptying: (3.26±1.51)% vs (3.32±1.55)%, P=0.006; longitudinal HDF pulse during active atrial emptying: (-2.60±1.28)% vs (-2.76±1.30)%, P<0.001]. Conclusions:The ventricular function related HDF parameters obtained from the analysis of mitral valve orifice diameter using single plane and multi plane methods have good consistency, and can be evaluated using relatively simple single plane methods for left ventricular HDF.

The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies; however, the underlying mechanism remains underexplored. In this study, we discovered that impaired macrophage phagocytosis contributed to the psychological stress-evoked tumor susceptibility, and the stress hormone glucocorticoid (GC) was identified as a principal detrimental factor. Mechanistically, GC disturbed the balance of the "eat me" signal receptor (low-density lipoprotein receptor-related protein-1, LRP1) and the "don't eat me" signal receptor (signal regulatory protein alpha, SIRPα). Further analysis revealed that GC led to a direct, glucocorticoid receptor (GR)-dependent trans-repression of LRP1 expression, and the repressed LRP1, in turn, resulted in the elevated gene level of SIRPα by down-regulating miRNA-4695-3p. These data collectively demonstrate that stress induces the imbalance of the LRP1/SIRPα axis and entails the disturbance of tumor cell clearance by macrophages. Our findings provide the mechanistic insight into psychological stress-evoked tumor susceptibility and indicate that the balance of LRP1/SIRPα axis may serve as a potential therapeutic strategy for tumor treatment.

Objective:To explore the dynamic changes of inflammatory cytokines and T lymphocyte activation in the peripheral blood of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients during anti-retroviral therapy (ART).Methods:Two hundred and six HIV/AIDS patients with ART at clinic of the Department of Infectious Diseases in Second Xiangya Hospital, Central-South University between January 2017 and December 2019 were selected as HIV infection group. They were followed up regularly and the blood samples before treatment and at month 6, month 12, month 24 of treatment were collected. Meanwhile, 52 healthy cases were enrolled in the healthy control group and their blood samples were collected. Enzyme-linked immunosorbent assay was used to detect the plasma concentrations of interleukin (IL)-6, hypersensitive C-reactive protein (hsCRP) and tumor necrosis factor (TNF)-α. Flow cytometry was used to detect the CD3 + CD4 + T lymphocytes count and the percentage of CD4 + CD38 + T lymphocytes and CD8 + CD38 + T lymphocytes in the peripheral blood mononuclear cells. Plasma HIV RNA viral load was determined using a quantitative real-time polymerase chain reaction technique. Statistical methods used paired t test and Pearson correlation analysis. Results:The concentrations of IL-6, hsCRP and TNF-α in HIV infection group were (13.42±2.35) pg/mL, (4 012.46±1 012.35) μg/L and (51.78±11.32) μg/L, respectively, which were higher than those in healthy control group ((6.14±0.78) pg/mL, (707.21±305.76) μg/L and (19.01±6.48) μg/L, respectively). The differences were all statistically significant ( t=12.56, 16.79 and 13.45, respectively, all P<0.001). They decreased gradually after initiation of ART in HIV infection group, and returned to normal levels at month 24 of ART. CD3 + CD4 + T cells count was (256.00±65.32)/μL and HIV RNA viral load was (4.467±4.244) lg copies/mL before ART in HIV infection group, which were negatively correlated ( r=-0.625, P=0.041). The percentages of CD8 + CD38 + T lymphocytes before treatment and at month 12 or month 24 of treatment in HIV infection group were higher than those in healthy control group. The differences were all statistically significant ( t=3.85, 6.84 and 2.57, respectively, all P<0.050). The percentage of CD8 + CD38 + T lymphocytes was positively correlated with HIV RNA viral load before ART ( r=0.768, P=0.026). The percentages of CD4 + CD38 + T lymphocytes before treatment and at month 12 or month 24 of treatment in the HIV infection group were lower than those in the healthy control group, and the differences were all statistically significant ( t=6.80, 1.10, and 2.11, respectively, all P<0.050). Conclusions:HIV infection could not only cause insufficiency in immune system, but also abnormal activation of immune system, which could get better gradually with ART.

A 66-year-old male patient with anxiety and depression received lorazepam 1 mg twice daily and buspirone 10 mg twice daily. Two months later, the patient developed chills, fever, drowsiness, and stiffness of limbs, etc. Laboratory tests showed white blood cell count 13.5×10 9/L, neutrophils 0.89, C-reactive protein 68.7 mg/L, serum creatinine 211 mmol/L, direct bilirubin 10.3 mmol/L, alanine aminotransferase 96 U/L, aspartate aminotransferase 121 U/L, creatine kinase (CK) 4 557 U/L, CK-MB 83 U/L, lactate dehydrogenase 462 U/L, α-hydroxybutyrate dehydrogenase 339 U/L, and troponin 116 ng/L. Malignant syndrome caused by buspirone was considered. The drug was stopped, lorazepam was continued, and oxygen inhalation, ECG monitoring, physical cooling, anti-infection, and other treatments were given. The patient still had fever and developed deep coma, with brown urine and myoglobin >3 000 mg/L. Secondary rhabdomyolysis was considered. Anti-infection treatment was continued and treatments such as correcting electrolyte balance, alkalizing urine, and diuresis were given. On the 10th day of drug withdrawal, the patient had normal limb activity and urine color, his creatine kinase was 246 U/L, and myoglobin was 856 mg/L. One month later, the laboratory tests showed no obvious abnormalities and no malignant syndrome releted symptoms recurred. The rhabdomyolysis secondary to malignant syndrome in the patient was considered to be possibly related to buspiron and the combination with lorazepam might promote its occurrence.

A 66-year-old male patient with anxiety and depression received lorazepam 1 mg twice daily and buspirone 10 mg twice daily. Two months later, the patient developed chills, fever, drowsiness, and stiffness of limbs, etc. Laboratory tests showed white blood cell count 13.5×10 9/L, neutrophils 0.89, C-reactive protein 68.7 mg/L, serum creatinine 211 mmol/L, direct bilirubin 10.3 mmol/L, alanine aminotransferase 96 U/L, aspartate aminotransferase 121 U/L, creatine kinase (CK) 4 557 U/L, CK-MB 83 U/L, lactate dehydrogenase 462 U/L, α-hydroxybutyrate dehydrogenase 339 U/L, and troponin 116 ng/L. Malignant syndrome caused by buspirone was considered. The drug was stopped, lorazepam was continued, and oxygen inhalation, ECG monitoring, physical cooling, anti-infection, and other treatments were given. The patient still had fever and developed deep coma, with brown urine and myoglobin >3 000 mg/L. Secondary rhabdomyolysis was considered. Anti-infection treatment was continued and treatments such as correcting electrolyte balance, alkalizing urine, and diuresis were given. On the 10th day of drug withdrawal, the patient had normal limb activity and urine color, his creatine kinase was 246 U/L, and myoglobin was 856 mg/L. One month later, the laboratory tests showed no obvious abnormalities and no malignant syndrome releted symptoms recurred. The rhabdomyolysis secondary to malignant syndrome in the patient was considered to be possibly related to buspiron and the combination with lorazepam might promote its occurrence.