Objective To investigate the application of cardiovascular magnetic resonance feature tracking(CMR-FT)in assessing myocardial strain in dilated cardiomyopathy(DCM)patients residing at high altitudes.Methods We retrospectively enrolled 29 DCM patients living at high altitudes(DCM-H),27 DCM patients living in a low-altitude plain environment(DCM-P),23 healthy volunteers living at a high altitude(HV-H),and 24 healthy volunteers living in a low-altitude plain environment(HV-P).All subjects underwent cine MRI scanning using a 3.0T rapid steady-state free precession sequence.The CMR images thus acquired were analyzed using cvi42,a post-processing software,to obtain left ventricular function and myocardial strain parameters.Results Compared with the HV-H group,the DCM-H group showed higher left ventricle end-diastolic volume(LVEDV)and left ventricle end-systolic volume(LVESV),and lower left ventricular ejection fraction(LVEF)and stroke volume(LVSV)(all P＜0.01).No significant difference was observed in cardiac function between the DCM-H and DCM-P groups(all P＞0.05).The absolute values of global radial strain(GRS),global circumferential strain(GCS),and global longitudinal strain(GLS)in the DCM-H group were lower than those in the HV-P group([14.5±6.5]％vs.[34.2±10.7]％,[-11.1±4.4]％vs.[-19.9±2.8]％,and[-7.7±3.2]％vs.[-13.6±4.1]％,respectively),with the differences being statistically significant(all P＜0.001).The DCM-H group had higher absolute GRS,GCS,and GCS values than the DCM-P group did([14.5±6.5]％vs.[7.0±2.7]％,[-11.1±4.4]％vs.[—5.4±2.2]％,and[—7.7±3.2]％vs.[—4.3±1.7]％,respectivley,all P＜0.01).Conclusion Myocardial strain in DCM patients living at a high altitude is lower than that in healthy volunteers living at a high altitude,but higher than that in DCM patients living in a low-altitude plain environment.CMR-FT can be used to quantitatively assess myocardial contractility in DCM patients living at a high altitude,showing promise for clinical application.

Objective To establish a hypobaric hypoxia rat model in a real high-altitude environment,to investigate the effects of the real high-altitude environment on rat bone mass and bone microstructure using multiple methods such as Micro CT,blood biochemistry,and pathology,and to explore the potential mechanisms involved.Methods Sprague Dawley(SD)rats were transported to the Yushu Plateau Laboratory(at 4250 m above sea level)in Qinghai Province and kept there for 4,or 8,or 18 months.These groups were designated as H-4,H-8,and H-18,respectively.Upon completion of the high-altitude exposure,these animals were transported to the Molecular Imaging Laboratory,West China Hospital,Sichuan University(at 500 m above sea level)in Chengdu for relevant testing and comparison with the control animals raised in a low-altitude environment for the same durations(designated L-4,L-8,and L-18).The tests performed included blood biochemistry,Micro CT imaging,and pathological assessments such as ELISA,Western blot,and HE and TRAP staining.Results Compared with that of the control group,the body mass of rats in the H-4 and H-18 groups decreased significantly(H-4 group vs.L-4 group:[513.75±35.10]g vs.[649.18±60.03]g,P＜0.01;H-18 group vs.L-18 group:[535.58±66.65]g vs.[670.86±44.96]g,P＜0.01).The serum Ca2+concentration was higher in the H-8 group and H-18 group compared to that in the control group(H-8 group vs.L-8 group:[2.48±0.09]mmol/L vs.[2.38±0.07]mmol/L,P＜0.05;H-18 group vs.L-18 group:[2.55±0.11]mmol/L vs.[2.13±0.27]mmol/L,P＜0.05).No statistically significant difference was observed in the concentration of P3+.Bone metabolism indicator cross-linked carboxy-terminal telopeptide of type Ⅰ collagen(CTX-Ⅰ)was significantly increased in all high-altitude groups compared to the low-altitude groups(H-4 group vs.L-4 group:[1.44±0.08]ng/mL vs.[0.70±0.13]ng/mL,P＜0.01;H-8 group vs.L-8 group:[1.52±0.10]ng/mL vs.[0.75±0.10]ng/mL,P＜0.01;H-18 group vs.L-18 group:[2.70±0.13]ng/mL vs.[1.94±0.15]ng/mL,P＜0.01).In addition,CT results showed a decrease in bone volume fraction of trabecular bone in the three high-altitude groups(H-4 group vs.L-4 group:[7.48±2.35]％vs.[10.40±2.93]％,P＜0.05;H-8 group vs.L-8 group:[7.17±2.68]％vs.[10.09±2.95]％,P＜0.05;H-18 group vs.L-18 group:[2.90±2.91]％vs.[8.68±4.11]％,P＜0.01),and increased trabecular separation in the three high-altitude groups(H-4 group vs.L-4 group:[0.70±0.12]mm vs.[0.60±0.06]mm,P＜0.05;H-8 group vs.L-8 group:[0.68±0.07]mm vs.[0.59±0.05]mm,P＜0.01;H-18 group vs.L-18 group:[0.80±0.09]mm vs.[0.70±0.09]mm,P＜0.05).TRAP staining showed an increase in osteoclasts in the H-4 and H-18 groups.Western blot results indicated an increase in the expression of receptor activator of nuclear factor-κB ligand(RANKL)and hypoxia inducible factor-1α(HIF-1α)in high-altitude environment,while the expression of osteoprotegerin(OPG)was inhibited.Conclusion The impact of high-altitude environment on rat femurs is characterized primarily by a reduction in trabecular bone mass and damage to bone microstructure.

Objective To explore the therapeutic effect of Cang-ai volatile oil(CAVO)on rats with myocardial hypertrophy(MH)exposed to the hypobaric hypoxic environment of the Qinghai-Tibet Plateau using 7.0-tesla(7.0T)cardiac magnetic resonance imaging(CMR).Methods A total of 50 male specific pathogen-free(SPF)Sprague-Dawley(SD)rats were randomly assigned to a low-altitude control(CON)group,hypobaric hypoxia(HH)group,myocardial hypertrophy modeling(MH)group,MH modeling plus CAVO treatment(MH+CAVO)group,and MH modeling plus benadryl hydrochloride treatment(MH+RX)group,with 10 rats in each group.Except for the CON group,the rats in all the groups were kept and fed in the standard way for 8 weeks in a high-altitude environment(at 4250 m above sea level),and then given the corresponding treatment drugs by gastric gavage.Afterwards,7.0T high field strength CMR was used to measure left ventricular(LV)function and myocardial strain.Hematoxylin-eosin(HE)staining and Masson staining were performed to observe myocardial interstitial fibrosis.Wheat germ agglutinin(WGA)staining was performed to analyze the cross-sectional area of cardiomyocytes.Transmission electron microscopy was used to observe the ultrastructural changes of the myocardium.Serum levels of cardiac troponin T(cTnT),superoxide dismutase(SOD),malondialdehyde(MDA),and glutathione peroxidase(GSH-PX)were measured by ELISA.Results Compared with those of the control group,the MH group had significantly lower left ventricular global circumferential strain(LVGCS)at(-18.85±1.67)％and left ventricular global longitudinal strain(LVGLS)at(-20.39±1.48)％(P＜0.05).However,the MH+CAVO group had significantly higher LVGCS at(-22.10±1.08)％and LVGLS at(-24.60±1.72)％compared with those of the MH group(both P＜0.05),indicating that CAVO treatment improved LV function.The MH group had a decreased level of serum glutathione peroxidase(GSH-Px)in comparison with the CON group([1173.49±27.10]U/mL vs.[300.83±47.25]U/mL,P＜0.01),a decreased SOD level in comparison with the CON group([302.27±3.65]U/mL vs.[105.96±4.03]U/mL,P＜0.01),and an increased level of serum malondialdehyde(MDA)in comparison with the CON group([57.91±1.13]μmol/L vs.[6.65±2.99]μmol/L,P＜0.01),suggesting that the antioxidant capacity of rats in the MH group was decreased.After CAVO intervention,rats in the MH+CAVO group exhibited an increase in the serum levels of SOD at(278.51±5.97)U/mL and GSH-Px at(961.82±17.56)U/mL,as well as a decrease in MDA at(17.79±1.33)μmol/L(all P＜0.05).Conclusion CAVO can effectively improve cardiac function in rats with cardiac hypertrophy exposed to high-altitude environment by modulating oxidative stress and ameliorating cardiac hypertrophy.

Indolylarylsulfones (IASs) are classical HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a unique scaffold and possess potent antiviral activity. To address the high cytotoxicity and improve safety profiles of IASs, we introduced various sulfonamide groups linked by alkyl diamine chain to explore the entrance channel of non-nucleoside inhibitors binding pocket. 48 compounds were designed and synthesized to evaluate their anti-HIV-1 activities and reverse transcriptase inhibition activities. Especially, compound R₁₀L₄ was endowed with significant inhibitory activity towards wild-type HIV-1 (EC_50(WT) = 0.007 μmol/L, SI = 30,930) as well as a panel of single-mutant strains exemplified by L100I (EC₅₀ = 0.017 μmol/L, SI = 13,055), E138K (EC₅₀ = 0.017 μmol/L, SI = 13,123) and Y181C (EC₅₀ = 0.045 μmol/L, SI = 4753) which were superior to Nevirapine and Etravirine. Notably, R₁₀L₄ was characterized with significantly reduced cytotoxicity (CC₅₀ = 216.51 μmol/L) and showed no remarkable in vivo toxic effects (acute and subacute toxicity). Moreover, the computer-based docking study was also employed to characterize the binding mode between R₁₀L₄ and HIV-1 RT. Additionally, R₁₀L₄ presented an acceptable pharmacokinetic profile. Collectively, these results deliver precious insights for next optimization and indicate that the sulfonamide IAS derivatives are promising NNRTIs for further development.

Chronic liver disease (CLD) is one of the major public health problems,and liver fibrosis is a common feature of CLD.To date,there is no noninvasive method with high sensitivity and specificity for diagnosing and monitoring liver fibrosis in clinical practice.MRI T1ρ,a new technology developed in recent years,is sensitive to macromolecular (such as protein) composition and proton exchange between water and macromolecules,and therefore may be sensitive for the evaluation of liver fibrosis.This review introduces the principle and state of the art of liver MRI T1ρ technology,and summarizes the applications of MRI T1ρ for evaluation of liver fibrosis.