Low-dose nifedipine rescues impaired endothelial progenitor cell-mediated angiogenesis in diabetic mice.

It is of great clinical significance to develop potential novel strategies to prevent diabetic cardiovascular complications. Endothelial progenitor cell (EPC) dysfunction is a key contributor to diabetic vascular complications. In the present study we evaluated whether low-dose nifedipine could rescue impaired EPC-mediated angiogenesis and prevent cardiovascular complications in diabetic mice. Diabetes was induced in mice by five consecutive injections of streptozotocin (STZ, 60 mg·kg-1·d-1, i.p.). Diabetic mice were treated with low-dose nifedipine (1.5 mg·kg-1·d-1, i.g.) for six weeks. Then, circulating EPCs in the peripheral blood were quantified, and bone marrow-derived EPCs (BM-EPCs) were prepared. We showed that administration of low-dose nifedipine significantly increased circulating EPCs, improved BM-EPCs function, promoted angiogenesis, and reduced the cerebral ischemic injury in diabetic mice. Furthermore, we found that low-dose nifedipine significantly increased endothelial nitric oxide synthase (eNOS) expression and intracellular NO levels, and decreased the levels of intracellular O2.- and thrombospondin-1/2 (TSP-1/2, a potent angiogenesis inhibitor) in BM-EPCs of diabetic mice. In cultured BM-EPCs, co-treatment with nifedipine (0.1, 1 µM) dose-dependently protected against high-glucose-induced impairment of migration, and suppressed high-glucose-induced TSP-1 secretion and superoxide overproduction. In mice with middle cerebral artery occlusion, intravenous injection of diabetic BM-EPCs treated with nifedipine displayed a greater ability to promote local angiogenesis and reduce cerebral ischemic injury compared to injection of diabetic BM-EPCs treated with vehicle, and the donor-derived BM-EPCs homed to the recipient ischemic brain. In conclusion, low-dose nifedipine can enhance EPCs' angiogenic potential and protect against cerebral ischemic injury in diabetic mice. It is implied that chronic treatment with low-dose nifedipine may be a safe and economic manner to prevent ischemic diseases (including stroke) in diabetes.

Targeting Glutaminolysis to Treat Multiple Myeloma: An In Vitro Evaluation of Glutaminase Inhibitors Telaglenastat and Epigallocatechin-3-gallate.

BACKGROUND: Cancer is associated with metabolic changes from increased cell proliferation and growth. Compared to normal differentiated cells, MM cells use the glycolytic pathway even when adequate oxygen is present triggering "Glutamine addiction". OBJECTIVE: To investigate the single and combined effects of epigallocatechin-3-gallate (EGCG) and telaglenastat, a glutaminase inhibitor, on the proliferation and apoptosis of the multiple myeloma cell line KM3/BTZ. METHODS: KM3/BTZ cells were treated with different concentrations of telaglenastat and EGCG alone or in combination to investigate their effect on proliferation and apoptosis using the CCK8 assay, flow cytometry, and western blotting. The Chou-Talalay combination index analysis was used to explore the effect of telaglenastat combined with EGCG, while the Combination Index (CI) was calculated to analyze whether the combination of the two drugs had a synergistic effect. RESULTS: Telaglenastat and EGCG alone as well as in combination (5 µmol/L telaglenastat + 120 µmol/L EGCG) significantly inhibited the proliferation of KM3/BTZ cells compared to the inhibition effect of the control. Additionally, the combined treatment increased the proportion of KM3/BTZ cells in the G2 phase and decreased the proportion of cells in the G1 phase. The apoptosis rate of EGCG alone and the combined treatment was significantly higher than that of the control group. Bax protein expression was highest in the combined treatment group, whereas Bcl-2 expression was lowest, with the combined treatment group having the highest ratio of Bax/Bcl-2. CONCLUSION: Telaglenastat and EGCG act synergistically to inhibit cell proliferation and promote apoptosis in KM3/BTZ cells, possibly by targeting glutamine metabolism and glycolysis.

Addressing the problem of hook effect in sandwich lateral flow immunoassay: review and impact on future solutions / 中华检验医学杂志

Lateral flow immunoassay (LFIA) is a rapid detection technique that allows researchers to move the antigen-antibody reaction from a test tube or laboratory vessel to a test strip. Due to the chromatographic effect of the test strip, the solution would move to a specified direction based on the test and complete the whole antigen-antibody specific reaction. A qualitative judgment can be made with the naked eye by observing the color change of the reagent strip at a specific location. Because of its advantages of being fast, simple, specific, inexpensive, and requiring no specialized personnel, LFIA is now widely used in medical testing, food quality monitoring, environmental monitoring, agriculture and animal husbandry. A major bottleneck for the development of LFIA technology is the hook effect. This paper summarizes the current methods, means and research progresses to combat the hook effect, hoping to provide a strong technical reference for researchers to design test strips, select suitable nanoparticles, and achieve quantitative LFIA detection.

Research status and progress on the influence of high myopia on ocular structure and visual function / 中华眼底病杂志

High myopia has a high genetic tendency, it not only shows in the excessive elongation of the axial length, but also lends to the formation and progression of various eye lesions, such as peripheral retinopathy, optic disc changes, posterior staphyloma, and myopic maculopathy, due to the mechanical stretching of the axial length to the ocular structure. In addition, high myopia increases the risk of several complications, such as glaucoma, cataract, and corneal disease. All these pathological changes will affect visual function and lead to irreversible vision impairment and blindness in the future. Therefore, it is important to pay attention to screening for optic disc abnormalities and posterior staphyloma, and regular monitor the changes of fundus, intraocular pressure, and lens. At the same time, high myopia has an impact on personal life such as study, psychology, sport, and work, and can reduce the quality of life as well as increase the cost of health care. The clinic should pay more attention to high myopia, prevent and control the development of high myopia from an early stage, in order to minimize its impact on ocular structure and visual function as well as its hazard to personal life and society.

A systematic review of metabolomic studies on the mechanism of myopia / 中华实验眼科杂志

Myopia has become a global public health concern with its increasing prevalence.It is the interaction result of genetic and environmental factors.Exploration of the changes of metabolites in myopia is helpful to know new clues about its pathogenic mechanism.Metabolomics focuses on the integral analysis of all small molecular metabolites (relative molecular mass <1 000) which form a biological system and it is used as an effective tool to discover potential biomarkers.Metabolomic analysis of the myopic population could discover the metabolic changes related to myopia and screen the markers with potential biological significance, which can be used in the early diagnosis and treatment of myopia.It has been found that metabolites related to oxidative stress and inflammation play an important role in the development of myopia.Abnormal energy metabolism and amino acid metabolism are associated with myopic fundus changes.In addition, classical myopia-associated metabolites such as retinoic acid, dopamine and vitamin D, other metabolites such as melatonin, cyclic adenosine monophosphate and 5-hydroxy indole acetic acid, as well as multiple metabolic pathways such as fatty acid metabolism and mitochondrial metabolism are all closely related to myopia.This article systematically reviewed metabolomics researches on myopia, providing clues for better prevention and control of myopia in the future.

Multiple osteolytic primary peripheral T-cell bone lymphoma: the first case report.

Peripheral T-cell lymphoma accounts for about 10% of all cases of non-Hodgkin's lymphoma. However, less than 5% of patients with non-Hodgkin's lymphoma present with hypercalcaemia as the initial symptom, and less than 1% present with primary bone lesions. We herein describe a 76-year-old Chinese man who was diagnosed with primary bone adult T-cell lymphoma with extensive osteolysis, including bone loss in the radius, as the initial manifestation. He had developed severe generalised bone pain and an inability to raise his arms. X-ray examination revealed osteolytic destruction of the forearm with loss of the radial diaphysis. The patient was diagnosed with peripheral T-cell lymphoma based on his immunohistochemical results. He began treatment with the CHOPE chemotherapy regimen, which resulted in significant improvement of his bone pain.

The expression of PDCD1 and CD274 in T cells and macrophages correlated positively with COVID-19 severity

The immune responses underlying the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain unclear. To help understand the pathology of coronavirus disease 2019 (COVID-19) pandemics, public data were analyzed and the expression of PDCD1 (encoding PD-1) and CD274 (encoding PD-L1) in T cells and macrophages were identified to correlate positively with COVID-19 severity.

The change of COX-2 expression in rats with stress urinary incontinence and its significance / 医学研究生学报

Objective　There are a few researches on the mechanism of stress urinary incontinence (SUI). The article aimed to examine the changes of COX-2 expression in the urethra, vagina and urethral smooth muscle of SUI rat mode to evaluate the effect of estrogen on COX-2 expression. Methods　Sixty unbearing healthy female SD rats and fifteen male SD rats were gathered for spontaneous delivery. SUI rat models were constructed using expanded vagina, expanded vagina + ovariectomy respectively after delivery, which were expanded vagina group and expanded vagina + ovariectomy group. Six successfully modeled rats were chosen for the follow-up experiment. SD rats modeled after normal pregnancy were the control group. Sneezing experiment and urodynamic examination were used to examine the maximum bladder capacity (MBC) and abdominal leak point pressure (ALPP). Fluorescent quantitative PCR and western blot were applied to detect the expressions of COX-2 mRNA and protein, and immunohistochemistry was used to detect the expressions of COX-2 in urethra, vagina and urethral smooth muscle. Results Compared with control group, ALPP in two experimental groups were significantly decreased, among which ALPP in expanded vagina + ovariectomy group was significantly decreased in comparison to expanded vagina group(P<0.05). Compared with control group, the expressions of COX-2 mRNA and protein in expanded vagina group and expanded vagina+ovariectomy group were significantly higher, among which the figures in expanded vagina+ovariectomy group were significantly higher than those in expanded vagina group(P<0.05). The result of immunohistochemistry showed staining intensity integral expression of COX-2 in vaginal tissues of control group, expanded vagina group and expanded vagina+ovariectomy group were 0.50±0.54, 5.55±0.54, 9.33±0.81, so differences between any two groups were of statistical significance(P<0.05); staining intensity integral expression of COX-2 in urethral smooth muscle of control group, expanded vagina group and expanded vagina+ovariectomy group were 0.66±0.51, 5.33±0.51, 8.50±0.54, so differences between any two groups were of statistical significance (P<0.05). Conclusion The expression of COX-2 was related to the mechanism of SUI. The decrease of estrogen may increase the expression of COX-2 in SUI rats, which supports the treatment of SUI.

[Correlations between apparent diffusion coefficient in diffusion?weighted magnetic resonance imaging and molecular subtypes of invasive breast cancer masses].

OBJECTIVE: To study the correlation of apparent diffusion coefficient (ADC) measured by diffusion-weighted magnetic resonance imaging (MRI) with the molecular subtypes and biological prognostic factors of invasive breast cancer masses. METHODS: Breast MRI data (including dynamic enhanced and diffusion-weighted imaging) were collected from 64 patients with pathologically confirmed invasive breast cancer masses (a total of 69 lesions). The mean ADC values of the lesions were calculated and their correlations were analyzed with the 5 molecular subtypes of invasive breast cancer and the biological prognostic factors including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki-67 index. RESULTS: The ADC values did not differ significantly among the 5 molecular subtypes of invasive breast cancer masses (P>0.05) or among lesions with different ER, PR, or HER2 status (P>0.05). The mean ADC values were significantly higher in Ki-67-positive lesions than in the negative lesions (P=0.023 and negatively correlated with the expressions of Ki-67 (r=-0.249). CONCLUSION: ADC value can not be used to identify the molecular subtypes of invasive breast cancer masses or to evaluate the biological prognosis of the lesions, but its correlation with Ki-67 expression may help in prognostic evaluation and guiding clinical therapy of the tumors.

Association of serum FGF23 with abdominal aortic calcification and outcomes in maintenance hemodialysis patients / 中华肾脏病杂志

Objective To explore the association of fibroblast growth factor-23 (FGF23) with abdominal aortic calcification(AAC) and adverse outcomes in maintenance hemodialysis patients.Methods One hundred and fourteen cases of MHD patients were collected prospectively.Serum intact FGF23 was detected by ELISA.Abdomen lateral plain was used as a criteria to determine the abdominal aortic calcification and the abdominal aortic calcification score was counted.Logistic regression analysis was used to determine the risk factors of AAC.Kaplan-Meier analysis was applied to compare the survival rate among different groups and COX regression analysis was used to determine the association of FGF23 and mortality in MHD patients.Results Seventy-six patients present abdominal aortic calcification.The median of AACS was 4.0(0.0,11.0).The median level of FGF23 was 7277.4(2535.0,9990.8) pg/ml.The median follow-up duration was 72.0(67.8,72.8) months.During the follow-up,22 patients (19.3％) died of all-cause death and 17 cases (14.9％) died of cardiovascular diseases.Serum FGF23 level was positively correlated with AAC (r=0.285,P=0.002).Logistic regression analysis showed that longer age (OR=1.059,95％CI:1.020-1.100,P=0.003) and dialysis vintage (OR=I.009,95％CI 1.000-1.017,P=0.039),smoking history (OR=3.010,95％CI 1.177-7.696,P=0.021) and higher FGF23 level(OR=2.831,95％CI 1.010-7.937,P=0.048) were independent risk factors of moderate to severe AAC in MHD patients.Kaplan-Meier survival curves showed that the patients with AACS≥ 5 had significantly higher all-cause mortality(P=0.028) and CVD mortality (P=0.035) than those with AACS ＜ 5.However,the Kaplan-Meier analysis showed no significant difference regarding the level of serum FGF23 with the all-cause and CVD mortality.Cox regression demonstrated that FGF23 was not associated with increased mortality risk,neither in crude nor in multivariate adjusted models.Conclusions Abdominal aortic calcification had a high prevalence in MHD patients.The all-cause and CVD mortality was higher in patients with moderate to severe AAC.FGF23 was an independent risk factor of moderate to severe AAC,but it can't yet be a predictor for the allcause and CVD mortality of MHD patients.

Association of serum FGF23 with abdominal aortic calcification and outcomes in maintenance hemodialysis patients / 中华肾脏病杂志

Objective To explore the association of fibroblast growth factor-23 (FGF23) with abdominal aortic calcification(AAC) and adverse outcomes in maintenance hemodialysis patients.Methods One hundred and fourteen cases of MHD patients were collected prospectively.Serum intact FGF23 was detected by ELISA.Abdomen lateral plain was used as a criteria to determine the abdominal aortic calcification and the abdominal aortic calcification score was counted.Logistic regression analysis was used to determine the risk factors of AAC.Kaplan-Meier analysis was applied to compare the survival rate among different groups and COX regression analysis was used to determine the association of FGF23 and mortality in MHD patients.Results Seventy-six patients present abdominal aortic calcification.The median of AACS was 4.0(0.0,11.0).The median level of FGF23 was 7277.4(2535.0,9990.8) pg/ml.The median follow-up duration was 72.0(67.8,72.8) months.During the follow-up,22 patients (19.3％) died of all-cause death and 17 cases (14.9％) died of cardiovascular diseases.Serum FGF23 level was positively correlated with AAC (r=0.285,P=0.002).Logistic regression analysis showed that longer age (OR=1.059,95％CI:1.020-1.100,P=0.003) and dialysis vintage (OR=I.009,95％CI 1.000-1.017,P=0.039),smoking history (OR=3.010,95％CI 1.177-7.696,P=0.021) and higher FGF23 level(OR=2.831,95％CI 1.010-7.937,P=0.048) were independent risk factors of moderate to severe AAC in MHD patients.Kaplan-Meier survival curves showed that the patients with AACS≥ 5 had significantly higher all-cause mortality(P=0.028) and CVD mortality (P=0.035) than those with AACS ＜ 5.However,the Kaplan-Meier analysis showed no significant difference regarding the level of serum FGF23 with the all-cause and CVD mortality.Cox regression demonstrated that FGF23 was not associated with increased mortality risk,neither in crude nor in multivariate adjusted models.Conclusions Abdominal aortic calcification had a high prevalence in MHD patients.The all-cause and CVD mortality was higher in patients with moderate to severe AAC.FGF23 was an independent risk factor of moderate to severe AAC,but it can't yet be a predictor for the allcause and CVD mortality of MHD patients.

Renji acute kidney injury score is a useful tool to predict acute kidney injury after cardiac surgery / 中华肾脏病杂志

Objective To validate the effect of Renji acute kidney injury score (RAKIS) on predicting patients with acute kidney injury (AKI) after cardiac surgeries,and make comparison with Cleveland score,simplified renal index (SRI) and acute kidney injury following cardiac surgery (AKICS).Methods Patients undergoing open heart surgery from 2008/01/01 to 2010/10/31 in Renji hospital were enrolled,and their scores of those four scoring models were calculated.AKI patients were diagnosed by KDIGO,and those scores of AKI patients and non-AKI patients were compared.Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to decide the predictive values of those models.Results A total of 1126 patients were chosen in this cohort,with the average age of (58.43±14.88) years (rang from 18 to 88).The male to female ratio was 1.47:1.And 355(31.5％) patients were developed AKI.AKI stage Ⅰ,Ⅱ and Ⅲ were 65.4％,23.7％ and 11.0％ respectively.RAKIS was significantly higher in AKI patients than in non-AKI patients (17.5 vs 9.0,P ＜ 0.001).The AUCs of RAKIS to predict AKI,AKI Ⅱ-Ⅲ stages,renal replacement therapy (RRT)and in-hospital death were 0.818,0.819,0.800 and 0.784 respectively.The AUCs of Cleveland score and SRI were 0.659 to 0.710,lower than those of RAKIS and AKICS.AKICS had lower value for predicting AKI and AKI Ⅱ-Ⅲ stages (AUC 0.766 and 0.793),but good value in predicting RRT and inhospital death after surgery (AUC 0.804 and 0.835) as compared with RAKIS.Conclusions RAKIS is valid and accurate in the discrimination of KDIGO defined AKI patients,while for predicting the composite end point,AKICS may be more useful.

Association between serum soluble Klotho level and outcome in patients on maintenance hemodialysis / 中华肾脏病杂志

Objective To determine the relationship between serum soluble Klotho (sKL) level and adverse outcome in maintenance hemodialysis (MHD) patients.Methods One hundred and twenty nine cases of MHD patients were collected prospectively.Serum sKL was detected by ELISA.Abdomen lateral plain was used as a criterion to determine the abdominal aortic calcification.The abdominal aortic calcification score (AAC) was calculated.Cox regression analysis was used to determine the risk factor of cardiovascular death (CVD) in MHD patients.Kaplan-Meier showed the relationship between sKL and CVD in MHD patients.Results There were 27 cases (20.9％) of allcause death and 19 cases (14.7％) of cardiovascular death.The median sKL was 612.6(379.2-816.6) nig/L,and log[iPTH] was an independent factor of sKL concentration.Low sKL had high AAC and CVD death rate.Kaplan-Meier method showed that the all-cause death rate was similar between two groups,and CVD death rate increased significantly in low sKL patients (P=0.036).Cox regression indicated that lower sKL level was associated with high CVD death rate [OR=0.352,95％CI(0.127-0.977),P=0.045].After adjustment for the general condition,biochemical indicators,the relationship still existed [OR=0.331,95％ CI (0.117-0.933),P=0.037].In no or mild vascular calcification patients (AAC ≤4),compared with high sKL patients,low sKL patients had no significant difference rate in all-cause mortality.The CVD mortality was significantly higher in high sKL (P=0.035) compared with low sKL.In severe calcification group (AAC ＞ 4),all-cause death and CVD death rates were similar between different sKL groups (P=0.991 and 0.522,respectively).Conclusions Lower sKL has the high CVD death rate and sKL level decreasing is an independent risk factor for CVD death in MHD patients.The lower sKL concentration in MHD patients with no or mild calcification may predict CVD mortality.This study suggests that sKL levels may be helpful in predicting the outcome of patients with MHD.

Value of urine L-FABP and its combination with urine NGAL in early diagnosis of acute kidney injury after cardiac surgery in adults / 中华肾脏病杂志

Objective To investigate the value of urinary liver-type fatty acid-binding protein (L-FABP),neutrophil gelatinase-associated lipocalin (NGAL) and their combination in predicting the development and the severity of acute kidney injury (AKI) following cardiac surgery in adults. Methods Scr,urinary L-FABP and NGAL corrected by urine creatinine at preoperation,0 h and 2 h postoperative time points were examined.The differences of above indexes between AKI and non-AKI groups were compared.Receiver operating characteristic (ROC)curves and area under curves (AUC) were used to evaluate the diagnostic value of urinary L-FABP,NGAL and their combination for AKI. Results The cohort consisted of 109 patients,26(23.9％) developed AKI,and AKIN stage Ⅰ, Ⅱ and Ⅲ was 46.2％,34.6％ and 19.2％ respectively.Levels of urinary L-FABP and NGAL were significantly higher in AKI patients at 0 h and 2 h postoperatively.AUC to predict AKI or AKI stage Ⅱ-Ⅲ was 0.81 to 0.87 using either of the biomarkers.The performance of combining two biomarkers was better with AUC of 0.911 to 0.927. Conclusions Urinary L-FABP and NGAL increase at the early stage after cardiac surgery.Combination of these two biomarkers enhances the accuracy of the early diagnosis of postoperative AKI after cardiac surgery before a rise of Scr.

Acute kidney injury is a risk factor for the long-term prognosis of cardiac surgery / 中华肾脏病杂志

Objective To investigate the long-term prognosis and possible risk factors of acute kidney injury(AKI)following cardiac surgeries. Methods Clinical data of 941 patients undergoing open heart surgery from January 2004 to June 2007 were retrospectively analyzed.Survival and renal function of above patients were informed through telephone or clinic follow-up till February 2010.Long-term survival was analyzed using risk-adjusted Cox proportional hazards regression model. Results Of the 941 patients after cardiac surgery,275(29.2%)developed AKI and 666(70.8%)did not.Survival was worse in patients with AKI(67.8%vs 85.6%,P<0.01)and was proportional to its severity (AKIN 1,2 and 3 stages:70.7%,62.3%and 58.6%,P<0.01).Although 90.5% of patients had complete renal recovery after AKI at discharge of hospital,they still had an increased risk for death during follow-up compared with patients without AKI (69.6% vs 85.6%,P<0.01).In the Cox proportional hazards regression model,age(HR=2.238),anemia (HR=1.625),prolonged operation time (HR=1.153),AKI severity (HR=1.473)were independent risk factors for long-term prognosis after cardiac surgery.At the end of the follow-up,patients with AKI had statistically higher Scr than non-AKI patients(107.6 μmol/L vs 83.0 μmol/L,P=0.014),and among those AKI patients,34.0%progressed into CKD 3-5 stages,34.8%developed double serum creatinine. Conclusions AKI is a risk factor for the long-term prognosis of cardiac surgery.Patients with complete renal recovery after AKI still has an increased risk for death and poor renal function compared with patients without AKI.