Icariin,which belongs to the class of flavonoids,is the main active ingredient of the traditional tonic Chinese herb Epimedii Folium.Modern studies have shown that icariin has a wide range of effects on the male reproductive system.It has various pharmacological activities such as regulating cell proliferation and apoptosis,antioxidants,promoting testosterone secretion,improving erectile function,inhibiting prostate cancer cell migration,invasion,and regulating cell cycle.It has research value and application prospects in the field of urology and assisted reproduction.Therefore,Icariin's pharmacological effects and molecular mechanisms on the male reproductive system are reviewed in this paper combined with literature visualization analysis.It is expected to provide a theoretical basis for the therapeutic value development and application of icariin in male reproductive health.

Objective To establish a finite element model of the T2-L5 thoracolumbar spine and verify its validity,to provide numerical model support for exploring the dynamic response characteristics and injury mechanism under spinal impact loads.Methods A three-dimensional(3D)finite element model of the T2-L5 thoracolumbar spine was established based on CT scanning data.The load-rotation angle curve of the T12-L1 segment under different moments(flexion,extension,rotation,and lateral bending conditions)was calculated and compared with the data reported in the literature.Free-fall loads at different heights were applied to the finite element models of the T2-6,T7-11,and T12-L5 spine.The peak axial force and bending moment were obtained by finite element simulation analysis and compared with data reported in the literature.Results The maximum rotation angle of the T12-L1 finite element model was-2.24°-1.55° under moments in different directions,which was in good agreement with the literature data.The peak axial force of T2-6,T7-11,and T12-L5 spine finite element models subjected to different free-fall loads was 1.7-5.3 kN,1.3-5.5 kN,and 1.3-7.5 kN respectively,which were within the error range reported in the literature.Stress nephograms of the spine and intervertebral discs showed that the vertebral body was first stressed from the outer edge.The intervertebral disc was subjected to the main load by the nucleus pulposus,consistent with the actual spinal injury mechanism.Conclusions The T2-L5 spine model established in this study can correctly simulate the biomechanical behavioral characteristics of the spine under different working conditions,and the analysis results are effective.

Mild hypothermia, as a common means of intraoperative nerve protection, has been used in clinical practice. Compared with the traditional methods such as freezing helmet and nasopharyngeal cooling, hypothermic blood perfusion is considered to be a promising treatment for mild hypothermia, but it lacks experimental and theoretical verification of its cooling effect. In this study, the commercial finite element simulation software COMSOL combined the Pennes equation with the cerebrovascular network model to construct a new simplified human brain model, which was further used to simulate the cooling process of cerebral hypothermic blood perfusion. When the hypothermic blood perfusion was 33 ℃, the human brain could enter the mild hypothermic state within 4 minutes. By comparing with helmet cooling, the feasibility and efficiency of the blood perfusion scheme were verified. By comparing with the calculation results based on Pennes equation, the rationality of the model constructed in this study were verified. This model can non-intrusively predict the changes of brain temperature during surgery, and provide a reference for the setting of treatment parameters such as blood temperature, so as to provide personalized realization of safer and more effective mild hypothermia neuro protection.
Humans ; Hypothermia, Induced/methods* ; Hypothermia ; Hemoperfusion ; Brain/physiology* ; Body Temperature

Objective:To investigate whether it is by regulating interleukin 1β ( IL-1β) gene expression that androgen receptor (AR) in macrophages affects hyperphosphate-induced vascular smooth muscle cell calcification. Methods:The chromatin immunoprecipitation (ChIP) experiment was used to determine whether AR was bound to the androgen receptor element (ARE) sequence of IL-1β promoter in THP-1 cells. Whether the AR regulated IL-1β gene expression was detected by luciferase assay experiments. AR of THP-1 cells was silenced and transfected by lentivirus with vector or shRNA. Flow cytometry was used to select positive transfected cells THP-1ARsc (control) and THP-1ARsi (AR silencing) with fluorescent markers. Western blotting was used to detect AR protein levels of THP-1ARsc (control) and THP-1ARsi cells (AR silencing in monocytes). Macrophages MФARsc (control) or MФARsi (AR silencing) were induced by 50 ng/ml phorbol ester. Enzyme-linked immunosorbent assay was used to detect IL-1β expression levels of MФARsc or MФARsi conditioned medium. The human aortic smooth muscle cells (HASMC) were cultured in MФARsc or MФARsi conditioned medium with phosphate (2.5 mmol/L final concentration of sodium dihydrogen phosphate), and Alizarin red S staining was used to analyze HASMC calcification degree. Western blotting was used to detect the expression levels of RUNX2 (osteoblast marker) and SM22α (HASMC marker), and neutralization assay was performed to test IL-1β-mediating effect of macrophages AR on HASMC calcification. Results:AR was bound to ARE sequence of IL-1β promoter and regulated IL-1β gene expression. The expression level of IL-1β protein in conditioned medium of MФARsi cells decreased significantly compared to MФARsc cells ( P<0.001). Compared with MФARsc conditioned medium group, HASMC calcium deposition in MФARsi conditioned medium group decreased significantly, RUNX2 protein decreased and SM22α protein increased (all P<0.05). The degree of HASMC calcification in the MФARsi conditioned medium+IgG antibody group decreased than that in the MФARsc conditioned medium+IgG antibody group significantly, and the degree of HASMC calcification in the MФARsc conditioned medium+IL-1β antibody group decreased significantly than that in the MФARsc conditioned medium+IgG antibody group; while the degree of HASMC calcification in the MФARsi conditioned medium+IgG antibody group and MФARsi conditioned medium+IL-1β antibody group decreased than that in the MФARsc conditioned medium+IL-1β antibody group (all P<0.05). Conclusions:Macrophage AR regulates IL-1β expression by binding to ARE sequence within IL-1β promoter, and IL-1β mediates the effect of macrophage AR on hyperphosphate-induced HASMC calcification.

Objective:To systematically evaluate the predictive value of neutrophil-lymphocyte ratio (NLR) in acute kidney injury (AKI).Methods:All studies about the predictive effect of NLR on AKI were searched in the National Medical Library of the United States PubMed Database, the Embase database in the Netherlands, the Chinese Biology Medicine disc (CBMdisc) and the Chinese Evidence Based Medicine Cochrane Centre Database (CEBM/CCD). The data updated by October 2020, and regardless of language, region or whether blind method was used. Two authors independently extracted data and evaluated the quality of the studies. Data extracted from the studies were analyzed with RevMan 5.3 to assess the predictive value of NLR on AKI. A subgroup Meta-analysis was conducted to assess the predictive value of NLR on AKI according to different countries, different disease types (cardiovascular surgery, infectious diseases, other diseases including burns, cirrhosis, and emergency), and different sample sizes (≤ 300 cases and > 300 cases). The publication bias of included studies about the predictive effect of NLR on AKI were assessed by funnel plots.Results:A total of 11 studies were included in this Meta-analysis, including 4 997 patients, 1 308 patients in AKI group, and 3 689 patients in non-AKI group. The Meta-analysis results showed that: increased NLR had predictive value for the occurrence of AKI [mean difference ( MD) = 2.73, 95% confidence interval (95% CI) was 1.78-3.68, P < 0.000 01]. Subgroup analysis showed that increased NLR had predictive value for the occurrence of AKI in patients from Southeast Asia ( MD = 4.04, 95% CI was 1.09-6.99, P = 0.007) and Eurasia ( MD = 2.51, 95% CI was 1.12-3.90, P = 0.000 4). Increased NLR had predictive value for the occurrence of AKI in patients undergoing cardiovascular surgery ( MD = 0.77, 95% CI was 0.34-1.20, P = 0.000 4), infectious diseases ( MD = 4.74, 95% CI was 1.51-7.96, P = 0.004) and other diseases ( MD = 8.53, 95% CI was 6.26-10.80, P<0.000 01). Increased NLR had predictive value for the occurrence of AKI in studies with a sample size of ≤ 300 cases ( MD = 6.02, 95% CI was 4.90-7.14, P <0.000 01) and > 300 cases ( MD = 1.32, 95% CI was 0.61-2.03, P = 0.000 3). There was no significant publication bias in the included studies assessed by funnel plots. Conclusion:NLR is an important predictive tool for AKI.

Objective:To investigate the effects of abdominal aortic calcification (AAC) progression on outcomes in maintenance hemodialysis (MHD) patients.Methods:Patients who were on MHD between Jun. 2014 and Oct. 2014 in the dialysis center of the Second Hospital of Tianjin Medical University and finished the AAC examination at baseline and two years later were included prospectively. The progression of AAC by AAC score (AACs) at baseline and two years later was evaluated. According to the change of AACs, the patients were divided into rapid AAC progression group and non-rapid AAC progression group. The effect of AAC progression on outcomes in MHD patients in the follow-up period was investigated. Kaplan-Meier analysis was used to compare their survival rates. Multivariable Cox regression model was used to determine the risk factors of all-cause mortality, cardiovascular mortality and cardiovascular events.Results:A total of 111 MHD patients were included, including 51 males and 60 females, aged (52.24±12.69) years. Baseline AAC prevalence was 45.9% (51/111), and median AACs was 0 (0, 5); After 2 years, the prevalence of AAC was 78.4% (87/111), and the median AACs was 6 (2, 11). There were 54 cases in the AAC rapid progression group (AACs change value>2) and 57 cases in the non-rapid AAC progression group (AACs change value≤2). The median follow-up duration was 27.9(27.1, 28.0) months. Kaplan-Meier analysis showed that patients in rapid AAC progression group had a higher risk of mortality as compared to patients in non-rapid AAC progression group (Log-rank χ2=5.695, P=0.017). Multivariate Cox regression analysis demonstrated that high baseline AACs ( HR=1.135, 95% CI 1.001-1.286, P=0.048), hypoalbuminemia ( HR=0.789, 95% CI 0.640-0.972, P=0.026) were independent risk factors for all-cause mortality in MHD patients. High baseline AACs ( HR=1.187, 95% CI 1.038-1.356, P=0.012), low spKt/V ( HR=0.103, 95% CI 0.013-0.801, P=0.030) were independent risk factors for cardiovascular mortality in MHD patients. Low spKt/V ( HR=0.018, 95% CI 0.003-0.115, P<0.001), hypoalbuminemia ( HR=0.736, 95% CI 0.608-0.890, P=0.002) were independent risk factors for cardiovascular events in MHD patients. Conclusions:Abdominal aortic calcification progression may increase the risk of cardiovascular events and death in MHD patients. Severity of AAC, adequacy of dialysis, and nutritional status are predictors of outcomes in MHD patients.

Objective To determine the effects of ginkgolide A (GA) in a neutrophil-predominant murine model of asthma and explore underlying mechanisms. Methods Thirty-five female BALB/c mice were randomly divided into sham operation group (Sham group), asthma group, dexamethasone intervention control group (DEX group), low dose GA intervention group (L-GA group) and high dose GA intervention group (H-GA group), with 7 mice in each group. The asthma model was induced by intraperitoneal injection of 20 μg ovalbumin (OVA) and 75 μL Fluorine complete adjuvant (FCA) on day 0, 14 and 21, and challenged 30 minutes with 5% OVA atomization on days 22-24 consecutively; phosphate buffer (PBS) was sensitized and stimulated in Sham group. The mice in L-GA group and H-GA group were intraperitoneally injected with GA of 40 mg/kg and 80 mg/kg at 1 hour before each challenge, while the mice in DEX group were intraperitoneally injected with dexamethasone of 1 mg/kg. After 24 hours of the last OVA stimulation, the airway resistance was measured at the time of 0, 3, 6, 12, 25, 50 g/L acetylmethacholine aerosol stimulation. The total number of cells and cell classification in bronchoalveolar lavage fluid (BALF) were counted. The transforming growth factor-β1 (TGF-β1) and interleukin-17 (IL-17) in BALF were detected by enzyme linked immunosorbent assay (ELISA). The proportion of helper T cell 17 (Th17) to CD4+ T cell in lung tissue was detected by flow cytometry, and the pathological characteristics of lung tissue were evaluated. Results Compared with the Sham group, the airway hyper responsiveness (AHR), the total cells, the neutrophil counts, the levels of TGF-β1, IL-17 in BALF, and the proportion of Th17 cells in the lung tissue in the asthma group were significantly increased, obvious inflammatory cell infiltration and collagen fiber deposition around airway were observed, and airway inflammation score and mucus score were significantly increased. Compared with the asthma group, low and high doses of GA significantly reduced AHR, and there was a significant difference in airway resistance at the time of 50 g/L acetylmethacholine stimulation (cmH2O·s-1·mL-1: 5.29±0.40, 3.99±0.57 vs. 7.34±0.77, both P < 0.05); the total cells, neutrophil counts, and levels of TGF-β1, IL-17 in BALF, and the proportion of Th17 cells in lung tissue were significantly decreased [total cells count (×104/L): 21.00±1.00, 17.00±1.02 vs. 27.50±2.50; neutrophil count (×104/L): 12.600±0.600, 10.610±0.210 vs. 16.875±1.125; TGF-β1 (ng/L): 371.40±107.80, 289.60±70.76 vs. 551.90±68.34; IL-17 (ng/L): 60.75±11.79, 44.77±7.09 vs. 122.50±38.87; the proportion of Th17 cells: (5.53±0.40)%, (3.76±1.10)% vs. (8.30±1.19)%, all P < 0.05]; inflammatory cell infiltration around the airway and mucus secretion was significantly reduced, airway inflammation score and mucus score were significantly decreased (2.16±0.28, 1.16±0.28 vs. 3.77±0.25; 1.33±0.58, 1.17±0.29 vs. 3.67±0.58, all P < 0.05). The AHR, total cells, neutrophil counts, and IL-17 level in BALF, the proportion of Th17 cells in lung tissue and airway inflammation score decreased more obviously with the increase of GA dosage (all P < 0.05). For index mentioned above, no significant differences were observed between DEX group and asthma group. Conclusion GA treatment was effective in a murine model of neutrophil-predominant asthma via inhibiting response in the immune cells Th17.

Objective To assess the effect of fenretinide (4-HPR) on proliferation,apoptosis and migration of B16F10 and A375 melanoma cells,and to evaluate the effect of liposomes and RGD peptidemodified liposomes on its uptake and therapeutic effects.Methods A film-hydration method was used to prepare 4-HPR liposomes (4-HPRL),which were modified with RGD peptide to prepare RGD-4-HPRL,and the concentration,particle size,electric potential,drug loading capacity and encapsulation efficiency were measured for 4-HPRL and RGD-4-HPRL.In vitro cultured B16F10 and A375 cells were divided into several groups:4-HPR group,4-HPRL group and RGD-4-HPRL group treated with Dulbecco's minimum essential medium (DMEM) containing 4-HPR bulk drug,4-HPRL and RGD-4-HPRL respectively at the same concentration of 4-HPR,and control group treated with culture solution at the same volume.After different durations of treatment,cell counting kit-8 (CCK8) assay was performed to evaluate cellular proliferative activity,annexin V/propidium iodide staining to detect apoptosis,and scratch wound healing assay to evaluate the effect of drug treatment on cell migration ability.Then,4-HPR was replaced by coumarin 6 (C6) to prepare C6 liposomes (C6L) and RGD-C6L,and flow cytometry was conducted to evaluate C6 uptake by B16F10 cells.Statistical analysis was carried out with SPSS22.0 software by one-way analysis of variance (ANOVA) for the comparison among several groups and t test for the comparison between two groups.Results The concentration of 4-HPR in the prepared 4-HPRL solution was over 1 300 mg/L.The encapsulation efficiency and drug loading capacity of 4-HPRL were (95.51 ± 1.22)％ and (7.27 ± 0.11)％ respectively,and those of RGD-4-HPRL were (95.82 ± 0.81)％ and (7.14 ± 0.13)％ respectively.The particle size distribution of 4-HPRL and RGD-4-HPRL was uniform,and their average particle size was below 100 nm.CCK8 assay showed that 4-HPR could markedly inhibit the proliferative activities of B16F10 and A375 cells.The cell proliferation inhibition rate of 4-HPRL was higher than that of 4-HPR at the same concentration of 4-HPR (P ＜ 0.01),and the inhibition rate of RGD-4-HPRL was higher than that of 4-HPRL (P ＜ 0.01 or P ＜ 0.05) and 4-HPR (P ＜ 0.01).As annexin V/propidium iodide apoptosis assay showed,when the concentration of 4-HPR was 10 mg/L,the total apoptosis rates of B16F10 cells in the control group,4-HPR group,4-HPRL group and RGD-HPRL group were (4.44 ± 0.35)％,(28.33 ± 0.66)％,(46.43 ± 0.77)％ and (51.33 ± 0.37)％ respectively.When the concentration of 4-HPR was 20 mg/L,the total apoptosis rates of A375 cells in the above 4 groups were (4.97 ± 0.62)％,(16.68 ± 3.81)％,(32.62 ± 1.24)％ and (44.85 ± 4.92)％ respectively.The apoptosis rates of B16F10 and A375 cells were significantly higher in the 4-HPRL group than in the 4-HPR group (both P ＜ 0.01),and higher in the RGD-4-HPRL group than in the 4-HPRL group (both P ＜ 0.01) and 4-HPR group (both P ＜0.01).Scratch wound healing assay showed that 4-HPR could inhibit scratch healing and migration of B16F10 and A375 cells,and the inhibitory effects of 4-HPRL and RGD-4-HPRL were distinctly superior to those of 4-HPR bulk drug.C6 uptake assay revealed that the fluorescence intensity of C6 in B16F10 cells in the control group,C6 group,C6L group and RGD-C6L group were 2.15 ± 0.28,8.56 ± 0.36,20.48 ± 0.13 and 22.55 ± 0.07 respectively,and there were significant differences between the 4 groups (F =67 194.186,P ＜ 0.01).Additionally,the fluorescence intensity of C6 was significantly higher in the C6L group and RGD-C6L group than in the C6 group (both P ＜ 0.01),and higher in the RGD-C6L group than in the C6L Group (P ＜ 0.01).Conclusions 4-HPR can inhibit the proliferation and migration of A375 and B16F10 cells,and induce their apoptosis.Liposomes and RGD-targeted liposomes can markedly enhance the effect of 4-HPR on melanoma cells.

One hundred and twenty maintenance hemodialysis patients with secondary hyperparathyroidism were randomly assigned to receive cinacalce,calcitriol or combination of cinacalce and cacitriol for treatment,with 40 cases in each group.Patients were followed up for 12 months;and the blood tests,echocardiography,examinations for osteoporosis and soft tissue calcification were performed every month.After 3 months of treatment,the serum levels of parathyroid hormone were decreased in all three groups (P ＜ 0.01);while the parathyroid hormone decreased more markedly with less influence on serum calcium and phosphorus levels in combination group.There were no significant changes in alkaline phosphatase,osteoporosis and cardiac valve calcification after treatment,compared with before treatment.There were no cases of hypercalcemia and hypocalcemia appearing in combination group after treatment.The study indicates that the combination of cinacalcet with calcitriol has better therapeutic effect for treatment of secondary hyperparathyroidism in maintenance dialysis patients.

Objective To evaluate the relationship between low vitamin D level and metabolic syndrome (MS) in maintenance hemodialysis (MHD) patients.Methods A total of 143 patients who had received MHD from Jan 2016 to Jan 2017 in the dialysis center of our hospital were enrolled.Their clinical and laboratory data were collected.The serum 25(OH)D3 levels were measured by chemiluminescence instrument.According to the levels of 25(OH)D3,patients were divided into three groups:sufficient group (＞ 30 μg/L),insufficient group (15-30 μg/L) and deficient group (＜ 15 μg/L) to explore how the 25(OH)D3 were associated with MS and abnormal metabolic parameters,including central obesity,raised triglycerides (TG),reduced high-density lipoprotein cholesterol (HDL-C),raised systolic blood pressure (SBP),raised diastolic blood pressure (DBP) and increased fasting blood glucose (FBG).The risk factors of MS and abnormal metabolic factors were analyzed by multivariate logistic regression model.Results Among the 143 MHD patients,the median of serum 25(OH)D3 was 24.30(12.90,29.50) μg/L and the prevalence of MS was 45.45％(65 cases).Among 3 groups the prevalence of MS,the abdominal circumference and the serum TG showed statistical differences,and they increased with the severity of 25(OH)D3 deficiency (all P ＜ 0.05).The body mass indexes of patients in the insufficient and deficient groups were elevated compared with that in the sufficient group (all P ＜ 0.05).SBP,TG and FBG in deficient group were significantly higher but HDL-C was lower than those in the other two groups (all P ＜ 0.05).The more abnormal metabolism existed,the lower 25(OH)D3 levels patients had (H=61.316,P＜0.001).Multivariate logistic regression analysis showed that in MHD patients low 25(OH)D3 negatively correlated with MS (OR=0.889,95％CI 0.846-0.934,P ＜ 0.001) and abnormal metabolic factors central obesity (OR=0.913,95％CI 0.874-0.953,P ＜ 0.001),raised TG (OR=0.932,95％ CI 0.894-0.971,P=0.001),reduced HDL-C (OR=0.901,95％ CI 0.845-0.959,P=0.001),raised SBP (OR=0.898,95％CI 0.847-0.953,P＜ 0.001) and raised FBG (OR=0.956,95％CI 0.920-0.994,P=0.024).Conclusions The prevalence of MS is high in MHD patients and low levels of 25(OH)D3 may be an independent risk factor for MS and abnormal metabolic factors.