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Background@#and Purpose To explore the causal relationships of elements of the exposome with ischemic stroke and its subtypes at the omics level and to provide evidence for stroke prevention. Methods We conducted a Mendelian randomization study between exposure and any ischemic stroke (AIS) and its subtypes (large-artery atherosclerotic disease [LAD], cardioembolic stroke [CE], and small vessel disease [SVD]). The exposure dataset was the UK Biobank involving 361,194 subjects, and the outcome dataset was the MEGASTROKE consortium including 52,000 participants. @*Results@#We found that higher blood pressure (BP) (systolic BP: odds ratio [OR], 1.02; 95% confidence interval [CI], 1.01 to 1.04; diastolic BP: OR, 1.03; 95% CI, 1.01 to 1.05; pulse pressure: OR, 1.03; 95% CI, 1.00 to 1.06), atrial fibrillation (OR, 1.18; 95% CI, 1.13 to 1.25), and diabetes (OR, 1.13; 95% CI, 1.07 to 1.18) were significantly associated with ischemic stroke. Importantly, higher education (OR, 0.69; 95% CI, 0.60 to 0.79) decreased the risk of ischemic stroke. Higher systolic BP (OR, 1.06; 95% CI, 1.02 to 1.10), pulse pressure (OR, 1.08; 95% CI, 1.02 to 1.14), diabetes (OR, 1.28; 95% CI, 1.13 to 1.45), and coronary artery disease (OR, 1.58; 95% CI, 1.25 to 2.00) could cause LAD. Atrial fibrillation could cause CE (OR, 1.90; 95% CI, 1.71 to 2.11). For SVD, higher systolic BP (OR, 1.04; 95% CI, 1.00 to 1.07), diastolic BP (OR, 1.06; 95% CI, 1.01 to 1.12), and diabetes (OR, 1.22; 95% CI, 1.10 to 1.36) were causal factors. @*Conclusions@#The study revealed elements of the exposome causally linked to ischemic stroke and its subtypes, including conventional causal risk factors and novel protective factors such as higher education.
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For quantitative analysis of related substances in TSD-1 active pharmaceutical ingredient, structures of prepared impurities were confirmed by NMR and UHPLC-MS, and a high performance liquid chromatographic method was established to determine the related substances in TSD-1. The analytical column was an Agilent ZORBAX Eclipe XDB-C8 (250 mm × 4.6 mm, 5 µm). The mobile phase A was 50 mmol·L-1 ammonium acetate solution (adjusted pH to 5.8 with acetic acid) and the mobile phase B was acetonitrile. The whole run was carried out by gradient elution at a flow rate of 1.0 mL·min-1. The detection wavelength was set at 240 nm and the column temperature was 30 ℃. The resolutions among peaks of TSD-1, impurity A, impurity B, TSD-D, and TSD-F were good. The calibration curves (n = 7) of TSD-1, impurity A, impurity B, TSD-D and TSD-F were linear in their respective weight ranges of 0.242-48.4 µg·mL-1 (r = 1.000 0), 0.244-9.75 µg·mL-1 (r = 0.999 9), 0.244-4.80 µg·mL-1 (r = 0.999 9), 0.254-1.02 µg·mL-1 (r = 0.999 9), and 0.247-0.987 µg·mL-1 (r = 0.999 9). The lower limits of quantitation were 0.244, 0.244, 0.254, and 0.247 µg·mL-1 for impurity A, impurity B, TSD-D, and TSD-F, respectively, and the average recovery of each impurity ranged from 99.08% to 103.00% with high accuracy. TSD-D and TSD-F were not detected in the three batches of TSD-1 active pharmaceutical ingredients, and impurity A and impurity B were not detected beyond the limit. The established HPLC method is simple, accurate, and suitable for determination of related substances of TSD-1, which can provide a valuable reference for the subsequent development of TSD-1.
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Anatomy is a subject in the field of medical morphology. Traditional experimental teaching of anatomy is confronted with the disadvantages of poor experimental conditions, high specimen loss rate and insufficient two-way interaction between teachers and students. Under the background of "Internet", we explore the development of new anatomy experimental teaching, by providing electronic screen and physical display platform, VR camera and elevating anatomic table, the entity learning space is created. And through the deployment of intelligent teaching platform and digital human anatomy system, the virtual learning space is built. Upon this, we have built the smart lab for online and offline integration based on big data, and also explored a new type of anatomy experiment teaching, aiming to promote the anatomy experiment teaching to meet the needs of modern medical education, and to provide reference for experimental teaching reform and overall wisdom campus construction.
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Background@#and Purpose The present study aimed to compare the efficacy and tolerability of different blood pressure (BP)-lowering strategies. @*Methods@#Randomized controlled trials that compared various antihypertensive treatments and stroke outcomes were included. Eligible trials were categorized into three scenarios: single or combination antihypertensive agents against placebos; single or combination agents against other agents; and different BP-lowering targets. The primary efficacy outcome was the risk reduction pertaining to strokes. The tolerability outcome was the withdrawal of drugs, owing to drug-related side effects (PROSPERO registration number CRD42018118454 [20/12/2018]). @*Results@#The present study included 93 trials (average follow-up duration, 3.3 years). In the pairwise analysis, angiotensin-converting enzyme inhibitors (ACEis) and beta-blockers (BBs) were inferior to calcium channel blockers (CCBs) (odds ratio [OR], 1.123; 95% confidence interval [CI], 1.008 to 1.252) (OR, 1.261; 95% CI, 1.116 to 1.425) for stroke prevention, BB was inferior to angiotensin II receptor blockers (ARB) (OR, 1.361; 95% CI, 1.142 to 1.622), and diuretics were superior to ACEi (OR, 0.871; 95% CI, 0.771 to 0.984). The combination of ACEi+CCB was superior to ACEi+diuretic (OR, 0.892; 95% CI, 0.823 to 0.966). The network meta-analysis confirmed that diuretics were superior to BB (OR, 1.34; 95% CI, 1.11 to 1.58), ACEi+diuretic (OR, 1.47; 95% CI, 1.02 to 2.08), BB+CCB (OR, 2.05; 95% CI, 1.05 to 3.79), and renin inhibitors (OR, 1.87; 95% CI, 1.25 to 2.75) for stroke prevention. Regarding the tolerability profile, the pairwise analysis revealed that ACEi was inferior to CCB and less tolerable, compared to the other treatments. @*Conclusions@#Monotherapy using diuretics, CCB, or ARB, and their combinations could be employed as first-line treatments for stroke prevention in terms of efficacy and tolerability.
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To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer's disease (sAD) and pathological biomarkers in cerebrospinal fluid (CSF), 462 sAD patients and 463 age-matched cognitively normal (CN) controls were genotyped for 35 single-nucleotide polymorphisms (SNPs) that are significantly associated with sAD. Then, the alleles found to be associated with sAD were used to build polygenic risk score (PRS) models to represent the genetic risk. Receiver operating characteristic (ROC) analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at onset. We measured the CSF levels of Aβ42, Aβ42/Aβ40, total tau (T-tau), and phosphorylated tau (P-tau) in a subgroup (60 sAD and 200 CN participants), and analyzed their relationships with the PRSs. We found that 14 SNPs, including SNPs in the APOE, BIN1, CD33, EPHA1, SORL1, and TOMM40 genes, were associated with sAD risk in our cohort. The PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls, and were able to predict the incidence rate of sAD and age at onset. Furthermore, the PRSs were correlated with the CSF levels of Aβ42, Aβ42/Aβ40, T-tau, and P-tau. Our study suggests that PRS models hold promise for assessing the genetic risk and development of AD. As genetic risk profiles vary among populations, large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.
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BACKGROUND@#Recent studies suggest that a healthy diet helps to prevent the development of Alzheimer disease (AD). This study aimed to investigate whether spicy food consumption is associated with cognition and cerebrospinal fluid (CSF) biomarkers of AD in the Chinese population.@*METHODS@#We enrolled 55 AD patients and 55 age- and gender-matched cognitively normal (CN) subjects in a case-control study, as well as a cohort of 131 participants without subjective cognitive decline (non-AD) in a cross-sectional study. Spicy food consumption was assessed using the Food Frequency Questionnaire (FFQ). Associations of FFQ scores with cognition and CSF biomarkers of AD were analyzed.@*RESULTS@#In the case-control study, spicy food consumption was lower in AD patients than that in CNs (4.0 [4.0-8.0] vs. 8.0 [4.5-10.0], P < 0.001); FFQ scores were positively associated with Mini-Mental Status Examination scores in the total sample (r = 0.218, P = 0.014). In the cross-sectional study, the association between spicy food consumption and cognition levels was verified in non-AD subjects (r = 0.264, P = 0.0023). Moreover, higher FFQ scores were significantly associated with higher β-Amyloid (1-42) (Aβ42) levels and lower phospho-tau/Aβ42 and total tau/Aβ42 ratios in the CSF of non-AD subjects (P < 0.05).@*CONCLUSION@#Spicy food consumption is closely related to higher cognition levels and reversed AD biomarkers in the CSF, suggesting that a capsaicin-rich diet might have the potential to modify the cognitive status and cerebral pathologies associated with AD.
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Humans , Alzheimer Disease , Amyloid beta-Peptides , Biomarkers , Case-Control Studies , Cognition , Cross-Sectional Studies , Peptide Fragments , tau ProteinsABSTRACT
Indoleamine 2,3-dioxygenase 1 (IDO1) is a key enzyme in the human tryptophan metabolism pathway, which can mediate tumor immune response. An IDO1 inhibitor would be a potential cancer immunotherapy drug. Based on the recently reported crystal of an IDO1 protein-inhibitor complex (PDBID: 6AZV), the structure of reported inhibitor, and by analyzing the interaction mode between the inhibitor and IDO1, new inhibitor molecules were designed and synthesized. All structures were confirmed by spectral data. Preliminary activity studies showed that compounds containing an azabiphenyl tetrazole structure (B1 and B2) and biphenyl compounds containing a sulfonamide structure (D1, D2 and D3) had excellent inhibitory activity of IDO1 at the enzyme and cell level, and were comparable or even better than the control drug INCB24360.
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Cranioplasty is one of the common operations in neurosurgery at present. It can not only restore the integrity of the cranial cavity and meet the aesthetic requirements, but also relieve the clinical symptoms of headache, dizziness, fatigue, mood swings and so on. Cranioplasty can improve cerebral hemodynamics to promote the recovery of neurological function. The researches on relationship between cerebral hemodynamics and clinical symptoms were reported in recent years. However, the results were not consistent. Cranioplasty is recommended as early as permit.
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OBJECTIVE To investigated the regulatory effect of paeoniflorin-6'-O-benzene sulfonate (CP-25) on B cell activating factor (BAFF)/BAFF receptor-nuclear factor of kappa B (NF-κB) signaling in B cell of collagen induced-arthritis (CIA) mice. METHODS Mice CIA was induced by injection of typeⅡcollagen (CⅡ). The arthritis index (AI) and swollen joint count (SJC) were assessed, and histopathology of spleen and joints were observed. The percentage of B cells subsets, BAFF receptor expressions were analyzed by flow cytometry. BAFF and immunoglobulin (Ig) levels were measured by protein antibody array. The expressions of TRAF2, MKK3, MKK6, p-P38, and p-NF-κB65 in NF-κB signaling mediated by BAFF were analyzed by western blot. RESULTS CP-25 decreased AI and SJC, restored abnormal weights, reduced thymus index and spleen index, inhibited T/B cells proliferation, alleviated the histopathology of spleen and joints in CIA mice. CP-25 also reduced high levels of serum BAFF and immunoglobulin, decreased CD19+B cells, CD19+CD27+B cells, and CD19-CD27+CD138+ plasma cells, inhibited BAFFR and TACI expressions, decreased the expressions of TRAF2, MKK3, MKK6, p-P38, and p-NF-κB65. Compared with biological agents etanercept and rituximab, CP-25 restored high T cells proliferation and percentages of B subsets to normal level, and recovered the high levels of IgA, IgD, IgG1, IgG2a and high expressions molecules in NF- κB signaling to normal levels. The action intensity of rituximab and etanercept was more strong than CP- 25. The inhibitor effects of rituximab and etanercept on AI and SJC, thymus index, proliferation of T cells and B cells subsets were strong, and down-regulated the indexes to under normal levels. CONCLUSION CP-25 might be a promising anti- inflammatory immune and regulation drug, which alleviated CIA and regulated the functions of B cells through BAFF/BAFF receptor-NF-κB signaling.
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?AIM:To compare the changes of the contrast sensitivity after LASIK with femtosecond laser and microkeratome and to explore the influence of different methods making corneal flap on visual quality.? METHODS: There were 212 eyes in 106 myopes underwent excimer operation . According to the different methods of operation, they were divided into two groups:microkeratome group ( SBK group ) and femtosecond laser group ( FS group) . FS group: a total of 112 eyes in 56 patients received LASIK with femtosecond laser. SBK group: a total of 100 eyes in 50 patients received LASIK with microkeratome. Contrast sensitivity was detected preoperatively, and 1wk, 3mo postoperatively and compared between the two groups.? RESULTS: At 1wk after operation, the contrast sensitivity under photopic environment decreased in the two groups, compared with those before operation ( P0. 05). No statistical significant difference was found in contrast sensitivity under photopic environment at 1wk, 3mo between the two groups ( P>0. 05 ). At 1wk after the operation, the contrast sensitivity under scotopic environment decreased in both groups compared with those before operation ( P0. 05). After 1wk, contrast sensitivity with glare stimulation in both groups decreased, compared with those before operation ( P0. 05).?CONCLUSION:LASIK with femtosecond laser can get a better visual quality than LASIK with microkeratome.
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Objective To explore the mechanism that gold nanorods trigger apoptosis in cancer cells.Methods Gold nanorods was synthesized by gold seed growing method, and its characterization was detected; gold nanorods on cell proliferation-toxicity were evaluated by CCK-8 Kit and apoptosis were detected by flow; mitochondrial membrane potential were tested by JC-1 and activation of Caspase 9 and Caspase 3 were detected by western blot. Results The results found that gold nanorods had nontoxic to normal cells, but highly toxic to tumor cells; and with the increasing of gold nanorods’ working time, the percentage of apoptotic cancer cells was increasing; in addition to, normal cells’ mitochondrial membrane potential did not change, but cancer cells had a significant reduction in mitochondrial membrane potential.Conclusion This study proves that gold nanorods induce apoptosis through the mitochondrial apoptosis pathway.
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Smart classroom as the basis support of classroom teaching, should set the function of smart teaching, real-time interaction, environmental control, video monitoring and remote control, teaching reform, evaluation feedback and other functions into an organic whole, and by using new technology integration and development, to achieve the optimization of the teaching effect. In view of the characteristics of practice and complexity of medical teaching, The spatial structure of smart class-room should provide long-distance education, remote operation, live classroom group discussion, group exhibition, HD recording, classroom attendance voting and other functions, and by choosing the appro-priate teaching mode in teaching to promote the innovation and development of medical teaching.
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<p><b>OBJECTIVE</b>To study characteristic presentations of Brucellar spondylitis on MRI in order to improve the diagnostic level.</p><p><b>METHODS</b>From October 2009 to December 2010,15 patients with Brucellar spondylitis were evaluated by MRI. They included 11 males and 4 females ranging in age from 31 to 64 (mean 49) years. The major clinical manifestations were different degrees of fatigue,fever and low back pain. All patients underwent MRI and treated with antibiotic drugs.</p><p><b>RESULTS</b>Brucellar spondylitis was mostly localized at the lumbar spine with obvious bony hyperostosis in the vertebral periphery. Most foci were in the edge, anterior and middle parts of the vertebral body, with low signals on T1WI and mixed low signals on T2WI, and high signals on T2 fat suppression, mostly without significant changes in intervertebral space. Paraspinal abscess was observed in 5 cases. Thirteen cases involved the lumbar vertebrae, 1 case involved the thoracic and lumbar vertebrae, and 1 case involved the lumbar and sacral vertebrae. Two vertebrae were affected in 14 cases, and 3 vertebrae were affected in 1 case.</p><p><b>CONCLUSION</b>MRI can provide imaging clues for diagnosis and differential diagnosis of Brucellar spondylitis, and has a high clinical value.</p>
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Adult , Female , Humans , Male , Middle Aged , Brucellosis , Diagnosis , Diagnosis, Differential , Magnetic Resonance Imaging , Methods , Spondylitis , DiagnosisABSTRACT
<p><b>OBJECTIVE</b>To study the rotation of femoral component and tibial component with CT and evaluate the relationship between patellofemoral complications and rotational alignment of the components.</p><p><b>METHODS</b>Thirty patients with isolated patellofemoral complications after total knee arthroplasty were compared with 20 patients with well functioning total knee replacements free of patellofemoral complications. The epicondylar axis and tibial tubercle were used as references on CT scans to quantify the rotational alignment of the femoral and tibial components.</p><p><b>RESULTS</b>Patients with patellofemoral complications had excessive combined (tibial plus femoral) internal component rotation, which was directly proportional to the severity of the patellofemoral complications. Mild combined internal rotation (1 degree-4 degrees) was correlated with patellar and lateral tracking tilting, moderate rotation (3 degrees-8 degrees) with patellar subluxation, and severe rotation (7 degrees-17 degrees) with early patellar dislocation or late patellar prosthesis failure. The control group had combined external rotation of 10 degrees-0 degree.</p><p><b>CONCLUSIONS</b>The direct correlation of combined internal component rotation to the severity of the patellofemoral complication suggests that internal component rotation may be the predominant cause of patellofemoral complications in patients with normal axis alignment. CT scans can be used intraoperatively and postoperatively to determine whether the rotational malalignment is present to require revision of one or both components.</p>
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Adult , Aged , Female , Humans , Male , Middle Aged , Arthroplasty, Replacement, Knee , Osteoarthritis, Knee , Diagnostic Imaging , General Surgery , Postoperative Complications , Prosthesis Failure , Radiography , RotationABSTRACT
Although it has been known that human seminal plasma (HSP) suppresses immune responses, there is little data concerning in vivo effects on humoral and cellular immune responses, particularly on immediate hypersensitivity. Thus, the present study was undertaken in an effort to investigate the in vivo effect of HSP on humoral and cellular immune responses, including active systemic anaphylaxis (ASA) in mice. The immune responses investigated were delayed-type hypersensitivity (DTH) reaction to sheep red blood cell (SRBC) or human sperm antigen, hemagglutinin response, and active systemic anaphylaxis induced by egg albumin (OVA). Effect of HSP on Candida albicans infection was also studied. It was found that intraperitoneal administration of HSP before or after immunization with SRBC significantly suppressed the DTH to SRBC. HSP given after immunization with SRBC failed to suppress hemagglutinin response whereas HSP given before immunization with SRBC significantly suppressed the hemagglutinin response. Interestingly, intravaginal administration of HSP together with human sperm significantly suppressed DTH to human sperm as measured by footpad swelling reactions. HSP inhibited phagocytic function of macrophage and enhanced germ tube producing phagocytosed yeasts. Colony forming unit (CFU) of Candida albicans in kidneys of HSP-treated mice were enumerated. HSP given to mice before infection significantly increased the number of CFU in kidneys, strongly suggesting that HSP may decrease the resistance of mice to Candida infection. For the ASA experiment, mice were sensitized by i.p. injection of 500 ug OVA, 1.0 mg alum and 2x1000000000 Bordetella pertussis in 0.5 ml PBS and were challenged by i.v. inje-ction of 0.25 ml PBS containing 500 big OVA 18 days after sensitization. Surpris-ingly,HSP injection before ASA induction inhibited intensity of ASA and improved survival of anaphylaxis. Taken together, this study strongly suggests that HSP may suppress in vivo immediate and delayed immune responses and that HSP may decrease the resistance against Candida albicans infection, and this study may be the first to show the immunosuppressive effect of HSP on the induction of active systemic anaphylaxis.