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Berberine (BBR) is the main pharmacological active ingredient of Coptidis, which has hypoglycemic effect, but its clinical application is limited due to its poor oral bioavailability. Polyphenols, derived from cinnamon, are beneficial for type 2 diabetes mellitus (T2DM). The combination of both may have an additive effect. The aim of this study was to investigate the hypoglycemic effect and mechanism of combined medication in diabetic rats. The modeling rats were randomly divided into 5 groups (berberine group, cinnamon group, combined group, metformin group, diabetic control group) and normal control group. The animal experiments were approved by the Animal Ethics Committee (approval number: HMUIRB2022003). The subjects were given orally, and the control group was given equal volume solvent and body weight was measured weekly. Thirty days after administration, oral glucose tolerance test and insulin sensitivity test were performed, and fasting blood glucose (FBG), glycated serum protein (GSP), and serum insulin (INS) levels were detected; high-throughput sequencing technology was used to detect intestinal microbiota structure; real-time quantitative PCR (RT-qPCR) and Western blot were used to detect G protein-coupled receptor 5 (TGR5) and glucagon-like peptide-1 (GLP-1) expression levels. The results showed that, compared with the diabetic control group, the levels of FBG (P < 0.01) and GSP (P < 0.01) in the combined group were lower, and the insulin resistance was improved, which was better than that in the berberine group. Combined treatment increased the relative abundance of Bacteroides, Prevotella and Lactobacillus, reversed the decrease in Lactobacillus in the berberine alone induction group, and the combination of the two could promote the expression of TGR5 and GLP-1. In summary, the combined application of cinnamon and berberine can regulate glucose metabolism better than the application of berberine alone. Berberine combined with cinnamon can improve the function of pancreatic islet β cells in diabetes mellitus type 2 rats by changing the intestinal microbiota, increasing the expression of TGR5 and GLP-1 proteins, and thereby better regulating glucose metabolism.
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Fibrosis can occur in diverse tissue and organs and is the common outcome as multiple chronic diseases progress. It is characterized by over-activation of fibroblasts and excessive deposition of extracellular matrix. Targeting transforming growth factor-β （TGF-β）， a classical signaling molecule in fibrosis， is currently a routine strategy for drug therapy of this disease. The use of traditional Chinese medicine （TCM） in the treatment of fibrotic diseases has been supported by mature theories. The theories emphasize that the internally-accumulated pathogens and mixed deficiency-excess underlie the shared pathology of fibrotic diseases. Qi stagnation， blood stasis， phlegm turbidity， and mass accumulation are key pathological factors. "Yin suppression by Yang" is the core thought for treatment with TCM of the disease. Pharmacological investigations reveal the scientific nature of TCM in treating fibrotic diseases， namely multilevelled and multitargeted. In other words， it refers to networked regulation of signaling activities of fibrosis-related molecules such as TGF-β/Drosophila protein homolog （Smad）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， Hedgehog， Wnt/β-catenin， and inflammatory cytokines， so as to inhibit fibroblast function and provide a promising insight into novel anti-fibrotic drug. This paper summarized the conventional understanding of fibrotic disease treatment with TCM and its mechanism of action by reviewing ancient literature and modern research reports， which offers an idea for follow-up research in this field.
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ObjectiveTo explore the therapeutic mechanism of Bushen Huoxue prescription from the perspective of bone metabolism by observing the clinical efficacy of this prescription in treating femoral head necrosis （ONFH， syndrome of liver and kidney deficiency） and its influences on bone metabolism indexes： N-terminal propeptide （PINP） and β-collagen degradation product （β-CTX）. MethodSixty-six ONFH patients with the syndrome of liver and kidney deficiency in Zhengzhou Traditional Chinese Medicine Hospital of Orthopedics from December 2021 to September 2022 were selected. The patients were randomized into an experimental group and a control group by the parallel control method， with 33 patients in each group. The experimental group received Bushen Huoxue prescription orally， while the control group received Xianlinggubao Capsules orally， with a treatment cycle of 6 months. The visual analogue scale （VAS） score， Harris score， Association Research Circulation Osseous （ARCO） staging， imaging changes， quantitative scores of TCM symptoms， and serum levels of PINP and β-CTX were determined before and after treatment. The occurrence of adverse events and reactions was recorded. ResultThe total response rate in the experimental group was 83.87% （26/31）， which was higher than that （68.75%， 22/32） in the control group （Z=-2.096， P<0.05）. After treatment， the single and total scores of TCM symptoms， VAS score， and β-CTX level decreased in the two groups （P<0.05）. Moreover， the decreases in the scores of hip pain， lower limb mobility， soreness of waist and knees， and lower limb flaccidity， total score of TCM symptoms， VAS score， and β-CTX level in the experimental were larger than those in the control group （P<0.05）. After treatment， the imaging results showed no significant improvement in the two groups. The Harris score and PINP level in both groups increased after treatment （P<0.05）， and the increases were more obvious in the experimental group than in the control group （P<0.05）. No serious adverse event or adverse reaction appeared during the observation period. ConclusionBushen Huoxue prescription can relieve pain and TCM symptoms and improve the hip joint function in treating ONFH patients with the syndrome of liver and kidney deficiency. It can inhibit the development of ONFH， increase PINP， and decrease β-CTX. No obvious side effect appears during the clinical observation period， which shows that Bushen Huoxue prescription has good safety.
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Objective: To investigate the association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years. Methods: A total of 5 048 male participants aged 18 to 79 years were recruited from the China National Human Biomonitoring (CNHBM) from 2017 to 2018. Questionnaires and physical examinations were used to collect information on demographic characteristics, lifestyle, food intake frequency and health status. Venous blood and urine samples were collected to detect the level of serum total testosterone, urinary arsenic and urinary creatinine. Participants were divided into three groups (low, middle, and high) based on the tertiles of creatinine-adjusted urinary arsenic concentration. Weighted multiple linear regression was fitted to analyze the association of urinary arsenic with serum total testosterone. Results: The weighted average age of 5 048 Chinese men was (46.72±0.40) years. Geometric mean concentration (95%CI) of urinary arsenic, creatinine-adjusted urinary arsenic and serum testosterone was 22.46 (20.08, 25.12) μg/L, 19.36 (16.92, 22.15) μg/g·Cr and 18.13 (17.42, 18.85) nmol/L, respectively. After controlling for covariates, compared with the low-level urinary arsenic group, the testosterone level of the participants in the middle-level group and the high-level group decreased gradually. The percentile ratio (95%CI) was -5.17% (-13.14%, 3.54%) and -10.33% (-15.68%, -4.63). The subgroup analysis showed that the association between the urinary arsenic level and testosterone level was more obvious in the group with BMI<24 kg/m2 group (Pinteraction=0.023). Conclusion: There is a negative association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years.
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Humans , Male , Adolescent , Young Adult , Adult , Middle Aged , Aged , Arsenic/urine , Creatinine , East Asian People , Testosterone/blood , UrinalysisABSTRACT
ObjectiveTo summarize the modeling methods, test indicators, and evaluation methods of the animal models of urticaria and provide a basis for the subsequent research on urticaria models. MethodWith the keywords of "urticaria" and "animal model" and the time interval from inception to July 13, 2022, relevant articles were retrieved from CNKI, Wanfang Data, VIP, CBM, Web of Science, Embase, and PubMed. Two evaluators independently screened the articles and extracted the publishing time, sources, animal conditions, modeling methods, modeling time, and test indicators from the articles meeting the inclusion criteria to establish a data library for quantitative statistics and analysis. ResultA total of 116 articles were included, involving 129 animal experiments (102 in Chinese and 27 in English) of urticaria. In the last three years, the studies about the animal models of urticaria presented an obvious upward trend, and the articles were dominated by dissertations. KM mice and SD rats of both females and males were mainly used for the modeling of urticaria, and the models were mainly established by passive sensitization of skin for 14-16 days. The models were mainly evaluated based on apparent indicators such as blue-stained lesion area and ear swelling, supplemented by the pathological indicators of the skin and serum. ConclusionAlthough the experimental studies of urticaria are increasing, the modeling methods lack unified modeling standards and have low coincidence with clinical symptoms. Therefore, this paper analyzed the modeling elements and evaluation criteria of urticaria animal models, and proposed that both male and female KM mice (6-8 weeks old) or SD rats (8-10 weeks old) of SPF grade should be preferentially selected for modeling. Active and passive sensitization can be combined for the modeling, and the specific modeling elements such as modeling time and sensitization times need to be further explored. The model evaluation should include four aspects of behavior, appearance, pathology, and immunity.
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Radiation pneumonia is a side effect that cannot be ignored in the current radiation therapy for lung cancer. At present, there are studies and reports of the introduction of functional imaging technology into lung cancer radiotherapy plans, in which 4DCT has better application prospects in radiotherapy for lung cancer because of its advantages of simple operation, high spatial resolution and no additional cost, etc. Compared with single-photon emission computed tomography (SPECT)-CT, positron emission tomography (PET)-CT, MRI has a better application prospect in radiotherapy of lung cancer. The use of 4DCT to obtain the patient's lung function status can predict radiation pulmonary toxicity and assist clinicians to deliver prompt interventions. Moreover, it can help carry out radiotherapy for functional lung avoidance, mitigate the damage of normal lung tissues, and alleviate chest toxicity, which may have wider application value in the future. In this article, research progress on functional lung imaging algorithms based on 4DCT and the application of radiation therapy for lung cancer was reviewed.
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Objective:To investigate the effect of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) guided by echocardiography on the Lown classification of ventricular arrhythmias in patients with hypertrophic obstructive cardiomyopathy (HOCM).Methods:A total of 85 patients with HOCM who received PIMSRA treatment at Xijing Hospital of Air Force Military Medical University from May 2017 to October 2019 were retrospectively selected. All patients underwent 24-hour Holter examinations before and 1 year after PIMSRA to obtain parameters related to Lown classification. The changes in Lown grades after PIMSRA were analyzed. The patients were divided into improved group and unimproved group according to whether there was significant improvement in Lowen′s grades, and the difference of the parameters related were compared. The influencing factors of the changes in Lown classification were analyzed.Results:Compared with before PIMSRA, there was a significant improvement in the Lown classification after PIMSRA ( P=0.001). The patients with Lown grade Ⅰ increased significantly ( P=0.001), and the patients with grade Ⅲ decreased significantly ( P=0.005). There were no significant changes in patients with Lown grades 0, Ⅱ, and Ⅳ (all P>0.05). The proportion of patients with family history of hypertrophic cardiomyopathy (HCM), the baseline Lown classes, the reduction rate of the maximum left ventricular wall thickness and the reduction rate of the provocative left ventricular outflow tract gradient (LVOTG) were higher in the improved group than the unimproved group (all P<0.05). Multivariate Logistic regression results showed that HCM family history ( OR=3.95, 95% CI=1.34-11.64, P=0.013), baseline Lown classes ( OR=2.01, 95% CI=1.25-3.22, P=0.004) and the reduction rate of the provocative LVOTG gradient ( OR=1.02, 95% CI=1.00-1.04, P=0.041) were independent factors of postoperative Lown classification improvement. Conclusions:The Lown classes of HOCM patients after PIMSRA is significantly improved.HCM family history, the baseline Lown classes, and the reduction rate of postoperative provocative LVOTG are independent influencing factors for the improvement of Lown grade.
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Objective:To evaluate the clinical efficacy of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) in the treatment of obstructive hypertrophic cardiomyopathy (HOCM) with mild septal hypertrophy.Methods:Forty-five HOCM patients with mild septal hypertrophy (the maximal left ventricular wall thickness is 15-19 mm) who were treated with PIMSRA between November 2016 to February 2021 in the Hypertrophic Cardiomyopathy Center of Xijing Hospital of Air Force Military Medical University were enrolled, and their clinical datas were collected and analyzed. The clinical symptoms and NYHA functional class before operation, 6 months and 1 year after operation were collected. Interventricular septum thickness, left ventricular outflow tract pressure gradient, left ventricular outflow tract diameter, mitral regurgitation, left ventricular systolic and diastolic function were evaluated by transthoracic echocardiography before operation, 6 months and 1 year after operation, intraoperative complications were monitored and recorded. Postoperative arrhythmias were monitored by routine 12 lead ECG and 24-hour ambulatory ECG.Results:All patients successfully completed PIMSRA procedure.No clinical adverse events such as death, bleeding and stroke occurred during and around the operation.No left bundle branch block, complete atrioventricular block and malignant arrhythmia occurred after the operation. All patients did not need permanent pacemaker implantation.NYHA functional class and clinical symptoms of patients were significantly improved after 6 months compared with values before operation (all P<0.001, respectively), it remained stable for 1 year after operation; Anterior interventricular septum, posterior interventricular septum, maximal left ventricular wall thickness all significantly decreased (all P<0.001, respectively), left ventricular outflow tract diameter widened ( P<0.001), continuous improvement 1 year after operation; left ventricular outflow tract gradient and provoked left ventricular outflow tract gradient all significantly decreased, mitral regurgitation decreased and SAM classification reduced after 6 months compared with values before operation (all P<0.001, respectively); left ventricular end-diastolic diameter widened and left atrial diameter decreased (all P<0.001, respectively), it remained stable for 1 year after operation. Left atrial volume index decreased ( P<0.001), with continuous improvement 1 year after operation; The ratio of early diastolic mitral valve velocity to early diastolic mitral annulus velocity (E/e′) decreased ( P=0.001), it remained stable for 1 year after operation. There were no significant differences in left ventricular end diastolic volume, left ventricular end systolic volume and left ventricular ejection fraction among the three groups (all P>0.05). Conclusions:PIMSRA is effective in the treatment of obstructive hypertrophic cardiomyopathy with mild ventricular septal hypertrophy.
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Objective:To establish a machine learning model for the diagnosis of clinically significant prostate cancer based on transrectal contrast-enhanced ultrasound parameters and clinically relevant data.Methods:A retrospective analysis was performed on 151 patients in Chongqing University Cancer Hospital who underwent transrectal contrast-enhanced ultrasonography and transrectal ultrasound-guided needle biopsy from November 2018 to September 2021. The time intensity curve was drawn using VueBox software and 12 parameters such as rise time, peak time, average transit time, peak intensity, and rising slope were quantitatively analyzed. Age, total prostate-specific antigen, free prostate-specific antigen, free prostate-specific antigen ratio, volume, prostate-specific antigen density, and transrectal contrast-enhanced ultrasonography parameters, a total of 18 characteristic parameters, were analyzed and screened through relevant attribute values and information gain attribute values. The screening features were trained and tested by the machine learning single algorithm and integrated algorithm, and then the model was evaluated by the F1 value and the area under the ROC curve(AUC).Results:Using the related attribute value and the information gain attribute value, 12 variables and 5 variables were screened out respectively to establish a machine learning model. The model established by the ensemble algorithm was better than the single algorithm. For the two variable selection methods, the AUC (0.810 vs 0.789) and F1 values (0.748 vs 0.742) of the Bagging ensemble algorithm model, which basic algorithm was decision tree, were the highest, followed by Logistic regression and support vector machine(SVM) in order of AUC and F1 values.Conclusions:Based on transrectal contrast-enhanced ultrasound parameters and clinical data, the Bagging ensemble model based on decision tree has the best performance in diagnosing clinically significant prostate cancer.
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There is no fast-acting treatment strate-gies against Alzheimer's disease(AD),in particular dementia-related wandering.N,N-dimethyltryptamine(DMT)is a natural psychedelic that may have rapid-onset nootropic effects.In this study,5×FAD transgenic mice which recapitulated amyloid neuropathological features of AD received one single injection of 6 or 12 mg·kg-1 DMT and tested at 0.5,1,and 2 h thereafter in Y-maze for spatial memory.5×FAD transgenic mice exhibited pro-nounced decreases in time spent,number entered,and distance travelled in the novel arm of Y-maze.DMT at 12 mg·kg-1 partially or completely reversed the three behavioral indices at multiple time points,up to 2 h post injection.The rapid-onset behavioral improvement was consistent with pharmacokinetic analysis of DMT,showing approximately 30 min to reach the maximum concentra-tion in the brain tissue.The transgenic mice also displayed dramatically impaired hippocampal long-term potentiation(LTP),an electrophysiological feature of memory forma-tion and consolidation.DMT potently enhanced LTP and restored intracellular calcium activity,expression and phosphorylation of calcium/calmodulin-dependent protein kinase Ⅱ(CaMK Ⅱ)and AMPA-type glutamate receptor 1(GluR1),the two key calcium-activated mediators involved in LTP induction.Adenosine triphosphate(ATP)is purinergic signalling molecules that are involved in LTP induction and maintenance.DMT rapidly increased mito-chondrial ATP dynamics in in vivo and in vitro models.These results suggest that DMT rapidly improve spatial memory and hippocampal LTP by restoring the CaMK Ⅱ-GluR1 signaling pathway and mitochondrial ATP produc-tion.It may be served as a fast-acting nootropic agent for the treatment of AD in particular wandering.
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Objective:To investigate the effect and mechanism of the Bushen Jianpi Kaixin formula on the learning and memory ability of Alzheimer's disease (AD) model rats.Method:A total of 72 SPF grade male SD rats were divided into control group, model group, Bushen group, Jianpi group, Kaixin group and Bushen Jianpi Kaixin group according to the random number table method ( n=12 in each group). The rats were intraperitoneally injected with D-galactose once a day for 6 weeks to replicate the model of AD.And the rats in different medication groups were given corresponding administration (Bushen formula: gavage 3.60 g·kg -1·d -1, Jianpi formula: gavage 4.05 g·kg -1·d -1, Kaixin formula: gavage 2.34 g·kg -1·d -1, Bushen Jianpi Kaixin formula: gavage 9.99 g·kg -1·d -1), while rats in control group and model group were treated with equal volume of 0.9% sodium chloride solution once a day for 28 days.The learning and memory ability was tested by Morris water maze.The expressions of phosphoinositide 3-kinase(PI3K), protein kinase B(Akt) and mammalian target of rapamycin(mTOR) in cerebral cortical tissues were detected by immunohistochemistry.The relative mRNA levels of p62 and Beclin in brain cortical tissue were detected by RT-PCR.SPSS 25.0 software was used for data processing, one-way ANOVA was used for inter group comparisons, and LSD test was used for further pairwise comparisons. Results:Morris water maze results showed statistically significant differences in escape latency and the times of crossing platform among the six groups ( F=368.10, 47.43, both P<0.01). The escape latency of Bushen Jianpi Kaixin group((29.30±1.64) s) was shorter than that of model group((55.58±3.23) s) ( P<0.01), the times of crossing platform ((5.17±0.72) times) in Bushen Jianpi Kaixin group was higher than that of model group (1.50±0.52)time, P<0.01). Compared with the Bushen Jianpi Kaixin group, the escape latencies of Bushen group, Jianpi group and Kaixin group were longer (all P<0.01), the times of crossing platform in Bushen group was lower ( P<0.01). Immunohistochemical results showed statistically significant differences in the positive protein expression of PI3K, Akt, and mTOR proteins among the six groups ( F=68.52, 22.22, 31.52, all P<0.01). Compared with the model group, the levels of positive protein of PI3K ((0.47±0.15), (0.57±0.12)), Akt ((0.31±0.02), (0.38±0.02)), and mTOR ((0.22±0.18), (0.28±0.11)) in Bushen Jianpi Kaixin group were less (all P<0.01). Compared with the Bushen Jianpi Kaixin group, the levels of positive protein of PI3K and mTOR of Bushen group, Jianpi group and Kaixin group were higher (all P<0.01). RT-PCR results showed statistically significant differences in the relative mRNA levels of Beclin and p62 among all the groups ( F=8.79, 21.01, both P<0.01). The relative mRNA level of Beclin in Bushen Jianpi Kaixin group was higher than that of the model group ((0.97±0.07), (0.64±0.12)), and the relative mRNA level of p62 of Bushen Jianpi Kaixin group was less than that of model group((0.98±0.16), (1.16±0.24))(both P<0.01). The relative mRNA levels of p62 in Bushen group, Jianpi group and Kaixin group were higer than those of Bushen Jianpi Kaixin group (all P<0.05). Conclusion:Bushen Jianpi Kaixin formula can improve cognitive impairment and learning and memory ability in AD model rats.The mechanism may be related to the regulation of PI3K/Akt/mTOR autophagy pathway.The combination prescription is better than the split prescription.
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Objective:To develop and validate the models based on mixed enhanced computed tomography (CT) radiomics and deep learning features, and evaluate the efficacy for differentiating pancreatic adenosquamous carcinoma (PASC) from pancreatic ductal adenocarcinoma (PDAC) before surgery.Methods:The clinical data of 201 patients with surgically resected and histopathologically confirmed PASC (PASC group) and 332 patients with surgically resected histopathologically confirmed PDAC (PDAC group) who underwent enhanced CT within 1 month before surgery in the First Affiliated Hospital of Naval Medical University from January 2011 to December 2020 were retrospectively collected. The patients were chronologically divided into a training set (treated between January 2011 and January 2018, 156 patients with PASC and 241 patients with PDAC) and a validation set (treated between February 2018 and December 2020, 45 patients with PASC and 91 patients with PDAC) according to the international consensus on the predictive model. The nnU-Net model was used for pancreatic tumor automatic segmentation, the clinical and CT images were evaluated, and radiomics features and deep learning features during portal vein phase were extracted; then the features were dimensionally reduced and screened. Binary logistic analysis was performed to develop the clinical, radiomics and deep learning models in the training set. The models' performances were determined by area under the ROC curve (AUC), sensitivity, specificity, accuracy, and decision curve analysis (DCA).Results:Significant differences were observed in tumor size, ring-enhancement, upstream pancreatic parenchymal atrophy and cystic degeneration of tumor both in PASC and PDAC group in the training and validation set (all P value <0.05). The multivariable logistic regression analysis showed the tumor size, ring-enhancement, dilation of the common bile duct and upstream pancreatic parenchymal atrophy were associated with PASC significantly in the clinical model. The ring-enhancement, dilation of the common bile duct, upstream pancreatic parenchymal atrophy and radiomics score were associated with PASC significantly in the radiomics model. The ring-enhancement, upstream pancreatic parenchymal atrophy and deep learning score were associated with PASC significantly in the deep learning model. The diagnostic efficacy of the deep learning model was highest, and the AUC, sensitivity, specificity, and accuracy of the deep learning model was 0.86 (95% CI 0.82-0.90), 75.00%, 84.23%, and 80.60% and those of clinical and radiomics models were 0.81 (95% CI 0.76-0.85), 62.18%, 85.89%, 76.57% and 0.84 (95% CI 0.80-0.88), 73.08%, 82.16%, 78.59% in the training set. In the validation set, the area AUC, sensitivity, specificity, and accuracy of deep learning model were 0.78 (95% CI 0.67-0.84), 68.89%, 78.02% and 75.00%, those of clinical and radiomics were 0.72 (95% CI 0.63-0.81), 77.78%, 59.34%, 65.44% and 0.75 (95% CI 0.66-0.84), 86.67%, 56.04%, 66.18%. The DCA in the training and validation sets showed that if the threshold probabilities were >0.05 and >0.1, respectively, using the deep learning model to distinguish PASC from PDAC was more beneficial for the patients than the treat-all-patients as having PDAC scheme or the treat-all-patients as having PASC scheme. Conclusions:The deep learning model based on CT automatic image segmentation of pancreatic neoplasm could effectively differentiate PASC from PDAC, and provide a new non-invasive method for confirming PASC before surgery.
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ObjectiveTo investigate the analgesic action and mechanism of intrathecal 2R， 6R-hydroxynorketamine （2R， 6R-HNK） on spared nerve injury （SNI）-induced chronic neuropathic pain （CNP） in female mice. MethodsSNI was used to establish acute and chronic CNP models in female mice. The mice were randomly divided into different groups with administration of vehicle， 2R， 6R-HNK or S-ketamine （10 mg/kg intraperitoneal injection/i.p. or 7， 21 μmol/L intrathecal injection/i.t.） at 3 weeks after or 30 min/1 d before operation （n = 3 - 7 mice/group）. The curative or preventive effect of 2R， 6R-HNK was evaluated by mechanical paw withdrawal threshold （PWT） and the analgesic efficiency. Finally， immunofluorescence and RT-PCR of dorsal root ganglion （DRG） and spinal dorsal horn （SDH） were used to explore the possible mechanisms. ResultsCompared with vehicle， intrathecal injection of 2R， 6R-HNK largely reversed SNI-induced bilateral mechanical allodynia in a delayed-and-dose-dependent way. Among them， 21 μmol/L 2R， 6R-HNK reached its maximum analgesic efficiency （75.32±7.69） % at 2 d. Pre-intrathecal delivery of 2R， 6R-HNK also delayed the development of bilateral mechanical hypersensitivity 2 - 3 d induced by SNI. Mechanically， 2R， 6R-HNK reversed not only the abnormal excitability of neurons in bilateral DRG and superficial SDH， but also the upregulation of calcitonin gene-related peptide （CGRP） and brain-derived nerve growth factor （BDNF） in DRG. ConclusionIntrathecal administration of 2R， 6R-HNK exerts an analgesic effect against CNP， probably via suppressing abnormal neuronal excitability in ascending pain pathway as well as down-regulating CGRP and BDNF expression in DRG neurons.
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The hyperacute stage of myocardial infarction refers to a period of time within 30 minutes after the occurrence of myocardial infarction, when the symptoms are not obvious and the diagnosis is difficult, and the related pathophysiological mechanism has received less attention. In this study, proteomics was used to investigate the pathological changes in the early hyperacute phase of myocardial infarction, aiming to provide experimental evidence for pathological mechanism of myocardial infarction hyperacute stage. Meanwhile, the intervention effect and related mechanism of salvianolate injection were discussed based on heat shock protein B6 (HSPB6), aiming to benefit the clinical rational use of salvianolate injection. The protein expression changes before and after myocardial infarction model establishment were detected by label-free proteomics via mass spectrometry and analyzed by bioinformatics method. Then the binding effect of salvianolate injection on the commonly differential protein HSPB6 was evaluated by molecular docking technology, which was finally verified by animal experiments. All animal experimental protocols were approved by the Ethics Committee of Xiyuan Hosptial (2022XLC041). The results of this study showed that a total of 2 166 proteins were quantified by lable-free proteomics, of which 194 shared differential proteins were involved in myocardial injury and body regulation in the hyperacute phase of myocardial infarction, mainly involving molecular functions such as protein homodimerization activity, oxygen binding and transport, and serine endopeptidase inhibitor activity. Among them, HSPB6 protein is involved in the regulation of myocardial function. Molecular docking results indicated that magnesium salvianolate acetate, which is the main component of salvianolate injection, had the lowest binding energy with HSPB6 protein: -14.53 kcal·mol-1. Animal experiments showed that compared with the Sham group, the model group had significantly lower ejection fraction (EF) and fractional shortening (FS) (P < 0.001), cardiac blood perfusion decreased significantly (P < 0.001). There were obvious pathological changes such as myocardial fiber disorder, cardiomyocyte edema and interstitial small blood vessel congestion; the injury of cardiac function of rats in the administration group was attenuated, and the FS of rats in the low-dose group was significantly improved (P < 0.05), the pathological injury of myocardial tissue was markedly mitigated, and the expression of HSPB6 protein was up-regulated to varying degrees (P < 0.01, P < 0.001). In conclusion, salvianolate injection could be able to improve the cardiac function and pathological morphology of rats in the early hyperacute stage of myocardial infarction, and its mechanism may be related to the promotion of expression of HSPB6.
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Based on the technology of platelet proteomics, the key regulatory proteins and pathogenesis of coronary heart disease with phlegm and blood stasis syndrome were explored and analyzed. Based on the previous laboratory research, the model of coronary heart disease in mini-swine with phlegm-stasis cementation syndrome was duplicated. The model was judged by the changes in blood lipid and myocardial tissue characteristics. Furthermore, the platelet proteins were studied by quantitative proteomics, and the differentially expressed proteins were screened. The critical regulatory proteins and biological pathways of coronary heart disease with phlegm-stasis cementation syndrome were analyzed by bioinformatics. After ten weeks of modeling, the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low density lipoprotein (VLDL-C), triglyceride (TG), creatine kinase (CK) and creatine kinase-MB (CK-MB) in the model group were significantly increased, reflecting the pathological changes such as increased blood lipid, abnormal coagulation function and myocardial ischemia in the model group. In addition, compared with the sham group, there were 26 up-regulated proteins and 8 down-regulated proteins in the platelets of the model group. Combined with bioinformatics analysis, it was found that differential proteins mainly involved in glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction. Among them, lactate dehydrogenase B (LDHB), alcohol dehydrogenase 5 (ADH5), neuroblastoma ratsarcoma viral oncogene homolog (NRAS) and Kirsten ratsarcoma viral oncogene homolog (KRAS) play a central role when interacting with other proteins and simultaneously participate in multiple action pathways. The results showed that LDHB, ADH5, NRAS, and KRAS may be the marker proteins in CHD with phlegm-stasis cementation syndrome by regulating glycolysis/gluconeogenesis, pyruvate metabolism, lipid and atherosclerosis, Ras protein signal transduction and other biological processes.
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AIM: To evaluate the effect of anterior capsule polishing on visual quality after phacoemulsification.METHODS: Prospective randomized control study. A total of 65 patients(73 eyes)with age-related cataract who underwent phacoemulsification combined with intraocular lens(IOL)implantation in the Emergency General Hospital between November 2021 and June 2022 were included. These patients were randomly assigned to two groups, with one group(anterior polishing group)underwent anterior and posterior capsule polishing(30 cases, 35 eyes), while the other(control group)receive routine posterior capsule polishing(35 cases, 38 eyes). Best corrected visual acuity was observed at 1wk, 1, 3 and 6mo after operation. Area of anterior capsule orifice was measured at 3 and 6mo after operation. Meanwhile, posterior capsular opacification(P score), IOL tilt and decentration were recorded by Pentacam Scheimpflug system. In addition, wavefront aberration, Strehl ratio(SR)of point spread function(PSF)and modulation transfer function(MTF)were evaluated by OPD-Scan Ⅲ.RESULTS: At 1wk, 1, 3 and 6mo after operation, best corrected visual acuity in anterior polishing group is significantly better than that of control group(P<0.05). There were no significant differences in area of anterior capsule opening, P score, IOL decentration, SR of PSF and MTF between two groups at 3 and 6mo after operation(P>0.05). At 3mo follow-up, no significant differences in IOL tilt and wavefront aberration were measured between two groups either(P>0.05). However, IOL tilt [(1.65±0.60)° vs.(2.34±0.43)°, P<0.001] and wavefront aberration(0.03±0.01μm vs. 0.06±0.03μm, P<0.001)in anterior polishing group were significant lower compared to control group at 6mo after operation.CONCLUSION: 360° polishing of anterior and posterior capsule during phacoemulsification can improve best corrected visual quality, with reduced IOL tilt, lower wavefront aberration and better visual quality.
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ObjectiveTo visualize the research trends of verbal and nonverbal cognitive functions in patients with post-stroke aphasia (PSA). MethodsPapers about verbal and nonverbal cognitive functions after stroke were extracted from Web of Science Core Collection from establishment to August, 2022, and a bibliometric analysis was conducted on the distribution of articles published by year, author, journal, institution, and country. Author cooperation, author co-citation, journal co-citation, country/institution cooperation, dynamic evolution, keyword hotspots, and trends were visually analyzed by using VOSviewer software. ResultsA total of 1 630 publications were identified for final analysis. The first article related to the topic was retrieved in 2004. After that, the number of published papers showed an increasing trend year by year, with some fluctuations after 2019. Matthew A. Lambon Ralph and Elizabeth Jefferies were the authors who produced the most, were cited the most, and were the most influential. Neuropsychologia was a highly productive and well-cited publication. The University of Manchester in the United Kingdom and Johns Hopkins University in the United States were the nations/institutions with high yield and high centrality. Although China had a high yield and was in the top five, the centrality was insufficient. The dynamic emergence of keywords revealed that the research had gone through the following stages: evaluating the mechanism of language and nonverbal cognitive function impairment based on neuroimage, exploring the role of nonverbal cognitive dysfunction in pathology and recovery mechanisms of patients with PSA, examining the therapeutic mechanism of non-invasive brain stimulation and electronic tele-rehabilitation equipment, and revealing not only the frontal and temporal areas but also brain network supporting nonverbal cognition. ConclusionIn recent years, some achievements have been made in the researches on verbal and nonverbal cognitive function, particularly in the studies of the neuroimaging-based mechanisms of common damage and the intervention effects of synergistic therapy. In the future, academic cooperation between different regions and different teams needs to be strengthened. Further exploration should be focused on refining the cognitive neuropsychology and exploring new technologies to improve the therapeutic effect of PSA.
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OBJECTIVE To establish HPLC fingerprint of Portulaca oleracea， establish quantitative analysis of multi- components by single-marker （QAMS） method for the content determination of caffeic acid， ferulic acid， genistin and quercetin， and provide reference for quality control of the medicine. METHODS The determination was performed on Eclipse XDB-C18 column with mobile phase consisted of methanol-0.2% phosphoric acid solution （gradient elution） at the flow rate of 1.0 mL/min. The column temperature was 25 °C， and detection wavelength was set at 360 nm. The sample size was 10 μL. HPLC fingerprint of P. oleracea was established according to the above chromatographic conditions. Cluster analysis （CA） and principal component analysis （PCA） were performed for 15 batches of specimens. Using caffeic acid as internal standard， relative correction factors of other three components were calculated by QAMS， and then the component content was calculated on the basis of relative correction factors， which was compared with the external standard method. RESULTS HPLC fingerprints of 15 batches of P. oleracea were calibrated with a total of 17 common peaks， and 4 components （caffeic acid， ferulic acid， genistin， quercetin） were identified； the similarities of 15 batches of samples were greater than 0.890. The results of CA showed that S1-S10 were clustered into one category， and S11-S15 were clustered into one category. The results of PCA revealed that the accumulative contribution rate of the two main components was 92.502%， and the classification results were basically consistent with CA. The linear range of caffeic acid， ferulic acid， genistin and quercetin were 0.003 1-0.157 1， 0.003 6-0.181 7， 0.008 5-0.425 6，0.000 4-0.021 8 mg/mL （R2≥0.999 7）； the results of precision， repeatability， stability （24 h） and recovery tests all complied with the requirements of Chinese Pharmacopoeia. The relative correction factors of ferulic acid， genistin and quercetin calculated by QAMS were 1.534， 5.302 and 0.174； there was no significant difference in the contents of components measured between this method and the external standard method. CONCLUSIONS The established HPLC fingerprint combined with QAMS can be used for the quality control of multiple index components in P. oleracea. The origin has a certain influence on the quality of P. oleracea， and the quality of P. oleracea produced in Sichuan is better than that produced in Anhui and Hebei.
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Objective To explore the starting point of pharmaceutical care by clinical pharmacists for patients after heart valve replacement. Methods Combined with typical cases, the content, focus and effects of pharmaceutical care for patients after heart valve replacement were summarized. Results Clinical pharmacists provided pharmaceutical services such as anticoagulant care and warfarin dosage adjustment, infection monitoring and rational use and care of antibacterial, perioperative airway management, stress ulcer (SU) prevention and pharmaceutical care, and warfarin medication education for patients, which had promoted the rational use of drugs and improved the treatment results of patients. Conclusion Pharmaceutical care by clinical pharmacists could be helpful to improve the safety and efficacy of drug treatment for patients after heart valve replacement.
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OBJECTIVE@#To explore the mechanisms of Buyang Huanwu Decoction (BYHWD) modulating the gut microbiome and trimethylamine oxide (TAMO) to exert cardioprotective effects.@*METHODS@#Ligation of the left anterior descending coronary artery was performed in rats to induce heart failure (HF). Except for the sham-operation group (n=10), 36 operation-induced models were randomized into 3 groups using a random number table (n=12 in each group): the model group, the BYHWD group (15.02 g/kg BYHWD), and the positive group (4.99 g/kg metoprolol succinate). After 4-week treatment (once daily by gavage), echocardiography was applied to evaluate the cardiac function and the Tei index (the ratio of ventricular isovolumic contraction time (IVCT) and isovolumic diastolic time (IVRT) to ejection time (ET)) was calculated; hematoxylin-eosin (HE) staining was observed to characterize the pathology of the myocardium and small intestinal villi. D-lactic acid was detected by an enzyme-linked immunosorbent assay (ELISA). Expressions of occludin, claudin-1, and zonula occludens (ZO-1) were detected by Western blot. 16S ribosomal ribonucleic acid (16S rRNA) sequencing was used to explore the changes in the intestinal flora. TMAO was detected via liquid chromatography-tandem mass spectrometry (LC-MS/MS).@*RESULTS@#In the echocardiography, the Tei index was considerably lower in the positive and BYHWD groups compared with the model group (P<0.05). Besides, BYHWD improved the pathology of myocardium and small intestine of HF rats and lowered the D-lactic acid content in the serum, when compared with the model group (P<0.05). BYHWD also improved the expression of occludin and claudin-1 (P<0.05); in the gut microbiota analysis, BYHWD slowed down modifications in the structure distribution of gut microbiota and regulated the diversity of intestinal flora in HF rats. The content of TMAO in the serum was significantly lowered by BYWHT compared with the model group (P<0.05).@*CONCLUSION@#BYHWD may delay progression of HF by enhancing the intestinal barrier structure, and regulating intestinal flora and TAMO.