Application and mechanisms of Sanhua Decoction in the treatment of cerebral ischemia-reperfusion injury.

Cerebral ischemia-reperfusion is a process in which the blood supply to the brain is temporarily interrupted and subsequently restored. However, it is highly likely to lead to further aggravation of pathological damage to ischemic tissues or the nervous system., and has accordingly been a focus of extensive clinical research. As a traditional Chinese medicinal formulation, Sanhua Decoction has gradually gained importance in the treatment of cerebrovascular diseases. Its main constituents include Citrus aurantium, Magnolia officinalis, rhubarb, and Qiangwu, which are primarily used to regulate qi. In the treatment of neurological diseases, the therapeutic effects of the Sanhua Decoction are mediated via different pathways, including antioxidant, anti-inflammatory, and neurotransmitter regulatory pathways, as well as through the protection of nerve cells and a reduction in cerebral edema. Among the studies conducted to date, many have found that the application of Sanhua Decoction in the treatment of neurological diseases has clear therapeutic effects. In addition, as a natural treatment, the Sanhua Decoction has received widespread attention, given that it is safer and more effective than traditional Western medicines. Consequently, research on the mechanisms of action and efficacy of the Sanhua Decoctions in the treatment of cerebral ischemia-reperfusion injury is of considerable significance. In this paper, we describe the pathogenesis of cerebral ischemia-reperfusion injury and review the current status of its treatment to examine the therapeutic mechanisms of action of the Sanhua Decoction. We hope that the findings of the research presented herein will contribute to a better understanding of the efficacy of this formulation in the treatment of cerebral ischemia-reperfusion, and provide a scientific basis for its application in clinical practice.

The association between plasma free amino acids and type 2 diabetes mellitus complicated with infection in Chinese patients.

BACKGROUND: Type 2 diabetes mellitus (T2DM), one of the most common public diseases threatening human health, is always accompanied by infection. Though there are still a variety of flaws in the treatment of some infectious diseases, metabolomics provides a fresh perspective to explore the relationship between T2DM and infection. Our research aimed to investigate the association between plasma free amino acids (PFAAs) and T2DM complicated with infection in Chinese patients. METHODS: A cross-sectional study was conducted from May 2015 to August 2016. We retrieved the medical records of 1032 inpatients with T2DM from Liaoning Medical University First Affiliated Hospital and we used mass spectrometry to quantify 23 PFAAs. Infections contained 15 individual categories that could be retrieved from the database. Principal component analysis was used to extract factors of PFAAs. Multi-variable binary logistic regression was used to obtain odds ratios (OR) and their 95% confidence intervals (CI). RESULTS: Among 1032 inpatients,109 (10.6%) had infectious diseases. Six factors, accounting for 68.6% of the total variance, were extracted. Factor 4 consisted of Glu, Asp and Orn. Factor 5 consisted of Hcy and Pip. After adjusting for potential confounders, factor 4 was positively correlated with T2DM complicated with infection in Chinese T2DM patients (OR: 1.27, 95%CI: 1.06-1.52). Individual Hcy in factor 5 was positively associated with T2DM complicated with infection (OR: 1.33, 95%CI: 1.08-1.64). Furthermore, factor 4 (OR: 1.44, 95%CI: 1.11-1.87), Orn (OR: 1.01, 95%CI: 1.00-1.02) and Hcy (OR: 1.56, 95%CI: 1.14-3.14) were positively associated with bacterial infection in Chinese T2DM patients, while factor 5 (OR: 0.71, 95%CI: 0.50-1.00) was negatively associated with bacterial infection. CONCLUSIONS: Urea cycle-related metabolites (Orn, Asp, Glu) and Hcy were positively associated with T2DM complicated with infection in China. Orn and Hcy were positively associated with bacterial infection in T2DM patients in China.

Anzhen Risk Evaluation System for Acute Aortic Syndrome (AZSCORE-AAS): protocol for a multicentre prospective cohort study in northern China.

INTRODUCTION: Acute aortic syndrome (AAS) is a group of acute and critical conditions, including acute aortic dissection (AAD), acute intramural haematoma and penetrating aortic ulcer. High mortality and morbidity rates result in a poor patient prognosis. Prompt diagnoses and timely interventions are paramount for saving patients' lives. In recent years, risk models for AAD have been established worldwide; however, a risk evaluation system for AAS is still lacking in China. Therefore, this study aims to develop an early warning and risk scoring system in combination with the novel potential biomarker soluble ST2 (sST2) for AAS. METHODS AND ANALYSIS: This multicentre, prospective, observational study will recruit patients diagnosed with AAS at three tertiary referral centres from 1 January 2020 to 31 December 2023. We will analyse the discrepancies in sST2 levels in patients with different AAS types and explore the accuracy of sST2 in distinguishing between them. We will also incorporate potential risk factors and sST2 into a logistic regression model to establish a logistic risk scoring system for predicting postoperative death and prolonged intensive care unit stay in patients with AAS. ETHICS AND DISSEMINATION: This study was registered on the Chinese Clinical Trial Registry website (http://www. chictr. org. cn/). Ethical approval was obtained from the human research ethics committees of Beijing Anzhen Hospital (KS2019016). The ethics review board of each participating hospital agreed to participate. The final risk prediction model will be published in an appropriate journal and disseminated as a mobile application for clinical use. Approval and anonymised data will be shared. TRIAL REGISTRATION NUMBER: ChiCTR1900027763.

Relationship between plasma glutamate and cardiovascular disease risk in Chinese patients with type 2 diabetes mellitus by gender.

Objectives: This study aimed to assess the association between plasma glutamate (Glu) and the risk of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM) and whether this association differs by gender. Material and methods: We retrieved clinical information on 1032 consecutive patients with T2DM from a same tertiary care center from May 2015 to August 2016. Glu was quantified by liquid chromatography-tandem mass spectrometry analysis. Glu was converted into a categorical variable based on the median concentration in the whole population, while logistic regression was used to obtain the odds ratio (OR) and 95% confidence interval (CI), and the correlation between Glu and various biochemical indices was analyzed. Results: We found that Glu was positively associated with the risk of CVD in patients with T2DM. This correlation was more significant in women. In T2DM patients, the higher the age, body mass index (BMI), weight and systolic blood pressure (SBP), the lower the glycosylated hemoglobin (HbA1C) concentration and the higher the Glu. In female patients, the correlation between age, weight, BMI, SBP, and plasma Triglycerides (TG), and Glu was also statistically significant. Conclusion: In conclusion, female T2DM patients with high levels of Glu have a higher risk of developing CVD.

Melatonin Alleviates Liver Fibrosis by Inhibiting Autophagy.

OBJECTIVE: Melatonin has been reported to suppress inflammation and alleviate liver fibrosis, but its effect on autophagy in liver fibrosis has not been studied. This study investigated the effect of melatonin on autophagy in an animal model of liver fibrosis and the hepatic stellate cell (HSC)-T6 cell line. METHODS: The model was established in rats through carbon tetrachloride treatment, and melatonin was administered at three doses (2.5, 5.0, and 10.0 mg/kg). Haematoxylin and eosin staining and Van Gieson's staining were performed to examine the pathological changes of liver. The expression of alpha-smooth muscle actin (α-SMA) and Beclin1 in liver tissues was detected by immunohistochemical staining. The protein levels of α-SMA, Beclin1 and LC3 in the animal model were detected by Western blot analysis, and gene levels of Beclin1 and LC3 were detected by quantitative real-time PCR (qRT-PCR) in the animal model. HSC-T6 cells were activated by platelet-derived growth factor-BB (PDGF-BB). The expression of α-SMA, Beclin1 and collagen I was detected by Western blot analysis, and the gene expression of Beclin1 and LC3 was detected by qRT-PCR. RESULTS: Melatonin reduced the expression of α-SMA, Beclin1 and LC3 in liver tissues. In addition, melatonin inhibited the activation of HSC-T6 cells and the expression of α-SMA, Beclin1 and LC3 in these cells. These results revealed that melatonin could inhibit autophagy and HSC activation. CONCLUSION: Melatonin might ameliorate liver fibrosis by regulating autophagy, suggesting that melatonin is a potential therapeutic agent for liver fibrosis.

A Super-Microsurgery Training Model: The Mouse Caudal Artery Anastomosis Model.

Objective: To establish a simple and practical model for super-microsurgery training using the middle caudal arteries of Kunming mice. Methods: A ⊔-shaped incision was made approximately 1 cm from the root of the tail in the mouse, and the skin, together with the subcutaneous tissue, was turned up into a rectangular shape to the opposite side with exposure of the mouse middle caudal artery and the accompanying veins. The artery was freed for approximately 1 cm in length. The middle caudal artery was cut transversely at the site, and then the severed middle caudal artery was anastomosed end-to-end using 12-0 microsutures in the order of 6, 12, 3, and 9 o'clock with four stitches. Results: The mouse caudal artery had a constant anatomical location accompanied by a vein. The immediate postoperative patency after vascular anastomosis was 100% (15/15) in all mouse models, the postoperative patency was 100% (5/5), 80% (4/5), and 75% (3/4) at 24 h, 3 days, and 1 week postoperatively, respectively. The outer diameter of the mouse middle caudal artery was 0.2 ~ 0.3 (0.22 ± 0.03) mm. The vascular anastomosis time was 6.5 ~ 15 (11.0 ± 2.5) min. Conclusion: The mouse middle caudal artery was superficially located and anatomically constant, making it easy to be located and exposed. The small size of the opening made it suitable for establishing a useful model for training in super-microsurgery vascular anastomoses.

Identification of traditional Chinese drugs containing active ingredients for treating myocardial infarction and analysis of their therapeutic mechanisms by network pharmacology and molecular docking / 南方医科大学学报

OBJECTIVE@#To identify traditional Chinese drugs that contain active ingredients for treatment of myocardial infarction (MI) and explore their therapeutic mechanisms using network pharmacology and molecular docking technology.@*METHODS@#The TCMSP database was used for screening the traditional Chinese drugs containing active ingredients for treating MI, and the related targets of MI and the candidate drugs were obtained from Genecards, OMIM, PharmGkb and PharmMapper databases. The common target network of the drug targets and disease targets was established using Venny2.1.0 software. GO and KEGG signal pathway enrichment analysis of the common targets was performed, and the protein-protein interaction (PPI) network was constructed for the targets. The targets in the PPI network were analyzed to identify the key targets, for which GO and KEGG pathway enrichment analyses were performed. Molecular docking was performed for the candidate ingredients and the key targets, and a total score ≥6 was used as the criteria for screening the therapeutic ingredients and their docking binding with key targets was verified. A human umbilical vein endothelial cell (HUVEC) model of oxygen-glucose deprivation (OGD) was used to validate the candidate ingredients and the key therapeutic targets for MI by Western blotting.@*RESULTS@#Our analysis identified Salvia miltiorrhiza and Dalbergiae odoriferae as the candidate drugs rich in active ingredients for treatment of MI. These ingredients involved 16 key therapeutic targets for MI, which participated in such biological processes as inflammatory response, angiogenesis, energy metabolism and oxidative stress and the pathways including HIF-1, VEGF, and TNF pathways. Sclareol and PTGS2 in Salvia miltiorrhiza and formononetin and KDR in Dalbergiae odoriferae all had high docking total scores. Western blotting showed that at medium and high doses, sclareol significantly inhibited PTGS2 expression and formononetin promoted KDR expressions in the cell models in a dose-dependent manner (P < 0.05).@*CONCLUSION@#Both Salvia miltiorrhiza and Dalbergiae odoriferae have good therapeutic effects on MI. Sclareol in Salvia miltiorrhiza and formononetin in Dalbergiae odoriferae regulate the expressions of KDR and PTGS2, respectively, to modulate the inflammatory response, angiogenesis, oxidative stress and energy metabolism and thus produce myocardial protective effects.

Diabetes mellitus exacerbates experimental autoimmune myasthenia gravis via modulating both adaptive and innate immunity.

BACKGROUND: Diabetes mellitus (DM) is a common concomitant disease of late-onset myasthenia gravis (MG). However, the impacts of DM on the progression of late-onset MG were unclear. METHODS: In this study, we examined the immune response in experimental autoimmune myasthenia gravis (EAMG) rats with DM or not. The phenotype and function of the spleen and lymph nodes were determined by flow cytometry. The serum antibodies, Tfh cells, and germinal center B cells were determined by ELISA and flow cytometry. The roles of advanced glycation end products (AGEs) in regulating Tfh cells were further explored in vitro by co-culture assays. RESULTS: Our results indicated clinical scores of EAMG rats were worse in diabetes rats compared to control, which was due to the increased production of anti-R97-116 antibody and antibody-secreting cells. Furthermore, diabetes induced a significant upregulation of Tfh cells and the subtypes of Tfh1 and Tfh17 cells to provide assistance for antibody production. The total percentages of B cells were increased with an activated statue of improved expression of costimulatory molecules CD80 and CD86. We found CD4+ T-cell differentiation was shifted from Treg cells towards Th1/Th17 in the DM+EAMG group compared to the EAMG group. In addition, in innate immunity, diabetic EAMG rats displayed more CXCR5 expression on NK cells. However, the expression of CXCR5 on NKT cells was down-regulated with the increased percentages of NKT cells in the DM+EAMG group. Ex vivo studies further indicated that Tfh cells were upregulated by AGEs instead of hyperglycemia. The upregulation was mediated by the existence of B cells, the mechanism of which might be attributed the elevated molecule CD40 on B cells. CONCLUSIONS: Diabetes promoted both adaptive and innate immunity and exacerbated clinical symptoms in EAMG rats. Considering the effect of diabetes, therapy in reducing blood glucose levels in MG patients might improve clinical efficacy through suppressing the both innate and adaptive immune responses. Additional studies are needed to confirm the effect of glucose or AGEs reduction to seek treatment for MG.

Immunoadsorption treatment for dilated cardiomyopathy: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: As one of the leading causes of heart failure, dilated cardiomyopathy (DCM) is characterized by dysfunctional muscle contraction and enlarged ventricular chamber. Patients with DCM have been shown to respond well to immunoadsorption (IA) therapies. However, the efficacy and safety of IA treatment for DCM patients remained to be evaluated. METHODS: This study was designed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis. We searched the databases such as Cochrane library, Cochrane Central Register of Controlled Trials, Embase, OVID, and Web of Science from January 1990 to March 20, 2020, and performed meta-analysis using Stata MP Version 13.0. RESULTS: We performed meta-analysis on 12 studies that included a total of 395 patients with DCM. Overall, IA treatment significantly improved the left ventricular ejection fraction (6.01, 95% confidence interval [CI] [4.84-7.19]), reduced the left ventricular end diastolic diameter (-3.62, 95% CI [-4.06 to -3.19]), reduced severity of symptoms according to the New York Heart Association (NYHA) functional classification (-1.37, 95% CI [-1.73 to -1.02]) as compared with the controls, but had no effect on values for safety parameters (1.13, 95% CI [0.58-2.19]). CONCLUSIONS: Results of this meta-analysis indicated that the IA treatment can improve the left ventricular ejection fraction, reduce left ventricular end diastolic diameter, and thus improve clinical outcome in DCM patients. However, further evidence are required to validate the relative safety of IA treatment. Multi-center, double blind studies should be conducted to elucidate the precise effect of IA treatment in DCM patients.

[Spectral Characteristics and Sources of Dissolved Organic Matter from Landscape River During Flood Season in Suzhou Based on EEMs and UV-vis].

Based on excitation emission matrix spectroscopy (EEMs) technology combined with the parallel factor analysis (PARAFAC) and UV-vis spectra, the spectral characteristics and sources of dissolved organic matter (DOM) from a landscape river were analyzed during different periods of the flood season in Suzou. Four fluorescent components were identified using the PARAFAC model, including two humus-like components (C1, C4) and two protein-like components (C2, C3), with a significant correlation coefficient (P<0.01) in C2 and C3/C4 and C3 and C4, respectively. During the early flood season, the total fluorescence intensity of the DOM in the river was relatively higher due to the influence of initial rainwater but reduced significantly towards the middle and late flood season. The fluorescence characteristic parameters indicated that the autochthonous contribution of DOM were substantial during the early stages of the flood season. On the contrary, there were increased levels of DOM largely from terrestrial origins during the middle flooding period. During the entire flood season, SUVA254, SUVA260, and E2/E3 exhibited the same trend, that is, decreasing first and then increasing. As a result of the continuous heavy rainfall during the flood season, the nitrogen and phosphorus nutrient content in the channel increased. The algae population did not proliferate in large quantities because of the strong hydrodynamic conditions experienced throughout the flood season. The fluorescence components C2, C3, and C4 exhibited a significant correlation coefficient (P<0.01) with the characteristic parameters (FI, HIX, BIX, and ß:α). All the fluorescence components had a high correlation (P<0.05) with DOC. There was a considerable correlation between fluorescence component C1 and Chla. The principal component analysis revealed that the DOM components in the landscape river during different periods of the flood season exhibited notable differences, and the continuous heavy rainfall during the flood season has a substantial influence on the content of C2, C3, and C4 components in the water body.

PP2Cm overexpression alleviates MI/R injury mediated by a BCAA catabolism defect and oxidative stress in diabetic mice.

Diabetic patients are sensitive to myocardial ischemia-reperfusion (MI/R) injury. During diabetes, branched-chain amino acid (BCAA) catabolism is defective and mitochondrial phosphatase 2C (PP2Cm) expression is reduced. This study aims to elucidate the relationship between PP2Cm downregulation and BCAA catabolism defect in diabetic mice against MI/R injury. PP2Cm was significantly downregulated in hearts of diabetic mice. The cardiac function was improved and the myocardial infarct size and apoptosis were decreased in diabetic mice overexpressing PP2Cm after MI/R. In diabetic mice, the cardiac BCAA and its metabolites branched-chain keto-acids (BCKA) levels, and p-BCKDE1α (E1 subunit of BCKA dehydrogenase)/BCKDE1α ratio were increased while the BCKD activity was decreased. Treatment of diabetic mice subjected to MI/R injury with BT2, a BCKD kinase (BDK) inhibitor, alleviated the BCAA catabolism defect, and improved the cardiac function alongside reduced apoptosis. PP2Cm overexpression alleviated the BCAA catabolism defect and MI/R injury. Similarly, MnTBAP ameliorated the oxidative stress and MI/R injury. BCKA treatment of H9C2 cells under simulated ischemia/reperfusion (SI/R) injury significantly decreased cell viability and increased LDH release and apoptosis. These effects were alleviated by BT2 and MnTBAP treatments. These results suggested that PP2Cm directly mediates the BCAA catabolism defect and oxidative stress observed after MI/R in diabetes. Overexpression of PP2Cm alleviates MI/R injury by reducing the catabolism of BCAA and oxidative stress.

CXCR5-negative natural killer cells ameliorate experimental autoimmune myasthenia gravis by suppressing follicular helper T cells.

BACKGROUND: Recent studies have demonstrated that natural killer (NK) cells can modulate other immune components and are involved in the development or progression of several autoimmune diseases. However, the roles and mechanisms of NK cells in regulating experimental autoimmune myasthenia gravis (EAMG) remained to be illustrated. METHODS: To address the function of NK cells in experimental autoimmune myasthenia gravis in vivo, EAMG rats were adoptively transferred with splenic NK cells. The serum antibodies, and splenic follicular helper T (Tfh) cells and germinal center B cells were determined by ELISA and flow cytometry. The roles of NK cells in regulating Tfh cells were further verified in vitro by co-culturing splenocytes or isolated T cells with NK cells. Moreover, the phenotype, localization, and function differences between different NK cell subtypes were determined by flow cytometry, immunofluorescence, and ex vivo co-culturation. RESULTS: In this study, we found that adoptive transfer of NK cells ameliorated EAMG symptoms by suppressing Tfh cells and germinal center B cells. Ex vivo studies indicated NK cells inhibited CD4+ T cells and Tfh cells by inducing the apoptosis of T cells. More importantly, NK cells could be divided into CXCR5- and CXCR5+ NK subtypes according to the expression of CXCR5 molecular. Compared with CXCR5- NK cells, which were mainly localized outside B cell zone, CXCR5+ NK were concentrated in the B cell zone and exhibited higher expression levels of IL-17 and ICOS, and lower expression level of CD27. Ex vivo studies indicated it was CXCR5- NK cells not CXCR5+ NK cells that suppressed CD4+ T cells and Tfh cells. Further analysis revealed that, compared with CXCR5- NK cells, CXCR5+ NK cells enhanced the ICOS expression of Tfh cells. CONCLUSIONS: These findings highlight the different roles of CXCR5- NK cells and CXCR5+ NK cells. It was CXCR5- NK cells but not CXCR5+ NK cells that suppressed Tfh cells and inhibited the autoimmune response in EAMG models.

Exosomes derived from statin-modified bone marrow dendritic cells increase thymus-derived natural regulatory T cells in experimental autoimmune myasthenia gravis.

BACKGROUND: The thymus plays an essential role in the pathogenesis of myasthenia gravis (MG). In patients with MG, natural regulatory T cells (nTreg), a subpopulation of T cells that maintain tolerance to self-antigens, are severely impaired in the thymuses. In our previous study, upregulated nTreg cells were observed in the thymuses of rats in experimental autoimmune myasthenia gravis after treatment with exosomes derived from statin-modified dendritic cells (statin-Dex). METHODS: We evaluated the effects of exosomes on surface co-stimulation markers and Aire expression of different kinds of thymic stromal cells, including cTEC, mTEC, and tDCs, in EAMG rats. The isolated exosomes were examined by western blot and DLS. Immunofluorescence was used to track the exosomes in the thymus. Flow cytometry and western blot were used to analyze the expression of co-stimulatory molecules and Aire in vivo and in vitro. RESULTS: We confirmed the effects of statin-Dex in inducing Foxp3+ nTreg cells and found that both statin-Dex and DMSO-Dex could upregulate CD40 but only statin-Dex increased Aire expression in thymic stromal cells in vivo. Furthermore, we found that the role of statin-Dex and DMSO-Dex in the induction of Foxp3+ nTreg cells was dependent on epithelial cells in vitro. CONCLUSIONS: We demonstrated that statin-Dex increased expression of Aire in the thymus, which may further promote the Foxp3 expression in the thymus. These findings may provide a new strategy for the treatment of myasthenia gravis.

Increased urinary adiponectin level is associated with contrast-induced nephropathy in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: Contrast-induced nephropathy (CIN) is one of major and serious complications in patients undergoing percutaneous coronary intervention (PCI). It is unknown whether increased urinary adiponectin (UAPN), a sensitive marker for early renal function impairment, is associated with an increased risk of CIN. Therefore, we prospectively investigate the association of UAPN with CIN. METHODS: We prospectively enrolled 208 patients who were undergoing elective PCI. The baseline UAPN was assessed prior to PCI. The ROC analysis was used to evaluate the predictive value of UAPN for CIN. Multivariate logistic regression analysis was performed to analyze the independent risk factors for CIN. RESULTS: Of 208 patients, CIN occurred in 19 patients (9.13%), and 6 of them (2.88%) required dialysis. Patients with CIN had a higher UAPN level than those without CIN (17.15 ± 12.36 vs. 10.29 ± 3.04 ng/ml, P < 0.01). ROC analysis showed that the optimal cutoff value of UAPN for predicting CIN was 12.24 ng/ml with 68.42% sensitivity and 76.72% specificity (AUC = 0.7204; 95% CI, 0.582-0.859; 푃< 0.01). Multivariate analysis demonstrated that UAPN (OR, 5.071; 95% CI,1.711-15.028; P < 0.01) and serum creatinine (Scr) > 124 µmol/L (OR, 4.210; 95% CI, 1.297-13.669; P < 0.01) were independently associated with CIN. CONCLUSIONS: Our present study showed that a higher baseline UAPN (≥12.24 ng/ml) level was significantly associated with an increased risk for developing CIN post PCI.

Sulfatides ameliorate experimental autoimmune neuritis by suppressing Th1/Th17 cells.

Sulfatides have immunomodulatory functions, and play protective roles in multiple autoimmune diseases. In the present study, we showed that sulfatides ameliorated experimental autoimmune neuritis in Lewis rats induced with bovine peripheral myelin, which was associated with decreased proportions of Th1 and Th17 cells. Furthermore, compared control group, cells from sulfatide-treated rats exhibited lower potential in proliferation and IL-17 secretion in the presence of BPM or ConA in vitro. Moreover, sulfatides also reduced the proportions of NK and NKT cells. In summary, our study indicated that sulfatides might become a new therapeutic agent in Guillain-Barré syndrome in the future.

Pharmacokinetics of two types of dipropofol crystal tablets in Beagle dogs / 药学学报

A method for determining dipropofol in the plasma of Beagle dogs was established by HPLC-MS/MS. We also studied the pharmacokinetic characteristics of two different forms of crystal tablets of dipropofol in Beagle dogs. All animal experiments were approved by the Animal Experimental Management, Welfare and Ethics Committee of Pharmacology Evaluation Research Center, Shanghai Institute of Pharmaceutical Industry. The results indicate that the maximum plasma concentration (Cmax) of dipropofol was 69.02 ± 20.16 μg·L-1 after 20 mg·kg-1 crystal form Ⅰ tablet taken orally, and the AUC0-t was 160.49 ± 55.26 μg·L-1·h. After 20 mg·kg-1 crystal form Ⅱ tablet taken, the Cmax of dipropofol was 92.58 ± 60.26 μg·L-1, and the AUC0-t was 243.59 ± 148.36 μg·L-1·h. The AUC0-t and Cmax of crystal form Ⅱ were significantly different from that of crystal form Ⅰ (P<0.05). Crystal form Ⅱ was the dominant crystal form. The results suggest that we should control crystal form during the development of dipropofol oral tablets.

Immunotherapy: Towards on early non-small cell lung cancer / 医学研究生学报

Surgery is the standard treatment for early resectable non-small cell lung cancer (NSCLC), but the recurrence rate is high. There is no effective cure for this. Immunological checkpoint inhibitors have altered the therapeutic model of patients with advanced gene therapy for advanced NSCLC, presenting new hope for early immunotherapy of NSCLC. Immunological checkpoint inhibitors have altered the therapeutic model of patients with driving gene-negative NSCLC patients, presenting new hope for early immunotherapy of NSCLC. Based on the analysis of the status of early NSCLC adjuvant therapy, the clinical study of immunological checkpoint inhibitors as a new adjuvant/adjuvant therapy in early operable NSCLC was explored in this paper.

An Integrated Analysis of Risk Factors of Cognitive Impairment in Patients with Severe Carotid Artery Stenosis.

OBJECTIVE: To investigate cognitive dysfunction in patients with carotid artery stenosis (CAS) and potential risk factors related to cognitive-especially memory-dysfunction. METHODS: Forty-seven patients with carotid artery stenosis were recruited into our study cohort. The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) were adopted to assess cognitive function, the Wechsler Memory Scale (WMS) to assess memory function, high-resolution MRI and enhanced ultrasound to evaluate carotid plaques, and computed tomography perfusion (CTP) imaging to evaluate intracranial blood perfusion. Single-factor analysis and multiple-factor regression analysis were used to analyze potential risk factors of cognitive impairment. RESULTS: Mini-Mental State Examination test results showed that 22 patients had cognitive impairment, and MoCA test results showed that 10 patients had cognitive impairment. Analysis of various risk factors indicated that the average memory quotient of female patients was higher than that of males (P = 0.024). The cognitive and memory performance of those with an educational background above high school were significantly better than those of participants with high school or lower (P = 0.045). Patients with abnormal intracranial perfusion performed worse on the MMSE test (P = 0.024), and their WMS scores were significantly lower (P = 0.007). The MMSE scores and the memory quotients were significantly lower in patients with a history of cerebral infarction (MMSE, P = 0.047, memory quotient score, P = 0.018). CONCLUSION: A history of cerebral infarction and abnormal cerebral perfusion are associated with decline in overall cognitive function and memory in patients with carotid stenosis. Being female and having an educational background above high school may be protective factors in the development of cognitive dysfunction.

Melatonin Ameliorates Liver Fibrosis Induced by Carbon Tetrachloride in Rats via Inhibiting TGF-ß1/Smad Signaling Pathway.

Melatonin has been reported to inhibit hepatic fibrosis and the mechanism may be correlated to its anti-oxidant effect. Nevertheless, the mechanism is not completely identified. This study was conducted to investigate the effects of melatonin on TGF-ß1/Smad signaling pathway in liver fibrosis in rats. The liver fibrosis model was made by the subcutaneous injection of CCl4. The liver pathology changes were detected using hematoxylin and eosin (H&E) staining and Van Gieson (VG) staining. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured with an autoanalyzer. Glutathione peroxidase (GPx) activities and levels of malondialdehyde (MDA) and hydroxyproline (Hyp) in liver were evaluated by spectrophotometry. Expression levels of TGF-ß1, Smad2/3, phosphorylated Smad2/3 (p-Smad2/3) and Smad7 in liver were detected by immunohistochemistry and Western blot analysis. Results showed that melatonin suppressed CCl4-induced liver fibrosis, along with an improvement in histological changes, significant decreases in pathologic grading sores and obvious decreases in Hyp levels in liver. Melatonin improved liver function indicated by decreased serum ALT and AST activities. In addition, melatonin exerted its anti-oxidant effects, as supported by decreased MDA levels and increased GPx activities in liver. Furthermore, melatonin inhibited TGF-ß1/Smad pathway, as evidenced by decreased TGF-ß1, Smad2/3 and p-Smad2/3 expression and increased Smad7 expression in liver. In conclusion, melatonin may suppress CCl4-induced hepatic fibrosis in rats via inhibiting TGF-ß1/Smad pathway. It is possible for melatonin to be a potential reagent to treat and cure liver fibrosis.