Endothelial cell-derived RSPO3 activates Gαi1/3-Erk signaling and protects neurons from ischemia/reperfusion injury.

The current study explores the potential function and the underlying mechanisms of endothelial cell-derived R-spondin 3 (RSPO3) neuroprotection against ischemia/reperfusion-induced neuronal cell injury. In both neuronal cells (Neuro-2a) and primary murine cortical neurons, pretreatment with RSPO3 ameliorated oxygen and glucose deprivation (OGD)/re-oxygenation (OGD/R)-induced neuronal cell death and oxidative injury. In neurons RSPO3 activated the Akt, Erk and ß-Catenin signaling cascade, but only Erk inhibitors reversed RSPO3-induced neuroprotection against OGD/R. In mouse embryonic fibroblasts (MEFs) and neuronal cells, RSPO3-induced LGR4-Gab1-Gαi1/3 association was required for Erk activation, and either silencing or knockout of Gαi1 and Gαi3 abolished RSPO3-induced neuroprotection. In mice, middle cerebral artery occlusion (MCAO) increased RSPO3 expression and Erk activation in ischemic penumbra brain tissues. Endothelial knockdown or knockout of RSPO3 inhibited Erk activation in the ischemic penumbra brain tissues and increased MCAO-induced cerebral ischemic injury in mice. Conversely, endothelial overexpression of RSPO3 ameliorated MCAO-induced cerebral ischemic injury. We conclude that RSPO3 activates Gαi1/3-Erk signaling to protect neuronal cells from ischemia/reperfusion injury.

Neuroprotective effect of engineered Clostridiumbutyricum-pMTL007-GLP-1 on Parkinson's disease mice models via promoting mitophagy.

Parkinson's disease (PD) is a common neurodegenerative disease with limited treatment and no cure, hence, broadening PD drug spectrum is of great significance. At present, engineered microorganisms are attracting increasing attention. In this study, we constructed an engineered strain of Clostridium butyricum-GLP-1, a C. butyricum (a probiotic) that consistently expresses glucagon-like peptide-1 (GLP-1, a peptide-based hormone with neurological advantage) in anticipation of its use in PD treatment. We further investigated the neuroprotective mechanism of C. butyricum-GLP-1 on PD mice models induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The results indicated that C. butyricum-GLP-1 could improve motor dysfunction and ameliorate neuropathological changes by increasing TH expression and reducing the expression of α-syn. Moreover, we confirmed that C. butyricum-GLP-1 improved microbiome imbalance of PD mice by decreasing the relative abundance of Bifidobacterium at the genus level, improved gut integrity, and upregulated the levels of GPR41/43. Surprisingly, we found it could exert its neuroprotective effects via promoting PINK1/Parkin mediated mitophagy and attenuating oxidative stress. Together, our work showed that C. butyricum-GLP-1 improves PD by promoting mitophagy, which provides an alternative therapeutic modality for PD.

Engineered probiotics Clostridium butyricum-pMTL007-GLP-1 improves blood pressure via producing GLP-1 and modulating gut microbiota in spontaneous hypertension rat models.

Hypertension is a significant risk factor of cardiovascular diseases (CVDs) with high prevalence worldwide, the current treatment has multiple adverse effects and requires continuous administration. The glucagon-like peptide-1 receptor (GLP-1R) agonists have shown great potential in treating diabetes mellitus, neurodegenerative diseases, obesity and hypertension. Butyric acid is a potential target in treating hypertension. Yet, the application of GLP-1 analogue and butyric acid in reducing blood pressure and reversing ventricular hypertrophy remains untapped. In this study, we combined the therapeutic capability of GLP-1 and butyric acid by transforming Clostridium butyricum (CB) with recombinant plasmid pMTL007 encoded with hGLP gene to construct the engineered probiotics Clostridium butyricum-pMTL007-GLP-1 (CB-GLP-1). We used spontaneous hypertensive rat (SHR) models to evaluate the positive effect of this strain in treating hypertension. The results revealed that the intragastric administration of CB-GLP-1 had markedly reduced blood pressure and improved cardiac marker ACE2, AT2R, AT1R, ANP, BNP, ß-MHC, α-SMA and activating AMPK/mTOR/p70S6K/4EBP1 signalling pathway. The high-throughput sequencing further demonstrated that CB-GLP-1 treatments significantly improved the dysbiosis in the SHR rats via downregulating the relative abundance of Porphyromonadaceae at the family level and upregulating Lactobacillus at the genus level. Hence, we concluded that the CB-GLP-1 greatly improves blood pressure and cardiomegaly by restoring the gut microbiome and reducing ventricular hypertrophy in rat models. This is the first time using engineered CB in treating hypertension, which provides a new idea for the clinical treatment of hypertension.

Mechanisms of self-control on health behavior change / 中华行为医学与脑科学杂志

Self-control brings important effects on the process and maintenance of health behavior change in individuals, but its mechanism is unclear.Healthy behavior change could be divided into goal-oriented behavior initiation stage, combating habit rejection stage, and habit acquisition and maintenance stage.Established theories of health behavior change mainly focus on the conflict between the goal-directed behavior initiation phase and habitual behavior.It is also indicated that disgust is the key mechanism to restrain the implementation of goal-oriented behavior, but ignore the mechanisms in the action implementation and new behavior acquisition phases.In fact, goal-directed and habitual behaviors work together to ensure that individuals adapt efficiently to their environment.However, when goal-oriented behavior becomes habitual, old habit and new goal-oriented behavior begin to compete, causing conflicts and aversion.The core phase of self-control functioning is just in the confrontation with habit rejection phase.On the one hand, self-control directly assists individual goal-directed behavior habituation through conflict sense adaptation.On the other hand, intensive management and stimulus control indirectly assist goal-directed behavior habituation through the relief of conflict sense.Further exploration of the theory and clinical practice of self-control affecting healthy behavior change is needed in the future.

Anti-Tumor Effects of Engineered VNP20009-Abvec-Igκ-mPD-1 Strain in Melanoma Mice via Combining the Oncolytic Therapy and Immunotherapy.

Programmed cell death protein 1/Programmed cell death ligand 1 (PD-1/PD-L1) immune checkpoint inhibitors are the most promising treatments for malignant tumors currently, but the low response rate limits their further clinical utilization. To address this problem, our group constructed an engineered strain of VNP20009-Abvec-Igκ-mPD-1 [V-A-mPD-1 (mPD-1, murine PD-1)] to combine oncolytic bacterial therapy with immunotherapy. Further, we evaluated its growth performance and mPD-1 expression ability in vitro while establishing the melanoma mice model to explore its potential anti-cancer effects in tumor therapy. Our results indicated that the V-A-mPD-1 strain has superior growth performance and can invade B16F10 melanoma cells and express PD-1. In addition, in the melanoma mice model, we observed a marked reduction in tumor volume and the formation of a larger necrotic area. V-A-mPD-1 administration resulted in a high expression of mPD-1 at the tumor site, inhibiting tumor cell proliferation via the down-regulation of the expression of rat sarcoma (Ras), phosphorylated mitogen-activated protein kinase (p-MEK)/MEK, and phosphorylated extracellular signal-regulated kinase (p-ERK)/ERK expression significantly inhibited tumor cell proliferation. Tumor cell apoptosis was promoted by down-regulating phosphoinositide 3 kinase (PI3K) and protein kinase B (AKT) signaling pathways, as evidenced by an increased Bcl-2-associated X protein/B cell lymphoma-2 (Bax/Bcl-2) expression ratio. Meanwhile, the expression levels of systemic inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α), were substantially reduced. In conclusion, our research demonstrated that V-A-mPD-1 has an excellent anti-tumor effect, prompting that the combined application of microbial therapy and immunotherapy is a feasible cancer treatment strategy.

[Probiotics' Ameliorating Effect on Side Effects of Cancer Treatment: Reflections and Prospects].

Surgical resection, radiotherapy, chemotherapy, and immunotherapy are the main therapies for cancers. These cancer therapies all prolong patient survival, but also bring multiple side effects. Gut microbiota participates in almost all the physiological and biochemical processes of the host, playing a key role in human health and diseases. As an exogenous intervention, probiotics can prevent diseases and enhance immunity. Their anti-cancer ability and ameliorative effect have received increasing recognition. Herein, we reported the latest findings on gut microbiota and cancer pathogenesis, focusing on the application of probiotics in reducing the side effects caused by cancer therapies and hoping to provide supportive references for the clinical use of probiotics in cancer treatment.

Association of temperament type and mother's emotional state with acute respiratory infection in children / 南方医科大学学报

OBJECTIVE@#To explore the correlation of temperament type and mother's emotional state with acute respiratory tract infections in children so as to provide evidence for comprehensive treatment of the infections.@*METHODS@#A total of 200 children aged between 3 and 6 were enrolled in this study from two kindergartens of Guangzhou and Hengyang. The mothers were invited to complete a questionnaire of the children's general information followed by assessment using children's temperament scale and the Depression-Anxiety-Stress Scale.@*RESULTS@#The total incidence of acute respiratory infection was significantly higher in children with a hard- to-raise temperament than the easy- to-raise children (P < 0.05); the incidences of acute rhinitis, acute pharyngitis, acute laryngitis and acute bronchitis were all significantly higher in the hard-to-raise children (P < 0.05). A significant positive correlation was identified between the total number of episodes of acute respiratory tract infection in children and their mothers' stress and anxiety levels (P < 0.01). Acute rhinitis and acute tracheitis in the children were both positively correlated with the mothers' stress scores (P < 0.05), while acute pharyngitis and acute laryngitis were positively correlated with the mothers' anxiety scores (P < 0.05), while acute bronchitis was positively correlated with the mothers' stress and anxiety scores (P < 0.05). Multiple linear regression analysis with the factors influencing the types of acute respiratory tract infections in children as the independent variables suggested that the easy-to-raise type of temperament was a protective factor against acute rhinitis in children (P < 0.05), while mothers' anxiety was a risk factor of acute laryngitis in children (P < 0.05); the mothers' stress was a risk factor for acute bronchitis in children (P < 0.05).@*CONCLUSION@#Acute respiratory tract infection in children is closely related to the temperament type of the children and the emotional state of the mothers, which are important therapeutic targets in comprehensive interventions of acute respiratory tract infection in children.

Preparation of active thiol metabolite of clopidogrel by isolated rat liver perfusion / 中国药房

OBJECTIVE To estab lish the pre paration method of clopidogrel active thiol metabolite （CATM），and to provide reference for the synthesis of cis-CATM. METHODS CATM was prepared ，separated and purified with isolated rat liver perfusion and ChromCore 120 C18 preparative column ，using（S）-2-oxo-clopidogrel as substrate. The target compounds were identified by mass spectrometry and nuclear magnetic resonance spectroscopy. The retention time of the active configuration of CATM in the human body （cis-CATM）were compared to confirm the proportion of active configuration in the target product. RESULTS The conversion rate of the target product was 11.71％. The target products were identified as CATM by MS and 1H-NMR. Peak 2-peak 5 of CATM were four stereoisomers. The retention time of them were 21.3，22.3，26.5，27.3 min. The peak area ratios of them were 7.13％，7.23％，63.52％，14.97％，respectively. Based on that retention time of the active configuration of CATM in human body was 26.3 min，the active cis-stereoisomer in the target product CATM accounted for 63.52％. CONCLUSIONS This method is low-cost ，simple，and can prepare CATM with higher active configuration.

Risk factors for clopidogrel resistance / 国际脑血管病杂志

Clopidogrel is the most commonly used antiplatelet agent for acute coronary syndrome, ischemic stroke, and before and after percutaneous coronary intervention, and endovascular treatment of large vessel occlusive stroke, but there are individual differences in antiplatelet effect, that is, clopidogrel resistance (CR). CR is usually attributed to the decrease of the concentration of sulfhydryl metabolites in plasma, and there are many factors that cause the decrease of the concentration of sulfhydryl metabolites. This article reviews the research progress of CR-related risk factors, so that clinicians can assess the risk of CR and adopt individualized antiplatelet therapy to improve the clinical outcome of patients.

Research update on emotion ability development of hearing impaired children / 中国学校卫生

Abstract@#Emotion ability has substantial influence on individuals survival and development as well as mental health. Emotion ability development disorder has become a prominent performance of hearing impaired children, which has attracted the attention of researchers at home and abroad. From the four aspects of emotion recognition, emotion understanding, emotion expression and emotion regulation, this paper sorts out and comments on the previous studies, puts forward the intervention measures in the light of the concrete problems existing in the development, and proposes some suggestions for the curtent study limitations, in order to provide fundamental evidance for promotion of emotion ability of hearing impaired children.

Recovery of a patient with severe COVID-19 by acupuncture and Chinese herbal medicine adjuvant to standard care / 中西医结合学报

There is currently no drug or therapy that can cure the coronavirus disease 2019 (COVID-19), which is highly contagious and can be life-threatening in severe cases. Therefore, seeking potential effective therapies is an urgent task. An older female at the Leishenshan Hospital in Wuhan, China, with a severe case of COVID-19 with significant shortness of breath and decrease in peripheral oxygen saturation (SpO

Recycling experimental investigation on end of life photovoltaic panels by application of high voltage fragmentation.

With the rapid development of photovoltaic industry, the recycling of waste solar photovoltaic (PV) panels is becoming a critical and global challenge. Considering PV panels recycling is significantly effective and worthwhile to save natural resources and reduce the cost of production, how to selectively recycle valuable components of PV panels is the hot and dominant topic. Different from current mechanical crushing, heat treatment and chemical operation processes, novel and environment-friendly recycling approaches by using high voltage pulse discharge in water, called high voltage fragmentation (HVF), was discussed under different discharge conditions. The results showed that discharging across surface and interior of PV panels produced ablation round holes, sputter metal particles and dendritic channels. The average particle size decreased with the ascent of pulse number and voltage amplitude. Considering the energy consumption, the optimal condition of HVF in this paper was 160 kV for 300 pulses with the energy consumption of 192.99 J/g, crushing the PV panels into particles of 4.1 mm in average (13.7% of the initial size). More particle was distributed among the 0.1-2 mm size fractions as the energy increased. Selective fragmented products, such as Cu, Al, Pb, Ag and Sn, are concentrated on the fractions under 1 mm. Finally, hybrid crushing energy consumption model combined with fractal theory was discussed, which presented close relationship between energy and average particle size. Walker's model (n = 2.047 determined by fractal theory) had the best fitting effect.

Effect of traditional Chinese medicine in improving human health by regulating bacterial quorum sensing system / 中国中药杂志

Quorum sensing(QS) is one of the research hotspots in the fields of microbiology and medicine in recent years. Quorum sensing is a cell communication regulatory system, which is used by bacterial flora to pass on information of population density by sensing specific signaling molecules to the environment. The QS system of bacteria can impact biological functions, such as bacterial growth, proliferation, biofilm formation, virulence factor production, antibiotic synthesis, and ultimately adapt the bacteria to environmental changes. At present, more and more active ingredients can regulate quorum sensing have been found in traditional Chinese medicines(TCM). TCM and their active ingredients can promote the growth of beneficial bacteria, inhibit the proliferation of pathogenic bacteria and finally achieve the purpose of treating diseases. It embodies multi-pathway and multi-target characteristics of traditional Chinese medicine. This article first introduces molecular types and regulation mechanisms of quorum sensing signals between bacteria. On this basis, the human health-related bacterial quorum sensing is summarized, and the regulatory effect of TCM on bacterial quorum sensing system is discussed. Finally, it is noted that the material basis and mechanisms of TCM in improving human health through bacterial quorum sensing system are still unclear. Future research hotspots will focus on quorum sensing active substances, quorum sensing key nodes and relevant targets. In a word, this article provides reference for the treatment of relevant diseases.

Apatinib for treatment of a pseudomyxoma peritonei patient after surgical treatment and hyperthermic intraperitoneal chemotherapy: A case report.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare benign, but progressive, disease according to myxoma histopathology. Surgical resection is the preferred and most effective treatment, but the outcomes are often unsatisfactory. CASE SUMMARY: A 63-year-old Chinese woman with PMP received apatinib at a daily dose of 0.5 mg for 15 d per cycle and at a daily dose of 0.4 mg to date for recurrent abdominal distension after surgical treatment and hyperthermic intraperitoneal chemotherapy. During the follow-up period, apatinib was the maintenance treatment with a progression-free period of 10 mo and the toxicity of apatinib was controllable and tolerable. Unfortunately, recurrence occurred 10 mo after administration. After two operations, the patient gave up treatment at the 18th mo and eventually died of intestinal obstruction and multiple organ failure. CONCLUSION: Apatinib may be an option for recurrent PMP after surgical treatment, but this conclusion remains to be confirmed.

CD38 Deficiency Alleviates D-Galactose-Induced Myocardial Cell Senescence Through NAD+/Sirt1 Signaling Pathway.

Our previous research showed that CD38 played vital roles in Ang-II induced hypertrophy and high fat diet induced heart injury. However, the role of CD38 in heart aging is still unknown. In the present study, we reported that CD38 knockdown significantly protected cardiomyocytes from D-galactose (D-gal)-induced cellular senescence. Cellular senescence was evaluated by ß-galactosidase staining, the expressions of genes closely related to aging including p16 and p21, and the ROS production, MDA content and the expressions of oxidant stress related genes were examined by biochemical analysis, Western blot and QPCR. Our results showed that the expression of CD38 was increased in H9c2 cells after D-gal treatment and the expressions of NAMPT and Sirt1 were downregulated in heart tissue from old mice. CD38 knockdown significantly reduced the number of SA-ß-gal-positive cells and the expressions of p16 and p21 in H9c2 cells with or without D-gal treatment. The acetylation level of total protein was decreased in CD38 knockdown group, but the expression of Sirt3 was increased in CD38 knockdown group treated with D-gal. In addition, knockdown of CD38 significantly attenuated D-gal induced ROS production, MDA content and NOX4 expression in the cells. Inhibition Sirt1 partially reversed the effects of CD38 knockdown on D-gal induced senescence and oxidative stress. Furthermore, NAD+ supplementation reduced D-gal induced cellular senescence, ROS production and MDA content. The expression of SOD2 was increased and the NOX4 expression was decreased in H9c2 cells after NAD+ supplementation. Taken together, our results demonstrated that CD38 knockdown alleviated D-gal induced cell senescence and oxidative stress via NAD+/Sirt1 signaling pathway.

Relation among personality, self-control and procrastination in young people / 中国心理卫生杂志

Objective:To explore the relationship between personality traits and procrastination in young people and the mediating role of self-control.Methods:A total of 344 college students (191 males and 153 females) were assessed with the Mini-IPIP Scale (Mini-IPIP), Dual-Mode of Self-Control Scale (DMSC-S, including control system and impulse system) and General Procrastination Scale (GPS).Results:The GPS scores were negatively correlated with scores of agreeableness subscale and conscientiousness subscale (r=-0.13, -0.53, Ps＜0.05), and positively correlated with scores of neuroticism subscales (r=0.27, P＜0.01).The structural equation modeling supported the impulse system fully mediated the relationship between neuroticism and procrastination (η2=0.15, 95％CI=0.02-0.25), and those two systems partly mediated the relationship between conscientiousness and procrastination (η2=0.20, 0.20;95％CI=-0.38——0.05, -0.70——0.24).Conclusion:The relationship between youth personality and procrastination may be mediated by a dual system of self-control.Additionally, the degree to how self-control affects the relationship between big five personality trait and procrastination is different under the different types of personality.

Harmine inhibits COX-2 expression in gastric cancer cells through PTEN/Akt/MDM2 signaling pathway / 中国药理学通报

Aim To further analyze the effects of PTEN/Akt/MDM2 signaling pathway in the harmine (HM)-mediated inhibition of COX-2 expression in gastric cancer cells. Methods PTEN-siRNA, Akt-siR-NA, MDM2-siRNA were constructed and respectively transfected into SGC-7901 and MKN45 cells,and then added or not added HM for 24 h. The expression of PTEN, Akt and phosphorylated Akt ( p-Akt), MDM2 and phosphorylated MDM2 ( p-MDM2), as well as COX-2 expression was detected by Western blot. Results HM increased PTEN expression, but inhibited p-Akt,p-MDM2 and COX-2 expression in SGC-7901 and MKN45 cells. Knockdown of PTEN blocked HM-induced inhibition of Akt and MDM2 phosphorylation, as well as down-regulation of COX-2 expression. Knockdown of Akt and treatment with HM synergisti-cally inhibited p-MDM2 and COX-2 expression. Knockdown of MDM2 and treatment with HM synergis-tically inhibited COX-2 protein expression. Conclusions HM down-regulates the expression of COX-2 protein in gastric cancer cells via PTEN/Akt/MDM2 signaling pathway.

Evaluating two methods of digital photography in retinopathy screening / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM:To evaluate the advantages of non - mydriatic fundus photography (NMFCS) and mydriatic fundus photography (MFCS) as eye - bottom screening and diagnosis methods in compared with gold standard fluorescein fundus angiography (FFA). ·METHODS: A total of 276 patients which involved in Chronic Diabetes Management Achieves within 4 streets of Pudong District Shanghai, were enrolled for diabetic retinopathy (DR) examination including NMFCS, MFCS and FFA. These DR examinations were proceeded after vision,slit-lamp and dioptroscopy tests,and reported by professionals. For those with suspicious fundus diseases, we would make appointments with specialist for further treatment. ·RESULTS: A total of 1104 colorful fundus images, and 1056 images (95.65%) could be used to analyze. There were 408 appreciable images, 116 basically appreciable images and 28 unusable images in 552 NMFCS images. In addition,there were 432 appreciable images,100 basically appreciable images and 20 unusable images in 552 MFCS images. There was no significant differences between NMFCS and MFCS (P>0.05). Compared with FFA with DRⅠ as the critical value, the specificity of digital photography for NMFCS was 95.71%, the sensitivity was 93.56%;however, MFCS are 95.43% and 98.02%. There was no statistically significant difference between the two screening methods (P>0.05). Compared with FFA with DR Ⅱ as the critical value, the specificity of digital photography for NMFCS was 95.35% and the sensitivity was 93. 44%; however, for MFCS were 95. 81% and 98.36%. There was no statistically significant difference between the two screening methods (P>0.05). ·CONCLUSION: Both NMFCS and MFCS could be used for the diagnosis and screening for eye diseases. NMFCS is easier and faster for digital photography, which is suitable for mass screening. MFCS is more likely to provide detailed information about the follow-up of the disease.

Investigation on the prevalence and awareness of DR in diabetic patients based on community chronic disease / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the prevalence and awareness of diabetic retinopathy ( DR ) among patients with diabetes mellitus in the Huamu Community of Shanghai.?METHODS: A total of 545 diabetic patients in the community's chronic disease file were enrolled in the Ophthalmologic Examination and DR Prevention Questionnaire. To know the prevalence rate of DR and to use chi-square test to check analysis the difference of prevalence rate. The descriptive statistical analysis of DR prevention and treatment knowledge was carried out in diabetes.?RESULTS: The prevalence of DR was 23. 5％. And the prevalence of non - proliferative retinopathy and proliferative retinopathy was 20. 9％ and 2. 6％. The patients with diabetes in the Huamu Community lacked sufficient awareness of DR prevention and treatment methods.?CONCLUSION: Using the chronic disease file for eye tests in diabetes can help prevent DR from beginning in the community. Awareness of DR in diabetic patients also needs to be improved.