Downregulation of SIRT1 and GADD45G genes and left atrial fibrosis induced by right ventricular dependent pacing in a complete atrioventricular block pig model.

The molecular and genetic mechanisms underlying left atrial (LA) enlargement and atrial fibrosis following right ventricular (RV) dependent pacing remain unclear. Our objective was to investigate genetic expressions in the LA of pigs subjected to RV pacing for atrioventricular block (AVB), as well as to identify the differential gene expressions affected by biventricular (BiV) pacing. We established an AVB pig model and divided the subjects into three groups: a sham control group, an RV pacing group, and a BiV pacing group. Differential expression genes (DEGs) analyses conducted through next-generation sequencing (NGS) and enrichment analyses were employed to identify genes with altered expression in the LA myocardium. The RV pacing group showed a significant increase in extracellular fibrosis in the LA myocardium compared to the control group. NGS analysis revealed suppressed expression of the sirtuin signaling pathway in the RV pacing group. Among the DEGs within this pathway, GADD45G was found to be downregulated in the RV pacing group and upregulated in the BiV pacing group. Remarkably, the BiV pacing group exhibited elevated levels of GADD45G protein. In our study, we observed significant downregulation of SIRT1 and GADD45G genes, which are associated with the sirtuin signaling pathway, in the LA myocardium of the RV pacing group when compared to the control group. Moreover, these genes, which were downregulated in the RV pacing group, displayed a noteworthy upregulation in the BiV pacing group when compared to the RV pacing group.

Arbuscular mycorrhizal fungi benefit plants in response to major global change factors.

Land plants play a key role in global carbon cycling, but the potential role of arbuscular mycorrhizal fungi (AMF) in the responses of a wide range of plant species to global change factors (GCFs) remains limited. Based on 1100 paired observations from 181 plant species, we conducted a meta-analysis to test the role of AMF in plant responses to four GCFs: drought, warming, nitrogen (N) addition and elevated CO2 . We show that AMF significantly ameliorate the negative effects of drought on plant performance. The GCFs N addition and elevated CO2 significantly enhance the performance of AM plants but not of non-inoculated plants. AM plants show better performance than their non-inoculated counterparts under warming, although neither of them showed a significant response to this GCF. These results suggest that AMF benefit plants in response to GCFs. Our study highlights the importance of AMF in enhancing plant performance under ongoing global change.

Baicalin promotes antiviral IFNs production and alleviates type I IFN-induced neutrophil inflammation.

Type I and III interferons (IFNs) both serve as pivotal components of the host antiviral innate immune system. Although they exert similar antiviral effects, type I IFNs can also activate neutrophil inflammation, a function not born by type III IFNs. Baicalin, the main bioactive component of Scutellariae radix, has been shown to exert therapeutic effects on viral diseases due to its anti-viral, anti-inflammatory and immunomulatory activities. There is uncertainty, however, on the association between the antiviral effects of baicalin and the modulation of anti-viral IFNs production and the immunological effects of type I IFNs. Here, a Poly (I:C)-stimulated A549 cell line was established to mimic a viral infection model. Our results demonstrated that baicalin could elevate the expression of type I and III IFNs and their receptors in Poly (I:C)-stimulated A549 cells. Moreover, the potential regulation effects of baicalin for type I IFN-induced neutrophil inflammation was further explored. Results showed that baicalin diminished the production of the pro-inflammatory cytokines (IL-1ß, IL-6, IL-17 and TNF-α), ROS, and neutrophil extracellular traps and suppressed chemotaxis. Collectively, all these data indicated that baicalin had a dual role on IFNs production and effects: (1) Baicalin was able to elevate the expression of type I and III IFNs and their receptors, (2) and it alleviated type I IFN-mediated neutrophil inflammatory response. This meant that baicalin has the potential to act as an eximious immunomodulator, exerting antiviral effects and reducing inflammation.

Shenlian extract protected ox-LDL-loaded macrophages against ER stress by promoting LAL-LXRα mediated cholesterol flux.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenlian (SL) extract is consisted of extracts from Salvia miltiorrhiza Bunge and Andrographis paniculata (Burm.f.) Nees, two herbs commonly used in Chinese clinical formula to treat atherosclerosis by removing blood stasis and clearing away heat. Pharmacologically, the anti-atherosclerotic effects of these two herbs are related to unresolved inflammation and the macrophage anergy or apoptosis in lesions led by the lipid flux blockage and ER stress. However, the deeper understanding of SL extract in protecting macrophage in plaques remains unknown. AIM OF THE STUDY: This study aimed to investigate the underlying mechanism of SL extract in protecting ER-stressed macrophages from apoptosis in atherosclerosis. METHODS: The ApoE-/- atherosclerotic mice model and ox-LDL loaded macrophages model were established to assess the effect of SL extract on ER stress in vivo and in vitro. Key markers related to ER stress in plaque were determined by immunohistochemical staining. Proteins involved in apoptosis and ER stress in macrophages loaded by ox-LDL were assessed by Western blot. ER morphology was observed by electron microscope. Lipid flux was temporally and quantitatively depicted by Oil red staining. The LAL and LXRα were blocked by lalistat and Gsk 2033 respectively to investigate whether SL extract protected the function of macrophages by the activation of LAL-LXRα axis. RESULTS: Our study reported that, in ApoE-/- atherosclerotic mice, SL extract effectively relieved ER stress of carotid artery plaque. In lipid-overloaded macrophage models, SL extract significantly alleviated ER stress by promoting cholesterol degradation and efflux, which finally prevented apoptosis of foam cells induced by ox-LDL. Blockage of ER stress by 4-Phenylbutyric acid (4-PBA), an inhibitor of Endoplasmic Reticulum (ER) stress, largely attenuated the protective effects of SL extract on macrophage. By utilizing the selective antagonists against both LAL and LXRα, this study further revealed that the beneficial effects of SL extract in macrophages was dependent on the proper functionalization of LAL-LXRα axis. CONCLUSIONS: By highlighting the therapeutic significance of macrophage protection in resolving atherosclerosis inflammation, our study pharmacologically provided convincing mechanistic evidence of SL extract in the activation LAL-LXRα axis and revealed its promising potential in the promotion of cholesterol turnover and prevention of ER stress induced apoptosis in lipid-loaded macrophages.

TANGO1 interacts with NRTN to promote hepatocellular carcinoma progression by regulating the PI3K/AKT/mTOR signaling pathway.

Transport and Golgi organization 1 (TANGO1) also known as MIA3, belongs to the melanoma inhibitory activity gene (MIA) family together with MIA, MIA2 and OTOR; these members play different roles in different tumors, but the mechanism underlying TANGO1s effect on hepatocellular carcinoma (HCC) is unclear. Our study confirmed that TANGO1 is a promoter of HCC, In HCC cells, TANGO1 can promote proliferation, inhibit apoptosis, promote EMT. These changes were reversed after TANGO1 inhibition. We explored the molecular mechanism of TANGO1 and HCC and found that the promoting effect of TANGO1 on HCC related to neurturin (NRTN) and the PI3K/AKT/mTOR signaling pathway based on RNA-seq results. NRTN is not only related to neuronal growth, differentiation and maintenance but is also involved in a variety of tumorigenic processes, and PI3K/AKT/mTOR signaling pathway has been shown to be involved in HCC progression. We verified that TANGO1 interacts with NRTN in HCC cells using endogenous Co-IP and confocal localization, and both promote HCC progression by activating the PI3K/AKT/mTOR signaling pathway. Our results reveal the mechanism by which TANGO1 promotes HCC progression, suggesting that the TANGO1/NRTN axis may be a potential therapeutic target for HCC worthy of further investigation.

[Research status and prospect of remyelination in multiple sclerosis based on "inflammation-tissue" homeostatic coupling].

Multiple sclerosis(MS) shows the pathological characteristics of "inflammatory injury of white matter" and "myelin repair disability" in the central nervous system(CNS). It is very essential for MS treatment and reduction of disease burden to strengthen repair, improve function, and reduce disability. Accordingly, different from the simple immunosuppression, we believe that key to strengthening remyelination and maintaining the "damage-repair" homeostasis of tissue is to change the current one-way immunosuppression strategy and achieve the "moderate pro-inflammation-effective inflammation removal" homeostasis. Traditional Chinese medicine shows huge potential in this strategy. Through literature research, this study summarized the research on remyelination, discussed the "mode-rate pro-inflammation-effective inflammation removal" homeostasis and the "damage-repair" homeostasis based on microglia, and summed up the key links in remyelination in MS. This review is expected to lay a theoretical basis for improving the function of MS patients and guide the application of traditional Chinese medicine.

Research status and prospect of remyelination in multiple sclerosis based on "inflammation-tissue" homeostatic coupling / 中国中药杂志

Multiple sclerosis(MS) shows the pathological characteristics of "inflammatory injury of white matter" and "myelin repair disability" in the central nervous system(CNS). It is very essential for MS treatment and reduction of disease burden to strengthen repair, improve function, and reduce disability. Accordingly, different from the simple immunosuppression, we believe that key to strengthening remyelination and maintaining the "damage-repair" homeostasis of tissue is to change the current one-way immunosuppression strategy and achieve the "moderate pro-inflammation-effective inflammation removal" homeostasis. Traditional Chinese medicine shows huge potential in this strategy. Through literature research, this study summarized the research on remyelination, discussed the "mode-rate pro-inflammation-effective inflammation removal" homeostasis and the "damage-repair" homeostasis based on microglia, and summed up the key links in remyelination in MS. This review is expected to lay a theoretical basis for improving the function of MS patients and guide the application of traditional Chinese medicine.

Non-ribosomal peptide biosynthetic potential of the nematode symbiont Photorhabdus.

Photorhabdus, the symbiotic bacteria of Heterorhabditis nematodes, has been reported to possess many non-ribosomal peptide synthetase (NRPS) biosynthesis gene clusters (BGCs). To provide an in-depth assessment of the non-ribosomal peptide biosynthetic potential of Photorhabdus, we compared the distribution of BGCs in 81 Photorhabdus strains, confirming the predominant presence (44.80%) of NRPS BGCs in Photorhabdus. All 990 NRPS BGCs were clustered into 275 gene cluster families (GCFs) and only 13 GCFs could be annotated with known BGCs, suggesting their great diversity and novelty. These NRPS BGCs encoded 351 novel peptides containing more than four amino acids, and 173 of them showed high sequence similarity to known BGCs encoding bioactive peptides, implying the promising potential of Photorhabdus to produce valuable peptides. Sequence similarity networking of adenylation (A-) domains suggested that the substrate specificity of A-domains was not directly correlated with the sequence similarity. The molecular similarity network of predicted metabolite scaffolds of NRPS BGCs and reported peptides from Photorhabdus and a relevant database demonstrated that the non-ribosomal peptide biosynthetic potential of Photorhabdus was largely untapped and revealed the core peptides deserving intensive studies. Our present study provides valuable information for the targeted discovery of novel non-ribosomal peptides from Photorhabdus.

[Galangin alleviates learning and memory impairments in APP/PS1 double- transgenic mice by regulating Akt/MEF2D/Beclin-1 signaling pathway].

The study aimed to investigate the effects of galangin on learning and memory impairments and Akt/MEF2 D/Beclin-1 signaling pathway in APP/PS1 double-transgenic mice. The mice in this experiment were divided into the normal group, model group, low-(25 mg·kg~(-1)), medium-(50 mg·kg~(-1)), and high-dose(100 mg·kg~(-1)) galangin groups, donepezil(3 mg·kg~(-1)) group, Akt inhibitor(25 mg·kg~(-1)) group, and autophagy inhibitor(30 mg·kg~(-1)) group, with ten in each group, and administered with the corresponding drugs for 30 successive days. On the 24 th day of medication, the water maze and dark avoidance tests were performed. The levels of p-tau, ß-amyloid peptide 1-42(Aß_(42)), acetylcholinesterase(AChE), ß-site amyloid precursor protein cleaving enzyme 1(BACE1), and amyloid precursor protein(APP) in hippocampus were detected by ELISA, the Beclin-1 mRNA expression by RT-PCR, the expression of Aß_(42) and glial fibrillary acidic protein(GFAP) by immunohistochemistry, and the expression of myocyte enhancer factor 2 D(MEF2 D) by immunofluorescence assay. The pathological changes in hippocampus were observed after HE staining, and the expression of Akt, MEF2 D, and Beclin-1 in hippocampus were assayed by Western blot. These results showed that compared with the normal group, the model group exhibited prolonged swimming time, increased number of errors and electric shocks, up-regulated p-tau, Aß_(42), APP, AChE, BACE1, GFAP, and Beclin-1, shortened incubation period, decreased p-Akt and MEF2 D, and obvious hippocampal injury. Compared with the model group, donepezil and galangin shortened the swimming time, reduced the number of errors and electric shocks, down-regulated the expression of p-tau, Aß_(42), APP, AChE, BACE1, GFAP, and Beclin-1, prolonged the incubation period, up-regulated p-Akt and MEF2 D, and improved the pathological changes in hippocampus. Compared with the autophagy inhibitor group, galangin prolonged the swimming time, elevated the number of errors and electric shocks, enhanced the expression of p-tau, Aß_(42), APP, AChE, BACE1, GFAP, and Beclin-1, shortened the incubation period, and diminished the expression of p-Akt and MEF2 D. In conclusion, galangin improves the learning and memory impairments and hippocampal neuron injury of APP/PS1 mice, which may be related to its regulation of Akt/MEF2 D/Beclin-1 signaling pathway.

Research progress and therapeutic perspective of iron transport balance based on "iron-inflammation" homeostatic coupling theory / 药学学报

The iron and inflammation homeostasis are closely coupled, forming an integrated functional unit under physiological conditions. "Iron transport balance" has become the key mechanism to maintain iron homeostasis through bidirectional regulation of iron uptake and release and dynamic management of transmembrane concentration. It is also the physiological basis for the inflammatory balance between promotion and resolution. Under pathological conditions, represented by inflammatory bowel disease (IBD), disturbed iron transportation was highly involved in almost every step of inflammatory diseases. Therefore, the iron transporting rebalancing provides the mechanistic basis and effective approach for the normalization of inflammatory microenvironment. Macrophage is the key regulator of inflammation homeostasis and determinant for iron transport balance. Unfortunately, the current clinical transformation based on iron transport balance theory has still been insufficient. Sometimes, this strategy even showed high complexity and contradiction, severely restricting its clinical application. By summarizing the theoretical research progress of iron transport balance, especially its relevance to macrophage phenotypic polarization, this review aims to explore the therapeutic value in inflammation intervention by targeting iron transporting balance. This review will provide the necessary knowledge and hints for the research and development of candidate drugs in treating inflammatory diseases.

Effecacy of Biejia (Carapax Trionycis) and Ezhu (Rhizoma Curcumae Phaeocaulis) couplet medicine on epithelial-mesenchymal transition, invasion and migration of MDA-MB-231 triple negative breast cancer cells via PI3K/Akt/mTOR signaling pathway.

OBJECTIVE: To investigate the efficacy of Biejia (Carapax Trionycis) and Ezhu (Rhizoma Curcumae Phaeocaulis) couplet medicine on epithelial-mesenchymal transition (EMT), invasion and migration of MDA-MB-231 triple negative breast cancer (TNBC) cells based on PI3K/Akt/mTOR signaling pathway. METHODS: MDA-MB-231 cells were treated with different medicated serum as Biejia-, Ezhu-, Biejia-Ezhu (BJ-, EZ-, BJ-EZ-) groups, intervened with no drug rat serum and paclitaxel with final concentration of 33 nM (IC50) as negative and positive control (NC and PC) groups. CCK-8 assay, scratch test, and Transwell assay were used to examine cell proliferation, invasion, and migration. The expression of E-cadherin, N-cadherin, Vimentin, MMP-2, MMP-9, PI3K, Akt, p-Akt, mTOR, and p-mTOR was determined by Western blot, and the mRNA expression of PI3K, Akt and mTOR was determined by real-time polymerase chain reaction. RESULTS: BJ-EZ group inhibited proliferation after 24, 48, and 72 h compared with the NC group (P < 0.05, < 0.01 or < 0.001) and reduced the invasion and migration of MDA-MB-231 cells (P < 0.01 or < 0.001). In addition, BJ-EZ group upregulated the expression of E-cadherin, downregulated the expression of N-cadherin, Vimentin, MMP-2, and MMP-9 (P < 0.05, P < 0.01 or P < 0.001), and inhibited the mRNA and protein expression of PI3K, Akt (p-Akt), mTOR (p-mTOR) (P < 0.05, < 0.01 or < 0.001). CONCLUSION: Biejia (Carapax Trionycis) and Ezhu (Rhizoma Curcumae Phaeocaulis) couplet medicine can inhibit the proliferation, invasion, migration and EMT of MDA-MB-231 cells through PI3K/Akt/mTOR signaling pathway, and the effect is better than that of Biejia (Carapax Trionycis) or Ezhu (Rhizoma Curcumae Phaeocaulis) alone.

Integrating Constituents Absorbed into Blood, Network Pharmacology, and Quantitative Analysis to Reveal the Active Components in Rubus chingii var. suavissimus that Regulate Lipid Metabolism Disorder.

Rubus chingii var. suavissimus (S. K. Lee) L. T. Lu (RS)-a sweet plant also known as Tiancha distributed in the south of China where it is used as a beverage-recently gained extensive attention as adjuvant therapy of diabetes and hypertension. Although pharmacological studies indicate that RS has beneficial effects in regulating lipid metabolism disorder characteristics, the active chemicals responsible for this effect remains unclear. The present study aims to predict the effective substances of RS on regulating lipid metabolism disorder through the analysis of the chemical profile of RS, the absorbed prototype components in rat plasma, and network pharmacology. Also, a UPLC method able to quantify the screened potential effective chemicals of RS products was established. First, a total of 69 components-including diterpene, triterpenoids, flavonoids, polyphenols, and lignans-were systematically characterized in RS. Of those, 50 compounds were detected in the plasma of rats administered with RS extract. Through network pharmacology, 9 potential effective components, 71 target genes, and 20 pathways were predicted to be involved in RS-mediated regulation of lipid metabolism disorder. The quantitative analysis suggested that the contents of potential effective components varied among samples from different marketplaces. In conclusion, the presented results provide a chemical basis for further research of Rubus chingii var. suavissimus.

Rubus chingii var. suavissimus alleviates high-fat diet-induced lipid metabolism disorder via modulation of the PPARs/SREBP pathway in Syrian golden hamsters.

While the underlying mechanism remains unknown, Rubus chingii var. suavissimus (S. K. Lee) L. T. Lu or Rubus suavissimus S. Lee (RS), a sweet plant distributed in southwest of China, has been used as beverage and folk medicine. Pharmacological studies indicated the potential of RS improving the obesity phenotype and hyperlipidemia. The mechanism is still not yet to be put forward. To verify the substantial effects of RS on lipid metabolism, a Syrian golden hamster model was adopted. The physiological and pathological evaluation of experimental animals demonstrated that RS can relieve the lipid metabolism disorder induced by high-fat diet and alleviated liver injury. RS upregulation the expressions of peroxisome proliferator-activated receptor α (PPARα), PPARγ and CCAAT/enhancer binding protein α (C/EBPα), as well as adipocyte-specific genes, glucose transporter 4 (Glut4), lipoprotein lipase (LPL) and fatty acid binding protein 4 (aP2). On the other side, RS suppressed the sterol regulatory element binding protein 1 (SREBP1) and downstream acetyl-CoA carboxylase 1 (ACC1), stearoyl-CoA desaturase-1 (SCD1) and fatty acid synthase (FAS). In conclusion, RS alleviated lipid metabolism disorder symptoms caused by high-fat diet accompanied with 8 weeks of treatment, involving enhanced ß-oxidation, increased adipogenesis and decreased the metabolism of fatty acids, via modulation of the PPARs/SREBP pathway in Syrian golden hamsters.

Recent Advances of Magnetic Resonance Neuroimaging in Trigeminal Neuralgia.

Trigeminal neuralgia (TN) is a disease of unclear pathogenesis. It has a low incidence and is not fatal, but it can cause afflicted patients' depression or suicide. In the past, neurovascular compression was considered to be the main cause of TN, but recent studies have found that neurovascular contact is also common in asymptomatic patients and the asymptomatic side in symptomatic patients. This indicates that the neurovascular contact is not, or is only to a lesser extent, a factor in the development of TN. Thus, the study of the peripheral branches of the trigeminal nerve is necessary to understand the etiology of TN. With the development of imaging technology and the emergence of various imaging modalities, it is possible to study the etiology of TN and the pathological changes of related structures by magnetic resonance neuroimaging. This article reviews the recent advances in magnetic resonance neuroimaging of the trigeminal nerve.

Effect of education and muscle relaxation program on anxiety, depression and care burden in caregivers of acute stroke survivors: A randomized, controlled study.

ABSTRACT: This study intended to discover the effect of education and muscle relaxation (EMR) program on anxiety, depression and care burden among caregivers of acute stroke survivors.This randomized, controlled study enrolled a total of 110 caregivers of first-ever acute stroke patients, and randomly assigned to EMR (N = 55) and control (N = 55) groups. The caregivers in the EMR group received 12-month health education and progressive muscle relaxation, and those in control group were provided common rehabilitation advices. Hospital Anxiety and Depression Scale (HADS) and Zarit Caregiver Burden Scale in caregivers were evaluated at the time of patients' discharge from hospital (M0), then at month(M) 3, M6 and M12 after the discharge.HADS-anxiety score, anxiety rate and severity were similar at M0, M3, while were reduced at M6 and M12 in EMR group compared to control group. Furthermore, HADS-depression score was similar at M0 and M3 but was decreased at M6 and M12 in EMR group compared with control group, however, there was no difference of depression rate and severity between the 2 groups at each time point. Moreover, Zarit Caregiver Burden Scale score was similar at M0 and M3, but was decreased at M6 and M12; meanwhile, degree of care burden was similar at M0, M3 and M6, but was reduced at M12 in EMR group compared to control group.EMR program decreases anxiety, depression and care burden in caregivers of acute stroke survivors, suggesting its potential in improving mental health and further promoting quality of lives in these caregivers.

Family Functioning Mediates the Relationship Between Activities of Daily Living and Poststroke Depression.

BACKGROUND: Poststroke depression is common and includes depressive and somatic symptoms. However, few studies have confirmed the influence of family functioning on poststroke depression or explored the association among daily activities, family functioning, and poststroke depression. OBJECTIVES: We examined the independent risk factors of daily activities and family functioning for poststroke depression and identified the mediating effect of family functioning on the association between daily activities and poststroke depression. METHODS: This cross-sectional study design used convenience sampling to recruit 422 stroke survivors from the neurology department of a hospital in Harbin, China, from February to July 2018. We assessed participants' demographic and clinical variables, including depression, daily activities, and family functioning. Pearson's correlations and multiple linear regression analyses were conducted, and a path analysis with bootstrapping was utilized to define direct/indirect effects. RESULTS: Daily activities and family functioning had a significant and direct negative effect on participants' depression. The indirect effect of 1,000 bootstrap samples after bias correction with a 95% confidence interval was below zero, indicating that family function had a significant mediating effect on the association between depression and daily activities. DISCUSSION: This study revealed the importance of family functioning in the association between depression and daily activities in stroke survivors. To the best of our knowledge, this study was the first to explore the mediating role of family functioning in poststroke depression, emphasizing the importance of family for the mental health of stroke patients. To reduce the incidence of poststroke depression, interventions that enhance daily activities and family functioning may include nurses, family therapists, rehabilitation physicians, and community workers.

Attenuation of periostin in retinal Müller glia by TNF-α and IFN-γ.

AIM: To investigate the regulation and mechanisms of periostin expression in retinal Müller glia, and to explore the relevance to retinal neovascularization. METHODS: The oxygen-induced retinopathy (OIR) mouse model and the human Moorfield/Institute of Ophthalmology-Müller 1 (MIO-M1) cell line were used in the study. Immunofluorescence staining was used to determine the distribution and expression of periostin and a Müller glial cell marker glutamine synthetase (GS). Cytokines TNF-α and IFN-γ were added to stimulate the MIO-M1 cells. ShRNA was used to knockdown periostin expression in MIO-M1 cells. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was conducted to assess the mRNA expression of periostin. RESULTS: Immunofluorescence staining showed that periostin was expressed by MIO-M1 Müller glia. GS-positive Müller glia and periostin increased in OIR retinas, and were partially overlaid. The stimulation of TNF-α and IFN-γ reduced the mRNA expression of periostin significantly and dose-dependently in MIO-M1 cells. Knockdown of periostin reduced mRNA expression of vascular endothelial growth factor A (VEGFA) in MIO-M1 cells, while VEGFA expression was not changed in periostin knock-out OIR retinas. CONCLUSION: Müller glia could be one of the main sources of periostin in the retina, and might contribute to the pathogenesis of retinal neovascularization. Proinflammatory cytokines TNF-α and IFN-γ attenuate the periostin expression in retinal Müller glia, which provides a potential and novel method in treating retinal neovascular diseases.

Melatonin Inhibits Reactive Oxygen Species-Driven Proliferation, Epithelial-Mesenchymal Transition, and Vasculogenic Mimicry in Oral Cancer.

Globally, oral cancer is the most common type of head and neck cancers. Melatonin elicits inhibitory effects on oral cancer; however, the biological function of melatonin and underlying mechanisms remain largely unknown. In this study, we found that melatonin impaired the proliferation and apoptosis resistance of oral cancer cells by inactivating ROS-dependent Akt signaling, involving in downregulation of cyclin D1, PCNA, and Bcl-2 and upregulation of Bax. Melatonin inhibited the migration and invasion of oral cancer cells by repressing ROS-activated Akt signaling, implicating with the reduction of Snail and Vimentin and the enhancement of E-cadherin. Moreover, melatonin hampered vasculogenic mimicry of oral cancer cells through blockage of ROS-activated extracellular-regulated protein kinases (ERKs) and Akt pathways involving the hypoxia-inducible factor 1α. Consistently, melatonin retarded tumorigenesis of oral cancer in vivo. Overall, these findings indicated that melatonin exerts antisurvival, antimotility, and antiangiogenesis effects on oral cancer partly by suppressing ROS-reliant Akt or ERK signaling.

Impact of Menopause on Quality of Life in Community-based Women in China: 1 Year Follow-up.

Quality of life (QOL) throughout menopause has become an outcome variable requiring measurement in clinical care. Staff nurses can provide earlier nursing during the menopausal transition (MT) stage. The purpose of this study was to describe the changes of QOL in different stages of the MT according to The Stages of Reproductive Aging Workshop (STRAW) in Chinese women in community settings. Prospective longitudinal study design was used to analyze QOL of 327 community women age 30-65years old. They were followed up at 1-year. An instrument including the Chinese version of the Menopause-Specific Quality of Life Questionnaire was used to obtain data. A gradual decline in QOL was seen from premenopausal to menopausal transition (MT) and in postmenopausal women. Significant differences were observed in vasomotor, physical and sexual scores at baseline and follow-up (P<0.05). Significant differences in vasomotor scores were observed between baseline and follow-up for women in the premenopausal and Late MT stages (P<0.05). There were significant differences in psychosocial and physical scores between baseline and follow-up in the Late MT stage (P<0.05). Menopause might have a negative impact on QOL independent of age in community-based women in China. There seemed to be a potential model of the relationship of menopause status to change in QOL, but this needs supporting evidence from longer longitudinal studies.

Consideration on Cultivation Mechanism of Clinical Medicine Postgraduates Based on Post Competency / 昆明医科大学学报

Objective To analyze the problems and reasons in the clinical medicine postgraduate cultivation.We stated the competency of clinical medicine postgraduates according to the transition of health demands global medical development and practical requirements for clinical personnel. Me thods Questionnaire surveys combined with interviews were conducted, and statistical analysis was performed. In the first part, we selected the permanent staff with qualifications of medical clinicians, including: chief physicians, associate chief physicians, physicians, residents, accounting for 72％ of the interviewees; And related personnel, including nurses, administrators and patients, were also interviewed, accounting for 28％ of the total. 90 questionnaires were distributed, and 86 valid questionnaires were recovered, with an effective rate of 95.56％. In the second part, graduate students with clinical professional degrees were selected for interviews, 96 questionnaires were distributed, and 92 valid questionnaires were collected, and the effective rate was 95.83％.Re s ults There was a certain gap between the expected goal and the actual situation of the post competency of clinical professional degree graduate students, and the gap had a certain statistical significance. The clinical professional degree graduate students paid more attention to the doctor-patient communication, teamwork. Conclus ions We elaborated the required post competence for clinical medicine postgraduates on the basis of its content and characteristic. We propose to strengthen the cultivation of clinical medicine postgraduates by the reform and support of the government enhanced construction of teachers improved course plan and cultivation process perfected assessment system in order to make the students competent to their posts.