The association between tea consumption and blood pressure in the adult population in Southwest China.

OBJECTIVES: Prior research on the effect of tea consumption on blood pressure (BP) generated inconsistent findings. The objective of this study was to explore the effects of different types of tea consumption on BP. METHODS: We included 76,673 participants aged 30-79 from the baseline data of the China Multi-Ethnic Cohort (CMEC) study. Binary logistic regression was used to analyze the influences of different types of tea consumption on the risk of hypertensive BP. Moreover, multiple linear regression was used to examine the association between tea drinking and BP. RESULTS: Tea consumption was associated with a reduced risk of hypertensive BP by 10% (AOR: 0.90, 95%CI: 0.86-0.94). While dark tea was related to a 1.79-5.31 mmHg reduction in systolic blood pressure (SBP) and a 0.47-1.02 mmHg reduction in diastolic blood pressure (DBP), sweet tea, regardless of the duration, frequency, or amount of consumption, significantly was associated with a reduced SBP by 3.19-7.18 mmHg. Green tea also was associated with a reduced SBP by 1.21-2.98 mmHg. Although scented tea was related to reduced SBP by 1.26-2.48 mmHg, the greatest effect came from the long duration (> 40 years:ß=-2.17 mmHg, 95%CI=-3.47 mmHg --0.87 mmHg), low frequency (1-2 d/w: ß = -2.48 mmHg, 95%CI=-3.76 mmHg--1.20 mmHg), and low amount (≤ 2 g/d: ß=-2.21 mmHg, 95%CI=-3.01 mmHg--1.40 mmHg). Additionally, scented tea was correlated to a decrease in DBP at the frequency of 1-2 d/w (ß=-0.84 mmHg, 95%CI=-1.65 mmHg--0.02 mmHg). Drinking black tea only was associated with lowered SBP. The protective effect of black tea on SBP was characterized by the long-duration (> 15 years, -2.63--5.76 mmHg), high frequency (6-7 d/w, -2.43 mmHg), and medium amount (2.1-4.0 g/d, -3.06 mmHg). CONCLUSION: Tea consumption was associated with lower SBP and a reduced risk of hypertensive BP. The antihypertensive effect varies across types of tea consumed.

Lansoprazole-induced osteoporosis via the IP3R- and SOCE-mediated calcium signaling pathways.

BACKGROUND: Many clinical studies have shown a correlation between proton pump inhibitors (PPIs) and osteoporosis or fractures. The purpose of this study was to establish a murine model of chronic oral PPI administration to verify whether PPIs caused bone metabolic impairment and investigate the relevant molecular mechanism underlying the effects of PPIs on MC3T3-E1 murine osteoblasts. METHODS: A lansoprazole-induced bone loss model was used to investigate the damaging effects of PPIs. In vivo, immunohistochemistry, Hematoxylin-Eosin (HE) staining, micro-CT analysis, and blood biochemical analyses were used to evaluate the effect of lansoprazole on bone injury in mice. In vitro, the effects of lansoprazole and related signaling pathways in MC3T3-E1 cells were investigated by CCK-8 assays, EdU assays, flow cytometry, laser confocal microscopy, patch clamping, reverse transcription-quantitative polymerase chain reaction and Western blotting. RESULTS: After 6 months of lansoprazole gavage in ICR mice, the micro-CT results showed that compared with that in the vehicle group, the bone mineral density (BMD) in the high-dose group was significantly decreased (P < 0.05), and the bone microarchitecture gradually degraded. Biochemical analysis of bone serum showed that blood calcium and phosphorus were both decreased (P < 0.01). We found that long-term administration of lansoprazole impaired skeletal function in mice. In vitro, we found that lansoprazole (LPZ) could cause calcium overload in MC3T3-E1 cells leading to apoptosis, and 2-APB, an inhibitor of IP3R calcium release channel and SOCE pathway, effectively blocked increase in calcium caused by LPZ, thus protecting cell viability. CONCLUSIONS: Longterm administration of LPZ induced osteoporotic symptoms in mice, and LPZ triggered calcium increases in osteoblasts in a concentration-dependent manner. Intracellular calcium ([Ca2+]i) persisted at a high concentration, thereby causing endoplasmic reticulum stress (ERS) and inducing osteoblast apoptosis.

Analysis of the Influence of High-Dose rhGH Therapy on Serum Vitamin D and IGF-1 Levels in School-Age Children with Idiopathic Short Stature.

OBJECTIVE: To discuss the influence of high-dose recombinant human growth hormone (rhGH) therapy on serum vitamin D and insulin-like growth factor-1 (IGF-1) levels in school-age children with idiopathic short stature (ISS). METHOD: A total of 103 school-age children with ISS were selected from June 2016 to June 2020 in our hospital. The enrolled cases were divided into the low-dose group (n = 59) and high-dose group (n = 44) according to the treatment dose of rhGH. After the treatment, the height (Ht), height standard deviation score (Ht SDS), growth velocity (GV), and other indicators were recorded. The serum 25-hydroxy vitamin D [25-(OH)D] and IGF-1 levels of the two groups were tested, and the occurrence of adverse reactions was recorded. RESULTS: After treatment, the high-dose group outperformed the low-dose group in various growth effect indicators such as Ht, Ht SDS, and GV (P < 0.05). After treatment, the serum 25-(OH)D of children with ISS in the two groups increased significantly, but there was no significant difference between the two groups (P > 0.05). After treatment, the serum IGF-1 of children with ISS in the two groups increased significantly, but there was no significant difference between the two groups (P > 0.05). For children with ISS, adverse reactions induced by rhGH therapy were very rare. There was no significant difference in the incidence of adverse reactions induced by different doses of rhGH in the treatment of ISS (P > 0.05). CONCLUSION: rhGH has definite efficacy in the treatment of ISS children, for it can significantly increase the annual growth rate of ISS children in a dose-dependent manner. High-dose rhGH for ISS has a better therapeutic effect. At the same time, regardless of the dose level of rhGH, serum 25-(OH)D and IGF-1 levels in children with ISS were increased, with less adverse reactions and higher safety.

Corosolic acid and its structural analogs: A systematic review of their biological activities and underlying mechanism of action.

BACKGROUND: The corosolic acid (CA), also known as plant insulin, is a pentacyclic triterpenoid extracted from plants such as Lagerstroemia speciosa. It has been shown to have anti-diabetic, anti-inflammatory and anti-tumor effects. Its structural analogs ursolic acid (UA), oleanolic acid (OA), maslinic acid (MA), asiatic acid (AA) and betulinic acid (BA) display similar individual pharmacological activities to those of CA. However, there is no systematic review documenting pharmacological activities of CA and its structural analogues. This study aims to fill this gap in literature. PURPOSE: This systematic review aims to summarize the medical applications of CA and its analogues. METHODS: A systematic review summarizes and compares the extraction techniques, pharmacokinetic parameters, and pharmacological effects of CA and its structural analogs. Hypoglycemic effect is one of the key inclusion criteria for searching Web of Science, PubMed, Embase and Cochrane databases up to October 2020 without language restrictions. 'corosolic acid', 'ursolic acid', 'oleanolic acid', 'maslinic acid', 'asiatic acid', 'betulinic acid', 'extraction', 'pharmacokinetic', 'pharmacological' were used to extract relevant literature. The PRISMA guidelines were followed. RESULTS: At the end of the searching process, 140 articles were selected for the systematic review. Information of CA and five of its structural analogs including UA, OA, MA, AA and BA were included in this review. CA and its structural analogs are pentacyclic triterpenes extracted from plants and they have low solubilities in water due to their rigid scaffold and hydrophobic properties. The introduction of water-soluble groups such as sugar or amino groups could increase the solubility of CA and its structural analogs. Their biological activities and underlying mechanism of action are reviewed and compared. CONCLUSION: CA and its structural analogs UA, OA, MA, AA and BA are demonstrated to show activities in lowering blood sugar, anti-inflammation and anti-tumor. Their oral absorption and bioavailability can be improved through structural modification and formulation design. CA and its structural analogs are promising natural product-based lead compounds for further development and mechanistic studies.

Electroacupuncture Attenuates Neuropathic Pain and Comorbid Negative Behavior: The Involvement of the Dopamine System in the Amygdala.

Neuropathic pain (NeuP) is an important clinical problem accompanying negative mood symptoms. Neuroinflammation in the amygdala is critically involved in NeuP, and the dopamine (DA) system acts as an important endogenous anti-inflammatory pathway. Electroacupuncture (EA) can improve the clinical outcomes in NeuP, but the underlying mechanisms have not been fully elucidated. This study was designed to assess the effectiveness of EA on pain and pain-related depressive-like and anxiety-like behaviors and explore the role of the DA system in the effects of EA. Male Sprague-Dawley rats were subjected to the chronic constrictive injury (CCI) model to induce NeuP. EA treatment was carried out for 30 min once every other day for 3 weeks. The results showed that CCI caused mechanical hyperalgesia and depressive and anxiety-like behaviors in rats and neuroinflammation in the amygdala, such as an increased protein level of TNFα and IL-1ß and activation of astrocytes. EA treatment significantly improved mechanical allodynia and the emotional dysfunction induced by CCI. The effects of EA were accompanied by markedly decreased expression of TNFα, IL-1ß, and glial fibrillary acid protein (GFAP) in the amygdala. Moreover, EA treatment reversed CCI-induced down-regulation of DA concentration, tyrosine hydroxylase (TH) expression, and DRD1 and DRD2 receptors. These results suggest that EA-ameliorated NeuP may possibly be associated with the DA system to inhibit the neuroinflammation in the amygdala.

Mind-body interventions on stress management in pregnant women: A systematic review and meta-analysis of randomized controlled trials.

AIM: To quantify the effect of mind-body interventions on stress in pregnant women. DESIGN: A systematic review and meta-analysis of randomized controlled trials was performed. DATA SOURCES: PubMed, Embase, CENTRAL, Web of Science and PsycINFO were searched from each database inception to January 2020. REVIEW METHODS: Randomized controlled trials regarding mind-body interventions for stress in pregnant women were included. Methodological quality was evaluated using the Cochrane Collaboration 'Risk of Bias' tool and meta-analysis was performed via RevMan 5.3. Subgroup analysis and publication bias assessment were conducted. Post hoc sensitivity analysis was performed to investigate the source of heterogeneity. RESULTS: In total, 28 studies comprising 1944 participants were included. The overall meta-analysis showed that antenatal stress of pregnant women in the mind-body interventions groups showed significant high improvements (SMD=-0.94; 95% CI [-1.25, -0.63]; p < .00001) compared with the control groups. Results of subgroup analyses indicated that all types of mind-body interventions including mindfulness intervention, cognitive behavioural therapy, relaxation techniques and yoga were beneficial to antenatal stress. Both groups and individual formats mind-body interventions were effective. 4-8 weeks mind-body interventions were seemed as the optimal choice. Moreover, mind-body interventions were concomitant with reducing antenatal anxiety and depression. CONCLUSION: Mind-body interventions are promising approaches for stress reduction in pregnant women. Nevertheless, the results should be interpreted with caution because of high heterogeneity and publication bias. Further high-quality studies are needed to verify the findings. IMPACT: Mind-body interventions have been widely implemented to ameliorate antenatal stress, but conflicting results were found across studies. This systematic review and meta-analysis suggested that mind-body interventions are relatively safe and convenient and can successfully promote antenatal stress. The suggestions proposed in this review may be useful for developing a scientific mind-body interventions regimen and encouraging the application of mind-body interventions in pregnant women, thereby managing antenatal stress effectively.

The effectiveness of massage on peri-operative anxiety in adults: A meta-analysis of randomized controlled trials and controlled clinical trials.

BACKGROUND AND PURPOSE: and purpose: Massage has gained increasing attention for reducing peri-operative anxiety. We aimed to investigate the effectiveness of massage for peri-operative anxiety in adults. METHODS: Six English electronic databases were comprehensively searched from their inception to February 2020. Subgroup analysis, quality assessment, sensitivity analysis, meta-regression and publication bias assessment were performed. RESULTS: Twenty-five controlled trials comprising 2494 participants were included. The meta-analysis indicated that massage could significantly reduce peri-operative anxiety for most types of surgical patients. Specifically, it was effective for pre-, intra- and post-operative anxiety. Acupoint or specific body reflex area massage showed a larger effect than general massage did. Massage delivered by professionals and non-professionals were both effective. Massage lasting 10-20 min per session was the most worthy of recommendation. Massage was concomitant with the improvement of peri-operative vital signs and post-operative pain. CONCLUSION: Massage is a promising complementary therapy for ameliorating peri-operative anxiety in adults.

The effectiveness of aromatherapy on preoperative anxiety in adults: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Preoperative anxiety is very common in adults awaiting all types of surgical procedures, which can interfere with the start and completion of surgery and increase the risk of postoperative complications. In this context, many researchers and clinical practitioners have attempted to use aromatherapy to help adults reduce preoperative anxiety. OBJECTIVE: To investigate systematically the efficacy of aromatherapy on preoperative anxiety in adults. DESIGN: A systematic review and meta-analysis of randomized controlled trials was undertaken. DATA SOURCES: PubMed, Embase, Cochrane Library, Web of Science, PsycINFO and CINAHL were comprehensively searched from their inception to June 2020. REVIEW METHODS: Studies on the use of aromatherapy for treating preoperative anxiety in adults were included. Two reviewers assessed the risk of bias of the included studies independently using the Cochrane Collaboration 'Risk of Bias' tool. Overall meta-analysis and five subgroup analyses regarding the type of control, the type of aroma preparations, delivery mode, session length and surgery type were performed using RevMan 5.3. The Higgins' I2 (%) statistic was used to measure heterogeneity. A funnel plot and Egger's test were used to evaluate publication bias. RESULTS: Twenty studies comprising 1717 participants were included. The meta-analysis indicated that aromatherapy could significantly ameliorate preoperative anxiety (standard mean difference=-0.57, 95% confidence interval [-0.75, -0.39], p<0.00001) for adults awaiting surgical procedures, compared to placebo control, conventional care and no intervention. The subgroup analysis based on the surgery type showed that aromatherapy had a great improvement on preoperative anxiety for patients awaiting cardiac surgery and relatively low-risk surgery. Lavender oil, citrus species preparations and rose oil were the three most commonly used aroma preparations that could significantly improve preoperative anxiety. Most delivery modes of aromatherapy, including inhalation, massage, and oral administration, were effective. Moreover, short length (≤20 min per session) aromatherapy showed a better effect on preoperative anxiety (mean difference=-5.84, 95% confidence interval [-8.09, -3.59], p<0.00001) than aromatherapy lasting more than 20-minutes per session (mean difference=-2.15, 95% confidence interval [-3.81, -0.49], p = 0.01). CONCLUSION: Aromatherapy is an effective intervention for reducing preoperative anxiety in adults. Short-length aromatherapy inhalation seems to be more worthy of being recommended in clinical settings. More well-designed randomized controlled trials containing a wider range of surgical types and participants from more countries are needed to verify our findings before we can make strong recommendations.

[Research advances in the limbic system involved in acupuncture treatment of chronic pain].

Pain, especially chronic pain, can cause multiple changes including sensory-discriminative, emotional-affective, and cognitive-behavior changes and thus greatly affects patients' physical and mental health and quality of life. Therefore, multi-dimensional regulation of paralgesia, cognitive impairment, and negative emotion in patients with chronic pain has become a hot spot in recent studies. The brain regions in the limbic system are involved in the formation and expression of "pain sensation-emotion-cognition". Existing evidence suggests that acupuncture has a multi-dimensional comprehensive regulatory effect on chronic pain, and the brain regions in the limbic system also mediate the analgesic effect of acupuncture. However, further studies are still needed to explore the role and mechanism of action of these brain regions in the multi-dimensional regulation of chronic pain by acupuncture. This article reviews the research advances in the neural mechanism of the limbic system in chronic pain and the role of the limbic system in mediating acupuncture analgesia and mainly elaborates on the mechanism of action of the brain regions in the limbic system in the multi-dimensional regulation of chronic pain.

The anticoagulants rivaroxaban and low molecular weight heparin prevent PICC-related upper extremity venous thrombosis in cancer patients.

Peripherally inserted central catheter (PICC) is often applied in chemotherapy patients and commonly causes upper extremity venous thrombosis (UEVT), which should be prevented.To assess the preventive effects of the anticoagulants rivaroxaban and low molecular weight heparin (LMWH) on UEVT in patients receiving chemotherapy through PICCs.A total of 423 chemotherapy patients with continuous PICC use between January 2014 and June 2015 at the Oncology Department of Dongying People's Hospital were divided into 3 groups: rivaroxaban (10 mg/day, orally), LMWH (Enoxaparine, 4000 anti-Xa IU/day, subcutaneous injection), and control (no anticoagulant). UEVT incidence and other complications during PICC use were observed and recorded.The rivaroxaban, LMWH, and control groups included 138 (79 males; 54.9 ±â€Š11.0 years), 144 (76 males; 56.0 ±â€Š10.9 years), and 141 (71 males; 53.3 ±â€Š10.9 years) patients, (P = .402 and P = .623 for age and sex respectively). There were no differences in cancer location (P = .628), PICC implantation site (P > .05), body mass index (BMI) (P = .434), blood pressure (all P > .05), blood lipids (5 laboratory parameters included, all P > .5), smoking (P = .138), history of lower limb venous thrombosis (P = .082), and 10 other associated comorbidities (all P > .5). Twenty-nine patients withdrew from the study (5 from the rivaroxaban, 12 from the LMWH, and 12 from the control groups, respectively), and 394 patients were analyzed. There were significant differences in the rivaroxaban group and the LMWH group compared to the control group (P = .010 and P = .009, respectively), but no significant difference was observed between the rivaroxaban group and the LMWH group (P = .743).Anticoagulants such as rivaroxaban and LMWH may reduce the incidence of PICC-related UEVT in patients receiving chemotherapy.

Complementary and alternative medicine for natural and treatment-induced vasomotor symptoms: An overview of systematic reviews and meta-analyses.

BACKGROUND AND PURPOSE: Vasomotor symptoms (VMS) are very common in menopausal populations and cancer patients and can cause physical and mental discomfort. We aim to summarize the findings of systematic reviews and meta-analyses (SRs/MAs) that assessed the effectiveness of complementary and alternative medicines(CAMs)on VMS to provide solid evidence for future practice. METHODS: PubMed, Embase, the Cochrane Library, and Web of Science were searched from inception to May 2019 to identify relevant SRs/MAs. The methodological quality of SRs/MAs and evidence levels of the outcomes were assessed. RESULTS: A total of 29 SRs/MAs were reviewed. Evidence has shown that acupuncture, hypnosis, paced respiration, cognitive behavioural therapy, genistein, soy isoflavones, S-equol, combined preparations of black cohosh, and omega-3 supplements could significantly reduce VMS. The methodological quality of the SRs/MAs was moderate or high. CONCLUSION: CAMs might be beneficial for reducing VMS, but the evidence levels were not high. Several priorities for future practice were identified.

Rosa rugosa flavonoids exhibited PPARα agonist-like effects on genetic severe hypertriglyceridemia of mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosa rugosa Thunb. is a traditional Chinese medicine that was used in the treatment of cardiovascular diseases and relative risk factors such as diabetes, hyperlipidemia, hypertension, and inflammation. Rosa rugosa flavonoids (RRFs) are the main components in Rosa rugosa Thunb. Several studies have demonstrated that RRFs can regulate plasma lipid contents, but the related mechanism of which has not yet been elucidated clearly. AIM OF THE STUDY: The goal of this study was to clarify the effects of RRFs on triglyceride metabolism and its related mechanisms. MATERIALS AND METHODS: RRFs were obtained by ethanol extraction from Rosa rugosa Thunb.. Transgenic mice expressing human Apolipoprotein C3 (ApoC3) were used as a mouse model of hypertriglyceridemia. Fenofibrate (FNB), a PPARα agonist, was used as a positive control drug of decreasing high triglyceride. FNB (100 mg/kg) or RRFs (300 mg/kg) were given to the mice by gavage daily. Two weeks later, the changes of plasma lipid levels in the mice were measured by commercial kits, the clearance of triglyceride was evaluated by oral fat load test, and expression of the genes related to lipid ß-oxidation and synthesis was detected in the mice livers by real time PCR. RESULTS: RRFs, as well as FNB, were found to significantly reduce plasma triglyceride (TG) levels in ApoC3 transgenic mice after administration of the drug for two weeks. Plasma lipid clearance rate was increased and lipid content in the mice livers was reduced after administration of RRF. Treatment with RRFs up-regulated mRNA expression of PPARα and its downstream gene of ACOX, while down-regulated mRNA expression of the genes related to fatty acid synthesis (FASN, SREBP-1c, and ACC1). The expression of LPL was raised, while the expression of ApoC3 was decreased, and Foxo1 was inhibited by RRFs in the mice livers. CONCLUSION: RRFs can reduce plasma TG levels by repressing the expression of ApoC3 and inducing the expression of LPL in liver. RRFs could also reduce triglyceride in hepatocytes through increasing ß-oxidation and decreasing synthesis of the lipids. These findings show the potency of further clinical application of RRFs as a hypolipidemic drug for treatment of cardiovascular diseases.

Effects of exercise on pregnant women's quality of life: A systematic review.

OBJECTIVES: Exercise is a promising approach to improve the health of pregnant women. However, data from studies investigating exercise and the quality of life of pregnant women are inconsistent and, to date, no systematic review on this topic has been published. The aim of this review was to comprehensively assess the effects of exercise on pregnant women's quality of life, and to determine whether exercise positively affects quality of life in this population. STUDY DESIGN: Literature was retrieved from electronic databases, namely PubMed, EMBASE, Web of Science and the Cochrane Library, from inception to 30 October 2018. Clinical trials published in English evaluating the effects of exercise on pregnant women's quality of life were included. The authors assessed the risk of bias in all eligible studies using the Effective Public Health Practice Project, and used a qualitative synthesis method to identify the effects of exercise on pregnant women's quality of life. RESULTS: Thirteen studies were included. Exercise was divided into the following four modes: aerobic exercise, resistance exercise, a combination (aerobic and resistance exercises), and yoga or physical activity. Aerobic and resistance training had a mixed effect on pregnant women's quality of life, while the combination of aerobic and resistance exercises and yoga or physical activity resulted in significant improvements. CONCLUSIONS: This systematic review is the first to suggest that group-based combined exercise and yoga or physical activity are associated with significant benefits related to improvements in pregnant women's quality of life. Furthermore, aerobic or resistance exercise could potentially improve pregnant women's quality of life. Therefore, it is recommended that medical service providers should pay more attention to the importance of exercise, and develop tailored exercise programmes to promote improvements in pregnant women's quality of life.

Effects of nonpharmacological interventions on depressive symptoms and depression among nursing students: A systematic review and meta-analysis.

OBJECTIVES: We aim to examine whether nonpharmacological interventions could effectively improve depressive symptoms and depression to provide more treatment options for nursing students. METHODS: PubMed, the Cochrane Library, EMBase, Web of Science, PsycINFO, and three Chinese electronic databases were comprehensively searched for papers that were published from January 1990 through March 2018. Quality assessment, sensitivity analysis and heterogeneity were performed. RESULTS: In our review, 13 controlled trials met the inclusion criteria. The meta-analysis indicated that the depressive symptoms and depression of nursing students in the intervention groups showed significantly moderate improvements compared with the control groups. Three subgroup analyses showed that mindfulness interventions and stress management programs were common and effective, short-term interventions were beneficial to depression, nonpharmacological interventions had great improvements for Asian nursing students and more rigorous researches on methodological quality are recommended. CONCLUSION: Nonpharmacological interventions can serve as promising complementary and alternative approaches in reducing the depressive symptoms and depression of nursing students.

Rosa rugosa flavonoids alleviate myocardial ischemia reperfusion injury in mice by suppressing JNK and p38 MAPK.

OBJECTIVE: Although Rosa rugosa has been applied for preventing coronary artery disease, the pharmacological mechanism is little explored. In this study, the effects and mechanisms of Rosa rugosa flavonoids (RRF) on myocardial ischemia reperfusion injury (MIRI) were investigated. METHODS: Mice were pretreated by intragastric administration of 600 mg/kg RRF for 7 days. Then MIRI was induced by 45 minutes coronary artery ligation and 3 hours reperfusion. Myocardial infarct size (MIS) and histopathology, activities of myocardial enzymes, and effects of RRF on inflammation and apoptosis were evaluated. RESULTS: Pretreating the mice with RRF significantly reduced MIS and inhibited activity of plasma myocardial enzymes. Activity of the enzymes associated with anti-oxidation, SOD, and TEAC, and mRNA expression of NOX2 were significantly elevated. RRF pretreatment significantly decreased the translocation of p65 from the cytoplasm into the nucleus and reduced the expression of the pro-inflammatory cytokines, IL-6 and IL-1ß. RRF pretreatment also significantly prevented the expression of caspase-3 and Bax, and increased the expression of Bcl-2. And RRF inhibited the phosphorylation of JNK and p38 MAPK. CONCLUSIONS: RRF significantly inhibited MIRI through anti-oxidative, anti-inflammatory, and anti-apoptosis effects, and mechanisms were associated with its inhibition on phosphorylation of JNK and p38 MAPK.

Mechanical performance of polymer-infiltrated zirconia ceramics.

OBJECTIVE: The aim of this study was to evaluate the microstructure and mechanical behavior of polymer-infiltrated zirconia ceramics as a function of pre-sintering temperature (1000-1150°C). METHODS: Polymer-infiltrated zirconia ceramics were prepared by combining the porous zirconia networks and polymer through infiltration and polymerization. XRD was employed to determine phase structure. The microstructure and fracture mechanism were observed by SEM. Flexural strength and fracture toughness were measured by three-point bending method and single-edge-notched beam method, respectively. A nanoindentation system was employed to determine elastic modulus and hardness. RESULTS: Different porosities and polymer contents can be obtained by tuning the pre-sintered temperature of zirconia ceramic precursors. Zirconia network porosity varies from 46.3% to 34.7% and the relevant polymer content ranges from 18.4wt.% to 12.3wt.% when the pre-sintered temperature is set from 1000°C to 1150°C. The flexural strength, fracture toughness, hardness, and elastic modulus values of the specimen pre-sintered at 1150°C are 240.9MPa, 3.69MPam1/2, 3.1GPa, and 58.8GPa, respectively. CONCLUSION: The pre-sintering temperature has a significant effect on the microstructure and mechanical properties of polymer-infiltrated zirconia ceramics and the optimal pre-sintering temperature is 1150°C. CLINICAL SIGNIFICANCE: Specimen pre-sintered at 1150°C shows tooth-like mechanical properties, suggesting a promising restorative material in dental clinic. Moreover, the synthesis process is simple and can be easily performed in a prosthesis laboratory.

Xinmailong mitigated epirubicin-induced cardiotoxicity via inhibiting autophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Using insects, such as the cockroach, for the treatment of disease has a long history in traditional Chinese medicine. Xinmailong (XML) Injection, a bioactive composite extracted from Periplaneta americana (a species of cockroach), shows reasonable protective effects against cardiovascular injury and was approved for the use in the treatment of cardiac dysfunction in 2006, yet its cardio protective mechanisms remain unclear. AIM: The present study aims to examine the protective effects of XML against epirubicin-induced cardiotoxicity in vivo and determine its underlying mechanisms. MATERIALS AND METHODS: The chemical characteristics of XML were identified using high performance liquid chromatography (HPLC). Rats were intraperitoneally injected with epirubicin and then treated with XML for 14 days. Survival rate, echocardiography, electrocardiographic recordings and Masson staining were used to evaluate the cardioprotective activity of XML. Western blot and quantitative real time reverse transcriptase polymerase chain reaction (RT-PCR) analyses were used to investigate the molecular mechanisms underlying the actions of XML. RESULTS: XML treatment significantly enhanced the survival rate of rats from epirubicin-induced heart failure. XML prevented left ventricle dilatation, improved cardiac function. Furthermore, treatment with XML also significantly inhibited the accumulation of collagen, reduced the levels of mRNA for matrix metalloproteinases-9 (Mmp9) and transforming growth factor-ß 1(Tgfb1). This action of XML therefore might be responsible, at least in part, for the attenuation of cardiac fibrotic remodeling. XML inhibited autophagy as evidenced by the decreased accumulation of Beclin1 and autophagy related 7 (Atg7), which are necessary to form autophagosome structures. Protein kinase B (PKB/Akt), phosphatidylinositol 3 kinase (PI3K) and B cell lymphoma2 (Bcl2) levels were up-regulated, while significantly decreased protein levels for phosphorylated P38 and extracellular regulated protein kinases 1/2 (Erk1/2) were observed in the XML treated rats. The autophagy related results suggested that the increase in PI3K/Akt levels and inhibition of the phosphorylation of P38 MAPK and Erk1/2 contributed to the anti-autophagic activity of XML. CONCLUSIONS: Our data suggest that XML may be effective for mitigating epirubicin-induced cardiomyopathy and inhibits autophagy via activating the PI3K/Akt signaling pathway and inhibiting the Erk1/2 and P38 MAPK signaling pathways.

Does Citrulline Have Protective Effects on Liver Injury in Septic Rats?

Citrulline (Cit) supplementation was proposed to serve as a therapeutic intervention to restore arginine (Arg) concentrations and improve related functions in sepsis. This study explored whether citrulline had positive effects on liver injury and cytokine release in the early stages of sepsis. The cecal ligation and puncture (CLP) model was utilized in our study. Rats were divided into four groups: normal, Cit, CLP, and CLP+Cit. The CLP group and CLP+Cit group were separated into 6-, 12-, and 24-hour groups, according to the time points of sacrifice after surgery. Intragastric administration of L-citrulline was applied to rats in Cit and CLP+Cit groups before surgery. Serum AST and ALT levels and levels of MDA, SOD, NO, and iNOS in the liver tissues were evaluated. Plasma concentrations of Cit and Arg were assessed using HPLC-MS/MS. Serum concentrations of cytokines and chemokines were calculated by Luminex. Results showed SOD activities of CLP+Cit groups were significantly higher than that of CLP groups, contrasting with the MDA and NO levels which were significantly lower in CLP+Cit groups than in CLP groups. In addition, plasma concentrations of TNF-α, IL-6, and IL-1ß were significantly lower in the CLP+Cit 6-hour group than in the CLP 6-hour group.

Analysis of patents on anti-rheumatoid arthritis therapies issued in China.

INTRODUCTION: The etiology of rheumatoid arthritis (RA) is complex and diverse. Chronic inflammatory processes with joint dysfunction can cause permanent disability. Therefore, the development of new drugs and therapies for RA is very important. AREAS COVERED: This review analyzes the existing patents on anti-RA products in China to help pharmaceutical companies and individuals patent potential candidate drugs for RA treatment. EXPERT OPINION: Three hundred and seventeen patents were analyzed, including 172 patents for Traditional Chinese Medicines (TCMs, 54.2%), 65 for synthetic compounds (20.5%), 55 for biological products (17.4%) and 25 patents for the drug preparation process (7.9%). Among the TCM patents, 73.8% were of various preparations for different Chinese medicines, 23.8% were of herbal extracts and 2.3% were of herbal extract derivatives. Synthetic compounds were involved in more than 30 targets, some small-molecule drugs that target signaling kinases such as p38 MAPK, Janus kinase may become important directions in the management of RA. Biological disease-modifying antirheumatic drugs (bDMARDs) are the most efficacious drugs for RA treatment. As the classic therapeutic target in RA, TNF-α has the largest number of bDMARD patents. In addition, it is expected that new targets such as high-mobility group protein B1, thioredoxin domain-containing protein 5 (TXNDC5) and B lymphocyte stimulator (BlyS) will play a significant role in RA as potential targets for new treatments. The largest number of all the published patent applications are claiming TCMs, which may provide substantial new information for anti-RA drug development. The largest number of all the published patent applications are claiming TCMs, which may provide huge information for anti-RA drug development.