Abstract It was determined if lipoxin A4 methyl ester (LXA4 ME) affects JAK2/STAT3 pathway following transient focal cerebral ischemia-reperfusion injury (CIRI) in rats. Adult male SD rats were randomly assigned to sham-operated, CIRI group, DMSO + CIRI, AG490 + CIRI, and LXA4 ME + CIRI. Neurologic deficit was evaluated in rats after 24 h reperfusion. IL-6 levels of brain tissue were determined 6 and 24 h post-reperfusion using an ELISA assay. STAT3 and SOCS3 mRNA levels were analyzed via real-time quantitative PCR. P-JAK2, p-STAT3, and SOCS3 were measured via Western blotting, and localized by fluorescent immunohitochemistry. Transient cerebral ischemia in rats caused a significantly elevated concentration of IL-6, levels of STAT3 and SOCS3 mRNA, phosphorylation of JAK2 and STAT3, and immunoreactive glia of ipsilateral cortex 24 h post-reperfusion versus sham rats. The AG490 intervention downregulated cerebral ischemia-induced JAK2 and STAT3 phosphorylation, and their immunoreactive glia located in the ischemic cortex. LXA4 ME reduced the concentration of IL-6, increased SOCS3 expression, inhibited phosphorylation and immunoreactive glia of JAK2 and STAT3, as well as ameliorated neurologic dysfunction. In conclusions, LXA4 ME inhibited JAK2/STAT3 activation, perhaps via upregulating SOCS3, as well as suppressed IL-6 expression to ameliorate cerebral ischemic injury.

Abstract Objectives Myocardial Infarction (MI) is the leading cause of chronic heart failure. Previous studies have suggested that Vav3, a receptor protein tyrosine kinase signal transducer, is associated with a variety of cellular signaling processes such as cell morphology regulation and cell transformation with oncogenic activity. However, the mechanism of Vav3-mediated MI development requires further investigation. Method Here, The authors established an MI rat model by ligating the anterior descending branch of the left coronary artery, and an MI cell model by treating cardiomyocytes with H2O2. Microarray analysis was conducted to identify genes with differential expression in heart tissues relevant to MI occurrence and development. Vav3 was thus selected for further investigation. Results Vav3 downregulation was observed in MI heart tissue and H2O2-treated cardiomyocytes. Administration of Lentiviral Vav3 (LV-VAV3) in MI rats upregulated Vav3 expression in MI heart tissue. Restoration of Vav3 expression reduced infarct area and ameliorated cardiac function in MI rats. Cardiac inflammation, apoptosis, and upregulation of NFκB signal in heart tissue of MI animals were assessed using ELISA, TUNEL staining, real-time PCR, and WB. Vav3 overexpression reduced cardiac inflammation and apoptosis and inhibited NFκB expression and activation. Betulinic Acid (BA) was then used to re-activate NFκB in Vav3-overexpressed and H2O2-induced cardiomyocytes. The expression of P50 and P65, as well as nuclear P65, was significantly increased by BA exposure. Conclusions Vav3 might serve as a target to reduce ischemia damage by suppressing the inflammation and apoptosis of cardiomyocytes. (MI failure Vav transducer activity However Vav3mediated Vavmediated mediated investigation Here artery H2O2 HO H O H2O2treated HOtreated treated LVVAV3 LVVAV LV VAV3 VAV (LV-VAV3 ELISA staining realtime real time PCR WB activation (BA reactivate re activate Vav3overexpressed Vavoverexpressed overexpressed H2O2induced HOinduced induced P P5 P65 exposure H2O (LV-VAV P6

Abstract To observe effect and safety of different doses of ketorolac tromethamine in patient controlled intravenous analgesia (PCIA) after hip arthroplasty. 60 hip arthroplasty patients injected with 0.5 mg/kg ketorolac tromethamine before anesthesia were randomly divided into group A, B and C in which the patients were injected 2, 3 and 4 mg/kg ketorolac tromethamine after operation respectively. Compared with group A, MAP and HR in group B and group C were lower at T1 (3 h after operation) and T2 (6 h after operation). In group A, MAP and HR at T3 (24 h after operation) and T4 (48 h after operation) were lower than at T1. Compared with group A, NRS scores of group B and C were significantly lower during the analgesia. Compared with group A, ramesay sedation scores in group B and group C were significantly higher at T1 and T2; Harris hip scores of group B and group C were significantly higher at T3 and T4; the total number of pushing PCA pump and dezocine dosage were significantly decreased in group B and group C. Preemptive analgesia combined with postoperative analgesia on patients after hip replacement was appropriate.

Abstract Background: Pulmonary hypertension (PH) is a frequent complication of systemic sclerosis (SSc) and is currently one of the primary causes of death in patients with this disease. We conducted a systematic review and meta-analysis to assess the association between PH and mortality in patients with SSc to verify trends in mortality in patients with SSc-associated PH. Methods: We searched the PubMed and Embase databases for published studies on SSc-associated PH from inception to May 2021. All cohort studies in which mortality and/or survival for SSc-associated PH were reported were included in the analysis. The outcome parameters were pooled and analyzed using a random-effects model via generic inverse-variance weighting in conventional and cumulative meta-analysis. Results: The literature search identified 1161 citations, and the full texts of 54 studies were examined. Sixteen articles, with a total of 7857 patients with SSc and 1140 patients with SSc-associated PH, were included in the metaanalysis. Patients with SSc-associated PH had a higher pooled risk of mortality than patients with SSc without PH (risk ratio = 3.12; 95% confidence interval: [2.44, 3.98]). Conclusions: This meta-analysis revealed a higher mortality in patients with SSc-associated PH. PH was a significant predictor of death in patients with SSc. Thus, early diagnosis and treatment of PH are important in patients with SSc.

SUMMARY OBJECTIVE: This study aims to compare the efficacy and safety of endoscopic transsphenoidal pituitary surgery and microscopic transseptal pituitary surgery in the treatment of Cushing's disease (CD). METHODS: A total of 46 patients with CD were randomized into endoscopic group and microscopic group, with 23 cases in each group. The endoscopic group received the endoscopic transsphenoidal pituitary surgery, and the microscopic group received the microscopic transseptal pituitary surgery. The retrospective data, surgical outcomes, surgical cure rates, and complications in two groups were compared. RESULTS: Compared with microscopic group, the operative time was significantly shorter (p<0.05), the estimated blood loss was significantly less (p<0.05), and the hospital stay was significantly shorter (p<0.05) in endoscopic group. The surgical cure rate in endoscopic and microscopic groups was 69.56% and 60.86%, respectively, with no significant difference between the two groups (p>0.05). The incidence of complications in endoscopic group was significantly lower than that in microscopic group (p<0.01). CONCLUSIONS: For the treatment of CD, the efficacy of endoscopic transsphenoidal pituitary surgery is basically the same as that of traditional microscopic transseptal pituitary surgery. However, the endoscopic surgery can further shorten the operative time, reduce the estimated blood loss, shorten the hospital stay, and reduce the complications.

RESUMO Introdução: A acupuntura tem sido amplamente utilizada para alívio de dor. No entanto, seus mecanismos são muito pouco conhecidos. Objetivo: Investigar a relação entre o efeito analgésico da eletroacupuntura e a regulação da expressão de adenosina e de substância P. Métodos: Utilizou-se um modelo de dor inflamatória crônica em ratos por injeção única do Adjuvante Completo de Freund e, em seguida, os animais foram tratados com eletroacupuntura diariamente. Foram aplicadas sete sessões bilaterais de eletroacupuntura (ST36 e BL60, 0,5 a 1,5 mA, força inicial de 0,5 mA, aumentada em 0,5 mA a cada 10 minutos, 30 minutos por sessão, uma sessão por dia) em ratos com Adjuvante Completo de Freund, por sete dias. O efeito analgésico da eletroacupuntura foi avaliado pela medida do limiar de retirada da pata em ratos que receberam estimulações mecânica e térmica. Resultados: A estimulação diária com eletroacupuntura aumentou efetivamente o limiar de retirada da pata em ratos com Adjuvante Completo de Freund. A eletroacupuntura aumentou o nível de adenosina na região zusanli. Estudos posteriores mostraram que a eletroacupuntura poderia diminuir os níveis de substância P, receptor de neurocinina-1, fator de necrose tumoral-alpha, interleucina-1β, interleucina-6 e CD68 nos gânglios da raiz dorsal. Curiosamente, a injeção direta de antagonistas do receptor de adenosina A1 ou de substância P, ou a transecção da raiz do nervo dorsal, podem prejudicar significativamente as ações analgésicas induzidas pela eletroacupuntura em ratos com Adjuvante Completo de Freund e reduzir os níveis de substância P, receptor de neurocinina-1, fator de necrose tumoral-alfa, interleucina-1β, interleucina-6 e CD68. Por fim, confirmamos que a injeção direta de um agonista do receptor da adenosina A1 reproduziu os efeitos analgésicos da eletroacupuntura. Conclusão: Nossos resultados indicam a regulação da secreção da substância P mediada pela adenosina. A via mediada pela substância P pode estar envolvida no processo de analgesia por eletroacupuntura em ratos.

ABSTRACT Background: Acupuncture has been widely used for alleviating pain. However, its mechanisms remain largely enigmatic. Objective: In the present study, we focused on whether the analgesic effect of electroacupuncture is related to its regulation on adenosine and substance P expression. Methods: We established chronic inflammatory pain model in rats through a single injection of Complete Freund’s Adjuvant, and then we treated animals using daily electroacupuncture. We applied seven bilateral sessions of electroacupuncture (ST36 and BL60, 0.5 to 1.5 mA, initial strength of 0.5 mA, increased by 0.5 mA every 10 minutes, for 30 minutes per session, one section per day) to Complete Freund’s Adjuvant rats for seven days. The analgesic effect of electroacupuncture was evaluated by measuring paw withdrawal threshold in rats that received mechanical and thermal stimulation. Results: Daily electroacupuncture stimulation effectively increased paw withdrawal threshold in Complete Freund’s Adjuvant rats. Electroacupuncture increased the adenosine level in zusanli. A further study showed that electroacupuncture could decrease substance P, neurokinin-1 receptor, tumor necrosis factor-alpha, interleukin-1β, interleukin-6 and CD68 levels in dorsal root ganglion. Interestingly, direct injection of adenosine A1 or substance P receptor antagonists, or dorsal nerve root transection could significantly impair electroacupuncture induced analgesic actions in Complete Freund’s Adjuvant rats could and reduce the levels of substance P, neurokinin-1 receptor, tumor necrosis factor-alpha, interleukin-1β, interleukin-6 and CD68. Finally, we confirmed that direct injection of adenosine A1 receptor agonist replicated the analgesic effect of electroacupuncture. Conclusion: Our results indicate regulation of adenosine-mediated substance P secretion. Substance P-mediated pathway may be involved in the analgesia process by electroacupuncture in rats.

With the widespread use of high-efficiency antiretroviral therapy (HAART), the life expectancy of HIV-infected patients has been significantly extended. However, the metabolic complications among HIV-infected patients treated with HAART have become the most common problem in the world. It is very important to explore the incidence of dyslipidaemia and studies on the role of potential risk factors in HIV-infected Chinese patients treated with HAART are sparse. Therefore, we designed current study, to investigate the effects of therapeutic intervention and continuous information support on the lifestyle of HIV/AIDS patients with dyslipidaemia. Three hundred and six HIV/AIDS patients admitted to the AIDS clinic in Beijing from January 2016 to January 2017 were recruited and assigned into two groups: the treatment group (n=64) and the control group (n=64). The median age of the participants was 38.8±11.0 years (range 20-75 years). The prevalence of dyslipidemia in control and treatment group was (59/64) 92.2% and (53/64) 82.8%, respectively. In this study, low HDL-cholesterol (HDLC) led to abnormalities 47/64 (73.3%) in the control group and 35/64 (54.7%) in HAART-treatment group. Additionally, HAART group showed higher triglyceride, total cholesterol, and low-density lipoprotein (246.1±171.8, 1.73±1.61 mmol/L, 4.46±1.1 mmol/L, 2.54±0.74 mmol/L). In multivariate analysis, gender, marital status, high BMI, dietary habits and physical activity were potential risk factors for dyslipidemia in HIV-infected Chinese patients. In this study, we reported high prevalence dyslipidemiain two HIV infected groups. We suggest that the appropriate diagnosis should be performed for analyzing the metabolic complications in HIV-infected Chinese patients. Further studies are very important to understand the role of potential risk factors in metabolic complications.

The development of chemotherapy resistance significantly impairs the efficiency of chemotherapy, but the underlying mechanisms of chemotherapy resistance in gastric cancer (GC) are complicated and still need to be further explored. Here, we aimed to reveal the effects of miR-4290/PDK1 (pyruvate dehydrogenase kinase 1) axis on chemotherapy resistance of GC in vitro. The expression patterns of miR-4290 in GC tissues and cell lines were determined by real-time quantitative PCR. Kaplan-Meier was used to assess the relationship between miR-4290 expression levels and patients' overall survival. CCK-8 and flow cytometry technologies were applied to detect cell proliferation and apoptosis. The luciferase gene reporter assay was used to evaluate the interaction between miR-4290 and PDK1. miR-4290 was lowly expressed in GC tissues and cell lines, which was closely associated with the shorter overall survival of GC patients. miR-4290 mimics significantly inhibited cell proliferation and induced cell apoptosis, as well as induced a significant reduction in the expression of PDK1. Moreover, miR-4290 significantly inhibited glycolysis and decreased the IC50 value to cisplatin in SGC7901 cells, whereas these effects were abolished and cell apoptosis was promoted when PDK1 was overexpressed. In conclusion, this study revealed that miR-4290 suppressed PDK1-mediated glycolysis to enhance the sensitivity of GC cells to cisplatin.

ABSTRACT Macamides and Macaenes are the bioactive marker compounds in maca (Lepidium meyenii Walp., Brassicaceae) tuber. To simultaneously quantify these two types of compound, HPLC method was studied. To distinguish and group the growing regions of different maca samples, Hierarchical cluster analysis, a chemometric method, was applied to analyze the HPLC data. The calibration curves obtained using the HPLC method showed satisfactory linearity with determination coefficients >0.9998. The precision and repeatability relative standard deviation values were <4%, and the accuracy relative standard deviation value was <5%. The limits of detection was <0.1 µg/ml and the limit of quantification was <0.3 µg/ml. Our HPLC method was successfully used for the separation and determination of macamides and macaenes in Maca within 45 min, i.e., two macaenes (9-oxo-10E,12Z-octadecadienoic acid and 9-oxo-10E,12E-octadecadienoic acid) and five macamides (N-benzyl-9-oxo-10E,12Z-octadecadienamide, N-benzyl-9-oxo-10E,12E-octadecadienamide, N-benzyl-9Z,12Z,15Z-octadecatrienamide, N-benzyl-9Z,12Z-octadecadienamide and N-benzyl-hexadecanamide). The HPLC method was applied to analyze and quantify the seven compounds in thirty maca samples with different colors and origins. The origins of all the maca samples were distinguished and grouped using hierarchical cluster analysis of the HPLC data. Accordingly, the metabolism of macaenes and macamides in maca post-harvest processing has also been proposed. The HPLC method is efficient to simultaneously quantify the macamides and macaenes in maca. Analyzing the HPLC data using hierarchical cluster analysis can distinguish maca growing origins.

Sarcopenia remains poorly managed in clinical practice due to the lack of simple and accurate screening tools. This study aimed to identify the cutoff values of the SARC-F questionnaire and Ishii's score using the variables age, grip strength, and calf circumference in older inpatients in China to compare the accuracy of the two methods and to explore their predictive ability for adverse outcomes (rehospitalization, falls, fracture, and death). Hospitalized patients (n=138) aged ≥60 years were included. The accuracy of the two tools was evaluated using the reference diagnosis recommended by the Asian Working Group on Sarcopenia (assessing patients with measurements of muscle mass, handgrip strength, and usual gait speed). Follow-up data were obtained by telephone and clinical visits combined with the inpatient medical record system after discharge for at least one year. The results showed that the SARC-F score reached the highest Youden's index when a score of 3 was set as the cutoff value. Ishii's score presented a higher accuracy than SARC-F (area under the receiver operating curve: 0.78 vs 0.64, P=0.01). The Kaplan-Meier survival analysis demonstrated a higher cumulative incidence of rehospitalization in sarcopenic individuals compared to non-sarcopenic individuals according to SARC-F (log-rank test, P<0.001). Cox analysis revealed that SARC-F was an independent risk factor for rehospitalization (adjusted hazard ratio: 4.23, 95%CI: 2.12-9.79, P<0.001). The SARC-F and Ishii's scores might facilitate the early detection of sarcopenia and help identify older adults at risk for adverse outcomes in clinical practice.

Abstract A new 3-node triangular hybrid displacement function Mindlin-Reissner plate element is developed. Firstly, the modified variational functional of complementary energy for Mindlin-Reissner plate, which is eventually expressed by a so-called displacement function F, is proposed. Secondly, the locking-free formulae of Timoshenko’s beam theory are chosen as the deflection, rotation, and shear strain along each element boundary. Thirdly, seven fundamental analytical solutions of the displacement function F are selected as the trial functions for the assumed resultant fields, so that the assumed resultant fields satisfy all governing equations in advance. Finally, the element stiffness matrix of the new element, denoted by HDF-P3-7β, is derived from the modified principle of complementary energy. Together with the diagonal inertia matrix of the 3-node triangular isoparametric element, the proposed element is also successfully generalized to the free vibration problems. Numerical results show that the proposed element exhibits overall remarkable performance in all benchmark problems, especially in the free vibration analyses.

Abstract The effects of allelochemicals and aqueous extracts from different Pogostemon cablin (Blanco) Benth., Lamiaceae, parts and rhizosphere soil on growth parameters, leaf membrane peroxidation and leaf antioxidant enzymes were investigated in patchouli. P. cablin seedlings were incubated in solutions containing allelochemicals and aqueous extracts from different patchouli parts and its rhizosphere soil at several concentrations. Firstly, the growth parameters were significantly reduced by the highest concentration of leaves, roots and stems extracts (p < 0.05). As compared to the control, plant height was reduced by 99.8% in the treatment with leaves extracts (1:10). The malondialdehyde content increased greatly when patchouli seedlings were subject to different concentrations of leaves, roots and stems extracts; meanwhile, the superoxide dismutase and peroxidase activities showed an increase trend at the low concentration, followed by a decline phase at the high concentration of roots and leaves extracts (1:10). What's more, leaves and roots extracts had a more negative effect on patchouli growth than stems extracts at the same concentrations. Secondly, the total fresh mass, root length and plant height were greatly reduced by the highest strength of soil extracts. Their decrements were 22.7, 74.9, and 33.1%, respectively. Thirdly, growth parameters and enzymatic activities varied considerably with the kinds of allelochemicals and with the different concentrations. Plant height, root length and total fresh weight of patchouli were greatly reduced by p-hydroxybenzoic acid (200 μM), and their decrements were 77.0, 42.0 and 70.0%, respectively. Finally, three useful measures on reducing the autotoxicity during the sustainable patchouli production were proposed.

South Africa has become one of the most developing countries in the world, and its economic growth has occurred along with rising energy-related CO2 emission levels. A deeper understanding of the driving forces governing energy-related CO2 emissions is very important in formulating future policies. The LMDI (Log Mean Divisia Index) method is used to analyse the contribution of the factors which influence energy-related CO2 emissions in South Africa over the period 1993-2011. The main conclusions drawn from the present study may be summarized as follows: the energy intensity effect plays the dominant role in decreasing of CO2 emission, followed by fossil energy structure effect and renewable energy structure effect; the economic activity is a critical factor in the growth of energy-related CO2 emission in South Africa.

Sesquiterpenes Essential oil produced by patchouli was one of the most important naturally occurring base materials used in the perfume industry, containing various sesquiterpenes. Three different parts (leaves, stems and roots) of Pogostemon cablin (Blanco) Benth., Lamiaceae, were profiled in relation to different maturation phases in this paper, evaluating the variations in content of the major sesquiterpenes in the essential oil. Twelve sesquiterpenes were analyzed by GC-MS throughout the maturity of P. cablin. Patchouli alcohol (37.54%-51.02% in leaves, 28.24%-41.96% in stems and 14.55%-35.12% in roots) was the major sesquiterpene during the maturation of the plant. The average content of several other sesquiterpenes (α-bulnesene, α-guaiene, seychellene, β-humulene and caryophyllene) were higher than 3% among leaves, stems and roots. The content of essential oil, patchouli alcohol, α-bulnesene and several other compounds were highly accumulated at 210 days of maturation after cultivation of P. cablin. Thus, this period was the best moment to exploit the maximum level of these high value-added compounds in P. cablin. Furthermore, our results indicated that the essential oil extracted from leaves of P. cablin has the highest potential to be used in the perfume industry.

The aim of this study was to enhance the production of vitamin K2 by using N-methyl-N-nitro-N-nitroso-guanidine (NTG) and low energy ion beam implantation and optimizing the fermentation medium. Mutation resulted in 1.66-fold higher production of vitamin K2 than that of the parentl strain. The production by the mutant BN-P15-11-1was increased 55% and reached 3.593±0.107 mg/L by using the Plackett-Burman and Box-Behnken designs to optimize the fermentation medium. The optimal fermentation culture medium was composed of (g/L) glycerol 69.6, sucrose 34.5, K2HPO4 4.0, peptone 20, yeast extract 25 and fermented at 37 °C and 150 rpm for 72 h. The results showed that the NTG and low energy ion beam implantation mutations and optimizing fermentation medium were effective methods to enhance vitamin K2production.