Effect of a moderate-intensity comprehensive exercise program on body composition, muscle strength, and physical performance in elderly females with sarcopenia.

Objective: This study aimed at examining an eight-week moderate-intensity comprehensive exercise training program on the parameters of sarcopenia in elderly females. Methods: A total of 49 community-dwelling elderly females with sarcopenia (65.5 ± 2.5) were assigned randomly to an experiment group (EG, n = 25) and a control group (CG, n = 24). In the EG, an eight-week comprehensive exercise training program was implemented, in 1 h, 3 times per week, a total of 24 sessions. The CG only received health public education per two weeks, a total of 4 times. Subsequently, the differences between the two groups were tested through two-way repeated ANOVA. Results: ASM, SMM, and SMI in the EG were significantly improved by 0.26 kg, 0.18 kg, and 0.10 kg/m2, respectively. Group-by-time interactions were significantly different on the ASM [F (1,47) = 6.25, η2 = 0.12] and SMI [F (1,47) = 6.77, η2 = 0.13]. Muscle strength was improved 0.8 kg in the EG. Significant group-by-time interaction differences were reported in the handgrip strength [F (1,47) = 6.8, η2 = 0.13] after the eight-week intervention. Compared with the baseline, gait speed was improved a 0.05 m/s and 5-time chair stand was decreased a 0.27 s in the EG. Group-by-time interactions were significantly different in 5-time chair stand [F (1, 47) = 6.35, η2 = 0.12]. Conclusions: The moderate-intensity comprehensive exercise was confirmed as a safe and convenient exercise program. Although a load of training intensity is not sufficient to improve the gait speed, this exercise protocol is promising in delaying overall results in community-dwelling sarcopenia elderly females and contributes to the improvement of muscle mass, handgrip strength, and 5TCS.

Efficacy of Tai Chi on lower limb function of Parkinson's disease patients: A systematic review and meta-analysis.

Background: At present, the effect of Tai Chi (TC) on lower limb function in patients with Parkinson's disease (PD) is controversial. Therefore, we conducted a meta-analysis on the influence of TC on lower limb function in PD patients. Methods: According to the PRISMA guidelines, seven databases were searched. Randomized controlled trials (RCTS) were selected and screened according to inclusion and exclusion criteria. We assessed the quality of the studies using the Cochrane Risk of Bias tool and then extracted the characteristics of the included studies. The random effect model was adopted, and heterogeneity was measured by I 2 statistic. Results: A total of 441 articles were screened, and 10 high-quality RCTs were with a total of 532 patients with PD met Our inclusion criteria. Meta-analysis showed that compared To control groups TC improved several outcomes. TC significantly improved motor function (SMD = -0.70; 95% CI = -0.95, -0.45; p < 0.001; I 2 = 35%), although The results were not statistically significant for The subgroup analysis of TC duration (SMD = -0.70; 95% CI = -0.95, -0.45; p = 0.88; I 2 = 0%;). TC significantly improved balance function (SMD = 0.89; 95% CI = 0.51, 1.27; p < 0.001; I 2 = 54%), functional walking capacity (SMD = -1.24; 95% CI = -2.40, -0.09; p = 0.04; I 2 = 95%), and gait velocity (SMD = 0.48; 95% CI = -0.02, 0.94; p = 0.04; I 2 = 78%), But Did Not improve endurance (SMD = 0.31; 95% CI = -0.12, 0.75; p = 0.16; I 2 = 0%), step length (SMD = 0.01; 95% CI = -0.34, 0.37; p = 0.94; I 2 = 29%), and cadence (SMD = 0.06; 95% CI = -0.25, 0.36; p = 0.70; I 2 = 0%). Conclusion: TC has beneficial effects on motor function, balance function, functional walking ability, and gait velocity, but does not improve walking endurance, stride length, and cadence.

Blood levels of omega-6 fatty acids and coronary heart disease: a systematic review and metaanalysis of observational epidemiology.

Individual omega-6 polyunsaturated fatty acids (PUFAs), principally linoleic acid (LA) and arachidonic acid (AA), may have differential impacts on cardiovascular risk. We aimed to summarize the up-to-date epidemiology evidence on the relationship between blood levels of omega-6 PUFAs and the risk of coronary heart disease (CHD). Population-based studies determining PUFA levels in blood were identified until May 2021 in PubMed, Embase, Web of Science, and Cochrane Library. Random-effects meta-analyses of cohorts comparing the highest versus lowest category were conducted to combine study-specific risk ratios (RRs) with 95% confidence intervals (CIs). Blood levels of omega-6 PUFAs were compared between the CHD case and non-case, presented as a weight mean difference (WMD). Twenty-one cohorts and eleven case-control studies were included. The WMD was -0.71 (95% CI: -1.20, -0.21) for LA and 0.08 (95% CI: -0.28, 0.43) for AA. LA levels were inversely associated with total CHD risk (RR: 0.85, 95% CI: 0.71, 1.00), but not AA. Each one-SD increase in LA levels resulted in 10% reductions in the risk of fatal CHD (RR: 0.90, 95% CI: 0.86, 0.95), but not in non-fatal CHD. Such findings highlight that the current recommendation for optimal intakes of omega-6 PUFAs (most LA) may offer a coronary benefit in primary prevention.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2022.2056867 .

Clinical Efficacy and Mechanism of Osteoking in Treatment of Knee Osteoarthritis Based on Real-world Data / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy and mechanisms of Osteoking in the treatment of knee osteoarthritis （KOA） in real-world practice， so as to provide a basis for the rational clinical use of Osteoking. MethodFrom the Osteoking for knee osteoarthritis case registration system， 638 KOA cases treated with Osteoking were selected and analyzed in SPSS 26.0. The clinical data were collected from 20 hospitals in China from May 2020 to December 2021. Descriptive analyses of patient age， gender， body mass index， course of treatment and other parameters were performed. The Mann-Whitney U test was performed to compare the visual analogue scale （VAS） and Western Ontario and McMaster universities arthritis index （WOMAC） scores before and after treatment. The integrative pharmacology-based research platform of traditional Chinese medicine （TCMIP） v2.0 was used for network analysis of the core targets of Osteoking in treating knee osteoarthritis. Furthermore， 20 KOA patients treated with Osteoking in the Third Affiliated Hospital of Beijing University of Chinese Medicine from October to December in 2022 were enrolled in the treatment group， and 20 healthy volunteers in the control group. The enzyme-linked immunosorbent assay was employed to measure the serum levels of related indicators to verify the prediction results. ResultA total of 638 KOA patients were treated with Osteoking， including 429 （67.24%） receiving Osteoking alone and 209 （32.76%） receiving Osteoking combined with other therapies. The female patients （415， 65.05%） were more than the male patients （223， 34.95%）. The patients showed the mean age of （63.48±13.51） years， mean body mass index of （24.09±2.98） kg·m-2， and mean course of treatment of （15.78±9.66） days. Most of the patients were rated as grades Ⅱ （46.24%） and Ⅲ （34.64%） in Kellgren-Lawrence （K-L） grading and in the relief stage （82.45%） in clinical staging. There was no significant correlation between clinical staging and K-L grading results. The cluster analysis identified three TCM syndromes： Qi stagnation and blood stasis， cold-dampness obstruction， and liver-kidney deficiency. The overall clinical efficacy evaluation showed that VAS score decreased from （6.01±0.85） scores before treatment to （2.54±1.73） scores after treatment （P<0.05）， and the WOMAC score decreased from （93.25±25.91） scores before treatment to （50.73±25.14） scores after treatment （P<0.05）. The network analysis predicted that Osteoking might regulate the transforming growth factor-beta （TGF-β）， tumor necrosis factor-alpha （TNF-α）， and nuclear factor-kappa B （NF-κB） signaling pathways to exert the therapeutic effect. The clinical trial showed elevated TGF-β1 level （P<0.01） and lowered NF-κB subunit RELA and tumor necrosis factor receptor superfamily， member 1A （TNFRSF1A） levels （P<0.05） after treatment. The synergistic effects of these changes provide a multidimensional and comprehensive therapeutic efficacy for KOA， alleviating the joint pain and limited mobility in patients. ConclusionOsteoking showed significant therapeutic efficacy in treating KOA. Osteoking may act on multiple pathways involved in cartilage metabolism and inflammation. The findings provide experimental evidence and theoretical support for elucidating the multi-target mechanism of Osteoking in treating KOA.

A mass spectrometry imaging approach on spatiotemporal distribution of multiple alkaloids in Gelsemium elegans.

Gelsemium elegans contains multiple alkaloids with pharmacological effects, thus researchers focus on the identification and application of alkaloids extracted from G. elegans. Regretfully, the spatiotemporal distribution of alkaloids in G. elegans is still unclear. In this study, the desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was applied to simultaneously analyze the distribution of pharmacologically important alkaloids in different organ/tissue sections of G. elegans at different growth stages. Finally, 23 alkaloids were visualized in roots, stems and leaves at seedling stage and 19 alkaloids were observed at mature stage. In mature G. elegans, 16 alkaloids were distributed in vascular bundle region of mature roots, 15 alkaloids were mainly located in the pith region of mature stems and 2 alkaloids were enriched in epidermis region of mature stems. A total of 16 alkaloids were detected in leaf veins of mature leaves and 17 alkaloids were detected in shoots. Interestingly, diffusion and transfer of multiple alkaloids in tissues have been observed along with the development and maturation. This study comprehensively characterized the spatial metabolomics of G. elegans alkaloids, and the spatiotemporal distribution of alkaloid synthesis. In addition, the results also have reference value for the development and application of Gelsemium elegans and other medicinal plants.

A Randomized Pilot Trial of Micronutrient Supplementation for Under-5 Children in an Urban Low-Cost Flat Community in Malaysia: A Framework for Community-Based Research Integration.

Early childhood nutritional deficiency has detrimental consequences on physical and cognitive development. We conducted a single-center, single-blind, two-arm pilot randomized no-treatment controlled trial (the Child of Urban Poverty Iron Project (CUPIP); NCT03819530) in a people's housing project locale in Selangor, Malaysia, between September 2019 and February 2020, to assess the trial's general feasibility and preliminary benefits of daily micronutrient supplementation for iron storage and anthropometric outcomes in under-5 children. Those with history of premature births, congenital abnormalities, or baseline hemoglobin <70 g/L were excluded. Participants received baseline deworming and were simply randomized in a 1:1 ratio to either micronutrient (4-month daily micronutrient packets) or control (no micronutrient supplementation) groups. Information on anthropometric, erythrocytic, and iron storage endpoints were collected. Overall, 45 (25 micronutrient and 20 controls) participants were enrolled and completed 4-month endpoint assessments. Micronutrient recipients demonstrated higher median mean corpuscular volume, serum ferritin level with no significant differences in all anthropometric endpoints. In conclusion, this pilot trial was implementable, demonstrating that micronutrient supplementation significantly improved hematological, but not anthropometric, endpoints, of under-5-year-old children living in an underprivileged environment. A definitive well-designed trial with larger sample sizes and greater attrition control should be contemplated in the future.

Comparative efficacy of omega-3 polyunsaturated fatty acids on major cardiovascular events: A network meta-analysis of randomized controlled trials.

The role of omega-3 polyunsaturated fatty acids (PUFAs) in primary and secondary prevention on major cardiovascular events (MCE) is inconclusive due to the potential heterogeneity in study designs of formulas, dosages, and ratios of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from the findings of previous randomized controlled trials (RCTs). Here we conducted a comprehensive narrative review of pre-clinical studies and updated a network meta-analysis (NMA) to determine the comparative efficacy against MCE with different EPA/DHA dosages and formulas. We found that pure EPA was ranked the best option in the secondary prevention (hazard ratio: 0.72, 95% confidence interval: 0.65 to 0.81) from the NMA of 39 RCTs with 88,359 participants. There was no evidence of omega-3 PUFAs' efficacy in primary prevention. The mechanisms of omega-3 PUFAs' cardiovascular protection might link to the effects of anti-inflammation and stabilization of endothelial function from PUFA's derivatives including eicosanoids and the special pre-resolving mediators (SPMs).

The receptor kinase OsWAK11 monitors cell wall pectin changes to fine-tune brassinosteroid signaling and regulate cell elongation in rice.

Rates of plant cell elongation change with day-night alternation, reflecting differences in metabolism related to cell wall remodeling. Information from cell wall surveillance pathways must be integrated with growth regulation pathways to provide feedback regulation of cell wall modification; such feedback regulation is important to ensure sufficient strength and prevent rupture of the cell wall during growth. Several lines of evidence suggest that cell wall perturbations often influence phytohormone signaling, but the identity of the nexus between these two processes remained elusive. Here, we show that wall-associated kinase11 (OsWAK11) acts as a linker connecting cell wall pectin methyl-esterification changes and brassinosteroid (BR) signaling in rice. Our data show that OsWAK11 controls several important agronomical traits by regulating cell elongation in rice. OsWAK11 directly binds and phosphorylates the BR receptor OsBRI1 at residue Thr752, within a motif conserved across most monocot graminaceous crops, thus hindering OsBRI1 interaction with its co-receptor OsSERK1/OsBAK1 and inhibiting BR signaling. The extracellular domain of OsWAK11 shows a much stronger interaction toward methyl-esterified pectin as compared with de-methyl-esterified pectin. OsWAK11 is stabilized in light but is degraded in darkness, in a process triggered by changes in the ratio of methyl-esterified to de-methyl-esterified pectin, creating fluctuations in plant BR signaling in response to day and night alternation. We conclude that OsWAK11 is a cell wall monitor that regulates cell elongation rates to adapt to the environment from the outside in, which complements the well-established inside-out signaling pathway affecting cell elongation in plants.

Excretion, Metabolism, and Tissue Distribution of Gelsemium elegans (Gardn. & Champ.) Benth in Pigs.

Gelsemium elegans (Gardn. & Champ.) Benth is a toxic flowering plant in the family Loganiaceae used to treat skin diseases, neuralgia and acute pain. The high toxicity of G. elegans restricts its development and clinical applications, but in veterinary applications, G. elegans has been fed to pigs as a feed additive without poisoning. However, until now, the in vivo processes of the multiple components of G. elegans have not been studied. This study investigates the excretion, metabolism and tissue distribution of the multiple components of G. elegans after feeding it to pigs in medicated feed. Pigs were fed 2% G. elegans powder in feed for 45 days. The plasma, urine, bile, feces and tissues (heart, liver, lung, spleen, brain, spinal cord, adrenal gland, testis, thigh muscle, abdominal muscle and back muscle) were collected 6 h after the last feeding and analyzed using high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Five natural products in plasma, twelve natural products and five metabolites in urine, and three natural products in feces were characterized, suggesting that multiple components from G. elegans were excreted in the urine. However, ten natural products and four metabolites were detected in bile samples, which suggested that G. elegans is involved in enterohepatic circulation in pigs. A total of seven of these metabolites were characterized, and four metabolites were glucuronidated metabolites. Ten natural products and six metabolites were detected in the tissues, which indicates that G. elegans is widely distributed in tissues and can cross the blood-brain barrier. Among the characterized compounds, a highly toxic gelsedine-type alkaloid from G. elegans was the main compound detected in all biological samples. This is the first study of the excretion, metabolism and tissue distribution of multiple components from G. elegans in pigs. These data can provide an important reference to explain the efficacy and toxicity of G. elegans. Additionally, the results of the tissue distribution of G. elegans are of great value for further residue depletion studies and safety evaluations of products of animals fed G. elegans.

Sex differences in the pharmacokinetics and tissue residues of Macleaya cordata extracts in rats.

Macleaya cordata extracts (MCE) are listed as feed additives in animal production by the European Food Authority. The core components of MCE are mainly sanguinarine (SA) and chelerythrine (CHE). This study aims to investigate sex differences in the pharmacokinetics and tissue residues of MCE in rats.Male and female rates were intragastrically administered MCE (1.25 mg·kg-1 body weight and 12.5 mg·kg-1 body weight dose for 28 days). SA and CHE concentrations were determined using high-performance liquid chromatography/tandem mass spectrometry.The peak plasma concentration (Cmax) and area under the curve (AUC) of both CHE and SA were higher in female than in male rats (12.5 mg·kg-1 body weight group), whereas their half-life (T1/2) and apparent volume of distribution (Vd) was lower (p < 0.05). Tissue rfesidue analysis indicated that SA and CHE were more distributed in male than in female rats and were highly distributed in the caecum and liver. SA and CHE were completely eliminated from the liver, kidney, lung, heart, spleen, leg muscle, and caecum after 120 h, indicating they did not accumulate in rats for a long time.Overall, we found that the pharmacokinetics and tissue residues of SA and CHE of male and female rats showed sex differences.

[Effect of Pien Tze Huang against EV71].

This study aims to investigate the inhibitory effect of Pien Tze Huang(PZH) on enterovirus 71(EV71). To be speci-fic, chemiluminescence method was adopted to evaluate the toxicity of PZH to African green monkey kidney(Vero) cells and human rhabdomyosarcoma(RD) cells, and cytopathic effect(CPE) method to assess the inhibition on EV71-GFP reporter virus and EV71 C4 wild-type virus. The results showed that PZH had low cytotoxicity to Vero cells and RD cells, with the half-maximal cytotoxic concentration(CC_(50)) of about 0.691 3-0.879 2 mg·mL~(-1) for the two. In addition, PZH can effectively inhibit the replication of EV71 within the non-cytotoxic concentration range, and dose-dependently alleviate the cytopathic changes caused by virus infection, with the half-maximal effective concentration(EC_(50)) of 0.009 2-0.106 3 mg·mL~(-1). On the basis of the above results, the green fluorescent protein(GFP), indirect immunofluorescence assay(IFA), and median tissue culture infective dose(TCID_(50)) were employed to assess and verify the anti-EV71-GFP and anti-EV71 C4 activity of PZH. The results demonstrated that PZH can dose-dependently lower the expression of GFP by EV71-GFP and structural protein VP-1 by EV71 C4 and decrease the production of progeny infectious viruses. The EC_(50) of PZH for EV71-GFP and EV71 C4 was about 0.006 0-0.006 2 mg·mL~(-1) and 0.006 6-0.025 6 mg·mL~(-1), respectively. This study suggested that PZH may exert antiviral activity by acting on EV71 and interfering with the expression of VP-1. At the moment, there is still a lack of specific anti-EV71 drugs. This study proposed a new idea for the symptomatic treatment of EV71 infections such as hand-foot-mouth disease and verified an effective drug for the treatment of EV71 infections.

Toxicity assessment of gelsenicine and the search for effective antidotes.

BACKGROUND: Gelsenicine, one of the most toxic alkaloids of Gelsemium elegans Benth (G. elegans), causes severe respiratory depression. However, its toxicity mechanisms are yet to be elucidated and no effective antidotes are available. OBJECTIVE: This study aimed to analyse the toxicity characteristics of gelsenicine. METHODS: Both acute and sub-acute toxicities were evaluated. Gelsenicine distribution and elimination in the central nervous system (CNS) and blood were observed. Effective antidotes for gelsenicine poisoning were screened. RESULTS: In the acute toxicity study, gelsenicine was highly toxic, and female rats exhibited greater sensitivity to gelsenicine than male rats (LD50 0.520 mg/kg vs 0.996 mg/kg, respectively). Death was primarily caused by respiratory failure. However, in the sub-acute toxicity study, no significant organ damage was observed. Gelsenicine was easily absorbed from the gastrointestinal tract and penetrated the blood-brain barrier, reaching peak concentrations in the CNS within 15 min and rapidly decreasing thereafter. Flumazenil or diazepam combined with epinephrine reversed gelsenicine toxicity and significantly improved survival rate in mice. CONCLUSIONS: Gelsenicine is a highly toxic substance that affects nerve conduction without causing damage; the potential toxic mechanism is possibly associated with GABAA receptors. Our findings provide insights into the clinical treatment of gelsenicine-related poisoning and its toxicity mechanisms.

The multicomponent residue depletion of Gelsemium elegans in pig tissues, urine, and plasma.

Introduction: Gelsemium elegans (G. elegans) as a traditional medicinal plant used in livestock production. The use of G. elegans in veterinary clinics may pose safety risks to human health. Objectives: The aim of this study was to investigate tissue residue depletion in pigs fed G. elegans powder. Methods: A precise quantitation method and a simultaneous semi-quantitation method for multiple components independently of standards in pig tissues were developed for the first time. The two methods were validated in terms of specificity, LODs, LOQs, linearity, accuracy, precision, and matrix effects. They were then applied to a tissue residue depletion study after G. elegans powder at a dose of 2% per kg feed were fed to pigs. Results: Compared with precise quantitation, the method validation results indicated that the semi-quantitation method was reliable and acceptable for multicomponent quantification independent of standards. Many G. elegans alkaloids are widely distributed in most tissues of pigs. Tissue residue depletion studies indicated that 14-hydroxygelsenicine, 11-hydroxygelsenicine, and gelsemoxonine could be used as potential residue markers, and pancreas, small intestine, and lung tissues could be considered as potential residue target tissues of G. elegans. In addition, both urine and plasma could be used to predict 14-hydroxygelsenicine and gelsemoxonine residues in the liver, pancreas, and small intestinal tissues of pigs. Conclusion: The developed semi-quantification method can be applied to monitor the application and residue of G. elegans. The results provide scientific evidence for evaluating the safety of animal-derived food from G. elegans for consumers and will be helpful for its application and future development.

Acupuncture for Quality of Life in Gastric Cancer Patients Undergoing Adjuvant Chemotherapy.

CONTEXT: Patients with gastric cancer experience health-related quality of life (HRQOL) decline during adjuvant chemotherapy following gastrectomy. OBJECTIVES: This pilot study aimed to evaluate the preliminary effect and feasibility of electro-acupuncture (EA) for HRQOL and symptom burden in these patients. METHODS: In this open-label, multicenter, parallel controlled trial, gastric cancer patients who planned to receive adjuvant chemotherapy were randomly assigned to receive high-dose EA (seven times each chemotherapy cycle for three cycles), low-dose EA (three times each chemotherapy cycle), or usual care only. The acupoints prescription consisted of bilateral ST36, PC6, SP4, and DU20, EX-HN3, and selected Back-shu points. Patients completed the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) weekly, and the Edmonton Symptom Assessment System (ESAS). The primary outcome was the difference among the groups on the gastric cancer subscale (GaCS) of the FACT-Ga. RESULTS: Of the 66 randomized patients, 58 were analyzed according to intention-to-treat principle, and 45 were in the per-protocol set (PPS). The average scores in PPS of GaCS were 52.12±9.71, 51.85±12.36, and 45.37±8.61 in high-dose EA, low-dose EA, and control groups, respectively. EA was significantly associated with improved average GaCS scores when compared with control group (51.98±10.91 vs. 45.37±8.61, P = 0.039). EA treatment also produced ESAS relief at the end of intervention (14.36 ± 12.28 vs. 23.91 ± 15.52, P = 0.027). Participants in EA groups had fewer grade ≥3 leukopenia (0% vs. 15.79%, P = 0.031) and neutropenia (2.56% vs. 26.31%, P = 0.012). CONCLUSION: EA showed promising effects in improving HRQOL, controlling symptom burden, and reducing toxicity during adjuvant chemotherapy in gastric cancer patients. Future adequately powered trials are feasible and needed to confirm the specific effect of EA.

Effect of Pien Tze Huang against EV71 / 中国中药杂志

This study aims to investigate the inhibitory effect of Pien Tze Huang(PZH) on enterovirus 71(EV71). To be speci-fic, chemiluminescence method was adopted to evaluate the toxicity of PZH to African green monkey kidney(Vero) cells and human rhabdomyosarcoma(RD) cells, and cytopathic effect(CPE) method to assess the inhibition on EV71-GFP reporter virus and EV71 C4 wild-type virus. The results showed that PZH had low cytotoxicity to Vero cells and RD cells, with the half-maximal cytotoxic concentration(CC_(50)) of about 0.691 3-0.879 2 mg·mL~(-1) for the two. In addition, PZH can effectively inhibit the replication of EV71 within the non-cytotoxic concentration range, and dose-dependently alleviate the cytopathic changes caused by virus infection, with the half-maximal effective concentration(EC_(50)) of 0.009 2-0.106 3 mg·mL~(-1). On the basis of the above results, the green fluorescent protein(GFP), indirect immunofluorescence assay(IFA), and median tissue culture infective dose(TCID_(50)) were employed to assess and verify the anti-EV71-GFP and anti-EV71 C4 activity of PZH. The results demonstrated that PZH can dose-dependently lower the expression of GFP by EV71-GFP and structural protein VP-1 by EV71 C4 and decrease the production of progeny infectious viruses. The EC_(50) of PZH for EV71-GFP and EV71 C4 was about 0.006 0-0.006 2 mg·mL~(-1) and 0.006 6-0.025 6 mg·mL~(-1), respectively. This study suggested that PZH may exert antiviral activity by acting on EV71 and interfering with the expression of VP-1. At the moment, there is still a lack of specific anti-EV71 drugs. This study proposed a new idea for the symptomatic treatment of EV71 infections such as hand-foot-mouth disease and verified an effective drug for the treatment of EV71 infections.

Treatment of Donor-derived Carbapenem-resistant Klebsiella pneumoniae Infection after Renal Transplantation with Tigecycline and Extended-infusion Meropenem.

OBJECTIVE: Donor-derived carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has recently emerged as a critical early complication after renal transplantation. Although CRKP is usually sensitive to tigecycline, monotherapy with this drug is often less than effective. We investigated the efficacy of a combined regimen of tigecycline with high-dose, extended-infusion meropenem in the treatment of donor-derived CRKP infection after kidney transplantation. METHODS: From Jan. 2016 to Dec. 2017, a total of 12 CRKP isolates were detected from cultures of the organ preservation solution used for soaking the donor kidneys at our institute. Probable or possible donor-derived infection (DDI) was identified in 8 transplant recipients. Clinical data were retrospectively analyzed. RESULTS: Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing CRKP was reported to be positive in organ preservation solution cultures at 3.5±0.9 days after transplantation, leading to surgical site (n=3), urinary tract (n=4), and/or bloodstream (n=2) infections in 8 recipients. The drug susceptibility tests showed that CRKP was sensitive to tigecycline, but resistant to meropenem. In 7 patients who received tigecycline combined with high-dose extended-infusion meropenem, DDIs were successfully cured. The length of hospital stay was 31 (18-129) days, and the serum creatinine at discharge was 105.8±16.7 µmol/L. The one remaining patient who received tigecycline combined with intravenous-drip meropenem died of septic shock. A median follow-up of 43 months (33-55) showed no recurrence of new CRKP infection in the 7 surviving recipients. CONCLUSION: It was suggested that a prompt and appropriate combination therapy using tigecycline with high-dose extended-infusion meropenem is effective in treating donor-derived KPC-2-producing CRKP infection after renal transplantation.

Shared and specific patterns of structural and functional thalamo-frontal disturbances in manic and euthymic pediatric bipolar disorder.

Bipolar disorder (BD) is clinically defined by alternating depressive and manic episodes with a separated period of euthymia. Thalamo-frontal loop plays vital role in psychotic symptoms, altered motor control and executive difficulties in BD. It remains unclear that structural and functional alterations of thalamo-frontal loop among the different mood states in BD, especially in pediatric BD(PBD).Twenty manic PBD (mPBD), 20 euthymic PBD (ePBD) and 19 healthy controls (HCs) were included in the study. By analyzing the T1 images and fMRI signals, thalamus volume and frontal grey matter cortical thickness were tested, and functional connectivity (FC) between bilateral thalamus and frontal cortex was calculated. Relationship between clinical indices and thalamo-frontal FC was also evaluated in mPBD and ePBD adolescents.Compared to HCs, the cortical thickness of left middle frontal gyrus (MFG), bilateral superior frontal gyrus (SFG) was significantly decreased in both mPBD and ePBD patients, and volume of left thalamus and cortical thickness of right MFG significantly decreased in mPBD patients. Compared to that of the HCs and ePBD subjects, thalamo-frontal hyperconnectivity with MFG was found in mPBD, and compared with that of HCs, thalamo-frontal hypoconnectivity with precentral gyrus/SFG was found in ePBD. In ePBD patients, episode times positively correlated with FC values between thalamus and precentral gyrus.The findings of the present study demonstrate detailed knowledge regarding shared and specific structural and functional disruption in thalamo-frontal loop in mPBD and ePBD subjects. Thalamo-frontal abnormalities reported in adult BD subjects were also observed in adolescent BD patients, and thalamo-frontal dysfunction may be a crucial treatment target in BD.

Diterpene Ginkgolides Meglumine Injection inhibits apoptosis induced by optic nerve crush injury via modulating MAPKs signaling pathways in retinal ganglion cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Diterpene Ginkgolides Meglumine Injection (DGMI) is made of extracts from Ginkgo biloba L, including Ginkgolides A, B, and K and some other contents, and has been widely used as the treatment of cerebral ischemic stroke in clinic. It can be learned from the "Compendium of Materia Medica" that Ginkgo possesses the effect of "dispersing toxin". The ancient Chinese phrase "dispersing toxin" is now explained as elimination of inflammation and oxidative state in human body. And it led to the original ideas for today's anti-oxidation studies of Ginkgo in apoptosis induced by optic nerve crush injury. AIM OF THE STUDY: To investigate the underlying molecular mechanism of the DGMI in retinal ganglion cells (RGCs) apoptosis. MATERIALS AND METHODS: TUNEL staining was used to observe the anti-apoptotic effects of DGMI on the adult rat optic nerve injury (ONC) model, and flow cytometry and hoechst 33,342 staining were used to observe the anti-apoptotic effects of DGMI on the oxygen glucose deprivation (OGD) induced RGC-5 cells injury model. The regulation of apoptosis and MAPKs pathways were investigated with Immunohistochemistry and Western blotting. RESULTS: This study demonstrated that DGMI is able to decrease the conduction time of F-VEP and ameliorate histological features induced by optic nerve crush injury in rats. Immunohistochemistry and TUNEL staining results indicated that DGMI can also inhibit cell apoptosis via modulating MAPKs signaling pathways. In addition, treatment with DGMI markedly improved the morphological structures and decreased the apoptotic index in RGC-5 cells. Mechanistically, DGMI could significantly inhibit cell apoptosis by inhibiting p38, JNK and Erk1/2 activation. CONCLUSION: The study shows that DGMI and ginkgolides inhibit RGCs apoptosis by impeding the activation of MAPKs signaling pathways in vivo and in vitro. Therefore, the present study provided scientific evidence for the underlying mechanism of DGMI and ginkgolides on optic nerve crush injury.

Integration of Metabolomics and Transcriptomicsto Comprehensively Evaluate the Metabolic Effects of Gelsemium elegans on Pigs.

Some naturalphytogenic feed additives, which contain several active compounds, have been shown to be effective alternatives to traditional antibiotics. Gelsemium elegans (G. elegans) is a whole grass in the family Loganiaceae. It is a known toxic plant widely distributed in China and has been used as a traditional Chinese herbal medicine for many years to treat neuropathic pain, rheumatoid pain, inflammation, skin ulcers, and cancer. However, G. elegans not only is nontoxic to animals such as pigs and sheep but also has an obvious growth-promoting effect. To our knowledge, the internal mechanism of the influence of G. elegans on the animal body is still unclear. The goal of this work is to evaluate the metabolic consequences of feeding piglets G. elegans for 45 days based on the combination of transcriptomics and metabolomics. According to growth measurement and evaluation, compared with piglets fed a complete diet, adding 20 g/kg G. elegans powder to the basal diet of piglets significantly reduced the feed conversion ratio. Results of the liver transcriptome suggest that glycine and cysteine-related regulatory pathways, including the MAPK signaling pathway and the mTOR signaling pathway, were extensively altered in G. elegans-induced piglets. Plasma metabolomics identified 21 and 18 differential metabolites (p < 0.05) in the plasma of piglets in the positive and negative ion modes, respectively, between G. elegans exposure and complete diet groups. The concentrations of glycine and its derivatives and N-acetylcysteine were higher in the G. elegans exposure group than in the complete diet group.This study demonstrated that G. elegans could be an alternative to antibiotics that improves the immune function of piglets, and the latent mechanism of G. elegans may be related to various signaling pathways, including the MAPK signaling pathway and the PPAR signaling pathway.

Combined effects of 3-nitrooxypropanol and canola oil supplementation on methane emissions, rumen fermentation and biohydrogenation, and total tract digestibility in beef cattle.

The individual and combined effects of 3-nitrooxypropanol (3-NOP) and canola oil (OIL) supplementation on enteric methane (CH4) and hydrogen (H2) emissions, rumen fermentation and biohydrogenation, and total tract nutrient digestibility were investigated in beef cattle. Eight beef heifers (mean body weight ± SD, 732 ± 43 kg) with ruminal fistulas were used in a replicated 4 × 4 Latin square with a 2 (with and without 3-NOP) × 2 (with and without OIL) arrangement of treatments and 28-d periods (13 d adaption and 15 d measurements). The four treatments were: control (no 3-NOP, no OIL), 3-NOP (200 mg/kg dry matter [DM]), OIL (50 g/kg DM), and 3-NOP (200 mg/kg DM) plus OIL (50 g/kg DM). Animals were fed restrictively (7.6 kg DM/d) a basal diet of 900 g/kg DM barley silage and 100 g/kg DM supplement. 3-NOP and OIL decreased (P < 0.01) CH4 yield (g/kg DM intake) by 31.6% and 27.4%, respectively, with no 3-NOP × OIL interaction (P = 0.85). Feeding 3-NOP plus OIL decreased CH4 yield by 51% compared with control. There was a 3-NOP × OIL interaction (P = 0.02) for H2 yield (g/kg DM intake); the increase in H2 yield (P < 0.01) due to 3-NOP was less when it was combined with OIL. There were 3-NOP × OIL interactions for molar percentages of acetate and propionate (P < 0.01); individually, 3-NOP and OIL decreased acetate and increased propionate percentages with no further effect when supplemented together. 3-NOP slightly increased crude protein (P = 0.02) and starch (P = 0.01) digestibilities, while OIL decreased the digestibilities of DM (P < 0.01) and neutral detergent fiber (P < 0.01) with no interactions (P = 0.15 and 0.10, respectively). 3-NOP and OIL increased (P = 0.04 and P < 0.01, respectively) saturated fatty acid concentration in rumen fluid, with no interaction effect. Interactions for ruminal trans-monounsaturated fatty acids (t-MUFA) concentration and percentage were observed (P = 0.02 and P < 0.01); 3-NOP had no effect on t-MUFA concentration and percentage, while OIL increased the concentration (P < 0.01) and percentage (P < 0.01) of t-MUFA but to a lesser extent when combined with 3-NOP. In conclusion, the CH4-mitigating effects of 3-NOP and OIL were independent and incremental. Supplementing ruminant diets with a combination of 3-NOP and OIL may help mitigate CH4 emissions, but the decrease in total tract digestibility due to OIL may decrease animal performance and needs further investigation.