Effects of direct-fed microbial supplementation on performance and immune parameters of lactating dairy cows.

We evaluated the effects of supplementing bacterial direct-fed microbial (DFM) on performance, apparent total-tract digestibility, rumen fermentation, and immune parameters of lactating dairy cows. One hundred fourteen multiparous Holstein cows (41 ± 7 DIM) were used in a randomized complete block design with an experiment comprising 14 d of a covariate (pre-experimental sample and data collection) and 91 d of an experimental period. Cows were blocked based on energy-corrected milk (ECM) yield during the covariate period and the following treatments were randomly assigned within each block: (1) control (CON), corn silage-based total mixed ration without DFM; (2) PRO-A, basal diet top-dressed with a mixture of Lactobacillus animalis and Propionibacterium freudenreichii at 3 × 109 cfu/d; and 3) PRO-B, basal diet top-dressed with a mixture of L. animalis, P. freudenreichii, Bacillus subtilis, and Bacillus licheniformis at 11.8 × 109 cfu/d. Milk yield, dry matter intake (DMI), and body weight were measured daily, while milk samples for component analysis were taken on 2 consecutive days of each week of data collection. Feces, urine, rumen, and blood samples were taken during the covariate period, wk 4, 7, 10, and 13 for estimation of digestibility, N-partitioning, rumen fermentation, plasma nutrient status and immune parameters. Treatments had no effect on DMI and milk yield. Fat-corrected milk (3.5% FCM) and milk fat yield were improved with PRO-B, while milk fat percent and feed efficiency (ECM/DMI) tended to increase with PRO-B compared with PRO-A and CON. Crude fat digestibility was greater with PRO-B compared with CON. Feeding CON and PRO-A resulted in higher total volatile fatty acid concentration relative to PRO-B. Percentage of neutrophils tended to be reduced with PRO-A compared with CON and PRO-B. The mean fluorescence intensity (MFI) of anti-CD44 antibody on granulocytes tended to be higher in PRO-B compared with CON. The MFI of anti-CD62L antibody on CD8+ T cells was lower in PRO-A than PRO-B, with PRO-A also showing a tendency to be lower than CON. This study indicates the potential of DFM to improve fat digestibility with consequential improvement in fat corrected milk yield, feed efficiency and milk fat yield by lactating dairy cows. The study findings also indicate that dietary supplementation with DFM may augment immune parameters or activation of immune cells, including granulocytes and T cells; however, the overall effects on immune parameters are inconclusive.

Assessing the Readiness for Implementing the World Health Organization's ICOPE Approach in Hong Kong: Perspectives from Social Care and Policy Stakeholders.

Although integrated care has been considered a key strategy in reforming health systems around the world, it seems hard to realise in practice, particularly in the part of medical social integration. Worse still, little is known about the capacity of social care professionals who implement it, or their perceived roles and responsibilities, as well as the barriers and facilitators that stakeholders from the health and social sectors identify as factors affecting the ICOPE implementation process. Therefore, the present study was performed to probe into these issues. Data were collected from an online survey based on the WHO ICOPE scorecard (N = 34), and focus groups with policy makers, managers, health and social care professionals (N = 47). Inductive analyses were performed in accordance with the service and system levels within the WHO ICOPE implementation framework. While the findings from the scorecard survey highlight the gap in actualizing the ICOPE approach within the existing social services and care structures, we found support for a model of integrated care underpinned by the WHO ICOPE approach. Factors that may hinder and facilitate ICOPE implementation include workforce capacity-building, coordinated networks and partnerships, and financial mechanisms. This finding can help inform subsequent actions that further support health and social care advancement and collaboration, and the implementation of the ICOPE approach.

Effect of integrative medicines on 28-day mortality from sepsis: a systematic review and network meta-analysis.

OBJECTIVE: The aim is to perform a network meta-analysis to evaluate the effect of different Chinese medicines combined with Western medicine treatment (WMT) on the 28-day mortality of patients with sepsis. MATERIALS AND METHODS: We searched multiple databases for randomized controlled trials (RCTs), using keywords such as sepsis, Shenfu, Shenmai, Shengmai, Dahuang Fuzi, Xuebijing, and mortality. The databases we searched included the China Knowledge Network (CNKI), Wanfang database, the Chinese scientific journal database (VIP), the Chinese biomedical literature database (CBM), PubMed, Embase and Cochrane. The collection time was from inception through September 22, 2020. Two researchers independently screened the articles, extracted data, and assessed the quality of the evidence. Stata15 was used for network meta-analysis, and Excel was used to summarize the list of adverse reactions. RESULTS: Twenty-nine studies with a total of 3201 patients were included in this study. Combined with WMT, Shenfu injection [OR = 0.63, 95% CI = (0.47, 0.83)] and Xuebijing injection [OR = 0.71, 95% CI = (0.52, 0.96)] can significantly reduce 28-day mortality among patients with sepsis, while Shenmai injection [OR = 0.40, 95% CI = (0.16, 1.03)] and Dahuang Fuzi decoction [OR = 1.00, 95% CI = (0.48, 2.10)] cannot significantly improve on the 28-day mortality. The efficacy ranking is as follows: Shenmai group (level of evidence: low) > Shenfu group (level of evidence: low) > Xuebijing group (level of evidence: very low) > WMT group > Dahuangfuzi group (level of evidence: very low). CONCLUSIONS: Combined with WMT, Shenfu injection or Xuebijing injection can reduce the 28-day mortality among patients with sepsis. The Shenfu group had the best effect on outcomes, and its level of evidence was higher than that of the Xuebijing group.

Testis Toxicants: Lesson from Traditional Chinese Medicine (TCM).

The testis is one of the organs in the mammalian body that is sensitive to toxicants. Accumulating evidence has shown that human exposure to toxic ingredients in Traditional Chinese Medicine (TCM), such as triptolide, gossypol, cannabidol, piperine, α-solanine, matrine, aristolochic acid, and emodin, lead to testis injury and reproductive dysfunction. The most obvious phenotype is reduced sperm counts due to defects in spermatogenesis. Studies have also shown that Sertoli cells in the seminiferous tubule, the functional unit of the testis that supports spermatogenesis, are the cell type that is most sensitive to the disruptive effects of toxicants. Since Sertoli cells are the "mother cells" that nurture germ cell development, Sertoli cell injury thus leads to failure in germ cell development in the seminiferous epithelium. Mounting evidence has shown that the Sertoli cell cytoskeletons, mitochondria function, Leydig cells steroidogenesis pathways and sperm ion channels are some of the prime targets of toxicants from TCM. We carefully evaluate recent findings in this area of research herein, and to provide a summary of these findings, including some insightful information regarding the underlying molecular basis of toxicant-induced testis injury that impede spermatogenesis.

[Salvianolic acid B and its magnesium salt inhibit SARS-CoV-2 infection of Vero-E6 cells by blocking spike protein-mediated membrane fusion].

OBJECTIVE: The investigate the inhibitory effects of the traditional Chinese medicine (TCM) monomer salvianolic acid B (Sal-B) and its magnesium salt Salvia Miltiorrhiza Polyphenolate Injection (ZDDY) against SARS-CoV-2 infection in vitro and explore the molecular mechanism. OBJECTIVE: The anti-SARS-CoV-2 activity of Sal-B and ZDDY was assessed using the authentic and pseudotyped SARS-CoV-2 infection assay. The antiviral targets of Sal-B were identified by molecular docking and molecular dynamics simulation. Circular dichroism spectroscopy was used to examine the structural characteristics of HR1 and HR2 regions of SARS-CoV-2 S protein, and the S protein-mediated cell-cell fusion assay was used to evaluate the effect of Sal-B on virus-cell membrane fusion. Flow cytometry was carried out to analyze the effect of Sal-B on the binding of SARS-CoV-2 RBD to hACE2 receptor. OBJECTIVE: The median effective concentrations (EC50) of Sal-B and ZDDY against SARSCoV-2 infection in Vero-E6 cells were 55.47 µmol/L and 36.07 µg/mL, respectively. Both Sal-B and ZDDY successfully inhibited the entry of SARS-CoV-2 pseudovirus into the cells that stably expressed human ACE2 (ACE2/293T), with half maximal inhibitory concentrations (IC50) of 1.69 µmol/L and 24.81 µg/mL, respectively. Sal-B showed a binding affinity of -8.2 kcal/mol to the 6-helix bundle (6-HB) of SARS-CoV-2 S protein. Molecular dynamics simulation showed stable binding between Sal-B and the 6-HB of SARS-CoV-2 S protein at the predicted binding site. Sal-B disturbed the formation of the secondary structure of 6-HB in HR1P/HR2P mixture, resulting in a significantly lowered α-helicity (P < 0.05). Sal-B dose-dependently inhibited SARS-CoV-2 S protein-mediated cell-cell fusion, with an IC50 of 3.33 µmol/L. Sal-B showed no effect on RBD-Fc protein binding to the ACE2 receptor. OBJECTIVE: Sal-B and its magnesium salt ZDDY can inhibit the entry of SARS-CoV-2 in Vero-E6 cells in vitro by blocking SARS-CoV-2 spike protein-mediated virus-cell membrane fusion.

Mindfulness-Based Cognitive Therapy for Late-Life Depression: a Randomised Controlled Trial.

BACKGROUND: Rumination and overgeneral autobiographical memory are dysfunctional cognitions commonly found in older adults with depression. The theoretical underpinnings of mindfulness-based cognitive therapy (MBCT) address the ruminative tendencies and the non-specific retrieval of autobiographical memories. This study aims to examine the efficacy and cognitive mechanisms of MBCT in older adults with active depressive symptoms. METHODS: 57 older adults (mean age, 70 years) with normal cognition and mild to moderate depressive symptoms were randomly allocated to either the MBCT group or the active control group for 8 weeks. The MBCT group consisted of eight 2-hour weekly sessions and a 7-hour full-day retreat, with different themes for each class, guided mindfulness exercises, feedback and discussion, homework review, and psychoeducation. The active control group comprised a 1-hour physical exercise and a standardised health education of the specific theme with group discussion (eg fall prevention, chronic pain). Participants were assessed before and after the 8-week intervention for four outcome measures: the Hamilton Depression Rating Scale (HAMD), the Ruminative Response Scale (RRS), the Autobiographical Memory Test (AMT), and the Mindful Attention Awareness Scale (MAAS). RESULTS: There was a significant reduction in severity of depressive symptoms (HAMD score) in both the MBCT group (F(1, 27) = 35.9, p < 0.001, η2 = 0.57) and the active control group (F(1, 28) = 9.29, p < 0.01, η2 = 0.24), but only the MBCT group showed substantial improvements in autobiographical memory specificity (AMT score), rumination (RRS score), and mindfulness (MAAS score). CONCLUSION: Although both MBCT and active control programme decrease the severity of depressive symptoms in older adults, only MBCT improves AMS, rumination, and mindfulness. Our findings provide empirical support for the theoretical underpinnings of MBCT. Older adults with more severe depression and more severe dysfunctional cognition may benefit more from the specific therapeutic effects of MBCT.

Rare Optic Neuropathy in a Jamaican Couple Linked to Cassava Root Consumption.

We report central visual loss with selective papillomacular bundle damage in a Jamaican couple, husband and wife, with long-term cassava root consumption. The two cases presented independently with gradual central visual loss. Examination revealed bilateral temporal pallor of the optic nerve head and automated static perimetry demonstrated a central or caecocentral scotoma in each patient. Optical coherence tomography findings are described. The only mutual risk factor, reported independently, was long-term cassava consumption. Cessation of cassava intake and vitamin supplementation resulted in partial recovery of visual function. As thiocyanate levels in urine were not measured, the aetiology in these patients is not definitively confirmed, but chronic cassava consumption should be considered in similar cases as a rare cause of potentially reversible optic neuropathy.

Caffeinated and decaffeinated coffee consumption and risk of all-cause mortality: a dose-response meta-analysis of cohort studies.

BACKGROUND: Previous meta-analysis showed an inverse association between coffee consumption and all-cause mortality. However, the relationship between caffeinated and decaffeinated coffee consumption and all-cause mortality is inconsistent. We aimed to identify and review the published evidence updating the association between coffee consumption and all-cause mortality and, furthermore, to investigate the association of caffeinated and decaffeinated coffee consumption and all-cause mortality. METHODS: We systematically searched PubMed and Web of Science for studies published up to 9 November 2017. Cohort studies in which authors reported relative risks (RRs) of all-cause mortality for at least three levels of coffee consumption were eligible. Random-effects models were used to estimate the pooled RR of all-cause mortality with coffee consumption. Restricted cubic splines were used to model the dose-response association. RESULTS: We included 21 cohort study articles (10 103 115 study participants and 240 303 deaths). We found a nonlinear association between coffee consumption and all-cause mortality (Pnonlinearity  < 0.001). Compared with no or rare coffee consumption, with a consumption of 3 cups day-1 , the risk of all-cause mortality might reduce 13% (RR = 0.87; 95% confidence interval = 0.84-0.89). CONCLUSIONS: The findings of the present study provide quantitative data suggesting that coffee consumption plays a role in reducing the risk of all-cause mortality. Similar inverse associations are found for caffeinated coffee and decaffeinated coffee.

Epidemiology, risk factors and characteristics of pediatric stroke: a nationwide population-based study.

BACKGROUND: Stroke, classically characterized as an acute acquired neurological deficit, is an important leading cause of death and chronic morbidity in children. AIMS: This study reported the period prevalence, incidence and risk factors of pediatric stroke in Taiwan. METHODS AND PROCEDURES: All Taiwan inhabitants aged 1 month to 18 years registered in the National Health Insurance Research Database between 2010 and 2011 were enrolled in this study. Factors including age, sex, location and household income levels were collected. Incidence, period prevalence, mortality rate and the possible risks were completely evaluated. Outcomes and results: Hemorrhagic stroke has a significantly higher mortality rate than ischemic stroke (27.6% vs. 10.2%, P<0.05). Risk factors or underlying diseases for stroke were identified in 77.8% of the patients and 16.2% had more than one risk factor. The most common risk factors were vascular diseases (26.3%), infection (14.0%) and cardiac disorders (9.1%). CONCLUSIONS AND IMPLICATIONS: Infants younger than 2 years, boys and children in lower socioeconomic status have a significantly higher risk of stroke. Hemorrhagic stroke has a significantly higher mortality rate than ischemic stroke. More than half of the children with stroke had underlying diseases and the causes of hemorrhagic stroke are significantly different from ischemic stroke.

Targeting multiple pathways reduces renal and cardiac fibrosis in rats with subtotal nephrectomy followed by coronary ligation.

AIM: Multiple interacting pathways contribute to progression of renal and cardiac damage in chronic kidney disease followed by chronic heart failure (renocardiac syndrome). We hypothesized that simultaneous pharmacological modulation of critical pathways implicated in renocardiac syndrome would effectively reduce fibrosis in and preserve function of heart and kidney. METHODS: Rats were subjected to subtotal nephrectomy followed 9 weeks later by coronary artery ligation. From week 11 until week 16, rats received vehicle or losartan, or a combination of the NF-kB inhibitor PDTC, the NO donor molsidomine and superoxide dismutase mimetic tempol, or a combination of all four of these plus metoprolol together. At week 16, renal and cardiac structure, function and gene expression were assessed. RESULTS: Individual and combined treatments were similarly effective in limiting cardiac fibrosis and further decline in systolic function. Combined treatment with all five drugs reduced renal fibrosis and CTGF gene expression more effectively than other strategies. Combining all five drugs reduced heart rate, inotropy and mean arterial pressure (MAP). CONCLUSION: Thus, in our model of chronic renocardiac syndrome, combined treatments similarly decreased cardiac fibrosis and stabilized systolic function as losartan alone, perhaps suggesting a dominant role for a single factor such as angiotensin II type 1 (AT1) receptor activation or inflammation in the network of aberrant systems in the heart. However, tubulointerstitial fibrosis was most effectively reduced by a five-drug regimen, pointing to additive effects of multiple pathophysiological pathways in the kidney.

Effects of the Zhikang capsule on healing of the flap after radical breast cancer surgery.

This study aimed to investigate the effect and mechanism of trauma flap healing promoted by the Zhikang capsule after radical breast cancer surgery. The enrolled breast cancer patients were randomly divided into two groups: treatment and observation. The patients in the treatment group were treated with the Zhikang capsule in addition to the conventional dressing changes, while patients in the observation group underwent only the regular dressing changes. Serum samples of 98 breast cancer patients (with complete clinical data) who underwent modified radical mastectomy were collected and analyzed for expressions of transforming growth factor beta (TGF-ß) and basic fibroblast growth factor (bFGF). The drainage fluid amount and tissue necrosis rate were found to be lower in the treatment group than in the observation group. Moreover, bFGF expression in peripheral blood was higher in the treatment group than in the observation group. However, no significant difference was found between the two groups in the expression of TGF-ß in peripheral blood. In conclusion, Zhikang capsule is effective in promoting flap healing after radical breast cancer surgery, and the increase of bFGF expression in peripheral blood may be the underlying mechanism.

Self-sensing porphysomes for fluorescence-guided photothermal therapy.

Porphysomes are highly quenched unilamellar porphyrin-lipid nanovesicles with structurally dependent photothermal properties. The high packing density of porphyrin molecules in the lipid bilayer enables their application in photothermal therapy, whereas the partial disruption of the porphysome structure over time restores the porphyrin fluorescence and enables the fluorescence-guided photothermal ablation. This conversion is a time-dependent process and cannot be easily followed using existing analytical techniques. Here we present the design of a novel self-sensing porphysome (FRETysomes) capable of fluorescently broadcasting its structural state through Förster resonance energy transfer. By doping in a near-infrared emitting fluorophore, it is possible to divert a small fraction of the absorbed energy toward fluorescence emission which provides information on whether the vesicle is intact or disrupted. Addition of bacteriopheophorbide-lipid into the vesicle bilayer as a fluorescence acceptor (0.5-7.5 mol %) yields a large separation of 100 nm between the absorption and fluorescence bands of the nanoparticle. Furthermore, a progressive increase in FRET efficiency (14.6-72.7%) is observed. Photothermal heating and serum stability in FRETysomes is comparable with the undoped porphysomes. The fluorescence arising from the energy transfer between the donor and acceptor dyes can be clearly visualized in vivo through hyperspectral imaging. By calculating the ratio between the acceptor and donor fluorescence, it is possible to determine the structural fate of the nanovesicles. We observe using this technique that tumor accumulation of structurally intact porphyrin-lipid nanovesicles persists at 24 and 48 h postinjection. The development of FRETysomes offers a unique and critical imaging tool for planning porphysome-enabled fluorescence-guided photothermal treatment, which maximizes light-induced thermal toxicity.

Mice lacking Axl and Mer tyrosine kinase receptors are susceptible to experimental autoimmune orchitis induction.

The mammalian testis is an immunoprivileged organ where male germ cell autoantigens are immunologically ignored. Both systemic immune tolerance to autoantigens and local immunosuppressive milieu contribute to the testicular immune privilege. Testicular immunosuppression has been intensively studied, but information on systemic immune tolerance to autoantigens is lacking. In the present study, we aimed to determine the role of Axl and Mer receptor tyrosine kinases in maintaining the systemic tolerance to male germ cell antigens using the experimental autoimmune orchitis (EAO) model. Axl and Mer double-knockout (Axl(-/-)Mer(-/-)) mice developed evident EAO after a single immunization with germ cell homogenates emulsified with complete Freund's adjuvant. EAO was characterized by the accumulation of macrophages and T lymphocytes in the testis. Damage to the seminiferous epithelium was also observed. EAO induction was associated with pro-inflammatory cytokine upregulation in the testes, impaired permeability of the blood-testis barrier and generation of autoantibodies against germ cell antigens in Axl(-/-)Mer(-/-) mice. Immunization also induced mild EAO in Axl or Mer single-gene-knockout mice. By contrast, a single immunization failed to induce EAO in wild-type mice. The results indicate that Axl and Mer receptors cooperatively regulate the systemic immune tolerance to male germ cell antigens.

Cloning and characterization of the nicotianamine synthase gene in Eruca vesicaria subsp sativa.

Nicotianamine (NA) is a ubiquitous metabolite in plants that bind heavy metals, is crucial for metal homeostasis, and is also an important metal chelator that facilitates long-distance metal transport and sequestration. NA synthesis is catalyzed by the enzyme nicotianamine synthase (NAS). Eruca vesicaria subsp sativa is highly tolerant to Ni, Pb, and Zn. In this study, a gene encoding EvNAS was cloned and characterized in E. vesicaria subsp sativa. The full-length EvNAS cDNA sequence contained a 111-bp 5'-untranslated region (UTR), a 155-bp 3'-UTR, and a 966-bp open reading frame encoding 322-amino acid residues. The EvNAS genomic sequence contained no introns, which is similar to previously reported NAS genes. The deduced translation of EvNAS contained a well-conserved NAS domain (1-279 amino acids) and an LIKI-CGEAEG box identical to some Brassica NAS and to the LIRL-box in most plant NAS, which is essential for DNA binding. Phylogenetic analysis indicated that EvNAS was most closely related to Brassica rapa NAS3 within the Cruciferae, followed by Thlaspi NAS1, Camelina NAS3, and Arabidopsis NAS3. A reverse transcription-polymerase chain reaction indicated that EvNAS expression was greatest in the leaves, followed by the flower buds and hypocotyls. EvNAS was moderately expressed in the roots.

Effects of supplemental nanoparticle trivalent chromium on the nutrient utilization, growth performance and serum traits of broilers.

The aim of this study was to investigate the effect of dietary supplementation of nanoparticle trivalent chromium on nutrient utilization, growth performance and serum traits of broilers. This study included two trials. In trial 1, 32 three-week-old broilers were divided into four groups: the control, chromium chloride (CrCl3), chromium picolinate (CrPic) and nanoparticle chromium picolinate (NanoCrPic). Chromium was added at a 1200 µg/kg level to evaluate the nutrient and chromium utilization. In trial 2, 160 one-day-old broilers were randomly divided into four groups as in trial 1, with four replicates. The results of trial 1 indicated that the chromium utilization is as follows: NanoCrPic > CrPic > CrCl3 and control groups, with significant differences between groups (p < 0.05). Crude fat utilization in CrCl3 group was lower than in that the control group (p < 0.05). The results of trial 2 indicated that feed intake of 4-5 weeks showed better result in the CrCl3 group than that in the CrPic group (p < 0.05). The results of serum traits indicated that the LDL-cholesterol in the NanoCrPic groups was lower than that in the CrPic group (p < 0.05). The NanoCrpic and CrPic groups showed significantly increased serum chromium concentration when compared with the control and CrCl3 groups; the triglyceride level in the CrCl3 group was lower than that in the CrPic group (p < 0.05). This study concluded that compared with CrPic, NanoCrpic supplementation could increase chromium utilization and lower the serum LDL-cholesterol of broilers.

Rhabdomyolysis induced by excessive coffee drinking.

Excessive ingestion of caffeine-containing beverages is a rare cause of rhabdomyolysis. Here, we describe the case of a 44-year-old woman presented with nausea, vomiting, palpitations, and tea-colored urine 6 h after drinking a liter of black coffee containing approximately 565 mg of caffeine for mental alertness. Laboratory studies were notable for myoglobinuria and markedly elevated plasma creatine kinase (CK) level of 7315 U/L. With volume expansion and alkalization, her plasma CK level returned to normal within 5 days. Rhabdomyolysis should be considered a potential health hazard from excessive consumption of caffeine-containing products.

Regulation of blood-testis barrier (BTB) dynamics during spermatogenesis via the "Yin" and "Yang" effects of mammalian target of rapamycin complex 1 (mTORC1) and mTORC2.

In mammalian testes, haploid spermatozoa are formed from diploid spermatogonia during spermatogenesis, which is a complicated cellular process. While these cellular events were reported in the 1960s and 1970s, the underlying molecular mechanism(s) that regulates these events remained unexplored until the past ∼10 years. For instance, adhesion proteins were shown to be integrated components at the Sertoli cell-cell interface and/or the Sertoli-spermatid interface in the late 1980s. But only until recently, studies have demonstrated that some of the adhesion proteins serve as the platform for signal transduction that regulates cell adhesion. In this chapter, a brief summary and critical discussion are provided on the latest findings regarding these cell-adhesion proteins in the testis and their relationship to spermatogenesis. Moreover, antagonistic effects of two mammalian target of rapamycin (mTOR) complexes, known as mTORC1 and mTORC2, on cell-adhesion function in the testis are discussed. Finally, a hypothetic model is presented to depict how these two mTOR-signaling complexes having the "yin" and "yang" antagonistic effects on the Sertoli cell tight junction (TJ)-permeability barrier can maintain the blood-testis barrier (BTB) integrity during the epithelial cycle while preleptotene spermatocytes are crossing the BTB.

Chinese herbal medicine for functional constipation: a randomised controlled trial.

1. This was an 18-week prospective, randomised, double-blind, placebo-controlled clinical study on a Chinese herbal medicine--ma zi ren wan (MZRW)--for the treatment of functional constipation. 2. 120 subjects with functional constipation (Rome III criteria) were randomised (60 per arm) into the MZRW and placebo groups. Respective responder rates for the two groups were 43.3% and 8.3% during treatment, and 30.0% and 15.0% in the follow-up period (p<0.05). The MZRW group was superior to the placebo group in terms of increased complete spontaneous bowel movement as well as reduction in severity of constipation, straining at evacuation, and use of rescue therapy. No serious adverse effects were reported. 3. The dose of MZRW (7.5 g bid) was determined in a separate clinical trial. This study entailed a dose determination study and then a placebo-controlled clinical trial and can be a good reference for future studies.

Anti-allergic action of anti-malarial drug artesunate in experimental mast cell-mediated anaphylactic models.

BACKGROUND: Allergy is an acquired hypersensitivity reaction of the immune system mediated by cross-linking of allergen-specific IgE-bound high-affinity IgE receptors, leading to immediate mast cell degranulation. Artesunate is a semi-synthetic derivative of artemisinin, an active component of the medicinal plant Artemisia annua. Artesunate is a clinically effective anti-malarial drug and has recently been shown to attenuate allergic asthma in mouse models. This study investigated potential anti-allergic effects of artesunate in animal models of IgE-dependent anaphylaxis. METHODS: Anti-allergic actions of artesunate were evaluated in passive cutaneous anaphylaxis and passive systemic anaphylaxis mouse models, and in ovalbumin-induced contraction of bronchial rings isolated from sensitized guinea pigs. Direct mast cell-stabilizing effect of artesunate was examined in RBL-2H3 mast cell line and in mature human cultured mast cells. Anti-allergic signaling mechanisms of action of artesunate in mast cells were also investigated. RESULTS: Artesunate prevented IgE-mediated cutaneous vascular hyperpermeability, hypothermia, elevation in plasma histamine level, and tracheal tissue mast cell degranulation in mice in a dose-dependent manner. In addition, artesunate suppressed ovalbumin-mediated guinea pig bronchial smooth muscle contraction. Furthermore, artesunate concentration-dependently blocked IgE-mediated degranulation of RBL-2H3 mast cells and human culture mast cells. Artesunate was found to inhibit IgE-induced Syk and PLCγ1 phosphorylation, production of IP(3) , and rise in cytosolic Ca(+2) level in mast cells. CONCLUSIONS: We report here for the first time that artesunate possesses anti-allergic activity by blocking IgE-induced mast cell degranulation, providing a foundation for developing artesunate for the treatment of allergic asthma and other mast cell-mediated allergic disorders.

Trends in maintenance immunosuppressive drugs used in taiwanese kidney transplant recipients: an analysis of the national health insurance research database.

Trends in maintenance immunosuppressive drugs used among Taiwanese kidney transplant recipients have not been reported before. We examined the National Health Insurance Research Database to analyze trends in maintenance immunosuppressive drugs used in Taiwanese kidney transplant recipients for the years 2002-2009. The new case number of kidney transplant recipients ranged from 302 to 673 per year. In 2009, 5276 kidney transplant recipients received immunosuppressive therapy. The 5-year renal graft survival rate of kidney transplant recipients was 93%. In 2009, the most common immunosuppressive therapy among Taiwanese kidney transplant recipients was a triple regimen that included tacrolimus, mycophenolate mofetil, and corticosteroid. There was a significant increase in the use of a tacrolimus-based regimen from 35.1%-58.2%, while the use of cyclosporine decreased from 62.2%-24.8% (P < .05). The percentage of calcineurin inhibitor-free regimen increased from 2.7%-17%. Moreover, the use of Rapamune dramatically increased from 8.2%-22.6% in 2002-2004. However, the percentage of kidney transplant recipients using Rapamune maintained 23 ± 1.6% in 2004-2009. The use of mycophenolic acid remained stable at about 74.9 ± 3.2% in 2002-2009. As predicted, the use of Imuran decreased from 6.9%-3.5%. In summary, although calcineurin inhibitors remained the mainstay of immunosuppressive drugs, these findings suggest a general trends toward individualized regimens and the use of calcineurin inhibitor-free and mammalian target of rapamycin inhibitors-based regimens in Taiwanese kidney transplant recipients.