Hyperbaric oxygen therapy promotes the browning of white fat and contributes to the healing of diabetic wounds.

Non-healing wounds are one of the chronic complications of diabetes and have remained a worldwide challenge as one of the major health problems. Hyperbaric oxygen (HBO) therapy is proven to be very successful for diabetic wound treatment, for which the molecular basis is not understood. Adipocytes regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes. Endothelial cell-derived extracellular vesicles could promote wound healing in diabetes. To study the mechanism by which HBO promotes wound healing in diabetes, we investigated the effect of HBO on fat cells in diabetic mice. A diabetic wound mouse model was established and treated with HBO. Haematoxylin and eosin (H&E) staining and immunofluorescence were used for the analysis of wound healing. To further explore the mechanism, we performed whole-genome sequencing on extracellular vesicles (EVs). Furthermore, we conducted in vitro experiments. Specifically, exosomes were collected from human umbilical vein endothelial cell (HUVEC) cells after HBO treatment, and then these exosomes were co-incubated with adipose tissue. The wound healing rate in diabetic mice treated with HBO was significantly higher. HBO therapy promotes the proliferation of adipose precursor cells. HUVEC-derived exosomes treated with HBO significantly promoted fat cell browning. These data clarify that HBO therapy may promote vascular endothelial cell proliferation and migration, and promote browning of fat cells through vascular endothelial cells derived exosomes, thereby promoting diabetic wound healing. This provides new ideas for the application of HBO therapy in the treatment of diabetic trauma.

A novel, robust mechanical strength, and naturally degradable double crosslinking starch-based bioplastics for practical applications.

The increasing number of petroleum-based plastics has caused severe environmental pollution, which has attracted great research interest in the development of low-cost, renewable, and degradable starch-based bioplastics. However, developing starch-based bioplastics with robust mechanical strength, excellent water resistance, and thermal resistance remains a great challenge. In this study, we presented a simple and efficient method for preparing high-performance novel starch-based bioplastics with chemical and physical double crosslinking network structures filled with 2,2,6,6-tetramethylpiperidine 1-oxy-oxidized cellulose nanofibers and zinc oxide nanoparticles. Compared with pure starch-based bioplastics, the tensile strength of the novel robust strength starch-based bioplastics increased by 431.2 %. The novel starch-based bioplastics exhibited excellent mechanical properties (tensile strength up to 24.54 MPa), water resistance, thermal resistance, and biodegradability. In addition, the novel starch-based bioplastics could be reused, crushed, dissolved, and re-poured after use. After recycling, the novel starch-based bioplastics could be discarded in the soil to achieve complete degradation within six weeks. Owing to these characteristics, the novel starch-based bioplastics are good alternatives used to replace traditional petroleum-based plastics and have great development prospects.

TET3 epigenetically controls feeding and stress response behaviors via AGRP neurons.

The TET family of dioxygenases promote DNA demethylation by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Hypothalamic agouti-related peptide-expressing (AGRP-expressing) neurons play an essential role in driving feeding, while also modulating nonfeeding behaviors. Besides AGRP, these neurons produce neuropeptide Y (NPY) and the neurotransmitter GABA, which act in concert to stimulate food intake and decrease energy expenditure. Notably, AGRP, NPY, and GABA can also elicit anxiolytic effects. Here, we report that in adult mouse AGRP neurons, CRISPR-mediated genetic ablation of Tet3, not previously known to be involved in central control of appetite and metabolism, induced hyperphagia, obesity, and diabetes, in addition to a reduction of stress-like behaviors. TET3 deficiency activated AGRP neurons, simultaneously upregulated the expression of Agrp, Npy, and the vesicular GABA transporter Slc32a1, and impeded leptin signaling. In particular, we uncovered a dynamic association of TET3 with the Agrp promoter in response to leptin signaling, which induced 5hmC modification that was associated with a chromatin-modifying complex leading to transcription inhibition, and this regulation occurred in both the mouse models and human cells. Our results unmasked TET3 as a critical central regulator of appetite and energy metabolism and revealed its unexpected dual role in the control of feeding and other complex behaviors through AGRP neurons.

Effects of dietary leucine and valine levels on growth performance, glycolipid metabolism and immune response in Tilapia GIFT Oreochromis niloticus.

An 8-week feeding trial was performed to evaluate the effects of dietary leucine (Leu) and valine (Val) levels on growth performance, glycolipid metabolism and immune response in Oreochromis niloticus. Fish (15.23 ± 0.05 g) were randomly fed four diets containing two Leu levels (1.2% and 2.3%) and two Val levels (0.7% and 1.4%) as a 2 × 2 experimental design (LL-LV, LL-HV, HL-LV and HL-HV). Compared with LL-LV group, the growth parameters (final weight, daily growth coefficient (DGC) and growth rate per metabolic body weight (GRMBW)), feed conversion rate (FCR), the activities of intestinal amylase, lipase, creatine kinase (CK) and Na+, K+-ATPase, liver NAD+/NADH ratio, as well as the expression of SIRT1, GK, PK, FBPase, PPARα, CPT IA, ACO and IL10 all increased significantly in the HL-LV group; however, in the high Val group, final weight, DGC, GRMBW, intestinal enzyme activities, as well as the expression of PEPCK, SREBP1, FAS, IL8 and IL10 of the HL-HV group were significantly lower than those of the LL-HV group, while the opposite was true for the remaining indicators. Significant interactions between dietary Leu and Val were observed in final weight, DGC, GRMBW, plasma IL1ß and IL6 levels, intestinal amylase and CK activities, liver NAD+/NADH ratio, as well as the expression of SIRT1, PK, PEPCK, FBPase, SREBP1, FAS, PPARα, CPT IA, ACO, NF-κB1, IL1ß, IL6 and IL10. The highest values of growth parameters, intestinal enzyme activities and expression of SIRT1, FBPase, PPARα, CPT IA and ACO were observed in the HL-LV group, while the opposite was true for the expression of SREBP1, FAS, PPARα, NF-κB1, IL1ß and IL6. Overall, our findings indicated that dietary Leu and Val can effect interactively, and fish fed with diets containing 2.3% Leu with 0.7% Val had the best growth performance and hepatic health status of O. niloticus.

Interactions between dietary carbohydrate and thiamine: implications on the growth performance and intestinal mitochondrial biogenesis and function of Megalobrama amblycephala.

A12-week experiment was conducted to evaluate the influences of thiamine ongrowth performance, and intestinal mitochondrial biogenesis and function of Megalobramaamblycephala fed a high-carbohydrate (HC) diet. Fish (24·73 (sem 0·45) g) were randomly assigned to one of four diets: two carbohydrate (CHO) levels (30 and 45 %) and two thiamine levels (0 and 1·5 mg/kg). HC diets significantly decreased DGC, GRMBW, FIMBW, intestinal activities of amylase, lipase, Na+, K+-ATPase, CK, complexes I, III and IV, intestinal ML, number of mitochondrial per field, ΔΨm, the P-AMPK: T-AMPK ratio, PGC-1ß protein expression as well as the transcriptions of AMPKα1, AMPKα2, PGC-1ß, mitochondrial transcription factor A, Opa-1, ND-1 and COX-1 and 2, while the opposite was true for ATP, AMP and reactive oxygen species, and the transcriptions of dynamin-related protein-1, fission-1 and mitochondrial fission factor. Dietarythiamine concentrations significantly increased DGC, GRMBW, intestinal activities of amylase, Na+, K+-ATPase, CK, complexes I and IV, intestinal ML, number of mitochondrial per field, ΔΨm, the P-AMPK:T-AMPK ratio, PGC-1ß protein expression as well as the transcriptions of AMPKα1, AMPKα2, PGC-1ß, Opa-1, ND-1, COX-1 and 2, SGLT-1 and GLUT-2. Furthermore, a significant interaction between dietary CHO and thiamine was observed in DGC, GRMBW, intestinal activities of amylase, CK, complexes I and IV, ΔΨm, the AMP:ATP ratio, the P-AMPK:T-AMPK ratio, PGC-1ß protein expression as well as the transcriptions of AMPKα1, AMPKα2, PGC-1ß, Opa-1, COX-1 and 2, SGLT-1 and GLUT-2. Overall, thiamine supplementation improved growth performance, and intestinal mitochondrial biogenesis and function of M. amblycephala fed HC diets.

Phototherapy Facilitates Tumor Recruitment and Activation of Natural Killer T cells for Potent Cancer Immunotherapy.

Adoptively transferred natural killer T (NKT) cells confer distinct cancer surveillance without causing obvious side effects, making them a promising candidate for cancer immunotherapy. However, their therapeutic efficacy is limited by inefficient tumor infiltration and inadequate activation in an immunosuppressive tumor microenvironment. To overcome these obstacles, we develop a strategy of using photothermal therapy (PTT) to promote the antitumor ability of adoptively transferred NKT cells. The transferred NKT cells are efficiently recruited to PTT-treated tumors in response to PTT-created inflammation. Moreover, PTT treatment promotes the activation of NKT cells and enhances the NKT cell-initiated immune cascade. As a consequence, the combined therapy of PTT plus NKT cell transfer exhibits excellent growth inhibition of local tumors. Moreover, it efficiently rejects distant tumors and elicits long-term immunological memory to prevent tumor recurrence. Overall, the current study opens new paths to the clinical translation of NKT cells for cancer immunotherapy.

Structural characterization and antioxidant activity of water-soluble lignin-carbohydrate complexes (LCCs) isolated from wheat straw.

Lignin-carbohydrate complex (LCC) was proven to possess antioxidant activities. To understand structures and antioxidant activities of LCC, water-soluble LCC-stalk, LCC-sheath and LCC-leaf were isolated from ball-milled wheat straw stalk, sheath and leaf by successive dissolution in LiCl/DMSO solvent, water extraction and purification. LCCs were later structurally characterized by wet chemistry, chromatography and spectroscopy respectively. Their antioxidant activities were evaluated by ferric reducing antioxidant power (FRAP) and DPPH radical scavenging assays. The results showed that three LCCs were carbohydrate-rich (≈70%) and presented relatively narrow molecular weight distribution (PI < 2.0). The lignin moieties of LCCs were mainly connected with ß-O-4' structures, and phenyl glycoside and γ-ester linkages were main LCC linkages in LCCs. However, guaiacyl units were the predominant lignin units in LCC-stalk and LCC-sheath, while syringyl units were predominant in LCC-leaf. Intermolecular cross-linkages were mainly pCA-bridges in LCC-stalk and FA-bridges in LCC-sheath and LCC-leaf. Besides, LCC-sheath featured higher polysaccharide content exhibited higher molecular weight, fewer LCC linkages and better antioxidant activities (DPPH radical scavenging rate up to 74.91%) than both LCC-stalk (74.55%) and LCC-leaf (64.52%). This work helped to know LCCs in wheat straw well and inspire the application of LCC as potential antioxidants.

Effect of Shoutai Pills on Th1/Th2 Cytokines in Serum and Endometrium of Rats with Stimulated Ovulation.

In our previous study, we found that Shoutai pills could improve the embryo implantation rate as well as the levels of estrogen, progesterone and estrogen receptor in rats with stimulated ovulation. However, the mechanism is not clear. This study was designed to investigate the effect of Shoutai pills on the levels of Th1 and Th2 cytokines in rats with stimulated ovulation and the mechanism. The rat model of stimulated ovulation was established by combined injection of pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (HCG). Then the rats were randomly divided into model group (M), Shoutai pills group (S), progesterone group (P) and normal group (N). All the pregnant rats were treated from the first day. The S and P groups were administrated with gavage of Shoutai pills and injection of progesterone respectively, and N and M groups were given the same volume of normal saline and distilled water respectively. After treatment for 7 days, the animals were executed for serum and uterine tissues. The ELISA method was adopted to detect the contents of Th1 cytokines [interferon-γ (INF-γ), interleukin-2 (IL-2)] and Th2 cytokines (IL-4, IL-6, IL-10). The expression of leukemia inhibitory factor (LIF) and leukemia inhibitory factor receptor (LIFR) was detected by Western blotting and real-time PCR. As compared with N group, the expression levels of IFN-γ and IL-2 in M group were significantly increased, and those of IL-4, IL-6, IL-10, LIF and LIFR were significantly decreased (P<0.05). As compared with M group, the levels of IL-4, IL-6, IL-10, LIF and LIFR in S group were significantly increased (P<0.05), and those of IFN-γ and IL-2 were significantly decreased (P<0.05). It was suggested that Shoutai pills can increase the levels of IL-4, IL-6, IL-10, LIF and LIFR as well as reduce the levels of INF-γ and IL-2 in rats with stimulated ovulation. The Shoutai pills may improve endometrial receptivity and promote embryo implantation by maintaining the balance of Th1/Th2 cytokines.

Identifying Clonal Origin of Multifocal Hepatocellular Carcinoma and Its Clinical Implications.

Hepatocellular carcinoma (HCC) is characterized by high prevalence of multifocality. Multifocal HCC can arise synchronously or metachronously either from intrahepatic metastasis (IM) or multicentric occurrence (MO). To date, there have been no established criteria to accurately distinguish whether multifocal HCC originates from IM or MO. Histopathological features remain the most convenient strategy but with subjectivity and limited accuracy. Various molecular biological techniques involving assessment of TP53 mutation status, hepatitis B virus integration sites, and chromosomal alterations have been applied to determine the clonal origin. The introduction of next-generation sequencing facilitates a more comprehensive annotation of intertumor heterogeneity, resulting in more sensitive and accurate clonal discrimination. Generally, MO-HCC has better overall survival than IM-HCC after curative resection. Adjuvant antiviral treatment has been proved to decrease post-treatment recurrence probably by reducing MO-HCC recurrence, whereas adjuvant sorafenib treatment targeting prior micrometastasis failed to reduce IM-HCC recurrence. Recent studies recommended transcatheter arterial chemoembolization (TACE) and traditional Chinese medicine Huaier granule as effective adjuvant treatments probably by preventing IM and both types of recurrences respectively. Immunotherapy that inhibits immune checkpoint interaction may be an optimal choice for both MO- and IM-HCC. In the future, effective personalized therapy against multifocal HCC may be achieved.

Hypertonic saline attenuates expression of Notch signaling and proinflammatory mediators in activated microglia in experimentally induced cerebral ischemia and hypoxic BV-2 microglia.

BACKGROUND: Ischemic stroke is a major disease that threatens human health in ageing population. Increasing evidence has shown that neuroinflammatory mediators play crucial roles in the pathophysiology of cerebral ischemia injury. Notch signaling is recognized as the cell fate signaling but recent evidence indicates that it may be involved in the inflammatory response in activated microglia in cerebral ischemia. Previous report in our group demonstrated hypertonic saline (HS) could reduce the release of interleukin-1 beta and tumor necrosis factor-alpha in activated microglia, but the underlying molecular and cellular mechanisms have remained uncertain. This study was aimed to explore whether HS would partake in regulating production of proinflammatory mediators through Notch signaling. RESULTS: HS markedly attenuated the expression of Notch-1, NICD, RBP-JK and Hes-1 in activated microglia both in vivo and in vitro. Remarkably, HS also reduced the expression of iNOS in vivo, while the in vitro levels of inflammatory mediators Phos-NF-κB, iNOS and ROS were reduced by HS as well. CONCLUSION: Our results suggest that HS may suppress of inflammatory mediators following ischemia/hypoxic through the Notch signaling which operates synergistically with NF-κB pathway in activated microglia. Our study has provided the morphological and biochemical evidence that HS can attenuate inflammation reaction and can be neuroprotective in cerebral ischemia, thus supporting the use of hypertonic saline by clinicians in patients with an ischemia stroke.

Design, Synthesis and Pharmacological Evaluation of Novel Piperlongumine derivatives as Potential Antiplatelet Aggregation Candidate.

A series of novel piperlongumine derivatives (4a-i, 6a-i) were designed and synthesized. The inhibitory activities of platelet aggregation induced by ADP and AA in vitro have been evaluated by bron turbidimetry and liver microsomal incubated assay. The assay results show that compounds 4e and 6e exhibited remarkable potency to that of the positive control piplartine and aspirin.

[Synthesis and biological evaluation of novel chalcone aromatic oxygen alkyl acids compounds].

Six novel ligustrazine chalcone aromatic oxygen alkyl acids compounds and two pyridine chalcone aromatic oxygen alkyl acids ester compounds were synthesized according to the traditional Chinese medicine theory removing blood stasis. The structures of target compounds were identified by IR, NMR and ESI-MS. The inhibitory activities of platelet aggregation induced by adenosine diphosphate (ADP) and arachidonic acid(AA) were measured by the liver microsomal incubation method in vitro. Hypolipidemic activities of compounds were tested in vivo for better inhibitory activities of platelet aggregation. Preliminary pharmacological results showed that compounds 7c, 8a and 11 a had potent inhibitory activity against platelet aggregation induced by AA, compounds 7c, 7d, 8a and 11 b showed significant inhibitory activity against platelet aggregation induced by ADP. Compounds 7c and 8a exhibited good hypolipidemic activities in high-fat-diet(HFD) induced hyperlipidemia C57/BL6 mice and worthy for further investigation.

[Traditional Chinese medicine syndrome distribution and neuroendocrine mechanisms of irritable bowel syndrome: cross-sectional study].

In order to clarify the traditional Chinese medicine(TCM) syndrome distribution and pathogenesis of irritable bowel syndrome(IBS), the patients in the first affiliated hospital of Guangzhou university of Chinese medicine were enrolled for the cross-sectional study. The data of 12 sociological variables, 13 risk factors, 84 symptoms and signs variables(in 9 aspects), and 19 neuroendocrine indices were extracted for group-between analysis with one-way ANOVA, chi-square test and nonparametric test, and the relationship analysis between clinical symptoms and diseases sub-types was done with binary Logistic regression. In addition, the patterns of TCM syndromes were divided by several syndrome factors to analyze the difference in neuroendocrine indices between various patterns and syndrome factors. A total of 383 IBS patients were enrolled, including 353(92.2%) cases of diarrhea, 14(3.7%) cases of constipation and 16(4.1%) cases of mixed types. In IBS-diarrhea patients, there were 291(76.0%), 18(4.7%), 48(12.5%) and 26(6.8%)cases of syndrome of liver depression and spleen deficiency (sLDSD), syndrome of liver depression and qi stagnation (sLDQS), syndrome of dampness-heat in the spleen and stomach (sDHSS), and syndrome of spleen deficiency with dampness encumbrance (sSDDE) respectively. There was significant differences in blood groups between IBS-diarrhea patients, IBS-constipation patients and IBS-mixed types patients; their disease classification was significantly correlated with the allergies, drinking, irregular meals habits, no or less vacations, and other causes of morbidity (P<0.05, f<0.3). A total of 15 symptoms and signs variables (e.g., chills, facial abnormalities, epigastric fullness, etc.) had significant differences between different groups (P<0.05), and 5, 8, 5 variables were respective independent factors for IBS-diarrhea, constipation and mixed type. There was no significant difference in neuroendocrine indices between various groups. The sLDSD, sLDQS, sDHSS, sSDDE patients had significant differences in genders, living conditions and occupations, and the TCM syndrome type was significantly correlated with the drinking, smoking, no or less breakfast, less than 8 sleeping hours(P<0.05, f<0.3). Meanwhile, a total of 14 symptoms and signs variables (e.g., dysphoria heat, fatigue, stretching, etc.) had significant differences between various groups(P<0.05) and 3, 4, 6, 3 variables were respective independent factors for sLDSD, sLDQS, sDHSS, and sSDDE. There were significant differences in acetylcholine(Ach) and angiotensin Ⅱ(AT-Ⅱ) between the sLDSD group and sSDDE group. There were significant difference in Ach, AT-Ⅱ, adrenotrophin(ACTH) and estradiol (E2) in comparison between several pattern factors. This study preliminary identified the sociological characters, risk factors, syndromes distribution, diseases and subgroup mechanisms of this disease. More samples and multi-centers are required for future study to improve the scientificity and representativeness.

[Development and Evaluation of GS-SF for Gastric Stuffiness (Wei PI) Patients Based on Item Response Theory, Computerized Adaptive Testing, and Data Simiuation].

OBJECTIVE: To develop and evaluate the short version of patient reported outcomes (PROs) questionnaire for gastric stuffiness (Wei Pi) patients with modern test theory and technologies, hoping to provide testing tools for related clinical practice and scientific researches with higher quality and less administrative and response burdens. METHODS: Using descriptive study design, clinical data were collected with sociological questionnaire and previous developed full items version of PROs instrument for gastric stuffiness (Wei Pi) patients via field and online surveys between Sep 2011 and Mar 2012. The statistical analysis group identified the termination parameters firstly, and then selected items with discrimination, fitting residual, item information curve (IIC) , item characteristic curve (ICC), and the rank of computerized adaptive testing (CAT) select proportion, etc. After assumption evaluation of item response theory (IRT), IIC, ICC, difficulty coefficient distribution, items-response relation and thresholds, etc. were used for psychometric evaluation of instrument. RESULTS: A total of 331 patients [Ages: 31.99 +/- 10.29 yrs; Male: 186 (56.3%)] were enrolled in statistical analysis. The test termination criterion was Max SE = 0.2 or Max items number =16. After items selection, a 15-item short version of instrument, which contains symptoms facet (8 items) and impact facet (7 items) was generated. With good unidimensionality, local independence, and monotonicity, the IC and ICC in IRT analysis showed good working capability of the questionnaire. The difficulty coefficient distribution and items-response relation were also rational, as well as response thresholds. CONCLUSIONS: The short version of PROs instrument for adult gastric stuffiness (Wei Pi) patients was successfully developed and assessed. The instrument with good methodological and reporting quality could be used in clinical and scientific evaluating their symptoms and impact.

Therapeutic effect of Jinzhen oral liquid for hand foot and mouth disease: a randomized, multi-center, double-blind, placebo-controlled trial.

BACKGROUND: No specific antiviral agent against hand foot and mouth disease (HFMD) is available for clinical practice today. OBJECTIVE: To evaluate the efficacy and safety of Jinzhen oral solution in treating uncomplicated HFMD. METHODS: In this randomized, double-blind, placebo-controlled trial, 399 children aged 1 to 7 years with laboratory confirmed HFMD were randomized to receive Jinzhen oral liquid or placebo 3 times daily for 7 days with a 3-day follow-up. The primary outcomes were time to the first disappearance of oral ulcers and vesicles on hand or foot and time to the first normalization of temperature (fever clearance). RESULTS: There were 199 children enrolling into the Jinzhen group including 79 with fever and 200 into the placebo group including 93 with fever. Jinzhen reduced the time to the first disappearance of oral ulcers and vesicles on hand or foot to 4.9 days (95% CI, 4.6 to 5.2 days), compared with 5.7 days (95% CI, 5.4 to 6.0 days) in the placebo group (P = 0.0036). The median time of fever clearance was shorter in the 79 children who received Jinzhen (43.41 hrs, 95% CI, 37.05 to 49.76) than that in the 93 children who received placebo (54.92 hrs, 95% CI, 48.16 to 61.68) (P = 0.0161). Moreover, Jinzhen reduced the risk of symptoms by 28.5% compared with placebo (HR, 0.7150, 95% CI, 0.5719 to 0.8940, P = 0.0032). More importantly, treatment failure rate was significantly lower in the Jinzhen group (8.04%) compared with that in the placebo group (15.00%) (P = 0.0434). The incidence of serious adverse events did not differ significantly between the two groups (9 in Jinzhen group vs. 18 in placebo, P = 0.075). CONCLUSIONS: Children with HFMD may benefit from Jinzhen oral liquid treatment as compared with placebo. TRIAL REGISTRATION: Chinese Clinical Trial Registry (http://www.chictr.org/en/) ChiCTR-TRC-10000937.

Literature review and analysis of the development of health outcomes assessment instruments in Chinese medicine.

OBJECTIVE: To evaluate the development of health outcomes assessment instruments in Chinese medicine. METHODS: A comprehensive literature search for all published articles in China National Knowledge Infrastructure Database, Chongqing VIP Database and WANFANG Data was conducted. The studies that met the inclusion and exclusion criteria were used to extract information according to a predesigned assessment instrument. RESULTS: A total of 97 instruments for health outcome assessment in Chinese medicine were identified. Of these questionnaires, 7 were generic, 12 were condition-specific and 78 were disease-specific. All instruments were suitable for adults, children, and both men and women. These instruments aimed to evaluate the health-related quality of life, signs and symptoms as well as patient satisfaction and doctor-reported outcome. However, the descriptions were poorly constructed for some of the most basic parameters, such as the domains and items, administrative mode, response options, memory recall periods, burden evaluation, format, copyright, content validity, and other properties. CONCLUSION: The instrument development for health outcomes assessment in Chinese medicine is increasing rapidly; however, there are many limitations in current methodologies and standards, and further studies are needed.

Homocysteine-lowering therapy with folic acid is effective in cardiovascular disease prevention in patients with kidney disease: a meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: The efficacy of homocysteine-lowering therapy with folic acid to lower homocysteine levels in an effort to reduce cardiovascular disease (CVD) risk in patients with kidney disease remains inconclusive. We conducted a meta-analysis of relevant randomized trials to further examine this issue. METHODS: This meta-analysis included 8234 patients with kidney disease from nine qualified randomized trials using folic acid therapy, and with CVD reported as one of the endpoints. Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of CVD using a random effects model. RESULTS: When pooling the nine randomized trials, folic acid therapy reduced the risk of CVD by 10%（RR = 0.90; 95% CI:0.81-1.00, P = 0.046). A greater beneficial effect was observed among those trials without a history of grain fortification with folic acid (0.82; 0.70-0.96, P = 0.01), with lower percent baseline diabetes (<30% (median), 0.80; 0.65-0.99, P = 0.04), and in patients with end-stage renal disease (ESRD) or advanced chronic kidney disease (ACKD) (0.85; 0.77-0.94, P = 0.002). Furthermore, a meta-regression analysis suggested a positive dose-response relationship between percent baseline diabetes and log-RR for CVD risk associated with folic acid supplementation (P = 0.007). Most importantly, even the inclusion of three subgroup results did not substantially affect the results (n = 11032, RR: 0.93; 95% CI:0.87-0.99, P = 0.03). CONCLUSIONS: Our meta-analysis indicates that folic acid supplementation may be effective for CVD prevention in patients with kidney disease, particularly in trials among patients without a history of grain fortification with folic acid, with lower percent baseline diabetes, and in patients with ESRD or ACKD.

Picrorhiza scrophulariiflora improves accelerated atherosclerosis through inhibition of redox-sensitive inflammation.

BACKGROUND: Accumulation of advanced glycation end products (AGEs) or advanced oxidation protein products (AOPPs) has been identified as a risk factor for accelerated atherosclerosis seen in diabetes and chronic kidney disease. However, little is known about the intervention for atherogenesis associated with these oxidized proteins. The rhizome of Picrorhiza scrophulariiflora (PS) has long been used to treat inflammatory diseases as a traditional medication. The study was performed to test the hypothesis that ethanol extraction of PS (EPS) may improve AGEs- or AOPPs-induced accelerated atherosclerosis in vivo. METHODS AND RESULTS: Hypercholesterolemic or normal rabbits were randomly assigned to 8 groups treated with intravenous injection of AGEs- or AOPPs-modified rabbit serum albumin (AGEs-RSA or AOPPs-RSA), unmodified RSA or vehicle in the presence or absence of EPS (10 mg/kg/2 days) gavage for 10 weeks. Compared with hypercholesterolemic rabbits without EPS treatment, EPS administration significantly decreased the aortic plaque volume and oxidized low density lipoprotein (Ox-LDL) deposition in hypercholesterolemic animals. This was accompanied by significant histological improvement including decrease of intimal and smooth muscle cell proliferation and macrophage influx in affected areas. EPS administration almost completely abolished the accelerated atherosclerosis induced by chronic treatment of AGEs- or AOPPs-RSA in both hypercholesterolemic and normal rabbits. EPS administration significantly restored the AGEs- or AOPPs-induced redox imbalance and inflammation, evidenced by decrease of plasma Ox-LDL, thiobarbituric acid reactive substances and TNF-alpha, and increase of glutathione peroxidase activity. CONCLUSION: These data suggested that EPS may improve atherosclerosis, particularly that induced by AGEs or AOPPs, through inhibition of redox-sensitive inflammation.

Ethanol extraction of Picrorhiza scrophulariiflora prevents renal injury in experimental diabetes via anti-inflammation action.

There is evidence that inflammatory processes are involved in the development and/or progression of diabetic nephropathy. However, effective treatment for inflammation in the kidneys of diabetic is practically unknown. The rhizomes of Picrorhiza scrophulariiflora (PS) are a traditional medication long used to treat inflammatory diseases. The aim of the present study was to test the hypothesis that the ethanol extract of PS (EPS) may reduce inflammation in patients with diabetic kidneys. Streptozotocin-induced diabetic rats were randomly assigned to two groups treated with a gavage of either EPS or vehicle. A group of non-diabetic control rats was treated concurrently. Compared with vehicle-treated diabetic rats, EPS-treated animals displayed a significant decrease in renal macrophage infiltration and overexpression of chemokine (C-C motif) ligand 2 (CCL2) and TGFB1. This was associated with attenuation of the structural and functional abnormalities of early diabetic nephropathy, such as glomerular hypertrophy, mesangial expansion, and albuminuria. Administration of EPS significantly reduced NADPH oxidase-dependent superoxide generation and decreased expression of malondialdehyde and advanced oxidation protein products in diabetic kidney. These data suggest that EPS might improve diabetic nephropathy, probably through inhibition of redox-sensitive inflammation.

[Diterpenes constituents of Tripterygium wilfordii].

AIM: To study the chemical constituents of Tripterygium wilfordii Hook. F. METHODS: Various column chromatographies with silica gel were used for the isolation and purification. The structures of compounds were established on the basis of its IR, MS, UV, 1H NMR, 13C NMR and HRMS, 1H-1H COSY, 1H-13C COSY and NOESY. RESULTS: Four diterpenoids were isolated: 16-hydroxytriptolide (I), triptolidenol (II), tripdiolide (III), 2-epitripdiolide (IV). CONCLUSION: Compound IV is a new diterpenoid.