[Interventional effect and inflammatory regulation mechanism of dihydroartemisinin combined with pregabalin on neuropathic pain mice].

This study aims to clarify the effects of dihydroartemisinin(DHA) combined with pregabalin(PGB) on neuropathic pain(NP) in mice and explore the neuroinflammatory regulatory mechanism. NP mice model was established using spinal nerve ligation, whereas the sham group exposed the spinal nerve without ligation. The mice were randomly divided into sham group, model group, PGB groups of low, medium, and high doses(PGB-L, PGB-M, and PGB-H, with 22, 45, and 91 mg·kg~(-1)), DHA group(16 mg·kg~(-1)), and DHA combined with PGB groups of low, medium, and high doses(DHA + PGB-L, DHA + PGB-M, and DHA + PGB-H). Administration by gavage 18 days after modeling. Von Frey and cold plate were used to detect mechanical pain threshold and cold pain sensitivity in mice. The tail suspension test and forced swimming test were used to investigate depressive behavior, and the open field test was used to estimate anxiety behavior. The Morris water maze was used to evaluate cognitive function. Liquid suspension chip technology was used to quantitatively analyze immune inflammation-related factors. Immunofluorescence was used to detect the expression of CC chemokine ligand 3(CCL3) and transmembrane protein 119(TMEM119). The results showed that compared with the sham group, the mechanical pain and cold pain sensitivity thresholds of the model group were significantly reduced, and the struggle time was significantly increased in the tail suspension test and forced swimming test. The activity time in the central area was significantly reduced in the open field test. The residence time in the second/fourth quadrant was significantly longer than that in other quadrants, and the latency time of platform climbing significantly increased after platform withdrawal in the Morris water maze experiment. The expression of CCL3 was significantly increased; the number of TMEM119 positive cells and the cell body area were significantly increased. Compared with the model group, the DHA + PGB-M group showed a significant increase in mechanical pain and cold pain sensitivity thresholds, as well as a significant increase in struggle time in the tail suspension test and forced swimming test. The activity time in the central area of the open field test was significantly reduced. The residence time in the second/fourth quadrant was significantly shorter than that in other quadrants, and the latency time of platform climbing after platform withdrawal was significantly reduced. Compared with the PGB-M group, the mechanical pain threshold of D14-17 in the DHA + PGB-M group was significantly increased, and the struggle time during forced swimming was significantly increased. The residence time in the second/fourth quadrant of the Morris water maze was significantly shorter than that in other quadrants. Compared with the model group, the expression of CCL3, the number of TMEM119 positive cells, and the cell body area in the DHA + PGB-M group were significantly decreased. This study indicates that DHA + PGB can enhance the analgesic effect of PGB on NP mice, break through the limitations of PGB tolerance, and make up for the shortcomings of PGB in antidepressant and cognitive improvement. Its mechanism may be related to regulating neuroinflammation by inhibiting the activation of microglial cells and expression of CCL3.

Tibetan medicine Ruyi Zhenbao Pill ameliorates neuropathic pain by inhibiting the CXCL10-CXCR3 pathway in spinal cord of spinal nerve ligation model.

ETHNOPHARMACOLOGICAL RELEVANCE: Ruyi Zhenbao Pill (RYZBP) is a traditional Tibetan medicine that has been used for over 300 years in China to treat neurological diseases, specifically neuropathic pain (NP). However, its characteristics and mechanism of action in treating NP remains unclear. AIM OF THE STUDY: Based on animal experiments and transcriptomics to evaluate the characteristics and mechanism of RYZBP in treating NP. METHODS: Mice were divided into six groups using random assignment: sham-operation group, spinal nerve ligation (SNL) group, RYZBP low (0.65 g kg-1), medium (1.30 g kg-1), high (2.60 g kg-1) doses groups, and positive drug pregabalin (PGB, 0.05 g kg-1) group. Mice received intragastrical administered for 14 consecutive days. SNL and intrathecal injection models were employed. The analgesic effects were assessed using the Von Frey test, Acetone test, and Hot Plate test. L5 spinal dorsal horns were collected for transcriptomics on day 15. The potential signaling pathways and Hub genes of RYZBP to ameliorate NP were obtained through transcriptomics and network pharmacology. Molecular docking was utilized to evaluate the binding ability of candidate active ingredients with the Hub genes. Finally, western blot (WB) and immunofluorescence (IF) were used to validate the predicted targets. RESULTS: RYZBP demonstrated a dose-dependent alleviation of mechanical allodynia, cold and heat stimulus-induced pain in SNL mice. Transcriptomics analysis identified 24 differentially expressed genes, and pathway enrichment analysis revealed that the CXCL10-CXCR3 signal axis may be the primary biological pathway through which RYZBP relieve NP. Molecular docking test indicated that the active ingredient in RYZBP exhibit a strong affinity for the target protein CXCL10. WB and IF tests showed that RYZBP can significantly inhibit CXCL10 and CXCR3 and its downstream molecules expression in the spinal dorsal horn of SNL mice. Additionally, intrathecal injection of rmCXCL10 worsened pain hypersensitivity, while RYZBP was able to suppress the pain hypersensitivity response induced by rmCXCL10 and reduce the expression levels of CXCL10 and CXCR3 and its downstream molecules. CONCLUSION: RYZBP had a significant analgesic effect on NP model, and this effect may be related to inhibiting the CXCL10-CXCR3 pathway in the spinal dorsal horn.

Effects of folic acid supplementation on chronic atrophic gastritis based on MTHFR C677T polymorphism.

BACKGROUND: It has been shown the methylenetetrahydrofolate reductase (MTHFR) 677TT (rs 1801133) genotype predicts histopathological alterations in the incisura of patients with chronic atrophic gastritis (CAG). MTHFR is a crucial enzyme in fatty acid (FA) metabolism. This study aimed to evaluate the influence of FA supplementation in CAG patients without Helicobacter pylori infection and the MTHFR C677T (rs 1801133) genotype as a potential CAG predictor. METHODS: A total of 96 CAG patients, aged 21 to 72 years old, were enrolled in this study. After 6 months of treatment, histopathological outcomes were compared among patients treated with weifuchun (WFC) (1.44 g 3 times per os per day), those treated with WFC and FA (5 mg once daily), and those treated with WFC, FA, and vitamin B12 (VB12) (0.5 mg 3 times per day) based on the Operative Link on Gastritis/Intestinal Metaplasia assessment staging systems. RESULTS: Atrophic lesions in patients treated with WFC and FA improved more than in patients treated only with WFC therapy (78.1% vs 53.3%, P = .04). Atrophic or intestinal metaplasia (IM) lesions in the incisura of patients with the TT genotype were better than those in patients with the CC/CT genotype (P = .02). CONCLUSION: The treatment of CAG patients with 5 mg of FA supplements daily for 6 months improved their gastric atrophy status, especially for the Operative Link on Gastritis/Intestinal Metaplasia assessment stages I/II. Moreover, our study is the first to reveal that patients with the MTHFR 677TT genotype require more timely and effective FA treatment than those with the CC/CT genotype.

Associations of blood metals with liver function: Analysis of NHANES from 2011 to 2018.

BACKGROUND: Heavy metals have been reported to affect liver function. However, there is currently little and inconsistent knowledge about the effects of combined and individual blood metals on specific parameters of liver function in the general population. Hence, this study aimed to elucidate their associations. METHODS: Data from National Health and Nutrition Examination Survey (NHANES) 2011-2018 were used in this cross-sectional study. Multivariate linear, and a quantile-based g-computation (qgcomp) were applied to explore the associations between blood metals [mercury (Hg), manganese (Mn), lead (Pb), cadmium (Cd), selenium (Se)], alone and in combination, and liver function parameters [alanine transaminase (ALT), aspartate transaminase (AST), ALT/AST, alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and serum total bilirubin (TBIL)]. RESULTS: A total of 15,328 were included. Multivariate linear models indicated that liver function was significantly associated with blood heavy metals. The most significant relationship was found between Se and AST (ß 5.09, 95%CI (3.28,6.91), p＜0.001), Mn and ALT (ß 1.24, 95%CI (0.57, 1.91), p＜0.001). Furthermore, the qgcomp analysis showed that the combination of five blood metals was positively associated with AST, ALT, GGT, TBIL and HSI. Cd contributed the most to the correlation of AST (weight = 0.447), Se contributed the most to the association of ALT (weight = 0.438) and HSI (weight = 0.570), Pb contributed the most to the association of GGT (weight = 0.421) and Hg contributed the most to the correlation of TBIL (weight = 0.331). CONCLUSIONS: Blood heavy metal levels were significantly associated with liver function parameters. Further studies are required to clarify the relationship between heavy metals and liver function.

Deoxycholic acid induces gastric intestinal metaplasia by activating STAT3 signaling and disturbing gastric bile acids metabolism and microbiota.

Intestinal metaplasia (IM) is the inevitable precancerous stage to develop intestinal-type gastric cancer (GC). Deoxycholic acid (DCA) is the main bile acid (BA) component of duodenogastric reflux and has shown an increased concentration during the transition from chronic gastritis to IM associated with continued STAT3 activation. However, the mechanisms underlying how DCA facilitates IM in the gastric epithelium need exploration. We evaluated IM and bile reflux in corpus tissues from 161 subjects undergoing GC screening. Cell survival and proliferation, proinflammatory cytokine expression and TGR5/STAT3/KLF5 axis activity were measured in normal human gastric cells, cancer cells, and organoid lines derived from C57BL/6, FVB/N and insulin-gastrin (INS-GAS) mice treated with DCA. The effects of DCA on IM development were determined in INS-GAS mice with long-term DCA supplementation, after which the gastric bacterial and BA metabolic profiles were measured by 16S rRNA gene sequencing and LC-MS. We revealed a BA-triggered TGR5/STAT3/KLF5 pathway in human gastric IM tissues. In gastric epithelial cells, DCA promoted proliferation and apoptotic resistance, upregulated proinflammatory cytokines and IM markers, and facilitated STAT3 phosphorylation, nuclear accumulation and DNA binding to the KLF5 promoter. DCA triggered STAT3 signaling and the downstream IM marker KLF5 in mouse gastric organoids in vitro and in vivo. In INS-GAS mice, DCA promoted the accumulation of serum total BAs and accelerated the stepwise development of gastric IM and dysplasia. DCA induced gastric environmental alterations involving abnormal BA metabolism and microbial dysbiosis, in which the Gemmobacter and Lactobacillus genera were specifically enriched. Lactobacillus genus enrichment was positively correlated with increased levels of GCA, CA, T-α-MCA, TCA and ß-MCA in DCA-administrated INS-GAS mice. DCA promotes nuclear STAT3 phosphorylation, which mediates KLF5 upregulation associated with gastric inflammation and IM development. DCA disturbs the gastric microbiome and BA metabolism homeostasis during IM induction.

Efficacy of keverprazan for duodenal ulcer: A phase II randomized, double-blind, parallel-controlled trial.

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

A discovery of clinically approved Panlongqi Tablet for repositioning to treat osteoarthritis by inhibiting PI3K/AKT activation.

BACKGROUND: Panlongqi Tablet (PLQT) is a Chinese patent drug composed of 29 kinds of traditional Chinese medicines. Clinical practice has shown that PLQT can relieve osteoarthritis-caused joint pain, but its effects and mechanisms in other pathological links of osteoarthritis have not been characterized. PURPOSE: The purpose of this study is to reposition the pharmacodynamic effects of PLQT through network pharmacology analysis combined with experimental validation, and also to preliminarily explore its possible mechanism. METHODS: On the basis of integrating the relevant targets of PLQT in multiple drug databases and osteoarthritis-related targets in the disease database, an interaction network of related genes was constructed. The hub candidate targets of PLQT in the treatment of osteoarthritis were determined by calculating the main network topological characteristics, The specific functions and pathways of these targets acting on osteoarthritis were modularly analyzed. In addition, the modified Hulth-induced rat model of osteoarthritis and IL-1ß-induced in vitro model of osteoarthritis were established to further validate the potential efficacy and possible mechanism of PLQT. RESULTS: A total of 138 key targets related to osteoarthritis were selected based on topological parameters, and their biological functions were mainly enriched in four over-expressed modules of cartilage degeneration, inflammatory response, immune response, and subchondral bone metabolism. The hub candidate targets had the highest enrichment degree in the TLR4-RAC1-PIK3CA-Akt-NFκB signaling axis of the PI3K/Akt signaling pathway. In vivo results showed that PLQT treatment significantly inhibited the degeneration of proteoglycan and collagen in the cartilage of osteoarthritis rats, suppressed chondrocyte apoptosis, and reduced the Mankin score of joints. Moreover, PLQT alleviated synovial inflammation, reduced the Krenn score of synovium, inhibited the formation of osteophytes in osteoarthritis rats, reduced the bone mineral density (BMD), fractional bone volume (BV/TV), and trabecular thickness (Tb.Th.), as well as increased the trabecular separation (Tb.Sp.) of subchondral bone and the thickness of the subchondral bone plate (SBP.Th.). PLQT suppressed the expressions of TLR4, RAC1, PIK3CA, p-Akt, MMP-13, and ADAMTS-5 in the cartilage, and inhibited the expression of NFκB p65 in the chondrogenic nucleus. Meanwhile, as downstream effector factors of the predictive pathways, the levels of serum interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), and prostaglandin E2 (PGE2) were decreased after PLQT treatment. In vitro results also showed that PLQT could inhibit the expression of key proteins and downstream effector factors of the signaling axis, and this inhibition disappeared when pathway agonists were added. CONCLUSION: PLQT exerted pharmacological effects on the key pathological links of osteoarthritis including chondrocyte apoptosis, extracellular matrix degradation, inflammation, and subchondral bone metabolism by inhibiting the TLR4-RAC1-PIK3CA-Akt-NFκB axis-related proteins.

The analgesic properties of Yu-Xue-Bi tablets in the inflammatory pain mice: By the inhibition of CCL3-mediated macrophage transmigration into the spinal cord.

ETHNOPHARMACOLOGICAL RELEVANCE: Until now, inflammatory pain, especially ones with central sensitization in the spinal cord, is far from effectively treated. Yu-Xue-Bi Tablets (YXB) is a patented medicine, which has been widely applied for inflammatory pain. However, its therapeutic characteristics and mechanism remain unknown. AIM OF THE STUDY: This study is designed to evaluate the analgesic characteristics and explore the underlying mechanism of YXB in the inflammatory pain model induced by Complete Freund's Adjuvant (CFA). MATERIALS AND METHODS: The analgesic effects were measured by Von Frey test. The expression of calcitonin gene-related peptide (CGRP) was quantified by immunofluorescence. The expression of immune factors was analyzed via Luminex assay. The further quantifications of C-C Motif chemokine ligand 3 (CCL3) were verified by Enzyme-linked immunosorbent assay (ELISA). The transmigration of macrophage and activation of microglia were evaluated by immunofluorescence. Spinal injections of purified CCL3, CCR1 antagonist (J113863) and CCR5 antagonist (Maraviroc) were used to clarify roles of CCL3 assumed in the pharmacological mechanism of YXB. RESULTS: In CFA mice, YXB ameliorated the mechanical allodynia in dose and time dependent way, suppressed the central sensitization in dose dependent way. In the L5 spinal cord, YXB downregulated the expression of macrophage M1 pro-inflammatory factors TNFRI and CCL3, inhibited the transmigration of circulating macrophage and the activation of microglia. Purified CCL3 led to the transmigration of macrophage, activation of microglia, central sensitization, and mechanical allodynia in the Sham mice. Inhibitors of CCR1 and CCR5 attenuated above symptoms in CFA mice. Purified CCL3 blocked YXB mediated down regulation of CCL3, inhibition of macrophage transmigration, but not activation of microglia. CONCLUSION: YXB exerts the analgesic effects by inhibiting CCL3-mediated peripheral macrophage transmigrate into spinal cord. This study provided a novel approach for inflammatory pain treatment and new insight into the pharmacological action of YXB.

Influence of Dietary Components and Traditional Chinese Medicine on Hypertension: A Potential Role for Gut Microbiota.

Hypertension (HTN) is an important worldwide public health issue affecting human health. The pathogenesis of HTN involves complex factors such as genetics, external environment, diet, and the gut microbial dysbiosis. The gut microbiota, as a medium of diet and drug metabolism, is closely correlated to host's health and disease (including HTN). Literatures were randomly collected from various databases including PubMed, ScienceDirect, Google Scholar, and China National Knowledge Infrastructure (CNKI). In this review, we elucidate the relationship between HTN and gut microbiota, as well as concerning the effects of different dietary components, diet-derived microbial metabolites, and traditional Chinese medicine (TCM) on intestinal flora. These studies have shown that diet and TCM can regulate and balance the intestinal flora, which are inclined to increasing the abundance of Akkermansia, Bifidobacterium, and Bacteroides and reducing the ratio of Firmicutes and Bacteroidetes. Moreover, monitoring the dynamic change of gut microflora may indicate patient prognosis and personalized response to treatment. This review aims to provide novel perspectives and potential personalized interventions for future HTN management from the perspective of gut microbiota.

Gastric cancer proliferation and invasion is reduced by macrocalyxin C via activation of the miR-212-3p/Sox6 Pathway.

Gastric cancer is a malignancy of very poor prognosis and survival rates. Macrocalyxin C is a Chinese herb-derived diterpenoid compound that has been postulated to possess anti-cancer characteristics. Gastic cell viability and stage of cell cycle were assessed using CCK8 assay and flow cytometry, respectively. Cell migration and invation were assessed using the wound healing and Transwell assays. Rate of apoptosis was determined via AV/PI-staining. Athymic nude mice xenograft models were used to evaluate the in vivo efficacy of macrocalyxin C. Western blot, luciferase experiments, cell transfection and real-time PCR allowed further study into the activation of the miR-212-3p/Sox6 pathway during macrocalyxin C treatment. We conclude that macrocalyxin C may halt the proliferation of gastric malignancies through alteration of cell invasion, apoptosis, progression through the cell cycle and cell growth. The macrocalyxin C→miR-212-3p┤Sox6 signal pathway was identified to be involved in Sox6 attenuation through augmentation of miR-212-3p values.

Tailored Therapy Versus Empiric Chosen Treatment for Helicobacter pylori Eradication: A Meta-Analysis.

Although various regimens are empirically accepted for Helicobacter pylori eradication, the efficacy might be declined by multiple individual factors. The necessity of a personalized eradication therapy still remains controversial. The aim of the study was to compare tailored therapy with empiric chosen regimens. Databases of PUBMED, EMBASE, and MEDLINE were searched for eligible studies, published up to October 2015. All relevant controlled clinical trials were included. A random-effect model was applied to compare pooled relative risk (RR) with related 95% confidence intervals (CIs).Thirteen controlled clinical trials integrating 3512 participants were assessed. Overall, the pooled eradication rates of tailored groups were higher than those of empiric ones (intention-to-treat: RR = 1.16, 95% CI 1.10-1.22; preprotocol: RR = 1.14, 95% CI 1.08-1.21). In subgroup analysis, tailored therapy was superior to 7-day standard triple therapy (RR = 1.22, 95% CI 1.16-1.29) and bismuth-quadruple therapy (RR = 1.14, 95% CI 1.07-1.22) on eradication rates; first-line tailored therapy achieved higher eradication rates than first-line empirical regimens (pooled RR = 1.18, 95%CI 1.14-1.22), whereas tailored rescue regimen showed no difference with empirical ones (pooled RR = 1.16, 95% CI 0.96-1.39). Moreover, among different tailored designs, susceptibility-guided tailored therapy obtained higher eradication rates than empiric groups, independent of CYP2C19 genotype detection (with CYP: RR = 1.16, 95% CI 1.09-1.23; without CYP: RR = 1.14, 95% CI 1.01-1.28). Both molecular test-based and culture-based tailored groups were better on eradication rates than empiric groups (molecular: RR = 1.23, 95% CI 1.11-1.35; culture: RR = 1.13, 95% CI 1.06-1.20). Compared with empiric chosen treatments, tailored therapy is a better alternative for H pylori eradication.

Lithium protects dopaminergic cells from rotenone toxicity via autophagy enhancement.

BACKGROUND: Previous studies have indicated that enhancement of autophagy lysosome pathway may be beneficial for Parkinson's disease (PD), in which aberrant accumulation of aggregated/misfolded proteins and mitochondrial dysfunction are considered as crucial pathogenesis. Recently, a number of studies have suggested the neuroprotective effects of lithium in models of several neurodegenerative diseases including PD. However, the exact mechanisms underlying this neuroprotection remain unclear. In our study, rotenone-exposed SH-SY5Y cells were used as an in vitro parkinsonian model to assess the autophagy-enhancing effect of lithium and the underlying mechanisms were further investigated. RESULTS: Similar to the common used autophagy enhancer rapamycin (Rap, 0.2 µM), lithium (LiCl, 10 mM) significantly recovered the shrinkage of SH-SY5Y cells, and alleviated rotenone-induced cell apoptosis, mitochondrial membrane potential reduction and reactive oxygen species accumulation. Furthermore, the protective effects induced by LiCl were partially blocked by the co-treatment of autophagy inhibitors such as 3-methyladenine (3-MA, 10 mM) or chloroquine (CHL, 10 µM). Moreover, 3-MA or Chl suppressed LiCl-induced autophagy in the immunoblot assay. In addition, the co-localization of LC3 and mitochondria and the preservation of mitochondrial function within LiCl-treated cells were observed, confirming that the damaged mitochondria were cleared through autophagy (mitophagy). CONCLUSIONS: These findings suggested that lithium exerted neuroprotection against rotenone-induced injuries partially through the autophagy pathway. Pharmacologically induction of autophagy by lithium may represent a novel therapeutic strategy as a disease-modifier in PD.

Effectiveness of traditional Chinese medicine as an adjunct therapy for Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND: Idiopathic Parkinson disease (PD) is a common neurodegenerative disease that seriously hinders limb activities and affects patients' lives. We performed a meta-analysis aiming to systematically review and quantitatively synthesize the efficacy and safety of traditional Chinese medicine (TCM) as an adjunct therapy for clinical PD patients. METHODS: An electronic search was conducted in PubMed, Cochrane Controlled Trials Register, China National Knowledge Infrastructure, Chinese Scientific Journals Database and Wanfang data to identify randomized trials evaluating TCM adjuvant therapy versus conventional treatment. The change from baseline of the Unified Parkinson's Disease Rating Scale score (UPDRS) was used to estimate the effectiveness of the therapies. RESULTS: Twenty-seven articles involving 2314 patients from 1999 to 2013 were included. Potentially marked improvements were shown in UPDRS I (SMD 0.68, 95%CI 0.38, 0.98), II (WMD 2.41, 95%CI 1.66, 2.62), III (WMD 2.45, 95%CI 2.03, 2.86), IV (WMD 0.32, 95%CI 0.15, 049) and I-IV total scores (WMD 6.18, 95%CI 5.06, 7.31) in patients with TCM plus dopamine replacement therapy (DRT) compared to DRT alone. Acupuncture add-on therapy was markedly beneficial for improving the UPDRS I-IV total score of PD patients (WMD 10.96, 95%CI 5.85, 16.07). However, TCM monotherapy did not improve the score. The effectiveness seemed to be more obvious in PD patients with longer adjunct durations. TCM adjuvant therapy was generally safe and well tolerated. CONCLUSIONS: Although the data were limited by methodological flaws in many studies, the evidence indicates the potential superiority of TCM as an alternative therapeutic for PD treatment and justifies further high-quality studies.

[Regulation effects of electroacupuncture with different acupoint combinations on blood lipid in rats with hyperlipemia].

OBJECTIVE: To observe the regulatory effects of electroacupuncture with different acupoints combinations on blood lipid and atherosclerosis index (AI) in rats with hyperlipemia, so as to make a preliminary screening for the optimal acupoints combination for hyperlipemia. METHODS: One hundred and five clean-grade SD male rats were randomly divided into 9 groups, including a normal group, a model group, a Quchi group, a Zhongwan group, a Fenglong group, a Quchi+Zhongwan group, a Quchi+Fenglong group, a Zhongwan+Fenglong group and a Quchi+Zhongwan+Fenglong group (three acupoints group), 17 rats in the normal group and 11 rats in the rest groups. The normal group was fed with normal diet, while the rest groups were fed with high-fat diet for 3 weeks to prepare the hyperlipemia model. All the rats were given unlimited water. After the establishment of model, the normal group was fed freely without any treatment; the model group was bundled and immobilized everyday; the rest groups were bundled, immobilized and treated with electroacupuncture at corresponding acupoints with disperse-dense wave, 20 min per time, once a day. After 4 weeks, the blood examples were collected from abdominal aorta to measure the total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C), and analyzed the AI in each group. RESULTS: After the treatment, TC, TG, HDL-C, LDL-C and AI in each acupuncture group were all lower than those in the model group (P<0.05, P<0.01). Compared with single acupoint group and the Quchi+Zhongwan group, the content of TC in the three acupoints group was lower (P<0.01). The differences of content of TG among each acupuncture group were not significant (all P>0.05). Compared with the rest 6 acupuncture groups, the content of HDL-C and AI in the three acupoints group were significantly different (all P<0.05). The content of LDL-C in the three acupoints group was decreased as compared with the Quchi group and the Zhong-wan group. CONCLUSION: The electroacupuncture at "Quchi" (LI 11), "Zhongwan" (CV 12) and "Fenglong" (ST 40) has more advantages on regulating the content of HDL-C and LDL-C as well as improving AI in hyperlipemia rats, and it has superior effects on blood lipid metabolism.

The effect of probiotics supplementation on Helicobacter pylori eradication rates and side effects during eradication therapy: a meta-analysis.

BACKGROUND: Previous meta-analyses reported that probiotics improve the effectiveness of Helicobacter pylori (H. pylori) eradication during antibiotic therapy, while results regarding a possible reduction of side effects remained inconclusive. Moreover, the effectiveness of different strains of probiotics has not been studied so far. It is further conceivable that probiotics will produce additional effects only if antibiotics are relatively ineffective. METHODS: This meta-analysis includes eligible randomized controlled trials examining effects of probiotics supplementation on eradication rates (ER) and side effects, published up to May 2014. Sub-group analysis was performed to compare different probiotic strains and antibiotic therapies with different effectiveness in controls (ER <80% vs.>80%). Publication bias was assessed with funnel plots and Harbord's test. The quality of the trials was assessed with the Cochrane risk of bias tool. RESULTS: Thirty-three RCTs involving a total of 4459 patients met the inclusion criteria in case of eradication rates of which 20 assessed total side effects in addition. Overall, the pooled eradication rate in probiotics supplementation groups was significantly higher than in controls (ITT analysis: RR 1.122, 95% CI 1.086-1.159, PP analysis: RR 1.114, 95% CI 1.070-1.159). Sub group-analysis could, however, confirm this finding only for four individual strains (Lactobacillus acidophilus, Lactobacillus casei DN-114001, Lactobacillus gasseri, and Bifidobacterium infantis 2036) and for relatively ineffective antibiotic therapies. There was a significant difference between groups in the overall incidence of side effects (RR 0.735, 95% CI 0.598-0.902). This result was, however, only confirmed for non-blinded trials. CONCLUSIONS: The pooled data suggest that supplementation with specific strains of probiotics compared with eradication therapy may be considered an option for increasing eradication rates, particularly when antibiotic therapies are relatively ineffective. The impact on side effects remains unclear and more high quality trials on specific probiotic strains and side effects are thus needed.

Graphene in mice: ultrahigh in vivo tumor uptake and efficient photothermal therapy.

Although biomedical applications of carbon nanotubes have been intensively studied in recent years, its sister, graphene, has been rarely explored in biomedicine. In this work, for the first time we study the in vivo behaviors of nanographene sheets (NGS) with polyethylene glycol (PEG) coating by a fluorescent labeling method. In vivo fluorescence imaging reveals surprisingly high tumor uptake of NGS in several xenograft tumor mouse models. Distinctive from PEGylated carbon nanotubes, PEGylated NGS shows several interesting in vivo behaviors including highly efficient tumor passive targeting and relatively low retention in reticuloendothelial systems. We then utilize the strong optical absorbance of NGS in the near-infrared (NIR) region for in vivo photothermal therapy, achieving ultraefficient tumor ablation after intravenous administration of NGS and low-power NIR laser irradiation on the tumor. Furthermore, no obvious side effect of PEGylated NGS is noted for the injected mice by histology, blood chemistry, and complete blood panel analysis in our pilot toxicity study. Although a lot more efforts are required to further understand the in vivo behaviors and the long-term toxicology of this new type of nanomaterials, our work is the first success of using carbon nanomaterials for efficient in vivo photothermal therapy by intravenous administration and suggests the great promise of graphene in biomedical applications, such as cancer treatment.

Advantages of Moxifloxacin and Levofloxacin-based triple therapy for second-line treatments of persistent Helicobacter pylori infection: a meta analysis.

OBJECTIVE: The main aim of this meta-analysis was to compare the efficacy and safety of clarithromycin and second-generation fluoroquinolone-based triple therapy vs. bismuth-based quadruple therapy for the treatment of persistent Helicobacter pylori infection. METHODS: A systematic literature search was conducted for articles and abstracts from 1981 to March 2009 using Medline, PubMed, EMBase, Google Scholar and CNKI (Chinese), Wanfang (Chinese) digital database and recent Digestive Disease Week, United European Gastroenterology Week, and European Helicobacter Study Group conferences were also performed. Boolean operators (NOT, AND, OR) were used in succession to narrow and widen the search. Sixteen articles and four abstracts met the inclusion criteria, and were included in the meta-analysis by using Review Manager 4.2.8. RESULTS: The eradication rates demonstrated that clarithromycin-based triple therapy is inferior to bismuth-based quadruple therapy (OR = 0.53, 95% CI: 0.35-0.80, P = 0.002). Thirteen RCTs compared levofloxacin-based triple therapy vs. bismuth-based quadruple therapy, the eradication rates of the two regimens were shown to have no significant difference (OR = 1.43, 95% CI: 0.82-2.51, P = 0.21). But the eradication rates demonstrated superiority of the 10-day levofloxacin-based triple therapy over 7-day bismuth-based quadruple therapy (OR = 4.79, 95% CI: 2.95-7.79, P < 0.00001). Levofloxacin-based triple therapy was better tolerated than bismuth-based quadruple therapy with lower rates of side effects (OR = 0.41, 95% CI: 0.27-0.61, P < 0.0001), and lower rates of discontinuation of therapy due to adverse events (OR = 0.13, 95% CI: 0.06-0.33, P < 0.0001). Furthermore, our meta-analysis suggested that the eradication rates of the moxifloxacin-based triple therapy has a slight superiority to bismuth-based quadruple therapy, but there was no significant difference between them. CONCLUSION: Second-generation fluoroquinolone-based triple therapy can be suggested as the regimen of choice for rescue therapy in the eradication of persistent H. pylori infection especially 10-day levofloxacin-based triple therapy.

Unprecedented marriage of a cationic pentanuclear cluster and a 2D polymeric anionic layer based on a flexible tripodal ligand and a Cu(II) ion.

The anionic CdI(2)-type topological net, [Cu(2)(tci)(2)](2-), and the pentanuclear copper cluster cation [Cu(5)(tci)(2)(OH)(2)(H(2)O)(8)](2+) [tci = tris(2-carboxyethyl)isocyanurate] form a complementary 3D supramolecular framework. Interestingly, there exist centrosymmetric cyclic (H(2)O)(18) clusters in the cavities.

Analysis of hupehenine in the total alkaloids from Fritillaria hupehensis by HPLC-ELSD.

A reverse-phase high pressure liquid chromatography (HPLC) method with evaporative light scattering detection (ELSD) has been developed for the quantitative analysis of hupehenine in the total alkaloids from Fritillaria hupehensis. Samples were analyzed on a reverse-phase column (Hypersil C-18) with a mobile phase of methanol:water:chloroform: triethylamine (85:15:1:0.6). The ELSD was set at the drift tube temperature of 68.3 degrees C and gas flow rate of 1.8 L/min. Hupehenine's retention time was 13.7 min with an asymmetry factor of 1.2. The validity of the method has been verified with linearity, limit of detection, accuracy and precision. The logarithmic linear curve was obtained from 8.936 to 134.04 microg/mL (r=0.9993). The detection limit (S/N>3) of hupehenine was 1.79 microg/mL on the column. Intra-day RSD was 1.42% and inter-day RSD was 2.26% (3 days within a week). The average recovery of hupehenine was 101.50%, and RSD was 1.62%.

[HPLC fingerprint of Fritillaria hupehensis].

AIM: To establish a fingerprint analysis method of Fritillaria hupehensis. METHODS: fingerprint was performed by HPLC-ELSD. Hypersil ODS column was used; the mobile phase was composed of methanol (with 0.05% triethylamine) and water with gradient elution; flow rate was 1.0 mL x min(-1); recording time was 60 min; drift tube temperature was 75 degrees C; gas flow rate was 1.9 L x min(-1). RESULTS: HPLC fingerprint of Fritillaria hupehensis was obtained. CONCLUSION: A reliable method was provided for controlling the quality of Fritillaria hupehensis.