A Meta-Analysis of Chinese Herbal Medicine in Treatment of Managed Withdrawal from Heroin

Chinese herbal medicine has shown promise for heroin detoxification. This review extends a prior meta-analysis of Chinese herbal medicine for heroin detoxification, with particular attention to the time course of symptoms. Both English and Chinese databases were searched for randomized trials comparing Chinese herbal medicine to either α2-adrenergic agonists or opioid agonists for heroin detoxification. The methodological quality of each study was assessed with Jadad’s scale (1–2 = low; 3–5 = high). Meta-analysis was performed with fixed- or random-effect models in RevMan software; outcome measures assessed were withdrawal-symptoms score, anxiety, and adverse effects of treatment. Twenty-one studies (2,949 participants) were included. For withdrawal-symptoms score relieving during the 10-day observation, Chinese herbal medicine was superior to α2-adrenergic agonists in relieving opioid-withdrawal symptoms during 4–10 days (except D8) and no difference was found within the first 3 days. Compared with opioid agonists, Chinese herbal medicine was inferior during the first 3 days, but the difference became non-significant during days 4–9. Chinese herbal medicine has better effect on anxiety relieving at late stage of intervention than α2-adrenergic agonists, and no difference with opioid agonists. The incidence of some adverse effects (fatigue, dizziness) was significantly lower for Chinese herbal medicine than for α2-adrenergic agonists (sufficient data for comparison with opioid agonists were not available). Findings were robust to file-drawer effects. Our meta-analysis suggests that Chinese herbal medicine is an effective and safety treatment for heroin detoxification. And more work is needed to determine the specific effects of specific forms of Chinese herbal medicine.     

Modification of the effects of naloxone in morphine-dependent mice

Mice were rendered dependent on morphine by mixing morphine with their food (2 mg/g) for three days. Increasing doses of naloxone precipitated dose-dependent withdrawal reactions such as weight loss and jumping. These withdrawal reactions were antagonized by morphine pretreatment. Effects of morphine, such as increased locomotor activity, inhibition of intestinal transport, and analgesia were antagonized by naloxone in both non-dependent and dependent subjects. The antagonist actions of naloxone were increased in dependent subjects; lower doses of naloxone were sufficient to antagonize effects of morphine. The present results confirm earlier studies indicating that precipitation of withdrawal can be antagonized by morphine pretreatment suggesting that withdrawal reactions are due to actions of naloxone at the same receptor at which opioid agonists act. The increased antagonist potency of naloxone in dependent subjects extends earlier results obtained with analgesic effects to several other agonist effects of morphine and is consistent with the interpretation that exposure to an opioid agonist induces a change in the conformation of opioid receptors.     

The Efficacy of Acupuncture in Post-Operative Pain Management: A Systematic Review and Meta-Analysis

Background

Postoperative pain resulting from surgical trauma is a significant challenge for healthcare providers. Opioid analgesics are commonly used to treat postoperative pain; however, these drugs are associated with a number of undesirable side effects.

Objective

This systematic review and meta-analysis evaluated the effectiveness of acupuncture and acupuncture-related techniques in treating postoperative pain.

Data Source

MEDLINE, Cochrane Library, and EMBASE databases were searched until Sep 30, 2014.

Study Eligibility Criteria

Randomized controlled trials of adult subjects (≥ 18 years) who had undergone surgery and who had received acupuncture, electroacupuncture, or acupoint electrical stimulation for managing acute post-operative pain were included.

Results

We found that patients treated with acupuncture or related techniques had less pain and used less opioid analgesics on Day 1 after surgery compared with those treated with control (P < 0.001). Sensitivity analysis using the leave-one-out approach indicated the findings are reliable and are not dependent on any one study. In addition, no publication bias was detected. Subgroup analysis indicated that conventional acupuncture and transcutaneous electric acupoint stimulation (TEAS) were associated with less postoperative pain one day following surgery than control treatment, while electroacupuncture was similar to control (P = 0.116). TEAS was associated with significantly greater reduction in opioid analgesic use on Day 1 post surgery than control (P < 0.001); however conventional acupuncture and electroacupuncture showed no benefit in reducing opioid analgesic use compared with control (P ≥ 0.142).

Conclusion

Our findings indicate that certain modes of acupuncture improved postoperative pain on the first day after surgery and reduced opioid use. Our findings support the use of acupuncture as adjuvant therapy in treating postoperative pain.     

Association between HFE polymorphisms and susceptibility to Alzheimer’s disease: a meta-analysis of 22 studies including 4,365 cases and 8,652 controls

Whether the variations in the hemochromatosis (HFE) gene increase Alzheimer’s disease (AD) risk is still undetermined. We performed a meta-analysis in order to systematically summarize the possible association. Studies were identified by searching PUBMED, Web of Science and EMBASE databases complemented with screening the references of the retrieved studies. The association was measured using random-effect or fixed-effect odds ratio (OR) combined with 95% confidence intervals (CIs) according to the studies’ heterogeneity. For C282Y polymorphism, we did not find any association using data from 22 studies including 4,365 cases and 8,652 controls. For H63D polymorphism, on the basis of 2,795 cases and 7,424 controls from 17 studies, we observed a significant association (allele contrast: OR = 0.902, 95% CI = 0.819–0.994, P = 0.037; minor-allele-dominant model: OR = 0.887, 95% CI = 0.790–0.996, P = 0.043). No publication bias was detected in this meta-analysis. The synthesis of available evidence supports mutant of HFE H63D polymorphism plays a protective role for AD risk.     

N-terminal guanidinylation of TIPP (Tyr-Tic-Phe-Phe) peptides results in major changes of the opioid activity profile

Derivatives of peptides of the TIPP (Tyr-Tic-Phe-Phe; Tic = 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) family containing a guanidino (Guan) function in place of the N-terminal amino group were synthesized in an effort to improve their blood–brain barrier permeability. Unexpectedly, N-terminal amidination significantly altered the in vitro opioid activity profiles. Guan-analogues of TIPP-related δ opioid antagonists showed δ partial agonist or mixed δ partial agonist/μ partial agonist activity. Guanidinylation of the mixed μ agonist/δ antagonists H-Dmt-Tic-Phe-Phe-NH₂ (DIPP-NH₂) and H-Dmt-TicΨ[CH₂NH]Phe-Phe-NH₂ (DIPP-NH₂[Ψ]) converted them to mixed μ agonist/δ agonists. A docking study revealed distinct positioning of DIPP-NH₂ and Guan-DIPP-NH₂ in the δ receptor binding site. Lys³-analogues of DIPP-NH₂ and DIPP-NH₂[Ψ] (guanidinylated or non-guanidinylated) turned out to be mixed μ/κ agonists with δ antagonist-, δ partial agonist- or δ full agonist activity. Compounds with some of the observed mixed opioid activity profiles have therapeutic potential as analgesics with reduced side effects or for treatment of cocaine addiction.     

Isoxyl Aerosols for Tuberculosis Treatment: Preparation and Characterization of Particles

Isoxyl is a potent antituberculosis drug effective in treating various multidrug-resistant strains in the absence of known side effects. Isoxyl has been used exclusively, but infrequently, via the oral route and has exhibited very poor and highly variable bioavailability due to its sparing solubility in water. These properties resulted in failure of some clinical trials and, consequently, isoxyl’s use has been limited. Delivery of isoxyl to the lungs, a major site of Mycobacterium tuberculosis infection, is an attractive alternative route of administration that may rescue this abandoned drug for a disease that urgently requires new therapies. Particles for pulmonary delivery were prepared by antisolvent precipitation. Nanofibers with a width of 200 nm were obtained by injecting isoxyl solution in ethanol to water at a volume ratio of solvent to antisolvent of 1:5. Based on this preliminary result, a well-controlled method, involving nozzle mixing, was employed to prepare isoxyl particles. All the particles were 200 to 400 nm in width but had different lengths depending on properties of the solvents. However, generating these nanoparticles by simultaneous spray drying produced isoxyl microparticles (Feret’s diameter, 1.19–1.77 μm) with no discernible nanoparticle substructure. The bulking agent, mannitol, helped to prevent these nanoparticles from agglomeration during process and resulted in nanoparticle aggregates in micron-sized superstructures. Future studies will focus on understanding difference of these isoxyl microparticles and nanoparticles/nanoparticle aggregates in terms of in vivo disposition and efficacy.     

Antinociceptive action of NOP and opioid receptor agonists in the mouse orofacial formalin test

Nociceptin/orphanin FQ (N/OFQ) modulates several biological functions, including pain transmission via selective activation of a specific receptor named NOP. The aim of this study was the investigation of the antinociceptive properties of NOP agonists and their interaction with opioids in the trigeminal territory. The orofacial formalin (OFF) test in mice was used to investigate the antinociceptive potential associated to the activation of NOP and opioid receptors. Mice subjected to OFF test displayed the typical biphasic nociceptive response and sensitivity to opioid and NSAID drugs. Mice knockout for the NOP gene displayed a robust pronociceptive phenotype. The NOP selective agonist Ro 65-6570 (0.1–1 mg kg⁻¹) and morphine (0.1–10 mg kg⁻¹) elicited dose dependent antinociceptive effects in the OFF with the alkaloid showing larger effects; the isobologram analysis of their actions demonstrated an additive type of interaction. The mixed NOP/opioid receptor agonist cebranopadol elicited potent (0.01–0.1 mg kg⁻¹) and robust antinociceptive effects. In the investigated dose range, all drugs did not modify the motor performance of the mice in the rotarod test. Collectively the results of this study demonstrated that selective NOP agonists and particularly mixed NOP/opioid agonists are worthy of development as innovative drugs to treat painful conditions of the trigeminal territory.     

CXCL12 G801A polymorphism and breast cancer risk: a meta-analysis

The G801A polymorphism in the CXCL12 gene has been implicated in breast cancer risk. However, the published findings are inconsistent. We therefore performed a meta-analysis to investigate this relationship. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively. Five published case–control studies, including 1,058 breast cancer cases and 1,023 controls were identified. No study had a deviation from the Hardy–Weinberg equilibrium (HWE) in controls. We found that the CXCL12 G801A (rs1801157) polymorphism was associated with a significantly increased risk of breast cancer risk when all studies were pooled into the meta-analysis (codomiant model: AA versus GG, OR = 1.64, 95% CI = 1.16–2.33; GA versus GG, OR = 1.42, 95% CI = 1.18–1.71; dominant model: AA/GA versus GG, OR = 1.44, 95% CI = 1.21–1.72). Furthermore, Egger’s test did not show any evidence of publication bias (P > 0.05 for the dominant model). In conclusion, the results suggest that the CXCL12 G801A polymorphism may be a low-penetrant risk factor for developing breast cancer.     

Purinoreceptors are involved in the control of acute morphine withdrawal.

The effects exerted by P1 and P2 purinoceptor agonists and antagonists on the acute opiate withdrawal induced by morphine were investigated in vitro. Following a 4 min in vitro exposure to morphine, the guinea-pig isolated ileum exhibited a strong contracture after the addition of naloxone. The P1 purinoceptor agonist, adenosine, was able dose-dependently to reduce morphine withdrawal whereas alpha,beta-methylene ATP (APCPP), a P2 purinoceptor agonist, increased morphine withdrawal. Caffeine, a P1 purinoceptor antagonist, was able significantly and in a concentration dependent manner to increase morphine withdrawal whereas quinidine, a P2 receptor antagonist, reduced it. The results of our experiments indicate that both P1 and P2 purinoceptor agonists and antagonists are able to influence opiate withdrawal in vitro, suggesting an important functional interaction between the purinergic system and opioid withdrawal.     

Association of C47T polymorphism in <Emphasis Type="Italic">SOD2</Emphasis> gene with coronary artery disease: a case–control study and a meta-analysis

Oxidative damage promotes atherosclerosis. SOD2 is an important antioxidant enzyme. A case–control study and a meta-analysis were performed to assess the association of C47T polymorphism in SOD2 gene with premature, late-onset and overall coronary artery disease (CAD) risk. A hospital-based case–control study was conducted with 269 premature CAD cases, 278 late-onset CAD cases and 299 healthy controls. Polymerase chain reaction (PCR) and Pyrosequencing were used to detect the polymorphism. Multinomial logistic regression model was performed to estimate odds ratio (OR) with 95% confidence intervals (CIs) and adjust potential confounders. A meta-analysis was performed using eight outcomes including our result. Fixed or random effect pooled measure was selected on the basis of homogeneity test among studies. Heterogeneity among studies was evaluated using I ². Meta-regression was used to explore potential sources of between-study heterogeneity. Publication bias was estimated using Peters’s linear regression test. In our case–control study, compared with the TT as the reference, the mutant genotype of CC + TC was significantly associated with a reduced premature CAD risk both in univariate (OR = 0.60, 95% CI = 0.41–0.87) and multivariate (OR = 0.59, 95% CI = 0.40–0.87) logistic regressions, but not with late-onset CAD risk. After excluding one article that deviated from Hardy–Weinberg equilibrium in controls, this meta-analysis showed a significant association of the C allele with reduced risk of CAD in dominant (FEM: OR = 0.69, 95% CI = 0.61–0.78), recessive (OR = 0.64, 95% CI = 0.50–0.82), and codominant (FEM: OR = 0.73, 95% CI = 0.65–0.80) models. Our study suggested that the mutant genotype of CC + TC was significantly associated with a reduced CAD risk.     

Association between paraoxonase 2 Ser311Cys polymorphism and ischemic stroke risk: a meta-analysis involving 5,008 subjects

Epidemiological studies have evaluated the association between paraoxonase 2 (PON2) Ser311Cys polymorphism and ischemic stroke risk which developed inconsistent conclusions. The aim of this study was to perform a meta-analysis to investigate a more authentic association between PON2 Ser311Cys polymorphism and ischemic stroke. Systematic searches in PUBMED, EMBASE, CBM, and CNKI databases were performed. Data analyses were carried out by Review Manager 5.1.2 and Stata 11.0. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used for additive model (Cys/Cys vs. Ser/Ser), dominant model (Ser/Cys+Cys/Cys vs. Ser/Ser), recessive model (Cys/Cys vs. Ser/Cys+Ser/Ser), and allelic model (Cys allele vs. Ser allele), respectively. Publication bias was analyzed by Begg’s funnel plot and Egger’s test. A total of 7 studies including 2,046 cases and 2,962 controls were involved. Overall, no significant association was found between PON2 Ser311Cys polymorphism and ischemic stroke risk when all studies were pooled into the meta-analysis (for additive model: OR = 0.87, 95% CI = 0.67–1.14; for dominant model: OR = 1.05, 95% CI = 0.91–1.22; for recessive model: OR = 0.90, 95% CI = 0.77–1.05; and for allelic model: OR = 1.17, 95% CI = 0.86–1.59). In the subgroup analysis by ethnicity, significant association was found among Europeans (for recessive model: OR = 0.83, 95% CI = 0.69–0.99). However, due to the small number of studies included in subgroup analysis, the result for European population should be interpreted cautiously.     

Association of p53 codon 72 polymorphism with prostate cancer: a meta-analysis

Relationship of prostate cancer with the polymorphism of p53 codon 72 was reported with inconsistent results. The purpose of this study was to quantitatively evaluate the association between p53 codon 72 polymorphism and prostate cancer susceptibility. We performed an extensive search of relevant studies and made a meta-analysis, including 8 studies with 815 prostate cancer cases and 1047 controls. The combined results showed that there were no significant differences in genotype distribution between prostate cancer cases and control on the basis of all studies, CC/GC versus GG (OR = 1.24, 95% CI: 0.93–1.65), GG/GC versus CC (OR = 0.96, 95% CI: 0.60–1.55), GC versus GG (OR = 1.27, 95% CI: 0.91–1.77), CC versus GG (OR = 1.25, 95% CI:0.74–2.12), GC versus CC (OR = 1.09, 95% CI: 0.63–1.87). When stratifying for the race, there were also no statistically significant differences in genotype distribution between prostate cancer cases and controls. This meta-analysis did not provide an evidence of confirming association between p53 codon 72 polymorphism and prostate cancer.     

Electrophysiological Effects of Three Groups of Glutamate Metabotropic Receptors in Rat Piriform Cortex

1. The effects of three metabotropic glutamate receptor (mGluR) agonists were tested in two pathways of rat piriform cortex. The group I, II and III mGluR agonists used were RS-3,5-dihydroxyphenenylglycine (DHPG) (10–100 μM), (2S,1′S,2′S)-2-Carboxycyclopropyl (L-CCG) (20–100 μM) and L(+)-2-amino-4-phosphonobutyric acid (L-AP4) (5–500 μM), respectively.2. The effects of the three groups of agonists on synaptic transmission in the two piriform cortex pathways also were examined. All three agonists reduced the amplitude of the monosynaptic EPSPs generated by stimulation of the lateral olfactory tract (LOT) or of the association fiber pathway (ASSN). This was always accompanied by an increase in paired pulse facilitation.3. Group I and II mGluR agonists had similar synaptic effects on the two pathways, while the group III mGluR agonist suppressed the LOT pathway more than the association pathway.4. The group II and III mGluR agonists had no effect on passive membrane properties of pyramidal neurons. Group I agonists depolarized the pyramidal neuron membrane potential, and enhanced both membrane resistance and noise.5. Our data suggest that all three types of mGluRs modulate synaptic transmission in both of these pathways in piriform cortex. Only group I agonists alter post-synaptic membrane properties, while all three types of receptor regulate synaptic transmission. Groups I and II are equally potent in the LOT and association fiber pathways, while group III receptors are more potent in the LOT than the association fiber pathways.     

Cross-dependence to opioid and alpha 2-adrenergic receptor agonists in NG108-15 cells

Clonidine, a partial alpha 2-agonist, has been used empirically to alleviate opiate withdrawal symptoms, but the mechanism of its effects is not completely understood. We studied the interactions of opioid and adrenergic receptor agonists in the NG108-15 cells, which are a model of opiate dependence. We determined that in these cells the adenylate cyclase (AC) [EC 4.6.1.1; ATP pyrophosphate-lyase (cyclizing) overshoot response to opioid or alpha 2-agonist withdrawal can be significantly attenuated or suppressed by the other agonist. Subsequently, the AC overshoot response can be triggered with the antagonist to the second agonist to which the cells were not dependent. These results demonstrate that convergent dependence to morphine and alpha 2 agonists can occur in a homogeneous cell population without neuronal loops. Therefore, the basic mechanisms that can account for convergent dependence in this model take place at the level of intracellular regulatory pathways that do not require neuronal networks.     

Icilin evokes a dose- and time-dependent increase in glutamate within the dorsal striatum of rats

Summary. Icilin, the peripheral cold channel agonist, activates TRPM8 and TRPA1, localized on dorsal root ganglia and trigeminal neurons in rats. Icilin precipitates immediate wet-dog shakes in this species, which are antagonized by centrally acting mu and kappa opioid agonists, implicating the central nervous system in the behavioral response. We studied the effect icilin has on glutamate levels in the dorsal striatum, a brain region involved in movement. Icilin (0.25, 0.5 and 0.75 mg/kg, i.p.) elicited a dose- and time-dependent increase in glutamate within the striatum, indicative of icilin’s neurochemical effect in rats.     

Molecular mechanisms of excitatory signaling upon chronic opioid agonist treatment

Opioid receptor agonists mediate their analgesic effects by interacting with Gi/o protein-coupled opioid receptors. Acute treatment with opioid agonists is thought to mediate analgesia by hyperpolarization of presynatic neurons, leading to the inhibition of excitatory (pain) neurotransmitters release. After chronic treatment however, the opioid receptors gradually become less responsive to agonists, and increased drug doses become necessary to maintain the therapeutic effect (tolerance). Analgesic tolerance is the result of two, partially overlapping processes: a gradual loss of inhibitory opioid function is accompanied by an increase in excitatory signaling. Recent data indicate that chronic opioid agonist treatment simultaneously desensitizes the inhibitory-, and augments the stimulatory effects of the opioids. In the present paper we review the molecular mechanisms that may have a role in the augmentation of the excitatory signaling upon chronic opioid agonist treatment. We also briefly review our recent experimental data on the molecular mechanism of chronic opioid agonist-mediated functional sensitization of forskolin-stimulated cAMP formation, in a recombinant Chinese hamster ovary cell line stably expressing the human delta-opioid receptor (hDOR/CHO). To interpret the experimental data, we propose that chronic hDOR activaton leads to activation of multiple redundant signaling pathways that converge to activate the protein kinase, Raf-1. Raf-1 in turn phosphorylates and sensitizes the native adenylyl cyclase VI isoenzyme in hDOR/CHO cells, causing a rebound increase in forskolin-stimulated cAMP formation upon agonist withdrawal.     

Association of hOGG1 Ser326Cys polymorphism with gastric cancer risk: a meta-analysis

Studies investigating the association between human 8-oxoguanine glycosylase 1(hOGG1) Ser326Cys polymorphism and gastric cancer (GC) risk have reported conflicting results. We performed a meta-analysis of published case–control studies to better compare results between studies. 11 eligible studies with 2,180 GC cases and 3,985 controls were selected. There were 5 studies involving Caucasians and 5 studies involving Asians. The combined result based on all studies did not show significant difference in any genetics models. Ser/Cys + Cys/Cys versus Ser/Ser (OR = 0.91, 95% CI 0.81–1.03), Cys/Cys versus Ser/Cys + Ser/Ser (OR = 1.07, 95% CI 0.80–1.44), Ser/Cys versus Ser/Ser (OR = 0.91, 95% CI 0.80–1.03), Sys/Cys versus Ser/Cys (OR = 1.10, 95% CI 0.83–1.47), Cys/Cys versus Ser/Ser (OR = 0.99, 95% CI 0.74–1.34), Cys versus Ser (OR = 1.01, 95% CI 0.88–1.17).When stratifying for ethnicity, there was still no significant association found between hOGG1 Ser326Cys polymorphism and GC risk. Funnel plot and Egger’s test showed some evidence of publication bias on the basis of all studies. Two studies were the main reason because their samples were too small. However, the result of sensitivity analysis suggested that the influence of these two studies and one mixed population study on the pooled OR was weak. Our result could explain the association between hOGG1 Ser326Cys polymorphism and GC risk. In conclusion, we did not found the evidence that the Cys allele at codon 326 of hOGG1 could increase GC risk in our analysis.     

A review of the effects of dopaminergic agents on humans,animals, and drug-seeking behavior,and its implications for medication development

Medication development for cocaine abuse has focused on potential mechanisms of action related to the abuse of cocaine. The hypothesis that mesolimbic dopamine (DA) is the key neurochemical mediator of cocaine’s addictive and reinforcing effects is well supported by a wide variety of data from animal studies. On the other hand, medications that increase DA or block its actions in humans can produce effects that appear incompatible with this hypothesis. This article reviews these incompatibilities between animal and human data with a focus on the DAergic actions of drugs, including DA reuptake inhibitors, direct DA agonists, DA increasers, and DA antagonists. Possible reasons for these discrepancies are discussed, and the potential role of high-affinity DA uptake inhibitors, such as GBR12909, for pharmacotherapeutic application to treat cocaine abuse is discussed. Since progress in developing pharmacotherapies for treating cocaine addiction in humans is likely to come from understanding its mechanisms of action, it is clear that further research on the effects of cocaine in humans and animals will be critical to the medication development effort. A shortened version of this paper was presented at the Satellite Meeting of the International Society for Neurochemistry on “Cellular and Molecular Mechanisms of Drugs of Abuse: Cocaine and Methamphetamine” held on August 19–20, 1993 in Nice, France.     

Polymorphisms of XRCC1 and gastric cancer susceptibility: a meta-analysis

Studies investigating the association between X-ray repair cross-complementing gene 1 (XRCC1) polymorphisms and gastric cancer (GC) risk have reported conflicting results. We performed a meta-analysis of published case–control and cohort studies to better compare results between studies. Published literature from PubMed, EMBASE, and China National Knowledge Infrastructure were retrieved. 18 studies with 3,915 GC cases and 6,759 controls were selected. For XRCC1 Arg194Trp polymorphism, we only found the Trp/Trp genotype carriers might be at high risk of GC (TT vs. CC+CT: OR = 1.31, 95%CI = 1.04–1.65). When stratifying for ethnicity, the results showed there was a significant difference in genotype distribution between GC cases and controls among Asians (especially, in Chinese population), but not among Caucasians. When stratifying for control sources, significant association between Arg194Trp polymorphism and GC risk was only observed in the hospital-based controls’ subgroup (TT vs. CC+CT: OR = 1.45, 95%CI = 1.13–1.87). Additionally, no significant association was detected in the gastric cardia cancer’s subgroup. The results of the overall meta-analysis did not suggest any association between Arg280His/Arg399Gln polymorphisms and GC susceptibility for all genetic models. There was no evidence for the association between these two gene polymorphisms and GC risk in subgroup analyses based on study design, ethnicity, country, tumor location, Helicobacter pylori infection and the Lauren’s classification of GC. In conclusion, XRCC1 Arg194Trp homozygous mutant genotype (Trp/Trp) was found to be associated with increased risk of GC.     

Acupuncture Therapy for Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

ObjectiveAcupuncture has commonly been used in China, either alone or in combination with Western medicine, to treat sudden sensorineural hearing loss (SSHL). The purpose of this systematic review is to assess the efficacy and safety of acupuncture therapy for patients with SSHL.MethodsWe searched PubMed, the Cochrane Library, Embase, China National Knowledge Internet (CNKI), Database for Chinese Technical Periodicals (VIP), and Chinese Biomedical literature service system (SinoMed) to collect randomized controlled trials of acupuncture for SSHL published before July 2014. A meta-analysis was conducted according to the Cochrane systematic review method using RevMan 5.2 software. The evidence level for each outcome was assessed using the GRADE methodology.ResultsTwelve trials involving 863 patients were included. A meta-analysis showed that the effect of manual acupuncture combined with Western medicine comprehensive treatment (WMCT) was better than WMCT alone (RR 1.33, 95%CI 1.19–1.49) and the same as the effect of electroacupuncture combined with WMCT (RR 1.33, 95%CI 1.19–1.50). One study showed a better effect of electroacupuncture than of WMCT (RR 1.34, 95%CI 1.24–1.45). For mean changes in hearing over all frequencies, the meta-analysis showed a better effect with the combination of acupuncture and WMCT than with WMCT alone (MD 10.85, 95%CI 6.84–14.86). However, the evidence levels for these interventions were low or very low due to a high risk of bias and small sample sizes in the included studies.ConclusionThere was not sufficient evidence showing that acupuncture therapy alone was beneficial for treating SSHL. However, interventions combining acupuncture with WMCT had more efficacious results in the treatment of SSHL than WMCT alone. Electroacupuncture alone might be a viable alternative treatment besides WMCT for SSHL. However, given that there were fewer eligible RCTs and limitations in the included trials, such as methodological drawbacks and small sample sizes, large-scale RCTs are required to confirm the current findings regarding acupuncture therapy for SSHL.