Antitumor effect of luteolin proven by patient-derived organoids of gastric cancer.

Luteolin (Lut) has been shown to inhibit gastric cancer (GC); however, its efficacy compared to other clinical drugs has not been examined in human samples. This study aimed to elucidate the antitumor activity of Lut in GC patient-derived organoids (PDOs). PDOs were established from GC cancer tissues, and the characterization of tissues and PDOs was performed using whole-exome sequencing. Drug sensitivity tests were performed by treating PDOs with Lut, norcantharidin (NCTD), and carboplatin (CP). RNA sequencing of PDOs was performed to elucidate the antitumor mechanism of Lut, which was further verified in three GC cell lines. Eleven PDOs were successfully constructed, and were highly consistent with the pathophysiology and genetic changes in the corresponding tumors. The IC50s of Lut, NCTD, and CP of PDOs were 27.19, 23.9, and 37.87 µM, respectively. Lut treatment upregulated FOXO3, DUSP1, and CDKN1A expression and downregulated IL1R1 and FGFR4 expression in GC cell lines, which was consistent with the results of PDOs. We demonstrate that Lut exerted stronger antitumor effects than CP, but a similar effect to that of NCTD, which was obtained in an in vitro PDO system. Additionally, Lut exerted varying degrees of antitumor effects against the PDOs, thereby indicating that PDO may be a useful preclinical drug screening tool for personalized treatment.

Therapeutic Effects of Huazhuojiedu Decoction on Precancerous Lesions of Gastric Cancer by Regulating Mitophagy.

This research aims to explore the therapeutic effect and potential mechanisms of Huazhuojiedu decoction (HZJD) for alleviating precancerous lesions of gastric cancer (PLGC) both in vivo and in vitro. HZJD is a traditional Chinese herbal formula consisting of 11 herbs. Sprague-Dawley (SD) rats were randomly divided into four subgroups: control group, model group, positive drug group, and HZJD group. Hematoxylin-eosin (H&E) staining, high iron diamine-alcian blue (HID-AB) staining, alcian blue-periodic acid Schiff (AB-PAS) staining, immunohistochemistry, immunofluorescence, RT-qPCR, and Western blot assays were performed after 10 weeks of HZJD treatment. In vitro, the cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were used to detect cell proliferation. RT-qPCR and Western blot assays were performed to evaluate mitophagy levels. The results indicated that HZJD could retard the pathological progression in PLGC rats and reduce PLGC cell proliferation. Treatment with HZJD significantly increased the mRNA and protein expression levels of Sirt3, Foxo3a, Parkin, and LC3 II/I, while decreasing the mRNA and protein expression levels of p62 and Tomm20. HZJD was found to have the ability to reverse the decline in mitophagy activity both in vivo and in vitro. In conclusion, the study assessed the impact of HZJD and provided evidence regarding its potential molecular mechanism.

Acupuncture for Patients With Chronic Tension-Type Headache: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Whether acupuncture is effective for chronic tension-type headache (CTTH) is inconclusive. We aimed to examine the effectiveness of acupuncture with a follow-up period of 32 weeks. METHODS: We conducted a randomized controlled trial, and 218 participants who were diagnosed with CTTH were recruited from June 2017 to September 2020. The participants in the intervention group received 20 sessions of true acupuncture (TA group) over 8 weeks. The acupuncture treatments were standardized across participants, and each acupuncture site was needled to achieve deqi sensation. Each treatment session lasted 30 minutes. The participants in the control group received the same sessions and treatment frequency of superficial acupuncture (SA group)-defined as a type of sham control by avoiding deqi sensation at each acupuncture site. The main outcome was the responder rate at 16 weeks after randomization (week 16) and was followed up at week 32. A responder was defined as a participant who reported at least a 50% reduction in the monthly number of headache days (MHDs). RESULTS: Our study included 218 participants (mean age: 43.1 years, mean disease duration: 130 months, MHDs: 21.5 days). The responder rate was 68.2% in the TA group (n=110) versus 48.1% in the SA group (n=108) at week 16 (odds ratio, 2.65; 95%CI, 1.5 to 4.77; p<0.001); and it was 68.2% in the TA group versus 50% in the SA group at week 32 (odds ratio, 2.4; 95%CI, 1.36 to 4.3; p<0.001). The reduction in MHDs was 13.1±9.8 days in the TA group versus 8.8±9.6 days in the SA group at week 16 (mean difference, 4.3 days; 95%CI, 2.0 to 6.5; p<0.001), and the reduction was 14±10.5 days in the TA group versus 9.5±9.3 days in the SA group at week 32 (mean difference, 4.5 days; 95%CI, 2.1 to 6.8; p<0.001). Four mild adverse events were reported; three in the TA group versus one in the SA group. CONCLUSION: The 8-week TA treatment was effective for the prophylaxis of CTTH. Further studies might focus on the cost-effectiveness of the treatment. TRIAL: Registration Information: ClinicalTrials.gov: NCT03133884 (https://clinicaltrials.gov/ct2/show/NCT03133884) CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that acupuncture (achieving deqi sensation) reduces mean headache days (per month) in patients with chronic tension-type headache.

Traditional Chinese medicine for precancerous lesions of gastric cancer: A review.

Gastric cancer (GC) is the fifth most common type of cancer and the third leading cause of death due to cancer worldwide. The gastric mucosa often undergoes many years of precancerous lesions of gastric cancer (PLGC) stages before progressing to gastric malignancy. Unfortunately, there are no effective Western drugs for patients with PLGC. In recent years, traditional Chinese medicine (TCM) has been proven effective in treating PLGC. Classical TCM formulas and chemical components isolated from some Chinese herbal medicines have been administered to treat PLGC, and the main advantage is their comprehensive intervention with multiple approaches and multiple targets. In this review, we focus on recent studies using TCM treatment for PLGC, including clinical observations and experimental research, with a focus on targets and mechanisms of drugs. This review provides some ideas and a theoretical basis for applying TCM to treat PLGC and prevent GC.

The therapeutic effect of Huazhuojiedu decoction on precancerous lesions in a gastric cancer model via the regulation of lnc 517368.

ETHNOPHARMACOLOGICAL RELEVANCE: Huazhuojiedu decoction, a Chinese herbal preparation, has been proven to be clinically effective in treating precancerous lesions in gastric cancer (PLGC). This formula is optimized from a classic formula called "Ganluxiaodu Dan." Although some experiments have shown that Huazhuojiedu decoction is effective against PLGC, the mechanism remains unclear. AIM OF THE STUDY: To investigate the treatment of PLGC with Huazhuojiedu decoction from the perspective of lncRNA in vitro and in vivo. MATERIALS AND METHODS: A PLGC rat model was prepared and randomly divided into a Huazhuojiedu decoction group (HG), a vitacoenzyme group (VG), a model group (MG), and a normal group (CG). Each group was given a corresponding concentration of medicine and distilled water for 10 weeks. The pathological changes in the gastric mucosa were observed by hematoxylin-eosin staining (HE). High-throughput sequencing was performed to detect the differentially expressed lncRNAs in the HG, MG, and CG. Quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) was used to verify differentially expressed lncRNAs, and rat-human homology information was obtained from the University of California, Santa Cruz (UCSC) Genome Database. Human gastric mucosal epithelial cells (GES-1) were used to prepare precancerous lesions of gastric cancer cells (MC). A Huazhuojiedu decoction drug-containing serum was prepared to treat the MC cells. The effects of the Huazhuojiedu decoction and the lncRNA ENST00000517368 (lnc 517368) knockdown or overexpression on PLGC cell proliferation and apoptosis were evaluated in vitro using CCK-8, flow cytometry, and RT-qPCR. RESULTS: The HE results showed that gastric mucosal pathology was significantly improved in the HG. High-throughput sequencing results showed that compared with the CG, 91 lncRNAs upregulated in the MG were restored and downregulated in the HG (P < 0.05), and 115 lncRNAs downregulated in the MG were restored and upregulated in the HG (P < 0.05). The results of RT-qPCR were consistent with the sequencing results. The differentially expressed genomic rat lncRNA ENSRNOT00000079699 is homologous to human lnc 517368. In cell experiments, high expression of lnc 517368 promoted proliferation and reduced apoptosis in PLGC cells, while the Huazhuojiedu decoction reduced the expression of lnc 517368 and improved cell morphology. CONCLUSIONS: Huazhuojiedu decoction inhibited cell proliferation and promoted apoptosis in PLGC cells, and its effect may be partially dependent on the downregulation of lnc 517368.

Identifying Chinese Medicine Patterns of Tension-Type Headache and Understanding Its Subgroups.

Tension-type headache (TTH) is common among adults. Individualized management strategies are limited due to lack of understanding of subtypes of TTH. Chinese medicine (CM) uses the pattern differentiation approach to subtype all health conditions. There is, however, a lack of evidence-based information on CM patterns of TTH. This study aimed to identity common CM patterns of TTH. TTH sufferers were invited for a survey, consisting of a validated Chinese Medicine Headache Questionnaire (CMHQ), Migraine Disability Assessment Test, and Perceived Stress Scale. The CMHQ consisted of information about headache, aggravating and relieving factors, and accompanying symptoms. Principal component analysis was used for factor extraction and TwoStep cluster analyses for identifying clusters. ANOVA was used to compare cluster groups with disability and stress. In total, 170 eligible participants took part in the survey. The commonest headache features were continuous pain (64%); fixed location (74%); aggravated by overwork (74%), stress (74%), or mental strain (70%); and relieved by sleeping (78%). The commonest nonpain symptoms were fatigue (71%) and neck stiffness (70%). Four clusters, differing in their key signs and symptoms, could be assigned to three different CM patterns including ascendant hyperactivity of liver yang (cluster 1), dual qi and blood deficiency (cluster 2), liver depression forming fire (cluster 3), and an unlabelled group (cluster 4). Additionally, over 75% participants in clusters 1 and 2 have episodic TTH, over one-third participants in cluster 3 have chronic TTH, and a majority of participants in cluster 4 have infrequent TTH. The three patterns identified also differed in levels of disability and some elements of coping as measured with PSS. The three CM patterns identified are common clinical presentations of TTH. The new information will contribute to further understanding of the subtypes of TTH and guide the development of targeted intervention combinations for clinical practice and research.

Determination of the protective effects of Hua-Zhuo-Jie-Du in chronic atrophic gastritis by regulating intestinal microbiota and metabolites: combination of liquid chromatograph mass spectrometer metabolic profiling and 16S rRNA gene sequencing.

BACKGROUND: Hua-Zhuo-Jie-Du (HZJD), a Chinese herbal prescription consisting of 11 herbs, is commonly used in China to treat chronic atrophic gastritis (CAG). We aimed to determine the effect of HZJD on the microbiome-associated metabolic changes in CAG rats. METHODS: The CAG rat models were induced by 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) combined with irregular fasting and 2% sodium salicylate, which was intragastrically administrated in fasted animals for 24 weeks. The CAG rats in the Chinese medicine (CM) group were administered a daily dose of 14.81 g/kg/day HZJD, and the vitacoenzyme (V) group were administered a daily dose of 0.08 g/kg/day vitacoenzyme. All animals were treated for 10 consecutive weeks, consecutively. Hematoxylin and eosin (H&E) staining was used to assess the histopathological changes in the gastric tissues. An integrated approach based on liquid chromatograph mass spectrometer (LC-MS) metabolic profiling combined with 16S rRNA gene sequencing was carried out to assess the effects of HZJD on CAG rats. Spearman analysis was used to calculate the correlation coefficient between the different intestinal microbiota and the metabolites. RESULTS: The H&E results indicated that HZJD could improve the pathological condition of CAG rats. The LC-MS results indicated that HZJD could significantly improve 21 gastric mucosal tissue perturbed metabolites in CAG rats; the affected metabolites were found to be involved in multiple metabolic pathways, such as the central carbon metabolism in cancer. The results of 16S rRNA gene sequencing indicated that HZJD could regulate the diversity, microbial composition, and abundance of the intestinal microbiota of CAG rats. Following HZJD treatment, the relative abundance of Turicibacter was increased, and the relative abundance of Desulfococcus and Escherichia were decreased in the CM group when compared with the M group. Spearman analysis revealed that perturbed intestinal microbes had a strong correlation with differential metabolites, Escherichia exhibited a negative correlation with l-Leucine, Turicibacter was negatively correlated with urea, and Desulfococcus exhibited a positive correlation with trimethylamine, and a negative correlation with choline. CONCLUSIONS: HZJD could protect CAG by regulating intestinal microbiota and its metabolites.

Acupoints for Tension-Type Headache: A Literature Study Based on Data Mining Technology.

OBJECTIVES: This study aimed to explore the characteristics and principles of acupoints, which were applied for treating tension-type headache (TTH). METHODS: Four databases were searched for the literature studies of treating TTH with acupuncture and moxibustion up to September 1, 2020. Titles, journals, authors, key words, interventions, main acupoints, and outcomes of the included literature studies were extracted and inputted into the self-established Data Excavation Platform of Acupoint Specificity for analysis. RESULTS: In total, 128 papers containing 137 prescriptions, 89 meridian acupoints, and 7 extraordinary acupoints of treating TTH with acupuncture and moxibustion were included. The total frequency of acupoints' application was 763 times. Fengchi (GB20), Baihui (GV20), Taiyang (EX-HN5), Hegu (LI4), and Taichong (LR3) were used most frequently. The acupoints in Yang meridians were utilized more than those in Yin meridians (66.1% vs. 17.8%), and the acupoints in the Gallbladder Meridian of Foot Shaoyang were applied most commonly. 59.9% (457/763) of the applied acupoints were on the head, face, and neck, and 31.7% (242/763) were on the four limbs. Additionally, the proportion of specific acupoints' application was 78.2% (597/763). CONCLUSIONS: The prescription of Fengchi (GB20), Baihui (GV20), Taiyang (EX-HN5), Hegu (LI4), and Taichong (LR3) might be relatively reasonable in clinical practices of treating TTH with acupuncture, which should be verified in further studies.

Integrating Network Pharmacology and Experimental Validation to Investigate the Mechanisms of Huazhuojiedu Decoction to Treat Chronic Atrophic Gastritis.

BACKGROUND: Chronic atrophic gastritis (CAG) is an important stage in the normal gastric mucosa's transformation into gastric cancer. Huazhuojiedu decoction (HZJD), a Chinese herbal preparation, has proven clinically effective to treat CAG. However, few studies have explored the mechanism of HZJD in CAG treatment. PURPOSE: This study aimed to shed light on the mechanisms underlying HZJD decoction CAG treatment using a network pharmacology approach and experimental validation. METHODS: The active components of HZJD decoction were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Their targets were predicted through the SwissTargetPrediction database. Disease targets were screened using the GeneCards database. The disease and drug prediction targets were intersected to select the common potential therapeutic targets, which then were input into the Search Tool for the Retrieval of Interacting Genes to build a protein-protein interaction network. The "herb-compound-target-disease" and the "herb-target-pathway" network diagrams were constructed in Cytoscape 3.3.0. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of effective targets were performed using the Database for Annotation, Visualization, and Integrated Discovery. Finally, the core targets were preliminarily verified by CAG rat model. The gastric mucosa's histopathological changes were observed via hematoxylin-eosin staining. The expressions of MAPK1, AKT1, TNF, VEGFA, and EGFR were detected by western blot and quantitative real-time reverse transcription-polymerase chain reaction. RESULTS: A total of 155 nodes, including 20 putative targets of HZJD decoction, were selected as core hubs based on topological importance and were closely associated with the regulation of cell proliferation, apoptotic process, and cancer-related pathways (AKT1, TNF, VEGFA, and EGFR) in CAG. Further animal experiments showed that the expression of AKT1 in CAG rats was significantly increased, which was suppressed by HZJD decoction. TNF and VEGFA expression increased in the model group, but did not change in the HZJD group. MAPK1 and EGFR expression showed no significant differences among control, model, and HZJD groups. CONCLUSION: Taken together, the results suggest that the components of HZJD decoction can alleviate and prevent the severity of gastric precancerous lesions via AKT1 inhibition in CAG.

Evaluating influential factors of acupuncture for tension-type headache: A protocol for systematic review and meta-analysis.

BACKGROUND: Acupuncture has been recommended for the treatment of tension-type headache (TTH). However inconsistent findings on the efficacy of acupuncture impacts on the uptake of this effective therapy for TTH. This systematic review aims to 1) Evaluate the efficacy of acupuncture for TTH; and 2) Clarify the factors contributing to conflicting findings through conducting a meta-analysis and meta-regression of randomized controlled trials. METHODS: Comprehensive literature search will be performed on PubMed, EMBASE, CINAHL, ProQuest, Cochrane Central Register of Controlled Trials, Acubriefs, ScienceDirect, Scopus, AMED, and 4 leading Chinese databases of the China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Data, and CBM (SinoMed). We will include Randomized controlled Trials or controlled trials of patients with TTH that compared acupuncture with sham interventions. The primary outcome is the number of days on headache (within 4 weeks) at the end of the treatment and follow-ups. Secondary outcomes include intensity of pain, frequency of attack, and the adverse effects resulting from the intervention. We will use pre-defined sub-group analysis and meta-regression to explore the influential factors of acupuncture effects. Heterogeneity assessment will be performed before carrying out meta-analysis, whereas the subgroup analyses and meta-regression will be used in verifying the possible factors of heterogeneity when significant heterogeneity detected. RESULTS: Review Manager 5.3 software will be used for meta-analysis. The synthesis will be performed by generating forest plots. Meta-regression will be used to understand influential factors for acupuncture in patients with TTH. CONCLUSION: By utilizing techniques of meta-regression, this study will provide evidence toward to a more focused understanding of influential factors for acupuncture in patients with TTH. This systematic review will provide quality evidence for the optimization of acupuncture therapeutic regimen. It will facilitate the development of clinical practice guideline on acupuncture for TTH.

Pregnancy outcomes and the dose-related effects of acupuncture therapies in women undergoing in vitro fertilization: A protocol for systematic review and meta-analysis.

BACKGROUND: Previous studies have given an inaccurate assessment of the role of acupuncture in in vitro fertilization (IVF). We will use acupuncture doses as an entry point, discussing the dose-related effects of acupuncture therapy in women undergoing IVF. METHODS: This study will search the following database: EMBASE, PubMed, Web of Science, the Cochrane Central Register of Controlled Trials (CENTRAL), and 4 Chinese databases. All databases will be searched from the date of database establishment to January 31, 2019. In addition, we will search possible studies which were included in previous meta-analyses. The primary outcomes are the clinical pregnancy rate (CPR) and the live birth rate (LBR). The secondary outcomes involved the biochemical pregnancy rate (BPR), the ongoing pregnancy rate (OPR), serum hormone level, the incidence of ovarian hyper-stimulation syndrome (OHSS), the cycle cancellation rates, and adverse events (AEs). After checking and integrating the raw data, we will use a 2-step to conduct the meta-analysis. Firstly, we will assess the effect of acupuncture on in vitro fertilization and embryo transfer (IVF-ET). Secondly, the meta-analysis will be performed for studies with similar total number of treatment sessions to investigate the dose-related effects of acupuncture. RevMan V.5.3 statistical software will be used for meta-analysis. If it is not appropriate for a meta-analysis, then a descriptive analysis will be conducted. RESULTS: This study will investigate the relationship between pregnancy outcomes and the doses of acupuncture therapy in women undergoing IVF, and answer whether a higher-doses of acupuncture treatment will contribute to a better outcome of IVF-ET. CONCLUSION: The funding of this meta-analysis may provide convincing evidence for clinicians, benefitting more patients who crave children. INPLASY REGISTRATION NUMBER: INPLASY202070072.

Electroacupuncture on ST36 and GB39 Acupoints Inhibits Synovial Angiogenesis via Downregulating HIF-1α/VEGF Expression in a Rat Model of Adjuvant Arthritis.

Introduction. The hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) play a key role in synovial angiogenesis in rheumatoid arthritis (RA). Therefore, this study aimed to test the hypothesis that electroacupuncture (EA) may inhibit RA synovial angiogenesis via HIF-1α/VEGF expression. Methods. Sprague-Dawley rats were randomly distributed to 4 groups: control, adjuvant arthritis (AA), AA+electroacupuncture (AA+EA), and AA+sham EA groups. AA model was induced by injection of Freund's complete adjuvant in bilateral hind footpad. 3 days after injection, EA was delivered to the acupoints Zusanli (ST 36) and Xuanzhong (GB 39) once every two days for a total of 8 times in the AA+EA group, while sham EA treatment was applied in the AA+sham EA group. The arthritis score, paw volume, and H&E staining for each animal were measured. CD34 expression in synovial tissue of ankle joint was observed by immunohistochemistry. HIF-1α and VEGF mRNA and protein levels in synovial tissue were determined by real-time quantitative PCR and Western blot, respectively. Results. Compared with rats in AA group, EA stimulation significantly decreased arthritis scores, paw volume, and pathological damage of synovial tissues. Moreover, EA markedly suppressed the synovial angiogenesis of AA rats, as evidenced by reduced CD34 positive expression. Furthermore, EA significantly reduced HIF-1α and VEGF mRNA and protein levels in synovial of AA rats. Finally, the CD34 expression in synovial tissue was positively correlated with HIF-1α and VEGF protein levels. Conclusion. EA on ST36 and GB39 acupoints can effectively inhibit synovial angiogenesis in the AA rat model via downregulating HIF-1α/VEGF expression.

Cinaciguat in combination with insulin induces a favorable effect on implant osseointegration in type 2 diabetic rats.

The osseointegration process of implant is seriously impaired in type 2 diabetes mellitus (T2DM) that causes high failure rate, and insufficiency exists in current insulin therapy, creating a demand for new bone-synergistic agent. Cinaciguat, a novel type of soluble guanylate cyclase (sGC) activator, plays a vital role in glucose metabolism, inflammation control and bone regeneration. We hypothesized that the combined application of cinaciguat and insulin could reverse poor implant osseointegration in diabetes. To test this hypothesis, streptozotocin-induced diabetic rats were placed implants in the femur, and divided into five groups: control, T2DM, cinaciguat-treated T2DM (7 µg/kg), insulin-treated T2DM (12 IU/kg), cinaciguat plus insulin combination-treated T2DM (7 µg/kg and 12 IU/kg respectively), according to different treatment received. The weight and glucose levels of rats were evaluated at fixed times, and plasma level of cyclic guanosine monophosphate (cGMP) was determined before euthanasia. Three months after therapy, the femurs were isolated for pull-out test, environmental scanning electron microscope observation, microscopic computerized tomography evaluation and various histology analysis. Results revealed that diabetic rats showed the highest blood glucose level and lowest cGMP content, which led to the worst structural damage and least osseointegration. Combined treatment could attenuate the diabetes induced hyperglycemia to be normal, restore the cGMP content, protein kinase G II (PKG II) expression, phosphodiesterase-5 (PDE5) activity and ameliorate the mechanical strength, the impaired bone microarchitecture and osseointegration to the highest level. Meanwhile, monotreatment (insulin or cinaciguat) also showed restorative effect, but less. Our findings demonstrated that the cGMP/PKG II signaling pathway activated by cinaciguat mediated the favorable effects of the combined application on improving implant fixation under T2DM condition.

Non-targeted metabolomics reveals diagnostic biomarker in the tongue coating of patients with chronic gastritis.

Analysis of the properties of the tongue has been used in traditional Chinese medicine for disease diagnosis. Notably, tongue analysis, which is non-invasive and convenient compared with gastroscopy and pathological examination, can be used to assess chronic gastritis (CG). In order to find potential diagnostic biomarkers and study the metabolic mechanisms of the endogenous small molecules in the tongue coating related to CG, a non-targeted metabolomic analysis method was developed using ultra high performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF-MS). It was performed using two different columns in positive and negative ion scanning modes separately. The stability of the samples was evaluated and the age and gender factors of the subjects were excluded to ensure the reliability of the data in this study. Finally, under the four analysis models, 130, 229, 113 and 92 differential compounds were found using multivariate statistical methods respectively. 37 potential biomarkers were putatively identified after removing the duplicate compounds and five potential diagnostic biomarkers were putatively identified by receiver operating characteristic (ROC) curve analysis, including inosine, oleamide, adenosine, N-acetylglucosamine (GlcNAc) and xanthine. The main metabolic pathways associated with CG were purine metabolism, amino acid metabolism, sphingolipid metabolism and energy metabolism, which suggested that oxygen free radicals and energy metabolism were altered in patients with CG. These results provided a potential new basis for the quantitative diagnosis and pathogenesis of CG.

The long-term effect of acupuncture for patients with chronic tension-type headache: study protocol for a randomized controlled trial.

BACKGROUND: The effectiveness of acupuncture for patients with chronic tension-type headache (CTTH) is controversial. In this article, we report the protocol for a randomized controlled trial aiming to evaluate the long-term effect of acupuncture for CTTH, in comparison with superficial acupuncture. DESIGN: A two-armed, parallel-design, patient-assessor blind, randomized controlled trial is underway in China. A total of 218 participants with CTTH will be randomly assigned to the treatment group or the control group in a 1:1 ratio. Participants in the treatment group and control group will receive acupuncture or superficial acupuncture treatments in a fixed prescription of acupoints respectively, for a total of 20 sessions over 8 weeks. The posttreatment follow-up period will be 24 weeks. The primary outcome will be the proportion of responders assessed at week 16 after randomization. The secondary outcomes will include the number of headache days, the mean intensity of headache, the reduction of medication intake, results from the 36-item short form health survey, the Hamilton Depression Scale and the Hamilton Anxiety Scale, the number of participants with adverse events, the expectation value of acupuncture treatment, and the intensity of deqi sensation. The first five secondary outcomes will be assessed or calculated at baseline, and at 4, 8, 12, 16, 20, 24, 28, and 32 weeks after randomization. Moreover, the expectation value will be collected at baseline and at week 8 after randomization, the intensity of deqi sensation will be assessed at 5 minutes after each treatment and adverse events will be summarized at the end of the follow-up period. DISCUSSION: Results from this trial will provide evidence for the long-term effect of acupuncture for CTTH with a long follow-up period. TRIAL REGISTRATION: ClinicalTrial.gov NCT03133884 . Registered on 25 April 2017.

Factors associated with conflicting findings on acupuncture for tension-type headache: qualitative and quantitative analyses.

OBJECTIVES: This study aimed to identify the factors that might have contributed to the conflicting outcomes about the efficacy of acupuncture for tension-type headache (TTH) through systematically reviewing relevant randomized controlled trials. METHODS: Thirteen (13) databases were searched from their inception until August 2010. There were no restrictions on language or year of publication. Included studies were randomized controlled trials comparing real with sham acupuncture, with patient selection guided by the International Headache Classification, and reported headache days. Meta-analyses and subgroup analyses were undertaken to compare the effects of real and sham acupuncture interventions and the effects of acupuncture with various needling techniques and treatment modes. RESULTS: Forty-three (43) studies were retrieved for further assessment from 120 potential studies. Finally, five studies of high methodological quality were included in this review. Standard mean difference (SMD) of the included studies showed no statistical significance between real and sham acupuncture (-0.31; 95% confidence interval [CI] -0.72 to 0.09), however, the heterogeneity among the studies was high (I(2)=81%). Subgroup analyses reduced heterogeneity, and showed that electro-acupuncture (SMD-1.60; 95% CI -2.33 to -0.88) to be more efficacious than manual acupuncture (SMD -0.13; 95% CI -0.41 to 0.14); needle retention with 30 minutes (SMD-0.46; 95% CI -0.87 to -0.06) being better than no needle retention (SMD 0.45; 95% CI -0.11, 1.01); and twice-a-week treatment (SMD -0.46; 95% CI -0.87 to -0.06) was better than once-a-week treatment (SMD 0.45; 95% CI -0.11, 1.01). CONCLUSIONS: Acupuncture stimulation mode, needle retention, and treatment frequency could be important factors contributing to the outcome of acupuncture for TTH. Further studies are warranted to determine treatment parameters to ensure effective translation of RCTs outcomes of acupuncture for patients with TTH.