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BackgroundAlcohol use disorder (AUD) has become a significant global factor in various diseases. As a non-pharmacological therapy, certain therapeutic potential has been found in acupuncture; however, in-depth mechanistic studies related to acupuncture for patients with AUD are still insufficient.MethodsBased on a randomized control design and a multi-omics analysis plan, this protocol details the recruitment (42 AUD patients), group allocation (21 in acupuncture group vs. 21 in sham acupuncture group), intervention and follow-up (replacement drugs as a normal treatment, 2 weeks acupuncture duration, and 3 month follow-up), and data collection and analytical processes. For the clinical outcomes, in addition to the time required for alcohol withdrawal symptoms to subside as the primary outcome, changes in the alcohol withdrawal symptoms, alcohol craving, mood dysfunction, sleep disorder, fatigue, self-efficacy, gastrointestinal symptoms, the quality of life, and the relapse outcomes will be compared between the groups to confirm the acupuncture clinical effectiveness on alcohol withdraw. The gut microbiome and the fecal metabolomics will also be assessed to explore the association of the structure and the function of gut microflora and the mediation of acupuncture effect on AUD fully utilizing gut microflora multi-modal data and clinical information, via the combination of multi-omics methods, feature screening algorithms and appropriate models.DiscussionThe results of this study may help to strengthen clinical evidence of the mechanism of acupuncture intervention in patients with AUD, through understanding of the regulatory mechanism of acupuncture in the gut microbiome and its metabolism as well as AUD-related clinical manifestations.Trial registrationChinese Clinical Trial Registry ChiCTR2200058120. Registered on 24 Mar 2022.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive motor neuron damage. Due to the complexity of the ALS, so far the etiology and underlying pathogenesis of sporadic ALS are not completely understood. Recently, many studies have emphasized the role of inflammatory networks, which are comprised of various inflammatory molecules and proteins in the pathogenesis of ALS. Inflammatory molecules and proteins may be used as independent predictors of patient survival and might be used in patient stratification and in evaluating the therapeutic response in clinical trials. This review article describes the latest advances in various inflammatory markers in ALS and its animal models. In particular, this review discusses the role of inflammatory molecule markers in the pathogenesis of the disease and their relationship with clinical parameters. We also highlight the advantages and disadvantages of applying inflammatory markers in clinical manifestations, animal studies, and drug clinical trials. Further, we summarize the potential application of some inflammatory biomarkers as new therapeutic targets and therapeutic strategies, which would perhaps expand the therapeutic interventions for ALS.

ObjectiveTo determine the diagnostic accuracy of serological tests for coronavirus disease-2019 (COVID-19).MethodsPubMed, Embase and the Cochrane Library were searched from January 1 2020 to September 2 2022. We included studies that measured the sensitivity, specificity or both qualities of a COVID-19 serological test and a reference standard of a viral culture or reverse transcriptase polymerase chain reaction (RT–PCR). The risk of bias was assessed by using quality assessment of diagnostic accuracy studies 2 (QUADAS-2). The primary outcomes included overall sensitivity and specificity, as stratified by the methods of serological testing [enzyme-linked immunosorbent assays (ELISAs), lateral flow immunoassays (LFIAs) or chemiluminescent immunoassays (CLIAs)] and immunoglobulin classes (IgG, IgM, or both). Secondary outcomes were stratum-specific sensitivity and specificity within the subgroups, as defined by study or participant characteristics, which included the time from the onset of symptoms, testing via commercial kits or an in-house assay, antigen target, clinical setting, serological kit as the index test and the type of specimen for the RT–PCR reference test.ResultsEight thousand seven hundred and eighty-five references were identified and 169 studies included. Overall, we judged the risk of bias to be high in 47.9 % (81/169) of the studies, and a low risk of applicability concerns was found in 100% (169/169) of the studies. For each method of testing, the pooled sensitivity of the ELISAs ranged from 81 to 82%, with sensitivities ranging from 69 to 70% for the LFIAs and 77% to 79% for the CLIAs. Among the evaluated tests, IgG (80–81%)-based tests exhibited better sensitivities than IgM-based tests (66–68%). IgG/IgM-based CLIA had the highest sensitivity [87% (86–88%)]. All of the tests displayed high specificity (97–98%). Heterogeneity was observed in all of the analyses. The detection of nucleocapsid protein (77–80%) as the antigen target was found to offer higher sensitivity results than surface protein detection (66–68%). Sensitivity was higher in the in-house assays (78–79%) than in the commercial kits (47–48%).ConclusionAmong the evaluated tests, ELISA and CLIA tests performed better in terms of sensitivity than did the LFIA. IgG-based tests had higher sensitivity than IgM-based tests, and combined IgG/IgM test-based CLIA tests had the best overall diagnostic test accuracy. The type of sample, serological kit and timing of use of the specific tests were associated with the diagnostic accuracy. Due to the limitations of the serological tests, other techniques should be quickly approved to provide guidance for the correct diagnosis of COVID-19.

IntroductionMultiple myeloma (MM) is still an incurable plasma cell malignancy. The efficacy of immunotherapy on MM remains unsatisfactory, and the underlying molecular mechanisms still are not fully understood.MethodsIn this study, we delineated the dynamic features of immune cell in MM bone marrow (BM) along with elevated tumor cell infiltration by single-cell RNA sequencing (scRNA-seq), and investigated the underlying mechanisms on dysfunction of immune cells associated with myelomagenesis.ResultsWe found that immune cells were activated in those patients with low infiltration of tumor cells, meanwhile suppressed with elevated infiltration of MM cells, which facilitated MM escaping from immune surveillance. Besides PD-1, abnormal expression of PIM kinases, KLRB1 and KLRC1 were involved in the defect of immune cells in MM patients. Importantly, we found aberrant metabolic processes were associated with the immunosuppressive microenvironment in MM patients. Disordered amino acid metabolism promoted the dysfunction of cytotoxicity CD8 T cells as well as lipid metabolism disorder was associated with the dysregulation of NK and DCs in MM. As metabolic checkpoints, PIM kinases would be potential effective strategies for MM immunotherapy.DiscussionIn summary, redressing the disordered metabolism should be the key points to get promising effects in immune-based therapies.

BackgroundPatients with MMT often face difficulties such as sleep disturbance, headaches, and difficulty in complete abstinence from drugs. Research has shown that acupuncture can mitigate side effects while attenuating methadone dependence. It also has a synergistic and attenuated effect on methadone maintenance treatment (MMT). Exploring the predictors of the efficacy of acupuncture intervention in MMT might help clinicians and patients promote acupuncture-assisted participation in MMT, and improve clinical treatment strategies for MMT.ObjectiveTo describe the effect of potential predictors on MMT after acupuncture intervention by building a decision-tree model of data from A Clinical Study of Acupuncture-assisted MMT.Design, setting, and participantsIn this randomized controlled trial, 135 patients with MMT underwent acupuncture at the Substance Dependence Department of Guangzhou Huiai Hospital in Guangzhou, Guangdong Province, China.InterventionA total of 135 patients were 1:1 randomly assigned to either an acupuncture plus routine care group (acupuncture plus methadone) or a routine group (methadone only) for 6 weeks, and followed up for 10 weeks. Sex, age, education level, route of previous opioid use, years of opioid use, and MMT time were recorded before the trial.Outcome measurements and statistical analysisAll analyses were based on the intention-to-treat (ITT) population. The two decision tree models used the change of methadone dosage and the VAS score for opioid desire as response variables, respectively, and the evaluation criteria were positive effect (decreased by ≥20%) and no effect (decreased by ResultsThe overall accuracy of methadone reduction and psychological craving VAS scoring decision trees were 0.63 and 0.74, respectively. The Methadone Dosage Efficacy decision tree identified years of opioid use (weight = 0.348), acupuncture (weight = 0.346), and route of previous opioid use (weight = 0.162) as key features. For the VAS Score decision tree, acupuncture (weight = 0.618), MMT time (weight = 0.235), and age (weight = 0.043) were the important features.ConclusionExploratory decision tree analysis showed that acupuncture, years of opioid use, route of previous opioid use, MMT time, and age were key predictors of the MMT treatment. Thus, acupuncture-assisted MMT strategy should consider the relevant influencing factors mentioned above.Patient summaryUnderstanding patient characteristics and the impact of acupuncture regimens on methadone dosage reduction in MMT patients may help physicians determine the best treatment regimen for patients. An analysis of data from our clinical trial showed that acupuncture, years of opioid use, route of previous opioid use, age, and MMT time were key predictors of progressive recovery in patients with MMT. Eligible patients may benefit most from the MMT rehabilitation that reduces consumption and psychological cravings for methadone.Clinical trial registrationhttp://www.chictr.org.cn/index.aspx, identifier: ChiCTR1900026357.

BackgroundNicotine dependence is an addictive behavioral disease facilitated by habitually smoking cigarettes. In many countries, acupuncture and auricular acupressure have attracted growing attention as complementary or alternative treatments for smoking cessation; however, there is a lack of rigorous randomized, controlled studies evaluating the combination of these two interventions specifically for smoking cessation. The aim of this study is to evaluate the efficacy and safety of using acupuncture combined with auricular acupressure (A&AA) to increase the rates of smoking cessation and ultimately reduce the rates of relapse.MethodsThis is a multicentre, prospective, parallel, randomized, controlled trial. A total of 360 patients with severe nicotine dependence will be randomized into test (A&AA) or control (nicotine replacement therapy, NRT) groups. The test group will be treated with A&AA twice weekly, while the control group will use an NRT patch daily. All treatments will be administered for 8 weeks, with a follow-up period of 4 months. The primary outcome will be the smoking abstinence rate at week 24, with a combined safety assessment. The secondary outcomes will be smoking cessation rates at other timepoints, saliva cortisone test results, and scores on the Fagerstrom Test for Nicotine Dependence, the Autonomy over Tobacco Scale, the Hamilton Anxiety Rating Scale, the Self-rating Anxiety Scale, and the Pittsburgh Sleep Quality Index. The cost of treatment will also be used to evaluate the economic effects of different smoking cessation interventions. Statistical analysis on the data collected from both the intention-to-treat (all randomly assigned patients) and per-protocol (patients who complete the trial without any protocol deviations) patients, will be performed using the statistical software package, IBM SPSS 27.0.DiscussionThis study will provide rigorous clinical evidence evaluating the efficacy and safety of using A&AA as a smoking cessation therapy.Trial registrationChinese Clinical Trial Registry (Registration number: ChiCTR1900028371).

Objectives: Opioid dependence has been a threat to public health for hundreds of years. With the increasing number of studies on acupuncture-related therapies for opioid dependence patients receiving methadone maintenance treatment (MMT), its effect of acupuncture therapy in treating MMT patients remains controversial. Therefore, we conducted a multiple-treatments meta-analysis, and incorporated both direct and indirect comparisons, in order to discover the most effective treatment for opioid dependence patients receiving MMT.Methods: Five English databases and three Chinese databases were searched from its inception to August 20, 2020, in order to compare the effects of acupuncture-related therapies and MMT, which was summarized as Western medicine (WM) in the following texts. The quality of studies was assessed according to Cochrane's risk of bias tool 5.1.0, and a pair-wise meta-analysis, cumulative meta-analysis, and the network meta-analysis was performed using the R software (Version 3.6.1) and STATA (Version 14.0). The primary outcome was the effective rate, which was calculated by the ratio of detoxifying patients to the total. The secondary outcome was the Modified Himmelsbach Opiate Withdrawal Scale (MHOWS).Results: A total of 20 trials were included, which consisted of comparisons among WM, traditional Chinese medicine (TCM), and the four types of acupuncture, namely, manual acupuncture (MA), electro-acupuncture (EA), auricular acupuncture (AA), and transcutaneous electrical acupoint stimulation (TEAS). Though none of the trials were at low risk of bias. In the pair-wise meta-analysis, no statistically significant differences were observed in terms of the effective rate. Furthermore, MA was more efficacious than WM, EA, and TEAS in MHOWS, with mean differences (MDs) of (−8.59, 95% CI: −15.96 to −1.23, P < 0.01), (−6.15, 95% CI: −9.45 to −2.85, P < 0.05), and (−10.44, 95% CI: −16.11 to −4.77, P < 0.05), respectively. In the network meta-analysis, MA was more effective than WM (RR: 1.40, 95% CI: 1.05 to 1.99) on the effective rate, and (MD: −5.74, 95% CI: −11.60 to −0.10) on MHOWS. TEAS was more effective than WM (MD: −15.34, 95% CI: −27.34 to −3.46) on MHOWS. Synthetically, MA had the highest probability to rank first in treating opioid dependence.Conclusions: The existing evidence shows that acupuncture related-therapies may effectively be used for treating patients receiving MMT, and that manual acupuncture may be the best choice for opioid dependence among all kinds of acupuncture-related therapies. Nevertheless, reducing the relapse and promoting the recovery of opioid dependence need more efforts from not only the medical industry but also government support, security system, and educational popularization. To strengthen the assurance of acupuncture-related therapies in the treatment of opioid dependence, we expected that clinical trials with high quality would be conducted, to provide more confident evidence.