Clinical Evidence for Association of Acupuncture with Improved Major Depressive Disorder: A Systematic Review and Meta-Analysis of Randomized Control Trials.

INTRODUCTION: Depression is the most significant contributor to non-fatal health reductions worldwide. Acupuncture is the most commonly used complementary alternative therapy to relieve major depressive disorder (MDD) effectively. Nevertheless, the effects of acupuncture for MDD are uncertain. This review aimed to determine the efficacy and safety of acupuncture for MDD. METHODS: Meta-analysis was performed for randomized controlled trials of acupuncture for MDD data from eight databases searched from inception until February 10, 2022. All RCTs with adult participants undergoing acupuncture treatment for MDD were included. The primary outcome measure was the Hamilton rating scale for depression (HAMD). We used random-effects meta-analysis to synthesize the results with a mean difference or odds ratio. Furthermore, the potential heterogeneity was tested through meta-regression/subgroup analyses/sensitive analysis. The quality of evidence for each outcome was assessed by the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Forty-three studies were included: 9 acupuncture versus sham acupuncture (n = 920), 26 acupuncture versus antidepressants (n = 2169), and 9 acupuncture plus antidepressants versus antidepressants (n = 667). Of the 43 high-quality articles, 24 and 8 were determined to have a low and moderate risk of bias, respectively. The pooled results for HAMD and SDS revealed the clinical benefits of acupuncture or acupuncture plus antidepressants compared to sham acupuncture or antidepressants, with high-quality evidence. Furthermore, high-quality evidence showed that acupuncture led to fewer adverse effects than antidepressants. CONCLUSIONS: Acupuncture or acupuncture plus antidepressants were significantly associated with reduced HAMD scores, with high-quality evidence. Also, more rigorous trials are needed to identify the optimal frequency of acupuncture for MDD and integrate such evidence into clinical care to reduce antidepressant use.

B-assembler: a circular bacterial genome assembler.

BACKGROUND: Accurate bacteria genome de novo assembly is fundamental to understand the evolution and pathogenesis of new bacteria species. The advent and popularity of Third-Generation Sequencing (TGS) enables assembly of bacteria genomes at an unprecedented speed. However, most current TGS assemblers were specifically designed for human or other species that do not have a circular genome. Besides, the repetitive DNA fragments in many bacterial genomes plus the high error rate of long sequencing data make it still very challenging to accurately assemble their genomes even with a relatively small genome size. Therefore, there is an urgent need for the development of an optimized method to address these issues. RESULTS: We developed B-assembler, which is capable of assembling bacterial genomes when there are only long reads or a combination of short and long reads. B-assembler takes advantage of the structural resolving power of long reads and the accuracy of short reads if applicable. It first selects and corrects the ultra-long reads to get an initial contig. Then, it collects the reads overlapping with the ends of the initial contig. This two-round assembling procedure along with optimized error correction enables a high-confidence and circularized genome assembly. Benchmarked on both synthetic and real sequencing data of several species of bacterium, the results show that both long-read-only and hybrid-read modes can accurately assemble circular bacterial genomes free of structural errors and have fewer small errors compared to other assemblers. CONCLUSIONS: B-assembler provides a better solution to bacterial genome assembly, which will facilitate downstream bacterial genome analysis.

ATP synthase inhibitory factor subunit 1 regulates islet ß-cell function via repression of mitochondrial homeostasis.

Mitochondrial homeostasis is crucial for the function of pancreatic ß-cells. ATP synthase inhibitory factor subunit 1 (IF1) is a mitochondrial protein interacting with ATP synthase to inhibit its enzyme activity. IF1 may also play a role in maintaining ATP synthase oligomerization and mitochondrial inner membrane formation. A recent study confirmed IF1 expresses in ß-cells. IF1 knockdown in cultured INS-1E ß-cells enhances glucose-induced insulin release. However, the role of IF1 in islet ß-cells remains little known. The present study investigates islets freshly isolated from mouse lines with global IF1 knockout (IF1-/-) and overexpression (OE). The glucose-stimulated insulin secretion was increased in islets from IF1-/- mice but decreased in islets from IF1 OE mice. Transmitted Electronic Microscopic assessment of isolated islets revealed that the number of matured insulin granules (with dense core) was relatively higher in IF1-/-, but fewer in IF1 OE islets than those of controlled islets. The mitochondrial ultrastructure within ß-cells of IF1 overexpressed islets was comparable with those of wild-type mice, whereas those in IF1-/- ß-cells showed increased mitochondrial mass. Mitochondrial network analysis in cultured INS-1 ß-cells showed a similar pattern with an increased mitochondrial network in IF1 knockdown cells. IF1 overexpressed INS-1 ß-cells showed a compromised rate of mitochondrial oxidative phosphorylation with attenuated cellular ATP content. In contrast, INS-1 cells with IF1 knockdown showed markedly increased cellular respiration with improved ATP production. These results support that IF1 is a negative regulator of insulin production and secretion via inhibiting mitochondrial mass and respiration in ß-cells. Therefore, inhibiting IF1 to improve ß-cell function in patients can be a novel therapeutic strategy to treat diabetes.

PAGER-scFGA: unveiling cell functions and molecular mechanisms in cell trajectories through single-cell functional genomics analysis.

Background: Understanding how cells and tissues respond to stress factors and perturbations during disease processes is crucial for developing effective prevention, diagnosis, and treatment strategies. Single-cell RNA sequencing (scRNA-seq) enables high-resolution identification of cells and exploration of cell heterogeneity, shedding light on cell differentiation/maturation and functional differences. Recent advancements in multimodal sequencing technologies have focused on improving access to cell-specific subgroups for functional genomics analysis. To facilitate the functional annotation of cell groups and characterization of molecular mechanisms underlying cell trajectories, we introduce the Pathways, Annotated Gene Lists, and Gene Signatures Electronic Repository for Single-Cell Functional Genomics Analysis (PAGER-scFGA). Results: We have developed PAGER-scFGA, which integrates cell functional annotations and gene-set enrichment analysis into popular single-cell analysis pipelines such as Scanpy. Using differentially expressed genes (DEGs) from pairwise cell clusters, PAGER-scFGA infers cell functions through the enrichment of potential cell-marker genesets. Moreover, PAGER-scFGA provides pathways, annotated gene lists, and gene signatures (PAGs) enriched in specific cell subsets with tissue compositions and continuous transitions along cell trajectories. Additionally, PAGER-scFGA enables the construction of a gene subcellular map based on DEGs and allows examination of the gene functional compartments (GFCs) underlying cell maturation/differentiation. In a real-world case study of mouse natural killer (mNK) cells, PAGER-scFGA revealed two major stages of natural killer (NK) cells and three trajectories from the precursor stage to NK T-like mature stage within blood, spleen, and bone marrow tissues. As the trajectories progress to later stages, the DEGs exhibit greater divergence and variability. However, the DEGs in different trajectories still interact within a network during NK cell maturation. Notably, PAGER-scFGA unveiled cell cytotoxicity, exocytosis, and the response to interleukin (IL) signaling pathways and associated network models during the progression from precursor NK cells to mature NK cells. Conclusion: PAGER-scFGA enables in-depth exploration of functional insights and presents a comprehensive knowledge map of gene networks and GFCs, which can be utilized for future studies and hypothesis generation. It is expected to become an indispensable tool for inferring cell functions and detecting molecular mechanisms within cell trajectories in single-cell studies. The web app (accessible at https://au-singlecell.streamlit.app/) is publicly available.

Body Weight Correlates with Molecular Variances in Patients with Cancer.

Overweight and obesity are identified by a high body mass index (BMI) and carry significant health risks due to associated comorbidities. Although epidemiologic data connect overweight/obesity with 13 cancer types, a better understanding of the molecular mechanisms underlying this correlation is needed to improve prevention and treatment strategies. In this study, we conducted a comprehensive analysis of molecular differences between overweight or obese patients and normal weight patients across 14 different cancer types from The Cancer Genome Atlas. Using the propensity score weighting algorithm to control for confounding factors, obesity-specific mutational features were identified, such as higher mutation burden in rectal cancer and biased mutational signatures in other cancers. Differentially expressed genes (DEG) in tumors from patients with overweight/obesity were predominantly upregulated and enriched in inflammatory and hormone-related pathways. These DEGs were significantly associated with survival rates in various cancer types, highlighting the impact of elevated body fat on gene expression profiles and clinical outcomes in patients with cancer. Interestingly, while high BMI seemed to have a negative impact on most cancer types, the normal weight-biased mutational and gene expression patterns indicated overweight/obesity may be beneficial in endometrial cancer, suggesting the presence of an "obesity paradox" in this context. Body fat also significantly impacted the tumor microenvironment by modulating immune cell infiltration, underscoring the importance of understanding the interplay between weight and immune response in cancer progression. Together, this study systematically elucidates the molecular differences corresponding to body weight in multiple cancer types, offering potentially critical insights for developing precision therapy for patients with cancer. SIGNIFICANCE: Elucidation of the complex interplay between body weight and the molecular landscape of cancer could potentially guide tailored therapies and improve patient management amid the global obesity crisis.

Endoluminal Biopsy for Vein of Galen Malformation.

BACKGROUND AND OBJECTIVES: Vein of Galen malformation (VOGM), the result of arteriovenous shunting between choroidal and/or subependymal arteries and the embryologic prosencephalic vein, is among the most severe cerebrovascular disorders of childhood. We hypothesized that in situ analysis of the VOGM lesion using endoluminal tissue sampling (ETS) is feasible and may advance our understanding of VOGM genetics, pathogenesis, and maintenance. METHODS: We collected germline DNA (cheek swab) from patients and their families for genetic analysis. In situ VOGM "endothelial" cells (ECs), defined as CD31+ and CD45-, were obtained from coils through ETS during routine endovascular treatment. Autologous peripheral femoral ECs were also collected from the access sheath. Single-cell RNA sequencing of both VOGM and peripheral ECs was performed to demonstrate feasibility to define the transcriptional architecture. Comparison was also made with a published normative cerebrovascular transcriptome atlas. A subset of VOGM ECs was reserved for future DNA sequencing to assess for somatic and second-hit mutations. RESULTS: Our cohort contains 6 patients who underwent 10 ETS procedures from arterial and/or venous access during routine VOGM treatment (aged 12 days to ∼6 years). No periprocedural complications attributable to ETS occurred. Six unique coil types were used. ETS captured 98 ± 88 (mean ± SD; range 17-256) experimental ECs (CD31+ and CD45-). There was no discernible correlation between cell yield and coil type or route of access. Single-cell RNA sequencing demonstrated hierarchical clustering and unique cell populations within the VOGM EC compartment compared with peripheral EC controls when annotated using a publicly available cerebrovascular cell atlas. CONCLUSION: ETS may supplement investigations aimed at development of a molecular-genetic taxonomic classification scheme for VOGM. Moreover, results may eventually inform the selection of personalized pharmacologic or genetic therapies for VOGM and cerebrovascular disorders more broadly.

Efficacy of acupuncture as an adjunctive treatment to patients with stable COPD: a multicenter, randomized, sham-controlled trial protocol.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease and the third leading cause of death worldwide. Previous evidence has shown that acupuncture may be an effective complementary alternative therapy for stable COPD. However, large-sample, rigorously designed long-term follow-up studies still need to be completed. Notably, the relationship between the frequency of acupuncture and clinical efficacy in studies on acupuncture for stable COPD still needs further validation. This study aims to evaluate the efficacy and safety of acupuncture for stable COPD and further investigate the dose-effect relationship of acupuncture. METHODS/DESIGN: This is a multicenter, randomized, controlled trial that uses central randomization to randomly allocate 550 participants in a 1:1:1:1:1 ratio to once a week acupuncture group, twice a week acupuncture group, three times a week acupuncture group, sham acupuncture group and waiting-list control group. The sham acupuncture group will receive placebo acupuncture treatments three times per week, and the waiting-list control group will not receive any form of acupuncture intervention. The study consists of a 2-week baseline, 12-week of treatment, and 52-week of follow-up. Patients with COPD between 40 to 80 years old who have received stable Western medication within the previous 3 months and have had at least 1 moderate or severe acute exacerbation within the past 1 year will be included in the study. Basic treatment will remain the same for all participants. The primary outcome is the proportion of responders at week 12. Secondary outcomes include the proportion of responders at week 64, change in the St. George's Respiratory Questionnaire (SGRQ) Scale, change in the Modified-Medical Research Council (mMRC) Scale, change in the COPD Assessment Test (CAT) Scale, change in the Lung Function Screening Indicators (LFSI), change in the 6-min walk distance (6-MWD), change in Short-Form 36 Health Survey (SF-36) Scale, the number of moderate and severe acute exacerbations and adverse event rate during the follow-up period. DISCUSSION: This study will provide robust evidence on whether acupuncture is safe and effective for treating stable COPD. Meanwhile, comparing the differences in efficacy between different acupuncture frequencies will further promote the optimization of acupuncture for stable COPD. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2200058757), on April 16, 2022.

Recent trends in acupuncture for chronic pain: A bibliometric analysis and review of the literature.

BACKGROUND: Acupuncture has been increasingly used in patients with chronic pain, yet no bibliometric analysis of acupuncture studies for chronic pain exists. OBJECTIVES: To investigate the characteristics, hotspots and frontiers of global scientific output in acupuncture research for chronic pain over the past decade. METHODS: We retrieved publications on acupuncture for chronic pain published from 2011 to 2022 from the Science Citation Index Expanded (SCI-expanded) of the Web of Science Core Collection (WoSCC). The co-occurrence relationships of journals/countries/institutions/authors/keywords were performed using VOSviewer V6.1.2, and CiteSpace V1.6.18 analyzed the clustering and burst analysis of keywords and co-cited references. RESULTS: A total of 1616 articles were retrieved. The results showed that the number of annual publications on acupuncture for chronic pain has increased over time, with the main types of literature being original articles (1091 articles, 67.5 %) and review articles (351 articles, 21.7 %). China had the most publications (598 articles, 37 %), with Beijing University of Traditional Chinese Medicine (93 articles, 5.8 %) and Evidence-based Complementary and Alternative Medicine ranked first (169 articles, 10.45 %) as the most prolific affiliate and journal, respectively. Liang FR was the most productive author (43 articles), and the article published by Vickers Andrew J in 2012 had the highest number of citations (625 citations). Recently, "acupuncture" and "pain" appeared most frequently. The hot topics in acupuncture for chronic pain based on keywords clustering analysis were experimental design, hot diseases, interventions, and mechanism studies. According to burst analysis, the main research frontiers were functional connectivity (FC), depression, and risk. CONCLUSION: This study provides an in-depth perspective on acupuncture for chronic pain studies, revealing pivotal points, research hotspots, and research trends. Valuable ideas are provided for future research activities.

Acupuncture as adjunctive therapy for patients with AECOPD: study protocol for a multicenter, randomized controlled trial.

Background: The acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common respiratory disease among older adults, which imposes a significant burden on individuals and society and poses a major challenge to the global public health system due to its high morbidity and mortality. Acupuncture is effective for AECOPD, but its efficacy has been questioned due to the limited methodological quality. Thus, we aim to investigate the efficacy of acupuncture as adjunctive therapy for AECOPD and determine whether the efficacy of acupuncture differs with the type of acupoint combinations. Methods and analysis: This study proposes a prospective, multicenter randomized controlled trial that will comprise four groups, including two acupuncture treatment groups, one sham acupuncture group, and one basic treatment group. The acupuncture treatment groups will be distinguished by their focus on different patterns of acupoint combination, namely the Xi-cleft and He-sea acupoint combination and the Eight Confluence points acupoint combination, which may vary in clinical efficacy based on traditional acupuncture theories. The study aims to randomize 556 patients in a 1:1:1:1 ratio across the four groups. Each patient in acupuncture group or sham acupuncture group will receive routine drug therapy and 7 sessions of acupuncture treatment over 1 week. Participants in the basic treatment group will only receive routine drug therapy. The trial will be conducted in seven hospitals located in China. The primary outcomes in this trial will include differences in the Breathlessness, Cough, and Sputum Scale (BCSS) before randomization, 7 days after randomization, 5 and 9 weeks after randomization. Ethics and dissemination: Ethical approval was obtained from the Sichuan Regional Ethics Review of Committee on Traditional Chinese Medicine (Approval ID: 2022KL-068). The results of this study will be distributed through peer-reviewed journals.Clinical Trial Registration: ClinicalTrials.gov, identifier ChiCTR2200064484.

The Application of Acupuncture Therapy for Postoperative Pain Over the Past 20 Years: A Bibliometric Analysis.

Purpose: The purpose of this study is to analyze and visualize the research trends on acupuncture therapy for postoperative pain over the past 20 years to identify hotspots and frontiers, and provide new research ideas. Methods: A search of the Web of Science database, with a time frame of 2001-01-01 to 2022-02-28, was conducted to collect literatures related to acupuncture therapy for postoperative pain. A bibliometric analysis and visualization of results was performed using CiteSpace software for the volume of annual publications, journals, countries, institutions, authors, keywords, and references. Results: A total of 840 literatures were eventually included in the analysis. The number of publications has fluctuated upwards each year over the past 20 years and reached a peak in the latest three years. Evidence-Based Complementary and Alternative Medicine was the journal with the most relevant publications and Pain was the most frequently cited journal. The country with the highest volume of publications was China, and the USA contributed most to the international collaboration. The most prolific and influential authors were Inhyunk Ha and Han JS respectively. The most frequent keyword was "acupuncture". References with highest frequency or centrality were both systematic evaluations focusing on different acupuncture therapies for postoperative pain relief. Conclusion: The field of acupuncture therapy for postoperative pain is currently in a period of high growth. China and the USA have made the largest contribution to the volume of publications. The most influential institutions and authors are mainly from China and South Korea. The overall collaborative network needs to be strengthened. Electroacupuncture and auricular acupuncture (therapeutic techniques), low back surgery (types of surgery), and "postoperative pain, nausea and vomiting" are research hotspots in this field. Improvement of postoperative life quality, proof of clinical efficacy and evidence-based evaluation are the current research trends and frontiers.

Effectiveness and Safety of Electroacupuncture for Depression: A Systematic Review and Meta-Analysis.

Purpose: The purpose of this systematic review and meta-analysis was to comprehensively evaluate the efficacy and safety of electroacupuncture as an effective adjunctive therapy for patients with depression. Methods: Randomized controlled trials (RCTs) about the treatment of depression by electroacupuncture therapy from inception to September 2021 were searched and collected in eight databases. HAMD, SDS, and Adverse Reactions were used as outcome indicators. The quality of relevant articles was evaluated using the Cochrane Collaboration's risk of bias tool. The quality of evidence for each outcome was assessed through the Grading of Recommendations Assessment and the Development and Evaluation approach. Stata 15.0 software was used for data analysis. Results: A total of 16 depression-related RCTs were included in this meta-analysis. For the main outcome, electroacupuncture significantly reduced HAMD scores (I2:0.0%, SMD: -2.28% (95% CI-3.16 to -1.39)), and the quality of evidence was moderate. The improvement effect of electroacupuncture plus antidepressants was better than that of western drugs in patients with depression (I2:26.2%, SMD: -1.18% (95% CI-1.42 to -0.94)), and the quality of evidence was moderate. Electroacupuncture significantly reduced HAMD scores without significant heterogeneity (I2:0.0%, SMD: -3.76% (95%CI-5.78-1.73)). Studies with very low quality of evidence found that electroacupuncture was as effective as antidepressants in reducing SDS scores (I2:36.4%, WMD: -1.15% (95%CI-2.93-0.63)), and electroacupuncture was found to be more effective than sham electroacupuncture stimulation as well. Moderate quality evidence showed no statistical difference between electroacupuncture plus antidepressants/electroacupuncture and antidepressants (I2:0%, RR:1.05% (95%CI 0.73 to 1.53)). Conclusions: Our meta-analysis shows that electroacupuncture reduces HAMD scores. It is suggested to use electroacupuncture plus antidepressants to improve the curative effect and effectively reduce drug side effects.

Acupuncture for Knee Osteoarthritis: A Systematic Review of Randomized Clinical Trials with Meta-Analyses and Trial Sequential Analyses.

Background: Knee osteoarthritis (KOA) can cause chronic pain and seriously affect the quality of patient lives. The continued emergence of high-quality RCTS requires us to update the quality of evidence. This study aims to evaluate the efficacy of acupuncture for KOA patients and calculate the required information size (RIS) to determine whether further clinical studies are required. Methods: We searched PubMed, Embase, WOS, CBM, CNKI, VIP, WHO ICTRP, ChiCTR, and Grey literature to collect randomized controlled trials (RCTs) of acupuncture for KOA from inception to December 2021. A meta-analysis was performed according to the Cochrane systematic review method by using Review Manager 5.4 and TSA 0.9.5.10 beta, and GRADE was used to evaluate the quality of the evidence. Trial sequential analysis was used to control random errors and calculate the required information size. Results: Eleven RCTs with 2484 patients were included in our meta-analysis, meeting the inclusion criteria for the meta-analysis. The meta-analysis indicated that acupuncture had beneficial effect on knee osteoarthritis in reducing pain [n = 2387; SMD = -0.12, 95% CI (-0.20, -0.04); I 2 = 0%] and improved patients function activities [n = 2408; MD = -1.25, 95% CI (-1.97, -0.53); I 2 = 0%], but true acupuncture showed no significant effect in relieve patient's stiffness [n = 1337; MD = -0.07, 95% CI (-0.30, 0.15); I 2 = 0%]. We pooled the studies which found no significant difference in improving the quality life of mental [n = 1462; SMD = 0.02, 95% CI (-0.23, 0.27); I 2 = 78%] and patients physical health (SF-36 or SF-12) [n = 1745; SMD = 1.01, 95% CI (-0.08, 2.11); I 2 = 0%] compared with sham acupuncture. The pain and function TSA graphs indicated that cumulative Z-curves intersected with the traditional level of statistical favoring acupuncture, and more RCTs will required in the future studies. Conclusion: Acupuncture has beneficial effect on pain relief and improves function activities, and this treatment can be recommended as a beneficial alternative therapy in patients with KOA, particularly for chronic patients and those currently undergoing long-term pain and help them increasing quality of life. But it should be further verified through more RCTs in function. Available studies suggested that acupuncture was superior to sham acupuncture in reduce pain and function as verified by TSA.

Effectiveness and Safety of Acupuncture-Related Therapies for Chronic Musculoskeletal Pain: A Protocol for Systematic Review and Network Meta-Analysis.

Introduction: Chronic pain is one of the major health problems worldwide in recent years, and acupuncture-related therapies have been reported to have definite analgesic effects. However, it is still unclear which treatment is the most effective. Our systematic review and network meta-analysis protocol aims to summarize the evidence and determine the most effective method to treat the chronic musculoskeletal pain. Methods and Analysis: Our literature search will be performed in five electronic databases-the Cochrane Library, EMBASE, and PubMed, AMED, CINAHL, until May 20, 2022. All randomized controlled trials of acupuncture-related therapies for chronic musculoskeletal pain will be included. The primary outcomes will be common pain-related scales, and the secondary outcomes will include quality of life and incidence of adverse events. Excel 2019 will be used for data extraction, RoB2 will be used for bias risk assessment. R 3.6.2 and WinBUGS V.1.4.3 software will be used for network data synthesis and to produce related plots. During the study, literature selection, data extraction, quality assessment and bias risk assessment will be independently completed by two reviewers, and differences will be judged by the third reviewer. Finally, the risk of bias and sources of heterogeneity in the study will be analyzed and explained in order to obtain reliable results. Results: Our study will evaluate the effectiveness and safety of acupuncture-related therapies for the treatment of chronic musculoskeletal pain, and we will rank all methods to recommend the best appropriate treatment option. Conclusion: This study will provide a good foundation for complementary and alternative medicine to treat chronic musculoskeletal pain. It will be also helpful to promote the clinical practice by providing evidence-based medical evidence.

The dose-effect association between acupuncture sessions and its effects on major depressive disorder: A meta-regression of randomized controlled trials.

BACKGROUND: The benefits of acupuncture on Major depressive disorder (MDD) have been well established in previous studies. However, uncertainty exists regarding the dose-effect relationship between acupuncture and MDD. This study aims to explore the association between acupuncture and its effects on MDD based on previously published data. METHODS: Nine databases were searched from inception until 10th September 2021. Randomized controlled trials that compared acupuncture with sham acupuncture, or anti-depressants, were included. The data extraction, and assessing the data quality and risk of bias completed by two researcher, respectively. A non-linear meta-regression approach with restricted cubic spline was used to investigate the dose-effect relationship between acupuncture sessions and their effects on the Hamilton rating scale for depression (HAMD) score. RESULTS: Of the 20,835 citations screened, 62 studies (2269 patients of MDD) were included. The dose-effect meta-analysis suggested that acupuncture session was associated with a decline in HAMD scores. Overall, an increase in the number of acupuncture sessions received was associated with symptom improvement in MDD patients. After 8 acupuncture sessions, the HAMD score decreased from 17.68 (95% CI: -11.81, -4.80) to 8.30 (95% CI: 14.23-21.13). After 24 acupuncture sessions, a decrease in HAMD scores was observed in 51% of cases (95% CI: 48% to 54%). After 36 acupuncture sessions, the effect of improvement in HAMD scores peaked at 66% of cases (95% CI: 59% to 72%). CONCLUSIONS: A dose-effect relationship was found between the number of acupuncture sessions and HAMD scores. 36 acupuncture sessions were associated with optimal clinical response. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021290143.

Selective suppression of melanoma lacking IFN-γ pathway by JAK inhibition depends on T cells and host TNF signaling.

Therapeutic resistance to immune checkpoint blockers (ICBs) in melanoma patients is a pressing issue, of which tumor loss of IFN-γ signaling genes is a major underlying mechanism. However, strategies of overcoming this resistance mechanism have been largely elusive. Moreover, given the indispensable role of tumor-infiltrating T cells (TILs) in ICBs, little is known about how tumor-intrinsic loss of IFN-γ signaling (IFNγR1KO) impacts TILs. Here, we report that IFNγR1KO melanomas have reduced infiltration and function of TILs. IFNγR1KO melanomas harbor a network of constitutively active protein tyrosine kinases centered on activated JAK1/2. Mechanistically, JAK1/2 activation is mediated by augmented mTOR. Importantly, JAK1/2 inhibition with Ruxolitinib selectively suppresses the growth of IFNγR1KO but not scrambled control melanomas, depending on T cells and host TNF. Together, our results reveal an important role of tumor-intrinsic IFN-γ signaling in shaping TILs and manifest a targeted therapy to bypass ICB resistance of melanomas defective of IFN-γ signaling.

Bibliometric Analysis of Functional Magnetic Resonance Imaging Studies on Acupuncture Analgesia Over the Past 20 Years.

BACKGROUND: Researches on the central mechanisms of acupuncture analgesia have been widely conducted worldwide. However, there is no bibliometric analysis of functional magnetic resonance imaging (fMRI) studies on acupuncture analgesia. This study visualized the current status, hot spots and frontiers of fMRI studies on acupuncture analgesia in the past 20 years to provide a theoretical basis for its clinical application. METHODS: All publications were obtained from Science Citation Index-Expanded (SCI-E) of Web of Science (WOS). We used CiteSpace to analyze publications, journals, cited journals, authors, cited authors, institutions, countries, references, and keywords. We also analyzed collaborative network maps and co-occurrence network maps. RESULTS: We retrieved a total of 797 articles. Regarding the volume of publications, the total number of annual publications showed a fluctuating but overall increasing trend. Evidence-based Complementary and Alternative Medicine (21 articles) was the most productive journal, and Pain (225 articles) was the most cited journal. The most productive author was Qin W (16 articles), and the most co-cited author was Hui KKS (111). The most prolific institution and country were Massachusetts General Hospital (34 articles) and USA (212 articles). "Pain" was the top-ranked for keyword frequency and centrality. "Functional connectivity" was the frontier hotspot for 2018-2021. CONCLUSION: First, fMRI researches on acupuncture analgesia involved several countries (regions) and institutions, mainly located in the USA, China and Korea, and most of them were universities. In addition, the USA was a major contributor in this field. Second, in terms of disciplinary distribution, the literatures were mainly from clinical neurology, neuroscience, and radiology nuclear medicine medical imaging. Third, the keyword co-occurrence analysis showed that the hot keywords included pain, fMRI, and lower back pain. Fourth, through keyword clustering analysis, the hot disease was found to be lower back pain, and the hot contents were acupuncture specificity and frequency specificity. Fifth, a timeline analysis of the references identified that chronic low back pain and specificity will remain a hot topic for future research.

CD4+ T cell activation and concomitant mTOR metabolic inhibition can ablate microbiota-specific memory cells and prevent colitis.

Microbiota-reactive CD4+ T memory (TM) cells are generated during intestinal infections and inflammation, and can revert to pathogenic CD4+ T effector (TE) cells, resulting in chronicity of inflammatory bowel disease (IBD). Unlike TE cells, TM cells have a low rate of metabolism unless they are activated by reencountering cognate antigen. Here, we show that the combination of cell activation and metabolic checkpoint inhibition (CAMCI), by targeting key metabolic regulators mTORC and AMPK, resulted in cell death and anergy, but enhanced the induction of the regulatory subset. Parenteral application of this treatment with a synthetic peptide containing multiple flagellin T cell epitopes (MEP1) and metabolic inhibition successfully prevented the development of CD4+ T cell-driven colitis. Microbiota-specific CD4+ T cells, especially the pathogenic TE subsets, were decreased 10-fold in the intestinal lamina propria. Furthermore, using the CAMCI strategy, we were able to prevent antigen-specific TM cell formation upon initial antigen encounter, and ablate existing TM cells upon reactivation in mice, leading to an altered transcriptome in the remaining CD4+ T cells after ablation. Microbiota flagellin-specific CD4+ T cells from patients with Crohn's disease were ablated in a similar manner after CAMCI in vitro, with half of the antigen-specific T cells undergoing cell death. These results indicate that parenteral activation of microbiota-specific CD4+ T cells with concomitant metabolic inhibition is an effective way to ablate pathogenic CD4+ TM cells and to induce T regulatory (Treg) cells that provide antigen-specific and bystander suppression, supporting a potential immunotherapy to prevent or ameliorate IBD.

Acylation of cellulose nanocrystals with acids/trifluoroacetic anhydride and properties of films from esters of CNCs.

To eliminate the effect of humidity on nanopapers from nanocellulose, esters of CNCs (ECNCs) were synthesized via acylation of cellulose nanocrystals (CNCs) with fatty acids and Trifluoroacetic anhydride (TFAA). The structure information of ECNCs was confirmed via FTIR, degree of substitution (DS) determination, and XRD, respectively. With the increase of DS, the ECNCs could be dissolved in dichloromethane, which provided a ready way for fabrication of ECNCs films via casting/evaporation method. The tensile property, transmittance, hydrophobicity, thermal property and oxygen permeability of films were tested with universal tensile tester, UV-vis spectrophotometer, Contact angle tester, Simultaneous thermal analyzer and Oxygen permeability tester, respectively. With the increase of DS, the contact angles of ECNCs increased, and the water uptake decreased. The enhancement of hydrophobicity promised the preservation of tensile parameters for films after water absorbing. The hydrophobicity, high transmittance, and high oxygen barrier property make films have potential application in packaging filed.

Knockout of the ATPase inhibitory factor 1 protects the heart from pressure overload-induced cardiac hypertrophy.

Mitochondrial ATP synthase catalyzes the coupling of oxidative phosphorylation. Under pathological conditions, ATP synthase hydrolyzes ATP to replenish protons from the matrix into the intermembrane space, sustaining mitochondrial membrane potential. ATPase inhibitory factor 1 (IF1) is a nuclear-encoded, ATP synthase-interacting protein that selectively inhibits the hydrolysis activity of ATP synthase, which may render the protective role of IF1 in ischemic hearts. However, the in vivo cardiac function of IF1 and the potential therapeutic application targeting IF1 remain obscure. In the present study, we uncovered that IF1 is upregulated in mouse hearts with pressure overload-induced hypertrophy and in human hearts with dilated cardiomyopathy. IF1 knockout (KO) mice were protected against cardiac dysfunction and pathological development induced by transverse aortic constriction (TAC) or isoproterenol infusion. The reduced ATP hydrolysis activated AMPK activity in IF1 KO hearts, which together facilitated autophagy. These results suggest that IF1 upregulation in the failing heart may be a maladaptive response. Inhibiting IF1 in the hypertrophied heart not only prevents cell death from excessive mitochondrial depolarization but also activates AMPK signaling and increases autophagy. Therefore, IF1 inhibition may serve as a potential therapeutic target in treating pathological cardiac hypertrophy and heart failure.

Histone deacetylase-high mobility group box-1 pathway targeted by hypaconitine suppresses the apoptosis of endothelial cells.

Hypaconitine is an active component of Aconitum carmichaelii Debx, a Chinese medicinal herb for the treatment of cardiovascular diseases, but the mechanism underlying its effect remains elusive. In this study, we found that hypaconitine, rather than aconitum alkaloids in A. carmichaelii (e.g. aconitine, mesaconitine and benzoylaconitine), prevented endothelial cells from damage due to oxidized low-density lipoprotein (oxLDL) challenge. Cleaved caspase 3 expression in endothelial cells was up-regulated by oxLDL and markedly attenuated by hypaconitine, suggesting that hypaconitine inhibited the oxLDL-induced cell apoptosis. Microarray analysis revealed that histone deacetylase 3 (HDAC3) was significantly increased by hypaconitine. The cytoplasmic relocation and extracellular release of high-mobility group box 1 (HMGB1, an HDAC3 downstream effector) in endothelial cells were significantly increased by oxLDL and markedly decreased by hypaconitine. The effect of hypaconitine on the oxLDL-induced apoptosis and HMGB1 release in endothelial cells was significantly reduced by the suppression of HDAC3 by siRNA or a specific inhibitor. Thus, this study proves that the histone deacetylase-HMGB1 pathway targeted by hypaconitine suppresses the apoptosis of endothelial cells. Our findings are of therapeutic significance and provide the potential of hypaconitine exploitation. Impact statement First, our study shows the antiapoptosis effect of Aconitum carmichaelii and its active component hypaconitine on endothelial cells. It may provide new strategies for the treatment of diseases involving endothelium damage. Second, this finding indicates the function of hypaconitine in regulating HDAC3-HMGB1 pathway, which suggests a new anti-inflammatory therapy. Third, due to its poisonousness, A. carmichaelii is always used with caution in clinics. Thus, the identification of hypaconitine as an active component of A. carmichaelii could contribute to the development of toxicity-decreasing procedure for A. carmichaelii.