Efficacy and safety of acupuncture-point stimulation combined with opioids for the treatment of moderate to severe cancer pain: a network meta-analysis of randomized controlled trials

BackgroundPain is one of the most common and troublesome symptoms of cancer. Although potential positive effects of acupuncture-point stimulation (APS) on cancer pain have been observed, knowledge regarding the selection of the optimal APS remains unclear because of a lack of evidence from head-to-head randomized controlled trials (RCTs).ObjectiveThis study aimed to carry out a network meta-analysis to compare the efficacy and safety of different APS combined with opioids in treating moderate to severe cancer pain and rank these methods for practical consideration.MethodsA comprehensive search of eight electronic databases was conducted to obtain RCTs involving different APS combined with opioids for moderate to severe cancer pain. Data were screened and extracted independently using predesigned forms. The quality of RCTs was appraised with the Cochrane Collaboration risk-of-bias tool. The primary outcome was the total pain relief rate. Secondary outcomes were the total incidence of adverse reactions, the incidence of nausea and vomiting, and the incidence of constipation. We applied a frequentist, fixed-effect network meta-analysis model to pool effect sizes across trials using rate ratios (RR) with their 95% confidence intervals (CI). Network meta-analysis was performed using Stata/SE 16.0.ResultsWe included 48 RCTs, which consisted of 4,026 patients, and investigated nine interventions. A network meta-analysis showed that a combination of APS and opioids was superior in relieving moderate to severe cancer pain and reducing the incidence of adverse reactions such as nausea, vomiting, and constipation compared to opioids alone. The ranking of total pain relief rates was as follows: fire needle (surface under the cumulative ranking curve (SUCRA) = 91.1%), body acupuncture (SUCRA = 85.0%), point embedding (SUCRA = 67.7%), auricular acupuncture (SUCRA = 53.8%), moxibustion (SUCRA = 41.9%), transcutaneous electrical acupoint stimulation (TEAS) (SUCRA = 39.0%), electroacupuncture (SUCRA = 37.4%), and wrist–ankle acupuncture (SUCRA = 34.1%). The ranking of total incidence of adverse reactions was as follows: auricular acupuncture (SUCRA = 23.3%), electroacupuncture (SUCRA = 25.1%), fire needle (SUCRA = 27.2%), point embedding (SUCRA = 42.6%), moxibustion (SUCRA = 48.2%), body acupuncture (SUCRA = 49.8%), wrist–ankle acupuncture (SUCRA = 57.8%), TEAS (SUCRA = 76.3%), and opioids alone (SUCRA = 99.7%).ConclusionsAPS seemed to be effective in relieving cancer pain and reducing opioid-related adverse reactions. Fire needle combined with opioids may be a promising intervention to reduce moderate to severe cancer pain as well as reduce opioid-related adverse reactions. However, the evidence was not conclusive. More high-quality trials investigating the stability of evidence levels of different interventions on cancer pain must be conducted.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/#searchadvanced, identifier CRD42022362054

A statistical study of railway safety in China and Japan 1990–2020

Safety is the precondition and guarantee of railway development. However, due to equipment failure, poor management, misoperation and so on, accidents on the railway occur from time to time. China and Japan, as leading countries in Railway Technology in the world, have done a lot of work in accident prevention and safety. Through the collection and comparison of transport data and typical casualty cases in China and Japan, this paper summarizes the main causes of accidents and the experience of accident prevention in the two countries. And further, puts forward suggestions for preventing accidents and large-scale casualty

Genetic Dissection of Seed Dormancy using Chromosome Segment Substitution Lines in Rice (Oryza sativa L.)

Timing of germination determines whether a new plant life cycle can be initiated; therefore, appropriate dormancy and rapid germination under diverse environmental conditions are the most important features for a seed. However, the genetic architecture of seed dormancy and germination behavior remains largely elusive. In the present study, a linkage analysis for seed dormancy and germination behavior was conducted using a set of 146 chromosome segment substitution lines (CSSLs), of which each carries a single or a few chromosomal segments of Nipponbare (NIP) in the background of Zhenshan 97 (ZS97). A total of 36 quantitative trait loci (QTLs) for six germination parameters were identified. Among them, qDOM3.1 was validated as a major QTL for seed dormancy in a segregation population derived from the qDOM3.1 near-isogenic line, and further delimited into a genomic region of 90 kb on chromosome 3. Based on genetic analysis and gene expression profiles, the candidate genes were restricted to eight genes, of which four were responsive to the addition of abscisic acid (ABA). Among them, LOC_Os03g01540 was involved in the ABA signaling pathway to regulate seed dormancy. The results will facilitate cloning the major QTLs and understanding the genetic architecture for seed dormancy and germination in rice and other crops

Tuning Microparticle Porosity during Single Needle Electrospraying Synthesis via a Non-Solvent-Based Physicochemical Approach

Porous materials, especially microparticles (MP), are utilized in almost every field of engineering and science, ranging from healthcare materials (drug delivery to tissue engineering) to environmental engineering (biosensing to catalysis). Here, we utilize the single needle electrospraying technique (as opposed to complex systems currently in development) to prepare a variety of poly(ε-caprolactone) (PCL) MPs with diverse surface morphologies (variation in pore size from 220 nm to 1.35 µm) and architectural features (e.g., ellipsoidal, surface lamellar, Janus lotus seedpods and spherical). This is achieved by using an unconventional approach (exploiting physicochemical properties of a series of non-solvents as the collection media) via a single step. Sub-micron pores presented on MPs were visualized by electron microscopy (demonstrating a mean MP size range of 7–20 μm). The present approach enables modulation in morphology and size requirements for specific applications (e.g., pulmonary delivery, biological scaffolds, multi-stage drug delivery and biomaterial topography enhancement). Differences in static water contact angles were observed between smooth and porous MP-coated surfaces. This reflects the hydrophilic/hydrophobic properties of these materials

The Role of Alternative Splicing Factors, DDB2-Related Ageing and DNA Damage Repair in the Progression and Prognosis of Stomach Adenocarcinoma Patients

DNA damage response is a key signal transduction pathway in triggering ageing and tumor progression. Abnormal alternative splicing (AS) is associated with tumors and ageing. However, the role of AS factors associated with DNA damage repair and ageing in stomach adenocarcinoma (STAD) remains unclear. We downloaded the percentage of splicing (PSI) values for AS in STAD from the TCGA SpliceSeq database. The PSI values of DNA repair gene AS events were integrated with STAD patient survival data for Cox regression analysis. The prediction model for the overall survival (OS) was constructed by the clinical traits. The tumor immune microenvironment was analyzed by CIBERSORT and ESTIMATE. We detected 824 AS events originating from 166 DNA repair genes. Cox regression analysis provided 21 prognostic AS events connected with OS statistically, and a prognostic prediction model was constructed. The expression of these AS factors was higher in STAD tumors. DDB2 high senescence levels were associated with active immune responses and better survival in STAD patients. We built a novel prognostic model founded on DNA repair genes with AS events and identified that DDB2 may be a potential biomarker to apply in clinics

Metallosupramolecular Polymer Precursor Design for Multi-Element Co-Doped Carbon Shells with Improved Oxygen Reduction Reaction Catalytic Activity

Heteroatom-doped carbon materials have been extensively studied in the field of electrochemical catalysis to solve the challenges of energy shortage. In particular, there is vigorous research activity in the design of multi-element co-doped carbon materials for the improvement of electrochemical performance. Herein, we developed a supramolecular approach to construct metallosupramolecular polymer hollow spheres, which could be used as precursors for the generation of carbon shells co-doped with B, N, F and Fe elements. The metallosupramolecular polymer hollow spheres were fabricated through a simple route based on the Kirkendall effect. The in situ reaction between the boronate polymer spheres and Fe3+ could easily control the component and shell thickness of the precursors. The as-prepared multi-element co-doped carbon shells showed excellent catalytic activity in an oxygen reduction reaction, with onset potential (Eonset) 0.91 V and half-wave (Ehalf-wave) 0.82 V vs reversible hydrogen electrode (RHE). The fluorine element in the carbon matrix was important for the improvement of oxygen reduction reaction (ORR) activity performance through designing the control experiment. This supramolecular approach may afford a new route to explore good activity and a low-cost catalyst for ORR

Single cell multiomic analysis reveals diabetes-associated β-cell heterogeneity driven by HNF1A

Abstract Broad heterogeneity in pancreatic β-cell function and morphology has been widely reported. However, determining which components of this cellular heterogeneity serve a diabetes-relevant function remains challenging. Here, we integrate single-cell transcriptome, single-nuclei chromatin accessibility, and cell-type specific 3D genome profiles from human islets and identify Type II Diabetes (T2D)-associated β-cell heterogeneity at both transcriptomic and epigenomic levels. We develop a computational method to explicitly dissect the intra-donor and inter-donor heterogeneity between single β-cells, which reflect distinct mechanisms of T2D pathogenesis. Integrative transcriptomic and epigenomic analysis identifies HNF1A as a principal driver of intra-donor heterogeneity between β-cells from the same donors; HNF1A expression is also reduced in β-cells from T2D donors. Interestingly, HNF1A activity in single β-cells is significantly associated with lower Na+ currents and we nominate a HNF1A target, FXYD2, as the primary mitigator. Our study demonstrates the value of investigating disease-associated single-cell heterogeneity and provides new insights into the pathogenesis of T2D

A Novel Proteogenomic Integration Strategy Expands the Breadth of Neo-Epitope Sources

Tumor-specific antigens can activate T cell-based antitumor immune responses and are ideal targets for cancer immunotherapy. However, their identification is still challenging. Although mass spectrometry can directly identify human leukocyte antigen (HLA) binding peptides in tumor cells, it focuses on tumor-specific antigens derived from annotated protein-coding regions constituting only 1.5% of the genome. We developed a novel proteogenomic integration strategy to expand the breadth of tumor-specific epitopes derived from all genomic regions. Using the colorectal cancer cell line HCT116 as a model, we accurately identified 10,737 HLA-presented peptides, 1293 of which were non-canonical peptides that traditional database searches could not identify. Moreover, we found eight tumor neo-epitopes derived from somatic mutations, four of which were not previously reported. Our findings suggest that this new proteogenomic approach holds great promise for increasing the number of tumor-specific antigen candidates, potentially enlarging the tumor target pool and improving cancer immunotherapy