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

Evaluation of Livability of Wuhan under Ecological Construction and Analysis of Its Spatial Pattern

With the continuous development of ecological city construction under the concept of “ecological civilization”, the creation of ecologically livable cities has become more and more important. Since urban livability involves a wide range of social life, the establishment of urban livability index evaluation system can help analyze urban livability and residents’ quality of life, and then optimize and control urban spatial structure to promote high-quality urban development. This study takes Wuhan, Hubei Province, as an example, and establishes a comprehensive index evaluation system based on 12 indicators in three criteria levels: economic, social, and environmental, and calculates a comprehensive score of urban livability for each district in Wuhan City, and conducts a comprehensive evaluation of the 13 administrative districts under Wuhan City. Based on the final scores, we analyze the livability and friendliness of each district in Wuhan, analyze the spatial pattern of the results, discuss the strengths and weaknesses of the livability of each district in Wuhan, make scientific reference suggestions to promote the coordinated development of each district, guide the rational allocation of resources, and provide a reference for decision-making to promote the livable communities in each district in Wuhan

Cold Chain-Free Storable Hydrogel for Infant-Friendly Oral Delivery of Amoxicillin for the Treatment of Pneumococcal Pneumonia

10.1021/acsami.7b01462ACS APPLIED MATERIALS & INTERFACES92218440-1844

Cold Chain-Free Storable Hydrogel for Infant-Friendly Oral Delivery of Amoxicillin for the Treatment of Pneumococcal Pneumonia

Pneumonia is the major cause of death in children under five, particularly in developing countries. Antibiotics such as amoxicillin greatly help in mitigating this problem. However, there is a lack of an infant/toddler-friendly formulation for countries with limited clean water orr electricity. Here, we report the development of a shear-thinning hydrogel system for the oral delivery of amoxicillin to infant/toddler patients, without the need of clean water and refrigeration. The hydrogel formulation consists of metolose (hydroxypropyl methylcellulose) and amoxicillin. It preserves the structural integrity of antibiotics and their antibacterial activity over 12 weeks at room temperature. Pharmacokinetic profiling of mice reveals that the hydrogel formulation increases the bioavailability of drugs by ∼18% compared to that with aqueous amoxicillin formulation. More importantly, oral gavage of this formulation in a mouse model of secondary pneumococcal pneumonia significantly ameliorates inflammatory infiltration and tissue damage in lungs, with a 10-fold reduction in bacterial counts compared to those in untreated ones. Given the remarkable antibacterial efficacy as well as the use of FDA-regulated ingredients (metolose and amoxicillin), the hydrogel formulation holds great promise for rapid clinical translation

Disruption of neuronal RHEB signaling impairs oligodendrocyte differentiation and myelination through mTORC1-DLK1 axis

Summary: How neuronal signaling affects brain myelination remains poorly understood. We show dysregulated neuronal RHEB-mTORC1-DLK1 axis impairs brain myelination. Neuronal Rheb cKO impairs oligodendrocyte differentiation/myelination, with activated neuronal expression of the imprinted gene Dlk1. Neuronal Dlk1 cKO ameliorates myelination deficit in neuronal Rheb cKO mice, indicating that activated neuronal Dlk1 expression contributes to impaired myelination caused by Rheb cKO. The effect of Rheb cKO on Dlk1 expression is mediated by mTORC1; neuronal mTor cKO and Raptor cKO and pharmacological inhibition of mTORC1 recapitulate elevated neuronal Dlk1 expression. We demonstrate that both a secreted form of DLK1 and a membrane-bound DLK1 inhibit the differentiation of cultured oligodendrocyte precursor cells into oligodendrocytes expressing myelin proteins. Finally, neuronal expression of Dlk1 in transgenic mice reduces the formation of mature oligodendrocytes and myelination. This study identifies Dlk1 as an inhibitor of oligodendrocyte myelination and a mechanism linking altered neuronal signaling with oligodendrocyte dysfunction

Developmental and Activity-Dependent Expression of LanCL1 Confers Antioxidant Activity Required for Neuronal Survival

SummaryProduction of reactive oxygen species (ROS) increases with neuronal activity that accompanies synaptic development and function. Transcription-related factors and metabolic enzymes that are expressed in all tissues have been described to counteract neuronal ROS to prevent oxidative damage. Here, we describe the antioxidant gene LanCL1 that is prominently enriched in brain neurons. Its expression is developmentally regulated and induced by neuronal activity, neurotrophic factors implicated in neuronal plasticity and survival, and oxidative stress. Genetic deletion of LanCL1 causes enhanced accumulation of ROS in brain, as well as development-related lipid, protein, and DNA damage; mitochondrial dysfunction; and apoptotic neurodegeneration. LanCL1 transgene protects neurons from ROS. LanCL1 protein purified from eukaryotic cells catalyzes the formation of thioether products similar to glutathione S-transferase. These studies reveal a neuron-specific glutathione defense mechanism that is essential for neuronal function and survival