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Normalization of Neuroinflammation: A New Strategy for Treatment of Persistent Pain and Memory/Emotional Deficits in Chronic Pain.

Chronic pain, which affects around 1/3 of the world population and is often comorbid with memory deficit and mood depression, is a leading source of suffering and disability. Studies in past decades have shown that hyperexcitability of primary sensory neurons resulting from abnormal expression of ion channels and central sensitization mediated pathological synaptic plasticity, such as long-term potentiation in spinal dorsal horn, underlie the persistent pain. The memory/emotional deficits are associated with impaired synaptic connectivity in hippocampus. Dysregulation of numerous endogenous proteins including receptors and intracellular signaling molecules is involved in the pathological processes. However, increasing knowledge contributes little to clinical treatment. Emerging evidence has demonstrated that the neuroinflammation, characterized by overproduction of pro-inflammatory cytokines and glial activation, is reliably detected in humans and animals with chronic pain, and is sufficient to induce persistent pain and memory/emotional deficits. The abnormal expression of ion channels and pathological synaptic plasticity in spinal dorsal horn and in hippocampus are resulting from neuroinflammation. The neuroinflammation is initiated and maintained by the interactions of circulating monocytes, glial cells and neurons. Obviously, unlike infectious diseases and cancer, which are caused by pathogens or malignant cells, chronic pain is resulting from alterations of cells and molecules which have numerous physiological functions. Therefore, normalization (counterbalance) but not simple inhibition of the neuroinflammation is the right strategy for treating neuronal disorders. Currently, no such agent is available in clinic. While experimental studies have demonstrated that intracellular Mg deficiency is a common feature of chronic pain in animal models and supplement Mg are capable of normalizing the neuroinflammation, activation of upregulated proteins that promote recovery, such as translocator protein (18k Da) or liver X receptors, has a similar effect. In this article, relevant experimental and clinical evidence is reviewed and discussed.

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A case report of cerebral venous sinus thrombosis presenting with rapidly progressive dementia.

Cerebral venous sinus thrombosis (CVST) is a rare but serious and treatable cause of neurologic symptoms. Due to the variable clinical presentation, CVST was often misdiagnosed. According to published case reports, common clinical manifestations of CVST include headache, focal neurological deficit, epilepsy, papilledema, etc. It is rare, nevertheless, to mention cases of rapidly progressive dementia (RPD).

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Desformylflustrabromine (dFBr), a positive allosteric modulator of α4β2 nicotinic acetylcholine receptors decreases voluntary ethanol consumption and preference in male and female Sprague-Dawley rats.

Alcohol use disorder is a medical condition that impacts millions of individuals worldwide. Although there are a few pharmacotherapeutic options for alcohol-dependent individuals; there is a need for the development of novel and more effective therapeutic approaches. Alcohol and nicotine are commonly co-abused, and there is evidence that neuronal nicotinic acetylcholine receptors (nAChRs) play a role in both alcohol and nicotine dependence. Desformylflustrabromine (dFBr), a positive allosteric modulator of the α4β2 nAChRs has been shown to reduce nicotine intake, compulsive-like behavior and neuropathic pain in animal models. dFBr has also been previously shown to cross the blood-brain-barrier. We have recently shown that dFBr can attenuate the response to an acute, hypnotic dose of ethanol, via β2 nAchR. Here, we have investigated the effect of dFBr in modulating ethanol consumption using the intermittent access two-bottle choice (IA2BC) model of voluntary ethanol consumption in male and female Sprague Dawley rats. We show that dFBr selectively reduced ethanol but not sucrose consumption in the IA2BC model. Furthermore, dFBr decreased preference for ethanol in both male and female rats. No rebound increase in ethanol intake was observed after the washout period after dFBr treatment. The ability of dFBr to decrease ethanol consumption, along with its previously demonstrated ability to decrease nicotine self-administration in rodents, suggest that dFBr is an attractive therapeutic candidate to target both nicotine and alcohol abuse.

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Ultrasound-Guided Percutaneous Transhepatic Gallbladder Drainage Improves the Prognosis of Patients with Severe Acute Cholecystitis.

The aim of this study was to investigate the clinical efficacy of ultrasound-guided percutaneous transhepatic gallbladder drainage (PTGD) for the treatment of severe acute cholecystitis (AC). The data of 40 patients diagnosed with severe AC at our hospital between August 2020 and June 2021 were retrieved and classified into a PTGD group, open cholecystostomy (OC) group, laparoscopic cholecystectomy (LC) group, and conventional conservative treatment (CT) group. Before treatment and on days 1, 3, 5, and 7 after treatment, their serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), total bilirubin (TBIL), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), white blood cell count (WBC), IL-2, IL-4, IL-6, IL-8, and cancer antigen 19-9 (CA19-9) were measured. Additionally, clinical manifestations such as body temperature and pain score were monitored before treatment and at 24, 48, and 72 hours after treatment. The recovery time and complications/adverse reactions were statistically analyzed, and the Kaplan-Meier survival curve was plotted. After treatment, compared with the other three groups, the PTGD group had a significant reduction in serum indicators, including WBC and inflammatory factors, recovery time, pain score, and complications, and benefitted from better treatment efficacy and higher survival rate. Thus, ultrasound-guided PTGD was found to be more effective in treating severe AC patients and was associated with improved patient prognoses.

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The Effectiveness of High-Frequency Repetitive Transcranial Magnetic Stimulation on Patients with Neuropathic Orofacial Pain: A Systematic Review of Randomized Controlled Trials.

Repetitive transcranial magnetic stimulation (rTMS) has been widely used in the treatment of neuropathic orofacial pain (NOP). The consistency of its therapeutic efficacy with the optimal protocol is highly debatable.

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A randomized, double-blinded, placebo-controlled, single dose analgesic study of preoperative intravenous ibuprofen for tonsillectomy in children.

Tonsillectomy is a recognized treatment for children with tonsil hypertrophy and results in significant postoperative oropharyngeal pain. Fentanyl and other morphine-like analgesics are widely used as perioperative analgesia but are associated with side effects such as vomiting, nausea, and respiratory depression. As the least toxic non-steroidal anti-inflammatory drug, ibuprofen may be effective and safe for pain control after tonsillectomy. We aimed to explore whether the addition of intravenous (IV) ibuprofen administered at induction can reduce the need for early postoperativeanalgesics.

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Gadolinium-Induced Acute Graft Pancreatitis in a Simultaneous Pancreas-Kidney Transplant Recipient.

Gadolinium-induced acute pancreatitis is a rare phenomenon associated with the administration of gadolinium-based contrast agents. Only five cases of gadolinium-induced acute pancreatitis have been reported worldwide in patients with native pancreas and none with a pancreatic graft. We present a 32-year-old woman with prior history of simultaneous pancreas-kidney transplant who presented with generalized abdominal pain associated with systemic inflammatory response syndrome requiring admission to the intensive care unit. This occurred within 48 hours after having a magnetic resonance imaging (MRI) with gadolinium for investigation of subacute left optic atrophy. She was noted to have a marked rise in serum lipase, and the computed tomography findings were consistent with acute graft pancreatitis. Other causes of pancreatitis were ruled out, and she was managed conservatively with aggressive hydration, bowel rest, and analgesia with good recovery. This is the first reported case of gadolinium-induced acute graft pancreatitis occurring in a simultaneous pancreas-kidney transplant recipient. Clinicians should consider this rare differential diagnosis as a cause of graft pancreatitis in patients who have received gadolinium-based contrast agents.

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Comparison on different traditional Chinese medicine therapies for chronic hepatitis B liver fibrosis.

Although different kinds of traditional Chinese medicines could reportedly improve the efficacy of antiviral therapy on liver fibrosis caused by HBV, the problem of clinicians on how to choose the appropriate treatment strategies for the patients fails to be solved. This study aims at comparing and ranking different traditional Chinese medicine (TCM) therapies in the treatment of liver fibrosis due to chronic hepatitis B (CHB). Eight electronic databases were searched from their establishment to 17 Aug 2021. All included data and pooled odds ratio were used for network meta-analysis (NMA) and statistical analysis. The consistency was evaluated by the node-splitting analysis. The stability of results and source of heterogeneity were tested by sensitivity analysis. Different treatment strategies (regimens) in this network meta-analysis were ranked with the aid of surface under the cumulative ranking curve (SUCRA) probability value. A total of 29 articles with 3,106 sufferers were recruited in this NMA. Results of SUCRA value rankings indicated that Fuzheng Huayu therapy or combined with entecavir had preferable effects in improving the clinical efficacy, recovering the level of hyaluronic acid, IV-C, ALT, ALB, and TBil, relieving the TCM symptoms including hypochondriac pain and poor appetite, regaining the width of portal vein and thickness of spleen, and lessening side effects. Apart from these, Ziyin Shugan therapy or combined with ETV could also be suitable to regain the level of laminin, PC-III, and AST, relieve fatigue and HBV-DNA conversion. This NMA confirmed the efficacy and safety of different treatment therapies for improving CHB liver fibrosis, including the serum biomarkers of live fibrosis and serum parameters for liver function, TCM symptoms, imaging indexes, HBV-DNA conversion rate, which offered the TCM practitioners crucial reference value on clinical medication.

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Optimal Dose of Dexmedetomidine for Preemptive Analgesia Combined with Transversus Abdominis Plane Block after Colon Cancer Surgery.

Pain after colon cancer surgery can be effectively relieved by transversus abdominis plane (TAP) block. We aimed to determine the optimal dose of dexmedetomidine for preemptive analgesia when combined with TAP block after colon cancer surgery.

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Biopsychosocial approach to tendinopathy.

Tendinopathy describes a spectrum of changes that occur in damaged tendons, leading to pain and reduced function that remains extremely challenging for all clinicians. There is an increasing awareness of the influence that psychological and psychosocial components, such as self-efficacy and fear-avoidance, have on rehabilitation outcomes in musculoskeletal medicine. Although it is widely accepted that psychological/psychosocial factors exist in tendinopathy, there is currently a distinct lack of trials measuring how these factors affect clinical outcomes. Biopsychosocial treatments acknowledge and address the biological, psychological and social contributions to pain and disability are currently seen as the most efficacious approach to chronic pain. Addressing and modulating these factors are crucial in the pathway of personalised treatments in tendinopathy and offer a real opportunity to drive positive outcomes in patients. In this education review, we also provide the current evidence-based guidance on psychological and psychosocial developments in musculoskeletal medicine and how these may be translated to treating tendinopathy using a biopsychosocial model.

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