Rejected

Herein, we summarize the steps of a common scientific path taken by the two Guest Editors, an Anesthesiologist (EA) and an Immunologist (AS), and started 25 years ago at the National Cancer Institute in Rome. When in 1980 WHO codified the usage of opioids for cancer pain relief, it was matter of debate whether only disease progression rather than opioid tolerance were the driving force of opioid escalation. The selective intratumoral accumulation of morphine observed in an experimental xenograft model – the initial scenario of our scientific collaboration – revealed a surprising interaction between the opioid and the opioid receptors expressed by cells of tumor microenvironment. This link could explain the peculiar opioid tolerance and likely hyperalgesia that were observed in the emerging clinical experience of cancer paradoxical pain and suggestive of opioid ambiguity. More elegant cancer pain experimental models, in particular of bone cancer demonstrated the relevance of inflammatory mediators produced and released by tumor microenvironment cells. These factors were the words of an immune-mediated cross-talk between the tumor and the peripheral and central nervous systems leading to neuroinflammation and consequent pain hypersensitivity, chronicization of acute pain and maladaptive neuroplasticity. Immunology identified in the microglia activation a crucial hub of neuroinflammation and pain centralization. Subsequently the discovery of TLR-4 capacity to bind to opioids on glial cells revealed that they shared the same neuroinflammatory mechanisms underlying cancer and non cancer pain, and could also worsen pain for which they were used. The late awareness of this knowledge and the poor integration between immunological and pain sciences contributed to the recent severe opioid crisis in the USA (opioid epidemic) with a consequent limitation of long-term use of these drugs in non cancer pain, and generated a new wave of opiophobia. Immunological evidence-based pain therapies are currently quite sophisticated, but only little clinically exploited yet. To save the analgesic use of opioids would require the overcome of their intrinsic ability to cause both analgesia and hyperalgesia in a very ambiguous manner. At moment not to hijack and not to usurp the immune system appears still a very far goal.

Epigynum auritum has been historically used as a "dai" or traditional medicine for the treatment of inflammation, swelling and severe pain during injury; these may reduce risk of disease and lead to healthier aging. Apart from this, Epigynum auritum extract was also used in arhritis treatment which is also a type of inflammation. Previous phytochemical studies of E. auritum revealed that steroids are main characteristic components with a number of biological activities (especially immunosuppressive and anti-inflammatory activity) Nevertheless, the underlying mechanism of the E. auritum on inflammatory diseases is still unresolved.

To explore the application of magnetic resonance imaging (MRI) information image-guided puncture intelligent surgical robot and robot combined with intercostal nerve block (INB) in the treatment of lung cancer.

Blood cultures (BCs) detect an estimated 50% of typhoid fever cases. There is need for validated clinical criteria to define cases that are BC negative, both to help direct empiric antibiotic treatment and to better evaluate the magnitude of protection conferred by typhoid vaccines. To derive and validate a clinical rule for defining BC-negative typhoid fever, we assessed, in a cluster-randomized effectiveness trial of Vi-polysaccharide (ViPS) typhoid vaccine in Kolkata, India, 14,797 episodes of fever lasting at least 3 days during 4 years of comprehensive, BC-based surveillance of 70,865 persons. A recursive partitioning algorithm was used to develop a decision rule to predict BC-proven typhoid cases with a diagnostic specificity of 97-98%. To validate this rule as a definition for BC-negative typhoid fever, we assessed whether the rule defined culture-negative syndromes prevented by ViPS vaccine. In a training subset of individuals, we identified the following two rules: rule 1: patients aged < 15 years with prolonged fever accompanied by a measured body temperature ≥ 100°F, headache, and nausea; rule 2: patients aged ≥ 15 years with prolonged fever accompanied by nausea and palpable liver but without constipation. The adjusted protective efficacy of ViPS against clinical typhoid defined by these rules in persons aged ≥ 2 years in a separate validation subset was 33% (95% CI: 4-53%). We have defined and validated a clinical rule for predicting BC-negative typhoid fever using a novel vaccine probe approach. If validated in other settings, this rule may be useful to guide clinical care and to enhance typhoid vaccine evaluations.

Neurological diseases are the leading cause of disability and the second leading cause of death worldwide. Physical and psychological pain, despair, and disconnection with the environment are observed after the diagnosis of numerous neurological processes, particularly neurodegenerative diseases.

Propofol is widely used in general anesthesia, and it has been reported to protect various organs against ischemia-reperfusion injury (IRI), including liver. To evaluate the hepatoprotective effects of ischemic preconditioning (IP) under propofol anesthesia, we investigated the possible underlying mechanisms in rats.

Osteoarthritis (OA) is an age-associated disease characterized by chronic joint pain resulting from degradation of articular cartilage, inflammation of the synovial lining, and changes to the subchondral bone. Despite the wide prevalence, no FDA-approved disease-modifying drugs exist. Recent evidence has demonstrated that epigenetic dysregulation of multiple molecular pathways underlies OA pathogenesis, providing a new mechanistic and therapeutic axis with the advantage of targeting multiple deregulated pathways simultaneously. In this review, we focus on the epigenetic regulators that have been implicated in OA, their individual roles, and potential crosstalk. Finally, we discuss the pharmacological molecules that can modulate their activities and discuss the potential advantages and challenges associated with epigenome-based therapeutics for OA.

Herpes zoster (HZ), commonly called shingles, it is a distinctive syndrome caused by reactivation of varicella zoster virus (VZV). A better understanding of the biological characteristics of HZ patients can help develop new targeted therapies to improve the prognosis. High-throughput proteomics technology can deeply study the molecular changes in the development and progression of HZ disease and integrate different levels of information, this is important to help make clinical decisions. Circulating blood contains a lot of biological information, we conducted a proteomics study of patient plasma, hoping to identify key proteins that could indicate the development of HZ. Compared to healthy human plasma, we found 44 differentially expressed proteins in the plasma of HZ patients, the main pathways involved in these molecules are MAPK signaling pathway, Neuroactive ligand-receptor interaction, Acute myeloid leukemia, Transcriptional misregulation in cancer. We found that 27 proteins have direct protein-protein interactions. Based on the comprehensive score, we identified six key molecules as candidate molecules for further study, and then validated another 80 plasma samples (40 HZ patient plasma and 40 healthy human plasma) using enzyme-linked immunosorbent assay (ELISA), immunoblot assay and receiver operating characteristic (ROC) curve analysis. Finally, we found that the expression levels of these three proteins (PLG, F2, VTN) were significantly lower than those of healthy controls (P < .05). To the best of our knowledge, we first used tandem mass tag (TMT) combined with liquid chromatography-mass spectrometry (LC-MS/MS) to screen for differentially expressed proteins in plasma between HZ patients and healthy individuals. It is preliminarily proved that the plasma protein expression profile of HZ patients is different from that of uninfected patients, it has also been found that these three altered key proteins may be used as biomarkers to test early HZ infection. This study reveals new insights into HZ that help to more accurately identify early HZ patients and to find new therapeutic targets. SIGNIFICANCE: Varicella-zoster virus (VZV; termed human alphaherpesvirus 3 by the International Committee on Taxonomy of Viruses) is a herpesvirus that is ubiquitous in humans and can cause chickenpox and herpes zoster (HZ). After the initial infection of varicella, the VZV goes into a dormant state in the sensory ganglia and cranial nerves. As age or immunosuppression increases, the cellular immunity to VZV decreases, and the virus reactivates and spreads along the sensory nerves to the skin, causing a unique prodromal pain followed by a rash. About one in five people around the world may be infected with VZV at some point in their lives. According to statistics, about one-third of infected people will develop HZ in their lifetime, and an estimated 1 million cases of herpes zoster occur in the United States each year. Herpes zoster can occur at any age and is usually less severe in children and young adults, but the greatest morbidity and mortality are observed in elderly and immunocompromised patients. 20% of patients with HZ have complications including vasculitis, increased risk of myocardial infarction, or postherpetic neuralgia, the overall mortality rate of patients with HZ in the United States is close to 5%. Considering the wide clinical severity and complications of this disease, there is a great need for biomarkers that contribute to early diagnosis, classification of risks, and prediction of outcomes, which will help elucidate the mechanisms underlying their clinical development. As a useful tool in biology, quantitative proteomics can repeatedly identify and accurately quantify proteins in a variety of biological samples. Proteomic analysis focuses on translational proteins, which play a direct role in most biological processes. Although a small number of proteins can be studied simultaneously with traditional methods, such as ELISA and Western blotting, typical proteomics studies can simultaneously analyze thousands of proteins for a more comprehensive identification. Proteomics has been successfully applied to human-based disease research, Analysis of exposed and unexposed subjects based on mass spectrometry (MS) has been found to reveal altered expression of proteins that can be identified as intermediate biomarkers of early disease effects. Tandem mass tags (TMTs) are chemical labels used for MS-based identification and quantification of biological molecules. TMTs play an important role in proteomic analysis in a variety of samples such as cells, tissues, and body fluids. The body fluids that are often detected clinically are blood, which are easy to obtain and contain abundant biological information related to physiological and pathological processes, we hope to develop protein biomarkers from these blood. Therefore, in order to better characterize the pathological process of HZ patients, we performed proteomic analysis of HZ patients and healthy human plasma using the TMT method. This comparison aims to identify specific processes in the development of HZ disease through protein profiling, which may help to improve our biological understanding of HZ.

There have been significant advancements in the safe delivery of anesthesia as well as improvements in surgical technique; however, the perioperative period can still be high risk for the pediatric patient. Perioperative respiratory complications (PRCs) are some of the most common critical events that can occur in pediatric surgical patients and they can lead to increased length of hospitalization, worsened patient outcomes, and higher hospital and postoperative costs. It is important to determine the various factors that put pediatric patients at increased risk of PRCs. This will allow for more detailed and accurate informed consent, optimized perioperative management strategy, improved allocation of clinical resources, and, hopefully, better patient experience. There are only a few risk prediction models/scoring tools developed for and validated in the pediatric patient population, but they have been useful in helping identify the key factors associated with a high likelihood of developing PRCs. Some of these factors are patient factors, while others are procedure-related factors. Some of these factors may be modified such that the patient's clinical status is optimized preoperatively to decrease the risk of PRCs occurring perioperatively. Fore knowledge of the factors that are not able to be modified can help guide allocation of perioperative clinical resources such that the negative impact of these non-modifiable factors is buffered. Additional training in pediatric anesthesia or focused expertise in pediatric airway management, vascular access and management of massive hemorrhage should be considered for the perioperative management of the less than 3 age group. Intraoperative ventilation strategy plays a key role in determining respiratory outcomes for both adult and pediatric surgical patients. Key components of lung protective mechanical ventilation strategy such as low tidal volume and moderate PEEP used in the management of acute respiratory distress syndrome (ARDS) in pediatric intensive care units have been adopted in pediatric operating rooms. Adequate post-operative analgesia that balances pain control with appropriate mental status and respiratory drive is important in reducing PRCs.