Stereoselective Photoredox Catalyzed (3+3) Dipolar Cycloaddition of Nitrone with Aryl Cyclopropane.

By resorting to the principle of remote activation, we herein demonstrate the first photoredox catalyzed (3+3) dipolar cycloaddition of nitrones with aryl cyclopropanes. Key to the fidelity of the reaction resides in a facile manner of substrate activation by single-electron transfer (SET) oxidation with photoredox catalysis, and the reaction takes place through a stepwise cascade encompassing a three-electron-type nucleophilic substitution triggered cyclopropane ring-opening and a diastereoselective 6-endo-trig radical cyclization manifold. The reaction proceeds under mild conditions with excellent regio- and stereoselectivity, nicely complementing the well-developed Lewis acid catalyzed cycloaddition of donor-acceptor cyclopropanes. Other merits of the protocol include wide scope of aryl cyclopropanes with diversified substitution patterns and good functional-group compatibility. A mechanism involving an aryl radical cation promoted remote activation mode was also proposed and supported by mechanistic experiments.

Analgesic effect of auricular point acupressure for acute pain in patients with dementia: study protocol for a randomized controlled trial.

BACKGROUND: Common and frequent as acute pain is, it is often underestimated and undertreated in older people with dementia in nursing homes and inadequate pain management remains an issue. METHODS: The study is designed to be a randomized, sham-controlled trial and is underway in nursing homes located in China. A total of 206 dementia patients are being recruited from nursing homes in Yinchuan, China. They are randomly allocated to an intervention or a controlled group in a 1:1 ratio. The intervention group will be treated with true APP therapy, while the other group will receive APP at sham point stimulation therapy. The patients will be assessed at baseline (T0), at 5 min during performing the intervention (T1), and at 5 min after completion of the intervention (T2). The primary outcome is the level of pain relief at T1 and T2. Physiological parameters, side effects and additional use of analgesics during the procedure, satisfaction from caregivers, and acceptance of patients are evaluated as secondary outcomes. DISCUSSION: The results of this study are expected to verify the analgesic effect of APP for acute pain in patients with mild dementia in nursing homes. It has the potential to prompt APP therapy to be implemented widely in dementia patients with acute pain in nursing homes. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100047932 . Registered on 27 June 2021. Currently, patient recruitment is ongoing. Recruitment is expected to take place from December 2020 to December 2021.

Effect of Auricular Acupressure on Acute Pain in Nursing Home Residents with Mild Dementia: A Single-Blind, Randomized, Sham-Controlled Study.

Introduction: Acute pain is a prevalent problem for dementia residents in nursing homes. A variety of intervention strategies have been applied to address this problem. However, there remains an issue of inadequate pain control. This study aims to explore the analgesic efficacy of auricular acupressure (AA) for dementia residents with acute pain in nursing homes. Methods: A multicenter, single-blind, randomized, and sham-controlled clinical trial was performed in three nursing homes in Yinchuan, China. All of the 206 eligible patients with acute pain were randomly divided into two groups for real AA therapy or sham AA (at sham point stimulation) therapy. The primary outcome was measured with a face pain scale revised (FPS-R) score before the procedure, 5 min after the start of the intervention, and 5 min after finishing the procedure. Secondary outcomes covered three physiological parameters, adverse reactions observed, satisfaction level of caregivers, acceptance of patients, and additional use of analgesics. Results: There was a significant difference in pain scores based on FPS-R between the two groups (p < 0.01). Pain score in the true AA group was 1.84 ± 0.23, compared with 2.22 ± 0.81 in the sham AA group. No adverse events were found during the whole procedure for all patients. The satisfaction level of caregivers and acceptance of patients in the real AA group were significantly higher than those in the sham AA group. Conclusion: This study shows that real AA was an alternative analgesic modality in reducing acute pain in patients with mild dementia.

A fixed nitrous oxide/oxygen mixture as an analgesic for patients with postherpetic neuralgia: study protocol for a randomized controlled trial.

BACKGROUND: The pain management of postherpetic neuralgia (PHN) remains a major challenge, with no immediate relief. Nitrous oxide/oxygen mixture has the advantages of quick analgesic effect and well-tolerated. The purpose of this study is to investigate the analgesic effect and safety of nitrous oxide/oxygen mixture in patients with PHN. METHODS/DESIGN: This study is a single-center, two-group (1:1), randomized, placebo-controlled, double-blind clinical trial. A total of 42 patients with postherpetic neuralgia will be recruited and randomly divided into the intervention group and the control group. The control group will receive routine treatment plus oxygen, and the intervention group will receive routine treatment plus nitrous oxide/oxygen mixture. Data collectors, patients, and clinicians are all blind to the therapy. The outcomes of each group will be monitored at baseline (T0), 5 min (T1), and 15 min (T2) after the start of the therapy and at 5 min after the end of the therapy (T3). The primary outcome measure will be the pain intensity. Secondary outcomes included physiological parameters, adverse effects, patients' acceptance of analgesia, and satisfaction from patients. DISCUSSION: Previous studies have shown that nitrous oxide/oxygen mixture can effectively relieve cancer patients with breakthrough pain. This study will explore the analgesic effect of oxide/oxygen mixture on PHN. If beneficial to patients with PHN, it will contribute to the pain management of PHN. TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR1900023730 . Registered on 9 June 2019.

Pre-mixed nitrous oxide/oxygen mixture treatment of pain induced by postoperative dressing change for perianal abscess: Study protocol for a randomized, controlled trial.

AIM: This study aims to evaluate the safety and analgesic efficacy of pre-mixed nitrous oxide/oxygen mixture treatment of pain induced by dressing change for perianal abscess. DESIGN: This protocol is a randomized, double-blind, placebo-controlled trial. METHODS: This study will be implemented in the Hospital of Traditional Chinese Medicine. Subjects enrolled in this study are hospitalized patients who suffered from moderate to severe pain due to dressing change after incision and drainage. Two hundred patients will be selected and randomly assigned to either an intervention or a control group. The intervention group will get routine pain treatment plus pre-mixed nitrous oxide/oxygen mixture treatment and the control group will be treated with routine pain management plus medical air treatment. All these patients, medical staff and investigators are blind to the nature of the gas in each cylinder, which is randomized. Data will be collected at baseline (T0), 5 min (T1) after the starting of intervention and 5 min post intervention (T2) for each group. The primary outcome is the level of pain relief at T1 and T2. The secondary outcomes cover physiological parameters, adverse events, satisfaction of patients and health professionals and the acceptance from patients. DISCUSSION: Results of this study will be discussed and the safety and effect of nitrous oxide/oxygen treatment of pain induced by dressing change will be proven. IMPACT: When the finding of this study has an active effect on the treatment of pain caused by dressing change, it may provide more options for nursing staff to choose nurse-led analgesia techniques and then improving the level and quality of pain care as well as patients' overall satisfaction with the Anorectal Department in China.

Immersive virtual reality as analgesia for women during hysterosalpingography: study protocol for a randomized controlled trial.

BACKGROUND: Hysterosalpingography (HSG) is an accepted radiologic diagnostic modality for initial infertility workup, and is generally considered uncomfortable and painful. However, the management of pain related to HSG remains inefficient. As an emerging nonpharmacologic and noninvasive pain control strategy, virtual reality (VR) distraction has been successfully used in areas such as burns, blunt force trauma, hospital-based needle procedures, dental/periodontal procedures, and urological endoscopy patients. This study aims to evaluate the analgesic effect of VR during HSG. METHODS/DESIGN: A single-center, parallel-group, randomized controlled trial will be carried out in the Radiology Department of Yinchuan Women and Children Healthcare Hospital, Yinchuan. A total of 200 participants who are scheduled for HSG will be enrolled in this study. The participants will be randomized (1:1) into two groups: a VR group and a blank control group. The VR group will receive routine care plus immersive VR intervention and the blank control group will receive routine care. Outcomes will be monitored at baseline, immediately after HSG and 15 min after HSG for each group. The primary outcome is the worst pain score during HSG by a visual analog scale (VAS). The secondary outcomes include: affective pain, cognitive pain, and anxiety during the HSG procedure; worst pain within 15 min after HSG; patient satisfaction and acceptance with pain management; physiological parameters; adverse effects; HSG results; and immersion perception score of the VR system (for the VR condition only). DISCUSSION: This study will focus on exploring a simply operated, noninvasive and low-cost analgesia during the HSG procedure. The results of this trial will provide data on the feasibility and safety of VR distraction therapy during HSG. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR1900021342. Registered on 16 February 2019.

Analgesic Effect of Nitrous Oxide/Oxygen Mixture for Traumatic Pain in the Emergency Department: A Randomized, Double-Blind Study.

BACKGROUND: Acute pain is the most common complaint in Emergency Department (ED) admissions, and options for analgesia are limited. Nitrous oxide/oxygen possesses many properties showing it may be an ideal analgesic in the ED. OBJECTIVES: The aim of this study is to evaluate the safety and analgesic effect of the fixed nitrous oxide/oxygen mixture for trauma patients in the ED. METHODS: We enrolled 60 patients in this double-blind, randomized study. The treatment group received conventional pain treatment plus a mixture of 65% nitrous oxide/oxygen. The control group received the conventional pain treatment plus oxygen. Primary outcome was the reduction in pain intensity at 5 and 15 min after the start of intervention. Secondary outcomes include adverse events, physiological parameters, and satisfaction from both patients and health care professionals. RESULTS: Initial pain scores for the nitrous oxide/oxygen group (6.0 [5.0-8.0]) and the oxygen group (6.75 [5.0-9.0]) were comparable (p = 0.57). The mean numerical rating scale scores at 5 min were 3.4 ± 1.8 and 7.0 ± 1.8 for nitrous oxide/oxygen and oxygen, respectively (p < 0.01). The mean pain intensity at 15 min in the treatment group was 3.0 ± 1.9, compared with 6.3 ± 2.2 in the control group (p < 0.01). Both patients' (8.0 [7.0-9.0] vs. 4.0 [2.0-6.0], p < 0.01) and physicians' (8.5 [8.0-9.0] vs. 4.0 [3.0-6.0], p < 0.01) satisfaction scores in the treatment group were significantly higher than the oxygen group. No serious adverse events were observed. CONCLUSIONS: This study gives supporting evidence for the safety and effectiveness of using self-administered nitrous oxide/oxygen mixture in the ED for moderate-to-severe traumatic pain.

MiR-34c-5p plays a protective role in chronic obstructive pulmonary disease via targeting CCL22.

Objective: To study the role of miR-34c-5p targeting CCL22 in affecting the progression of chronic obstructive pulmonary disease (COPD). Methods: The dual-luciferase reporter gene assay was applied to verify the targeting relationship of miR-34c-5p and CCL22. The rats were randomly assigned into Control, COPD, COPD + empty plasmids, COPD + agomir, COPD + CCL22 shRNA and COPD + agomir + CCL22 groups. COPD model was built by using cigarette smoke exposure and LPS instillation. After 28 days, the pulmonary function was examined. ELISA method was used to detect TNF-α and IL-8 levels in bronchoalveolar lavage fluid (BALF), HE staining and Masson staining to observe the pathomorphological changes of lung tissues, qRT-PCR and/or Western blot to determine miR-34c-5p and CCL22 levels, and immunohistochemical staining to measure the expression of MMP-9 and TIMP-1. Results: MiR-34c-5p could target CCL22 to down-regulate its expression. Both miR-34c-5p agomir and CCL22 shRNA could reduce breathing frequency (f), airway resistance (RI), and the levels of IL-8 and TNF-α in BALF of COPD rats with increased Cydn (dynamic lung compliance) and PIF (peak inspiratory flow). Besides, the inflammatory cell infiltration, rupture of partial alveolus, enlarged alveolar cavity, and increased deposition of collagen fibers were observed in COPD rat tissues, with rise in mean linear intercept (MLI) and reduction in mean alveolar number (MAN), which could be reversed by miR-34c-5p agomir or CCL22 shRNA. Conclusion: MiR-34c-5p may promote inflammation response and maintain the protease-antiprotease balance via targeting CCL22, which provides scientific basis for the clinical treatment of COPD.

A Fixed Nitrous Oxide and Oxygen Mixture for Analgesia in Children With Leukemia With Lumbar Puncture-induced Pain: A Randomized, Double-blind Controlled Trial.

CONTEXT: Leukemia is the most common cancer in the childhood population. Lumbar puncture (LP) plays central role in the diagnosis and treatment process, but options for analgesia are limited. OBJECTIVES: The present study aims to evaluate the efficacy of a fixed N2O/O2 mixture to reduce pain in children with leukemia during LP as compared with placebo. METHODS: A double-blind, placebo-controlled, and randomized clinical trial involving children who needed LP for diagnosis or treatment was conducted in the pediatrics department of the General Hospital of Ningxia Medical University. Eligible patients were randomly assigned to inhale either a fixed N2O/O2 mixture or O2. The primary endpoint was the maximal pain level felt by the patient during the procedure measured using a numerical rating scale (0-10). RESULTS: One-hundred fourteen consecutive patients were enrolled in this study and randomized. Pain scores during the procedure showed a significant decrease in N2O/O2 mixture-treated patients to 1.05 ± 1.40 versus 8.00 ± 2.13 in controls (P < 0.01). No serious adverse effects were attributed to N2O/O2 mixture inhalation. Analysis of the satisfaction of patients receiving N2O/O2 mixture indicated that medical staff were satisfied with this treatment. CONCLUSIONS: This study demonstrated that self-administered fixed N2O/O2 is efficient to reduce pain related to LP in children with leukemia.

miR-200c regulates crizotinib-resistant ALK-positive lung cancer cells by reversing epithelial-mesenchymal transition via targeting ZEB1.

Crizotinib is an orally administered drug for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non­small cell lung cancer (NSCLC). Despite the impressive efficacy of crizotinib in the treatment of ALK­positive lung cancer, acquired resistance eventually develops in the majority of patients. The microRNA (miR)­200c reverses the resistance of lung cancer cells to various chemotherapeutic drugs and molecular targeted drugs, however, whether it can reverse the resistance of crizotinib remains unknown. The present study established a crizotinib resistant cell line (NCI­2228/CRI), which was derived from the parental NCI­2228 cell line by long­term exposure to increasing concentrations of crizotinib. Through overexpression and suppression of miR­200c expression, the characteristics associated with epithelial­mesenchymal transition (EMT), including morphology, EMT marker proteins and cellular mobility, were investigated. Cell viability and invasion assays demonstrated that high expression of miR­200c significantly inhibited the proliferation, migration and invasion of NCI­2228 cells compared with the negative control. A luciferase reporter assay indicated that miR­200c directly targeted the 3'­untranslated region of zinc finger E­box binding homeobox 1. Additionally, reverse transcription­quantitative polymerase chain reaction analysis demonstrated that the mRNA levels of N­cadherin and Vimentin were decreased in NCI­2228 cells transfected with miR­200c mimic compared with negative control cells, whereas the mRNA level of E­cadherin was increased. In addition, EMT was reversed by miR­200c, which suggests that miR­200c may serve a role in mediating the sensitivity of NCI­2228/CRI cells to crizotinib. The present study may therefore contribute to improving the sensitivity of ALK positive lung cancer cells to crizotinib.

Theoretical study on the mechanism of Ag-catalyzed synthesis of 3-alkylideneoxindoles from N-aryl-α-diazoamides: a Lewis acid or Ag-carbene pathway?

The mechanism of the title reaction is found to consist of three steps by DFT calculations: (1) N(2) dissociation, (2) intramolecular Ag-carbene addition, and (3) proton transfer. The N(2) dissociation is turnover determining. The product 3-alkylideneoxindole is favored in tautomerization with 3-acetyl-2-hydroxyindole.