A nitrous oxide/oxygen fixed mixture to reduce pain induced by the hypodermic injection: study protocol for a randomized, controlled trial.

BACKGROUND: Patients with hematological malignancies received multiple hypodermic injections of recombinant human granulocyte colony-stimulating factor. Procedural pain is one of the most common iatrogenic causes of pain in patients with hematological malignancies. It is also identified as the most commonly occurring problem in clinical care in the Department of Hematology and Oncology at Shenzhen University General Hospital. However, providing immediate relief from pain induced by hypodermic injection of recombinant human granulocyte colony-stimulating factor remains a major challenge. This trial aims to evaluate the safety and analgesic efficacy of a fixed nitrous oxide/oxygen mixture for patients with hematological malignancies and experiencing procedural pain caused by hypodermic injection of recombinant human granulocyte colony-stimulating factor in the department. METHODS: The nitrous oxide/oxygen study is a single-center, randomized, double-blind, placebo-controlled trial involving patients with hematological malignancies who require hypodermic injections of recombinant human granulocyte colony-stimulating factor for treatment. This trial was conducted in the Hematology and Oncology Department of Shenzhen University General Hospital. A total of 54 eligible patients were randomly allocated to either the fixed nitrous oxide/oxygen mixture group (n = 36) or the oxygen group (n = 18). Neither the investigators nor the patients known about the randomization list and the nature of the gas mixture in each cylinder. Outcomes were monitored at the baseline (T0), immediately after hypodermic injection of recombinant human granulocyte colony-stimulating factor (T1), and 5 min after hypodermic injection of recombinant human granulocyte colony-stimulating factor (T2) for each group. The primary outcome measure was the score in the numerical rating scale corresponding to the highest level of pain experienced during hypodermic injection of recombinant human granulocyte colony-stimulating factor. Secondary outcomes included the fear of pain, anxiety score, four physiological parameters, adverse effects, total time of gas administration, satisfaction from both patients and nurses, and the acceptance of the patients. DISCUSSION: This study focused on the safety and analgesic efficacy during hypodermic injection of recombinant human granulocyte colony-stimulating factor procedure. Data on the feasibility and safety of nitrous oxide/oxygen therapy was provided if proven beneficial to patients with hematological malignancies during hypodermic injection of recombinant human granulocyte colony-stimulating factor and widely administered to patients with procedural pain in the department. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2200061507. Registered on June 27, 2022. http://www.chictr.org.cn/edit.aspx?pid=170573&htm=4.

Hypoxia Affects Mitochondrial Stress and Facilitates Tumor Metastasis of Colorectal Cancer Through Slug SUMOylation.

BACKGROUND: Colorectal cancer (CRC) is a malignant tumor. Slug has been found to display a key role in diversified cancers, but its relevant regulatory mechanisms in CRC development are not fully explored. OBJECTIVE: Hence, exploring the function and regulatory mechanisms of Slug is critical for the treatment of CRC. METHODS: Protein expressions of Slug, N-cadherin, E-cadherin, Snail, HIF-1α, SUMO1, Drp1, Opa1, Mfn1/2, PGC-1α, NRF1, and TFAM were measured through western blot. To evaluate the protein expression of Slug and SUMO-1, an immunofluorescence assay was used. Cell migration ability was tested through transwell assay. The SUMOylation of Slug was examined through CO-IP assay. RESULTS: Slug displayed higher expression and facilitated tumor metastasis in CRC. In addition, hypoxia treatment was discovered to upregulate HIF-1α, Slug, and SUMO-1 levels, as well as induce Slug SUMOylation. Slug SUMOylation markedly affected mitochondrial biosynthesis, fusion, and mitogen-related protein expression levels to trigger mitochondrial stress. Additionally, the induced mitochondrial stress by hypoxia could be rescued by Slug inhibition and TAK-981 treatment. CONCLUSION: Our study expounded that hypoxia affects mitochondrial stress and facilitates tumor metastasis of CRC through Slug SUMOylation.

Antinociceptive and neuroprotective effect of echinacoside on peripheral neuropathic pain in mice through inhibiting P2X7R/FKN/CX3CR1 pathway.

Clinically, neuropathic pain treatment remains a challenging issue because the major therapy, centred around pharmacological intervention, is not satisfactory enough to patient by reason of low effectiveness and more adverse reaction. Therefore, it is still necessary to find more effective and safe therapy to ameliorate neuropathic pain. The purpose of this study was to explore the antinociceptive effect of Echinacoside (ECH), an active compound of Cistanche deserticola Ma, on peripheral neuropathic pain induced by chronic constriction injury (CCI) in mice, and to demonstrate its potential mechanism in vivo and vitro. In the present study, results showed that intraperitoneal administration of ECH (50, 100, and 200 mg/kg) could alleviate mechanical allodynia, cold allodynia and thermal hyperalgesia via behavioural test. Moreover, the structure and function of injured sciatic nerve by CCI were taken a turn for the better to a certain extent after ECH treatment using histopathological and electrophysiological test. Furthermore, ECH repressed the expression of the P2X7R and FKN and reduced the expression and release of the IL-1ß, IL-6 and TNF-α. Besides, ECH could decrease Ca2+ influx and Cats efflux and inhibit phosphorylation of p38MAPK. To sum up, the present study illustrated that ECH could alleviate peripheral neuropathic pain by inhibiting microglia overactivation and inflammation through P2X7R/FKN/CX3CR1 signalling pathway in spinal cord. This study would provide a new perspective and strategy for the pharmacological treatment on neuropathic pain.

Increased joint loading induces subchondral bone loss of the temporomandibular joint via the RANTES-CCRs-Akt2 axis.

Early-stage temporomandibular joint osteoarthritis (TMJOA) is characterized by excessive subchondral bone loss. Emerging evidence suggests that TMJ disc displacement is involved, but the pathogenic mechanism remains unclear. Here, we established a rat model of TMJOA that simulated disc displacement with a capacitance-based force-sensing system to directly measure articular surface pressure in vivo. Micro-CT, histological staining, immunofluorescence staining, IHC staining, and Western blot were used to assess pathological changes and underlying mechanisms of TMJOA in the rat model in vivo as well as in RAW264.7 cells in vitro. We found that disc displacement led to significantly higher pressure on the articular surface, which caused rapid subchondral bone loss via activation of the RANTES-chemokine receptors-Akt2 (RANTES-CCRs-Akt2) axis. Inhibition of RANTES or Akt2 attenuated subchondral bone loss and resulted in improved subchondral bone microstructure. Cytological studies substantiated that RANTES regulated osteoclast formation by binding to its receptor CCRs and activating the Akt2 pathway. The clinical evidence further supported that RANTES was a potential biomarker for predicting subchondral bone loss in early-stage TMJOA. Taken together, this study demonstrates important functions of the RANTES-CCRs-Akt2 axis in the regulation of subchondral bone remodeling and provides further knowledge of how disc displacement causes TMJOA.

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.

Effect of Lycium barbarum polysaccharide supplementation in non-alcoholic fatty liver disease patients: study protocol for a randomized controlled trial.

BACKGROUND: Non-alcohol fatty liver disease (NAFLD) is the most common chronic liver disease in the world, with a high incidence and no effective treatment. At present, the targeted therapy of intestinal microbes for NAFLD is highly valued. Lycium barbarum polysaccharide (LBP), as the main active ingredient of Lycium barbarum, is considered to be a new type of prebiotic substance, which can improve NAFLD by regulating the gut microbiota. The purpose of this study is to evaluate the safety and efficacy of LBP supplementation in modulating gut microbiota for NAFLD patients. METHODS: This randomized, double-blind, placebo-control study will be conducted in the physical examination center of the Ningxia Hui Autonomous Region People's Hospital. A total of 50 patients with NAFLD confirmed by abdominal ultrasound, laboratory tests, and questionnaire surveys will be recruited and randomly assigned into the control group (maltodextrin placebo capsules) and the intervention group (LBP supplementation capsules) for 3 months. Neither patients, nor investigators, nor data collectors will know the contents in each capsule and the randomization list. The primary outcome measure is the level of ALT concentration relief after the intervention. Secondary outcomes include gut microbiota abundance and diversity, intestinal permeability, patient's characteristic demographic data and body composition, adverse effects, and compliance from patients. DISCUSSION: LBPs are potential prebiotics with the property of regulating host gut microbiota. Our previous studies have documented that LBP supplement can improve the liver damage and the gut microflora dysbiosis in NAFLD rats. This treatment would provide a more in-depth understanding of the effect of this LBP supplementation. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2000034740 . Registered on 17 July 2020.

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.

Glycosides for Peripheral Neuropathic Pain: A Potential Medicinal Components.

Neuropathic pain is a refractory disease that occurs across the world and pharmacotherapy has limited efficacy and/or safety. This disease imposes a significant burden on both the somatic and mental health of patients; indeed, some patients have referred to neuropathic pain as being 'worse than death'. The pharmacological agents that are used to treat neuropathic pain at present can produce mild effects in certain patients, and induce many adverse reactions, such as sedation, dizziness, vomiting, and peripheral oedema. Therefore, there is an urgent need to discover novel drugs that are safer and more effective. Natural compounds from medical plants have become potential sources of analgesics, and evidence has shown that glycosides alleviated neuropathic pain via regulating oxidative stress, transcriptional regulation, ion channels, membrane receptors and so on. In this review, we summarize the epidemiology of neuropathic pain and the existing therapeutic drugs used for disease prevention and treatment. We also demonstrate how glycosides exhibit an antinociceptive effect on neuropathic pain in laboratory research and describe the antinociceptive mechanisms involved to facilitate the discovery of new drugs to improve the quality of life of patients experiencing neuropathic pain.

[Proliferation-Inhibitory and Apoptosis-Inducing Effects of Targeting MTH1 on Multiple Myeloma Cells].

OBJECTIVE: To detect the expression of MutT homolog 1 (MTH1) in CD138-negative cells (CD138-) and CD138-positive cells (CD138+) cells of the patients with multiple myeloma (MM), and to explore the effect of MTH1 inhibitor TH588 on cell morphology, proliferation and apoptosis of MM cell U266. METHODS: CD138- and CD138+ cells of MM patients were isolated, and RNA was extracted. The expression of NUDT family was detected by Q-PCR. MM cell line U266 was used to observe the effect of IL-6 on MTH1 expression. Using fluorescence microscopy to observe the morphological changes of U266 after treatment by TH588 for 48 hours. DAPI staining was used to investigate the nuclear change. Luciferase was used to detect the effect of TH588 on U266 cell proliferation. After treatment with TH588 for 48 h, the change of apoptosis in MM U266 cells was detected by flow cytometer. RESULTS: In some MM patients, the expression of MTH1, NUDT2, NUDT5 and NUDT21 in CD138+ cells was higher than that in CD138- (P<0.05). The luciferase report showed that after treatment of U266 cells with TH588, the fluorescence intensity was significantly lower than that of the control group, and the fluorescence intensity decreased with the increase of drug concentration (r=-0.91). IL-6 could increase the expression of MTH1. Fluorescence microscopy showed that after TH588 treatment of U266 cells for 48 hours, the cells appeared shrinking, smaller, and irregular in shape. After DAPI staining, the TH588-treated cells showed apoptosis characteristics, such as nuclear shrinkage, uneven staining, petal, and radial shape. Flow cytometry showed that the proportion of U266 viable cells decreased significantly after treatment with TH588 for 48 h (P<0.05). CONCLUSION: MTH1 highly expresses in CD138+ cells of some MM patients. MTH1 expression can increase in U266 cells treated by IL-6. The MTH1 inhibitor TH588 possesses proliferation-inhibitory effect and apoptosis-inducing effect on MM cell U266.

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.

[Meta-analysis on effectiveness and safety of Pudilan Xiaoyan Oral Liquid on child upper respiratory infection].

To systematically review the effectiveness and safety of Pudilan Xiaoyan Oral Liquid on child upper respiratory infection and conduct Meta-analysis. We electronically retrieved databases, including PubMed, Web of Science, VIP, WanFang and CNKI, for published articles of randomized controlled trials(RCTs) of Pudilan Xiaoyan Oral Liquid on child upper respiratory infection from inception to April 2019. According to the inclusion and exclusion criteria, two reviewers independently screened out literatures, extracted data and assessed the risk of bias in included studies. Then, Meta-analysis were conducted by Stata 15.0 software. A total of 16 RCTs involving 1 924 patients with upper respiratory infection were included. The results of Meta-analysis showed that the improvement of clinical symptoms, such as fever subsided time(WMD=-3.66, 95%CI[-4.61,-2.72], P<0.001), cough time(WMD=-1.89, 95%CI[-2.51,-1.27], P<0.001), time of runny noses(WMD=-4.60, 95%CI[-5.85,-3.34], P<0.001) and time of sore throat(WMD=-2.62, 95%CI[-3.54,-1.70], P<0.001). Meanwhile, the results of Meta-analysis showed the improvement of laboratory indications, including TNF-α(WMD=-2.68, 95%CI[-2.98,-1.58], P<0.001) and IL-6(WMD=-2.26, 95%CI[-3.36,-2.36], P<0.01). The current evidence shows that Pudilan Xiaoyan Oral Liquid may significantly improve the effectiveness and safety. According to the limited quality of included studies, the above conclusion needs be to verified with more high-quality studies.

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.

Monitoring the course of Brucella infection with qPCR-based detection.

OBJECTIVES: To determine blood Brucella DNA loads between brucellosis patients and those without brucellosis. METHODS: The patient group included 350 brucellosis patients. The control was composed of 200 subjects without brucellosis. The extracted DNA from blood was tested by quantitative polymerase chain reaction (qPCR). The cutoff value was determined by receiver operating characteristic curve analysis. A portion of the brucellosis patients were monitored by qPCR during therapy. RESULTS: The detection limit of qPCR was between 1E+01cfu/µL and 1E+08cfu/µL. The standard curve R2 reached 0.998. The cutoff value was 4E+01cfu/µL, which was determined by comparison of the patient group and the control. The qPCR assay had a specificity of 100% and a sensitivity of 93.14%. The monitoring results showed that the Brucella DNA load decreased in most patients during the first 4 weeks of treatment. One patient with bad treatment compliance showed a rebound. CONCLUSIONS: The qPCR results were in accordance with the course of brucellosis in the clinic. The DNA load often reflects the situation of the Brucella-infected patient. The cutoff value provides an important reference of infection. This qPCR-based method can be used to assist in the diagnosis of brucellosis and to adjust the therapy.

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.

Analgesia effect of premixed nitrous oxide/oxygen during the rehabilitation after total knee arthroplasty: a study protocol for a randomized controlled trial.

BACKGROUND: The morbidity of knee arthritis is increasing among aged people and total knee arthroplasty has been its mainstream treatment to date. Postoperative rehabilitation is an important part of the procedure. However, the intense pain during the functional exercise involved has always been a challenge for both patients and health care professionals. The aim of this study is to test the analgesic effect of a mixture of nitrous oxide/oxygeb (1:1) inhalation for patients who are doing functional exercise 1 month after total knee arthroplasty. METHODS/DESIGN: This double-blind, randomized, placebo-controlled study will be implemented in the Rehabilitation Department in the General Hospital of Ningxia Medical University. Patients aged between 50 and 75 years who underwent a primary unilateral total knee arthroplasty are eligible for inclusion. The key exclusion criteria include: epilepsy, pulmonary embolism, intestinal obstruction, aerothorax. The treatment group (A) will receive a pre-prepared nitrous oxide/oxygen mixture plus conventional treatment (no analgesics), and the control group (B) will receive oxygen plus conventional treatment (no analgesics). Patients, physicians, therapists, and data collectors are all blind to the experiment. Assessments will be taken immediately after functional exercise begins (T0), 5 min (T1) after functional exercise begins, and 5 min after functional exercise has finished (T2). Patients will be randomly allocated between a treatment group (A) and a control group (B) in a ratio of 1:1. Primary outcome, including pain severity in the procedure, will be taken for each group. Secondary outcomes include blood pressure, heart rate, oxygen saturation, side effects, knee joint range of motion, Knee Society Score (KSS), rescue analgesia need, and satisfaction from both therapists and patients. DISCUSSION: This study will focus on exploring a fast and efficient analgesic for patients who are doing functional exercise after total knee arthroplasty. Our previous studies suggested that the prefixed nitrous oxide/oxygen mixture was an efficacious analgesic for the management of burn-dressing pain and breakthrough cancer pain. The results of this study should provide a more in-depth insight into the effects of this analgesic method. If this treatment proves successful, it could be implemented widely for patients doing functional exercise in the rehabilitation department. TRIAL REGISTRATION: ChiCTR-INR-17012891 . Registered on 6 October 2017.

miRNA-17-92 protects endothelial cells from erastin-induced ferroptosis through targeting the A20-ACSL4 axis.

Endothelial cell death is linked to vascular diseases such as atherosclerosis and tissue ischemia. miRNA-17-92 (miR-17-92) is a multiple functional oncogenic miRNA cluster which plays vital roles in tumor angiogenesis and tissue development. However, its role in regulation of endothelial cell ferroptosis remains unclear. In this study, we revealed that miR-17-92 protects endothelial HUVEC cells from erastin-induced ferroptosis. miR-17-92 overexpression significantly reduced erastin-induced growth inhibition and ROS generation of HUVEC cells. Furthermore, Zinc lipoprotein A20, a validated target of miR-17-92, was identified as a novel regulator of endothelial cell ferroptosis. Lentivirus mediated A20 overexpression increased ROS generation and enhanced erastin-induced ferroptosis, whereas A20 knockdown inhibited erastin-induced ferroptosis. Mechanistic studies revealed that erastin-induced ferroptosis is associated with GPX4 downregulation and ACSL4 upregulation. miR-17-92 overexpression or A20 inhibition increased the ACSL4 expression in HUVEC cells. A20 was identified to directly with and regulate ACSL4 expression by immunoprecipitation. It suggests that the A20-ACSL4 axis plays important roles in erastin-induced endothelial ferroptosis. In conclusion, this study revealed a novel mechanism through which miR-17-92 protects endothelial cells from erastin-induced ferroptosis by targeting the A20-ACSL4 axis.

The effectiveness of acupuncture therapy in patients with post-stroke depression: An updated meta-analysis of randomized controlled trials.

BACKGROUND: To assess the effectiveness of acupuncture in patients with post-stroke depression (PSD). METHODS: The Cochrane Library, CINAHL, EMBASE, PubMed, SCOPUS, Web of Science, and 4 Chinese databases were electronically searched for articles published between January 1, 2010 and May 31, 2018. Randomized controlled trials (RCTs) investigating the effects of acupuncture on PSD were included. The quality of all included trials was assessed according to guidelines published by the Cochrane Collaboration. RESULTS: Seven trials compared the effectiveness of acupuncture therapy with that of control in alleviating the symptoms of PSD. Pooled analysis demonstrated that patients in the acupuncture intervention group experienced a significantly higher treatment effect than controls (RR 1.16 [95% CI 1.08-1.24]; P < .0001), with low study heterogeneity (I = 4%). Based on intervention methods, further analysis revealed a statistically significant difference in effectiveness between the acupuncture alone and medicine groups (RR 1.25 [95% CI 1.11 1.41]; Z = 3.78; P = .0002). There was no statistically significant difference in efficacy between the acupuncture combined with medicine and medicine groups (RR 1.07 [95% CI 0.98-1.17]; P = .11). CONCLUSIONS: This meta-analysis provides evidence supporting the viewpoint that acupuncture is an effective and safe treatment for PSD. Subgroup analyses further revealed that acupuncture alone resulted in better outcomes than drug therapy in improving depressive symptoms. Further high-quality RCTs are needed to systematically evaluate the effectiveness of acupuncture for PSD and develop standardized acupuncture protocols.

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.