Esketamine inhibits the c-Jun N-terminal kinase pathway in the spinal dorsal horn to relieve bone cancer pain in rats.

Cancer-induced bone pain (CIBP) is one of the most common and feared symptoms in patients with advanced tumors. The X-C motif chemokine ligand 12 (CXCL12) and the CXCR4 receptor have been associated with glial cell activation in bone cancer pain. Moreover, mitogen-activated protein kinases (MAPKs), as downstream CXCL12/CXCR4 signals, and c-Jun, as activator protein AP-1 components, contribute to the development of various types of pain. However, the specific CIBP mechanisms remain unknown. Esketamine is a non-selective N-methyl-d-aspartic acid receptor (NMDA) inhibitor commonly used as an analgesic in the clinic, but its analgesic mechanism in bone cancer pain remains unclear. We used a tumor cell implantation (TCI) model and explored that CXCL12/CXCR4, p-MAPKs, and p-c-Jun were stably up-regulated in the spinal cord. Immunofluorescence images showed activated microglia in the spinal cord on day 14 after TCI and co-expression of CXCL12/CXCR4, p-MAPKs (p-JNK, p-ERK, p-p38 MAPK), and p-c-Jun in microglia. Intrathecal injection of the CXCR4 inhibitor AMD3100 reduced JNK and c-Jun phosphorylations, and intrathecal injection of the JNK inhibitor SP600125 and esketamine also alleviated TCI-induced pain and reduced the expression of p-JNK and p-c-Jun in microglia. Overall, our data suggest that the CXCL12/CXCR4-JNK-c-Jun signaling pathway of microglia in the spinal cord mediates neuronal sensitization and pain hypersensitivity in cancer-induced bone pain and that esketamine exerts its analgesic effect by inhibiting the JNK-c-Jun pathway.

Clinical effect of aerobic exercise training in chronic obstructive pulmonary disease: A retrospective study.

Aerobic exercise training is a kind of pulmonary rehabilitation for lung diseases. This was a retrospective study to assess the efficacy of aerobic exercise training in chronic obstructive pulmonary disease (COPD) at a stable stage. A total of one hundred and fifty-six stable COPD patients who had accepted self-education only or self-education combined with an aerobic exercise training between January 2017 to January 2019 were reviewed retrospectively. A total of 79 patients who had received self-education combined with an aerobic exercise training schedule comprised the aerobic exercise training group (AET group) and 77 patients who had received self-education only were regarded as the education group (EDU group). The acute incidence rate in AET group was 7.6% better than that in EDU group 20.7% (P < .05). The AET group patients expressed higher levels of 6 minutes walking distance (6MWD) (P < .05) and better evaluations of both lung function (P < .05) and T lymphocyte immune response (P < .05), as well as significantly decreased chronic obstructive pulmonary disease assessment test (CAT) scores and modified British medical research council (mMRC) grades (P < .05). Patients in EDU group did not report any changes in any of these characteristics. The aerobic exercise training intervention contributed to an increasing in 6MWD and decrease in CAT scores and mMRC grades, as well as improving the T lymphocyte immune response in stable COPD patients.

Long noncoding RNA POU3F3 enhances cancer cell proliferation, migration and invasion in non-small cell lung cancer (adenocarcinoma) by downregulating microRNA-30d-5p.

BACKGROUND: Long noncoding RNA POU class 3 homeobox 3 (POU3F3) is upregulated in esophageal squamous-cell carcinomas. The present study aimed to investigate the role of POU3F3 in non-small cell lung cancer (NSCLC). METHODS: A total of 80 patients with NSCLC (adenocarcinoma) admitted by Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine between May 2016 and May 2018 were enrolled in this study. All patients were diagnosed by histopathological approaches. Expression levels of POU3F3 and microRNA-30d-5p (miR-30d-5p) in cancer and non-tumor tissues from these NSCLC patients were determined by qRT-PCR. Cell transfections were performed to assess interactions between miR-30d-5p and POU3F3. Cell proliferation, Transwell migration and invasion assays were performed to investigate the role of miR-30d-5p and POU3F3 in the regulation of cell proliferation, migration and invasion. RESULTS: POU3F3 was upregulated, while miR-30d-5p was downregulated in cancer tissues than in adjacent healthy tissues of NSCLC patients. Correlation analysis showed that expression levels of POU3F3 and miR-30d-5p were inversely correlated in tumor tissues. Overexpression of miR-30d-5p did not affect the expression of POU3F3, while overexpression of POU3F3 resulted in the suppression of miR-30d-5p in NSCLC cell lines. Overexpression of POU3F3 mediated enhanced proliferation, migration and invasion of NSCLC cells. In addition, overexpression of miR-30d-5p played an opposite role and attenuated the effects of overexpressing POU3F3 on cancer cell proliferation, migration and invasion. CONCLUSIONS: POU3F3 might positively regulate NSCLC cell proliferation, migration and invasion through downregulation of miR-30d-5p.

Paravertebral Block with Compound Betamethasone in Laparoscopic Cholecystectomy: A Double-blind Randomized Controlled Trial.

Backgrounds The aim of this study was to evaluate the utility of unilateral single injection thoracic paravertebral block (TPVB) with and without the addition of betamethasone for the acute pain management of patient's undergoing laparoscopic cholecystectomy (LC). Methods Eligible patients were allocated randomly to three groups: (A) general anesthesia followed by surgeon infiltration at port sites with ropivacaine (n = 48), (B) general anesthesia after single injection TPVB at right T7-8 level with ropivacaine only, Ropi_TPVB (n = 43), and (C) general anesthesia after single injection TPVB with ropivacaine plus betamethasone, Ropi_Betamet_TPVB (n = 45). Primary outcome was TPVB duration assessed by the number of dermatomes at regular intervals up to 72 hours (h). Secondary outcomes included pain scores, analgesics consumption, and perioperative functional outcomes. Results The addition of betamethasone to ropivacaine in TPVB resulted in similar onset but significantly slower block regression between 4 h and 72 h as compared to ropivacaine alone (P < 0.001). When compared to the surgeon infiltration group, Ropi_TPVB and Ropi_Betamet_TPVB group had significantly lower pain scores for 24 h and 48 h, respectively, P ≤ 0.001. Both TPVB groups had less frequency of analgesics administration for 72 h, P < 0.001, and earlier mobilization, P < 0.001. Conclusions The addition of betamethasone to TPVB significantly prolonged block duration as compared to local anesthetic alone. TPVB both with and without the addition of betamethasone resulted in better perioperative analgesia and improved functional status when compared to surgical site local anesthetic infiltration.

Pleural amyloidosis with recurrent pleural effusion and pulmonary embolism: A case report.

RATIONAL: Clinical and radiologic manifestations of pleural amyloidosis are non-specific. And it can easily be missed or misdiagnosed. Meanwhile, few studies document amyloidosis presenting with pulmonary infarcts at the same time. Hereby, we report a case of immunoglobulin light chain amyloidosis (AL) pleural amyloidosis with pulmonary embolism rarely reported. PATIENT CONCERNS: A 66-year-old male patient who suffered recurrent pleural effusion for more than 6 months and coughed for 2 months was admitted to hospital for clear diagnosis and treatment. He was previously engaged in a job which exposed him to dust and talcum powder for a long time. He underwent right thoracentesis and anti-infective treatment before admission. The patient's cough and shortness of breath were slightly relieved. He still experienced pleural effusion and had symptoms of cough and shortness of breath. DIAGNOSIS: Chest X-ray demonstrated bilateral pleural effusion. Chest computed tomography (CT) angiography demonstrated left lower pulmonary embolism. The thorascopy showed hyperaemia and black tissue of the parietal pleura, which were biopsied. The pathological diagnosis was amyloidosis. The final diagnosis of this patient was AL pleural amyloidosis and left lower pulmonary embolism. INTERVENTION: During the hospitalization, the patient underwent thoracentesis several times without any conclusive diagnosis. After the diagnosis of pleural amyloidosis, the patient was repeatedly advised to undergo bone marrow biopsy and pleurodesis which the patient refused. For pulmonary embolism, Nadroparin calcium combined Warfarin were administered as anticoagulative therapy. OUTCOMES: The pulmonary embolism resolved 13 days after the anticoagulant therapy. The patient refused treatment for pleural effusion and requested for discharge. At the time of discharge, shortness of breath was relieved, and the pleural effusion had decreased. The patient was lost to follow-up. LESSONS: Amyloidosis is a rare disease which can be ignored by many clinicians. It needs to be diagnosed promptly since the prognosis of amyloidosis is poor. Clinicians must improve relevant understandings of this kind of disease so as not to delay the diagnosis and treatment. We must be alert to the occurrence of embolic disease among amyloidosis patients. Last but not least, we should also think of the possibility of amyloidosis in patients with pulmonary embolism and recurrent pleural effusion.

Antidiabetic properties of the histamine H3 receptor protean agonist proxyfan.

Proxyfan is a histamine H3 receptor protean agonist that can produce a spectrum of pharmacological effects including agonist, inverse agonist, and antagonist. We have discovered that proxyfan (10 mg/kg orally) significantly improved glucose excursion after an ip glucose tolerance test in either lean or high-fat/cholesterol diet-induced obese mice. It also reduced plasma glucose levels comparable to that of metformin (300 mg/kg orally) in a nongenetic type 2 diabetes mouse model. The dose-dependent decrease in glucose excursion correlated with inhibition of ex vivo H3 receptor binding in the cerebral cortex. In addition, glucose levels were significantly reduced compared with vehicle-treated mice after intracerebroventricular administration of proxyfan, suggesting the involvement of central H3 receptors. Proxyfan-induced reduction of glucose excursion was not observed in the H3 receptor knockout mice, suggesting that proxyfan mediates this effect through H3 receptors. Proxyfan reduced glucose excursion by significantly increasing plasma insulin levels in a glucose-independent manner. However, no difference in insulin sensitivity was observed in proxyfan-treated mice. The H1 receptor antagonist chlorpheniramine and the H2 receptor antagonist zolantidine had modest effects on glucose excursion, and neither inhibited the glucose excursion reduced by proxyfan. The H3 receptor antagonist/inverse agonist, thioperamide, had weaker effects on glucose excursion compared with proxyfan, whereas the H3 receptor agonist imetit did not affect glucose excursion. In conclusion, these findings demonstrate, for the first time, that manipulation of central histamine H3 receptor by proxyfan can significantly improve glucose excursion by increasing plasma insulin levels via a glucose-independent mechanism.