Rejected

The role of astrocytes in major depressive disorder has received great attention. Increasing evidence indicates that decreased astrocyte numbers in the hippocampus may be associated with depression, but the role of necroptosis in depression is unknown. Here, in a chronic unpredictable mild stress (CUMS) mouse model and a corticosterone (Cort)-induced human astrocyte injury model , we found that mice treated with chronic unpredictable mild stress for 3-5 weeks presented depressive-like behaviors and reduced body weight gain, accompanied by a reduction in astrocytes and a decrease in astrocytic brain-derived neurotropic factors (BDNF), by activation of necroptotic kinases, including RIPK1 (receptor-interacting protein kinase 1)/p-RIPK1, RIPK3 (receptor-interacting protein kinase 3)/p-RIPK3 and MLKL (mixed lineage kinase domain-like protein)/p-MLKL, and by upregulation of inflammatory cytokines in astrocytes of the mouse hippocampus. In contrast, necroptotic kinase inhibitors suppressed Cort-induced necroptotic kinase activation, reduced astrocytes, astrocytic necroptosis and dysfunction, and decreased Cort-mediated inflammatory cytokines in astrocytes. Treatment with fluoxetine (FLX) for 5 weeks improved chronic unpredictable mild stress-induced mouse depressive-like behaviors; simultaneously, fluoxetine inhibited depression-induced necroptotic kinase activation, reversed the reduction in astrocytes and astrocytic necroptosis and dysfunction, decreased inflammatory cytokines and upregulated brain-derived neurotropic factors and 5-HT1A levels. Furthermore, fluoxetine had no direct inhibitory effect on receptor-interacting protein kinase 1 phosphorylation. The combined administration of fluoxetine and necroptotic kinase inhibitors further reduced corticosterone-induced astrocyte injury. In conclusion, the reduction in astrocytes caused by depressive-like models and may be associated with the activation of necroptotic kinases and astrocytic necroptosis, and fluoxetine exerts an antidepressive effect by indirectly inhibiting receptor-interacting protein kinase 1-mediated astrocytic necroptosis.

To analyze and explore the clinical efficacy of ultrasound guided femoral nerve block combined with modified swelling anesthetic solution in high ligation and stripping of the great saphenous vein.

The syndrome of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare diagnosis that is often missed due to lack of both definitive diagnostic criteria and awareness of the disease. This case report describes a patient with chronic lymphocytic leukemia whose diagnosis of RS3PE was possibly delayed due to concomitant treatment-related arthralgias. The pathophysiology, presentation, and treatment of RS3PE are discussed. Greater awareness of malignancy-related RS3PE is crucial from a palliative care perspective as typical opioid pain management will prove ineffective and delay appropriate treatment.

Cyclovirobuxine D (CVB-D), the main active constituent of traditional Chinese medicine , was developed as a safe and effective cardiovascular drug in China. has also been used to relieve various pain symptoms for centuries. In this study, we examined and uncovered strong and persistent analgesic effects of cyclovirobuxine D against several mouse models of pain, including carrageenan- and CFA-induced inflammatory pain and paclitaxel-mediated neuropathic hypersensitivity. Cyclovirobuxine D shows comparable analgesic effects by intraplantar or intraperitoneal administration. Cyclovirobuxine D potently inhibits voltage-gated Ca2.2 and Ca3.2 channels but has negligible effects on a diverse group of nociceptive ion channels distributed in primary afferent neurons, including Na1.7, Na1.8, TRPV1, TPRA1, TRPM8, ASIC3, PX and PX. Moreover, inhibition of Ca3.2, rather than Ca2.2, plays a dominant role in attenuating the excitability of isolated dorsal root ganglion neurons and pain relieving effects of cyclovirobuxine D. Our work reveals that a currently in-use cardiovascular drug has strong analgesic effects mainly blockade of Ca3.2 and provides a compelling rationale and foundation for conducting clinical studies to repurpose cyclovirobuxine D in pain management.

Literature suggests an association between patent foramen ovale (PFO) and migraine, mostly migraine with aura (MA). Previous data suggest that air microembolism through PFO can lead to bioelectrical abnormalities detectable at electroencephalogram (EEG) in patients with MA, thus suggesting a pathophysiological mechanism for the MA-PFO association. However, those data lack replication.

To evaluate the association of tracheostomy timing with all-cause mortality in patients with mechanical ventilation (MV).

We reported a 22-year-old Emirati male with autosomal recessive primary hypertrophic osteoarthropathy caused by a possibly pathogenic homozygous non-synonymous variant in the gene (NM_005630.3: c.289C>T, p. Arg97Cys) presenting with joint swelling, forehead furrowing, and significant clubbing in all fingers and toes. Currently, no standard treatments are approved for this disease; medical care is palliative and includes non-steroidal anti-inflammatory drugs, corticosteroids, tamoxifen, retinoids, and risedronate. Colchicine may be helpful for the pain due to subperiosteal new bone formation. Our patient was treated with etoricoxib 60 mg once daily and showed a significant clinical improvement at the 6-month mark that was reversed upon the withdrawal of this medication. This case report highlights the importance of placing etoricoxib among first-line therapy recommendations for cases with confirmed primary hypertrophic osteoarthropathy diagnosis. To the best of our knowledge, this is the only case of primary hypertrophic osteoarthropathy from the Middle Eastern population of Arab ethnicity that has responded to non-steroidal anti-inflammatory drug therapy.

An inflammatory myofibroblastic tumor (IMT) is a rare neoplasm with an unclear origin that can arise anywhere on the body. It contains spindle cells (myofibroblasts) with different inflammatory elements. Primary IMT of the kidney is a clinically rare disease and is difficult to differentiate from other renal malignancies. We reported a 49-year-old male who presented with right flank pain in the past year. A computed tomography scan showed a mixed density with slight heterogeneous enhancement mass in the upper pole of the right kidney, two small hypodense nodules invading the liver, and another mass in the lateral aspect of inferior vena cava. The patient underwent right radical nephrectomy and metastasectomy. IMT was confirmed by both postoperative histopathological examination and immunohistochemical assay. The patient recovered well after the operation, and no recurrence or metastasis was noted during the 12-month follow-up.

Chronic pain is one of the major health problems worldwide in recent years, and acupuncture-related therapies have been reported to have definite analgesic effects. However, it is still unclear which treatment is the most effective. Our systematic review and network meta-analysis protocol aims to summarize the evidence and determine the most effective method to treat the chronic musculoskeletal pain.

Tuberculosis is a real public health problem in developing countries. The aim of our article was to study the epidemiological, clinical, diagnostic characteristics of female genital tuberculosis in Togo. This was a descriptive and cross-sectional study on all cases concerning histologically diagnosed female genital tuberculosis in the department of pathological anatomy of Lomé in 1997-2018 (20 years). We collected 22 cases of women's Genital tuberculosis (GT), representing 2.2% (1008 cases) of extra-pulmonary tuberculosis. The mean age of the patients was 33.8 ± 0.2 years. Nine (9) patients had a history of treated GT. Depending on the location, the ovaries and fallopian tubes were the most affected (n=9 cases, 40.9%). Eighteen patients (81.8%) had at least one immunosuppression factor including HIV in 13 patients (72.2%). The reasons for consultation were metrorrhagia and pelvic pain with an associated mass in 7 women discovered on clinical examination and imaging. The macroscopic appearance of the specimens was suggestive of the diagnosis of genital tuberculosis in 12 cases (54.5%). Histology revealed caseous necrosis isolated in 3 patients (13.6%) and associated with gigantocellular epithelioid granulomas in 19 patients (86.4%). The patients received standard antibiotic treatment combining rifampicin, isoniazid, ethambutol and pyrazinamide. Genital tuberculosis is a rare extra-pulmonary location in Togo, often occurring in women with HIV, and the clinical polymorphism can lead to confusion with gynecological cancers.