Rejected

Diabetic neuropathy (DN) is a serious microvascular complication of diabetes mellitus (DM) that impacts the nervous system. Several risk factors are involved in the progression and maintenance of DN-associated pain, such as higher expression of various inflammatory mediators, e.g., tumor necrotic factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), and cyclo-oxygenase-2 (COX-2). The present research explores the neuroprotective potential of natural isolates, including berbamine, bergapten, and carveol, on the DM-induced neuroinflammation and neurodegeneration that cause neuropathic pain. The study utilized computerized techniques, including computational analysis (a docking assay and a molecular dynamic simulation) before moving to protocols. Diabetic neuropathy was induced by intraperitonial injection (IP) of streptozotocin (65 mg/kg), and the animal subjects (rats) were kept for 4 weeks for the development of DN. Once diabetic neuropathy was confirmed, the subjects were treated with berbamine, bergapten, and carveol until the sixth week (i.e., 2 weeks of treatment). At the sixth week, the rats were sacrificed, and the sciatic nerve and spinal cord of each was collected for further molecular investigation. Docking and a molecular dynamic simulation (MDS) delivered the information that the natural compounds (berbamine, bergapten, and carveol) were interacting with the selected target protein (i.e., mitogen-activated protein kinase). After IP, it was found that berbamine, bergapten, and carveol had ameliorated mechanical allodynia and thermal hyperalgesia by the 28th day of the study (2 weeks after treatment) without affecting blood glucose levels. Berbamine, bergapten, and carveol markedly elevated the levels of glutathione (GSH) and glutathione s-transferase (GST), in both the sciatic nerve and spinal cord, and also reduced lipid peroxidase (LPO) and nitric oxide (NO). The abovementioned natural isolates reduced pathologic alterations provoked through DN, a finding confirmed through histopathological assays (hematoxylin and eosin staining and immuno-histochemical analysis). Treatment down regulated higher expressions of the inflammatory mediatorcyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), and nuclear factor kappa B (NF-κB), as confirmed by ELISA and polymerase chain reaction (PCR). The outcomes of berbamine, bergapten, and carveol are compared with those of pregabalin as a positive control group. Compared to pregabalin, treatment with the aforementioned three natural compounds improved nociception and reduced hyperalgesic effects, and consequently reduced pain perception and inflammation. Our results suggest the mechanism for the neuro-protective impact of berbamine, bergapten, and carveol might possibly be arbitrated via COX-2, TNF-α, and NF-κB, and regulated by mitogen-activated protein kinase, ultimately ameliorating STZ-provoked, DM-induced neuroinflammation and neurodegeneration, and associated neuropathic pain.

The acute respiratory distress syndrome (ARDS) is a life-threatening condition with the risk of developing hypoxia and thus requires for invasive mechanical ventilation a long-term analgosedation. Yet, prolonged analgosedation may be a reason for declining health-related quality of life (HRQoL) and the development of psychiatric disorders.

One-half of patients with newly diagnosed pancreatic cancer will have metastatic disease at the time of diagnosis, mainly due to its non-specific initial clinical presentation which includes abdominal pain, dyspepsia, weight loss, bowel habit changes, jaundice and pruritus. The signs, symptoms and stage of the disease at initial diagnosis depends on the origin of the primary tumor, with tumors of the head presenting earlier with obstructive symptoms while tumors of the body/tail are often diagnosed at an advanced stage due to their non-specific presentation. The most common sites of metastasis are the lymph nodes, liver, lung, and peritoneum. The presence of metastatic disease in the skeletal muscles is a rare manifestation of pancreatic cancer and has been described in a limited number of cases. We report the case of a pancreatic cancer patient with a solitary muscle lesion as the only site of extra-nodal metastasis upon initial presentation.

Cardiac paraganglioma is a kind of rare neuroendocrine tumor characterized by the persistent secretion of catecholamines. Under excessive exposure of catecholamines, some atypical symptoms are presented, including hypertension, arrhythmias, and headache. The case of surgical treatment of a 28-year-old woman with primary cardiac paraganglioma is presented for experience sharing and surgical skill improvements.

Hemorrhage in vestibular schwannoma (VS) is a rare but potentially devastating complication, owing to the proximity to the brainstem and small space in the posterior fossa.

Low back pain (LBP) induced by intervertebral disc degeneration (IDD) brings progressively painful status and impairs the normal daily living. Engeletin is a plant-derived medicine with anti-inflammation and antioxidant functions. Therefore, we aim to confirm its protective effects against the intervertebral disc degeneration in vivo and in vitro.

Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC) in ∼30% of all infected individuals. Here, we present a case of PASC in a patient with rheumatoid arthritis characterized by viral persistence in the nasopharynx for 6 months after acute infection. We demonstrate transient disappearance of antigen persistence and decreased antiviral and autoimmune T cell responses after nirmatrelvir/ritonavir and tocilizumab treatment.

. To explore the biological function and mechanism of TREK1 in neuropathic pain. Thirty-two healthy rats and rats with sciatic nerve chronic press-fitting model (chronic constriction injury of the sciatic nerve, CCI) were selected. Western blot, immunofluorescence staining, and patch clamp technique were performed to explore the biological functions of TREK1. The expression of TREK1 was decreased in the CCI model. The TREK1 channel current in the CCI model was decreased. After local administration of TREK1 channel activator in the anterior cingulate cortex area, the pain behavior of CCI rats and the expression of TREK1 protein were reversed. The expression of TREK1 was downregulated in the ACC area of CCI rats and the current of TREK1 was decreased, which played an important role in the regulation of neuropathic pain.

A 76-year-old man was admitted into the ER for upper abdominal pain. Physical exam and CT scan confirmed acute cholecystitis with multiple cholelithis, and a cholecystectomy was performed. The cholecystectomy specimen showed chronic cholecystitis with exuberant inflammatory infiltrate. On careful examination of the specimen, large atypical cells with vesicular chromatin, folded nuclei, and inconspicuous red nucleoli were noted percolating into the gallbladder wall and lining vascular spaces. These cells were positive for CD117, CD43, and myeloperoxidase and negative for CD20 and CD3 stains. Further workup including peripheral blood flow cytometry confirmed a population of circulating immature myeloid precursors comprising about 38% of events. This is a rare case of acute myeloid leukemia that came to clinical attention by incidentally involving the gallbladder.

In this study, clinical data from vestibular migraine (VM) patients and healthy control populations were collected to analyze the clinical data of VM patients, especially the history of motion sickness, and to understand their clinical characteristics.