Rejected

To study the mechanisms of the Hort.- L. herbal pair (LPHP) in the treatment of migraine using network pharmacology. The active constituents of LPHP and their targets were searched for and screened using the Chinese Medicine System Pharmacology Database. Genes related to migraine were searched on GeneCards, Online Mendelian Inheritance in Man and other databases. Cytoscape was used to construct and combine active component-target and disease-target networks. The core target was screened by network topology analysis, and the Metascape database was used for gene ontology analysis of key targets and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis to explore the molecular mechanisms in the treatment of migraine. A total of 28 active constituents of LPHP were obtained through database screening and literature review, and 60 cross-linking targets were obtained. The target sites were analysed using a protein-protein interaction network to obtain six target proteins with a greater degree of relevance. These were identified as the main targets for the treatment of hypertension, and these key targets were found to be associated with 20 signalling pathways, including neuroactive ligand-receptor interaction, the calcium signalling pathway, the cGMP-PKG signalling pathway, pathways in cancer and the cyclic adenosine 3',5'-cyclic monophosphate (cAMP) signalling pathway. This study reveals the molecular mechanism of LPHP in the treatment of migraine from the perspective of network pharmacology and provides a basis for further research and molecular mechanism research.

Canine atopic dermatitis (cAD) is a common allergic skin condition among dogs that may respond to treatment with mesenchymal stromal cells (MSCs). The aim of this pilot study was to evaluate the safety and efficacy of allogeneic uterine tissue-derived MSCs (UMSCs) for the reduction and control of clinical signs associated with cAD. At two sites, seven client-owned dogs with cAD received two doses of approximately 3.6 x 10 UMSCs given intravenously over 30 min, on Day 0 and Day 14, with monthly clinical follow-up until Day 90 and optional owner phone interview on Day 180. Primary outcomes were pruritus and skin lesions. Pruritus was measured by the owner-assessed Pruritus Visual Analog Scale (PVAS), with treatment success defined as a 2-point reduction in PVAS score at any timepoint after treatment. Skin lesions were evaluated by two veterinarians according to the Canine Atopic Dermatitis Extent and Severity Index (CADESI-4). The secondary outcome was safety, which was evaluated physical exam and hematology, including complete blood count (CBC), serum chemistry, and urinalysis (UA). Treatment was generally well tolerated and associated with a significant reduction in PVAS on Day 30 that was maintained through Day 180. On Day 60, five dogs (71%) achieved treatment success (at least 2-point reduction in PVAS), and three dogs (43%) had a PVAS improvement of 4-5 points. Mean CADESI-4 score was significantly improved on Day 14, Day 30, Day 60, and Day 90, with the lowest mean score observed on Day 60. Three dogs exhibited mild and transient adverse events. These findings suggest that IV-administered allogeneic UMSCs reduce and control clinical signs of cAD, with a durable benefit lasting 3-6 months.

The architecture of the vertebrate eye is optimized for efficient delivery and transduction of photons and processing of signaling cascades downstream from phototransduction. The cornea, lens, retina, vasculature, ciliary body, ciliary muscle, iris and sclera have specialized functions in ocular protection, transparency, accommodation, fluid regulation, metabolism and inflammatory signaling, which are required to enable function of the retina-light sensitive tissue in the posterior eye that transmits visual signals to relay centers in the midbrain. This process can be profoundly impacted by non-visual stimuli such as mechanical (tension, compression, shear), thermal, nociceptive, immune and chemical stimuli, which target these eye regions to induce pain and precipitate vision loss in glaucoma, diabetic retinopathy, retinal dystrophies, retinal detachment, cataract, corneal dysfunction, ocular trauma and dry eye disease. TRPV4, a polymodal nonselective cation channel, integrate non-visual inputs with homeostatic and signaling functions of the eye. The TRPV4 gene is expressed in most if not all ocular tissues, which vary widely with respect to the mechanisms of TRPV4 channel activation, modulation, oligomerization, and participation in protein- and lipid interactions. Under- and overactivation of TRPV4 may affect intraocular pressure, maintenance of blood-retina barriers, lens accommodation, neuronal function and neuroinflammation. Because TRPV4 dysregulation precipitates many pathologies across the anterior and posterior eye, the channel could be targeted to mitigate vision loss.

Short-term spinal cord stimulation (st-SCS) has been widely used to treat herpetic-related neuralgia (HN) in China for several years, but is still heavily debated as it has no strong evidence in clinical application. Therefore, a questionnaire survey among the Chinese pain specialist workgroup of the Chinese Neuromodulation Society and Chinese Medical Doctor Association was carried out to achieve a consensus about the clinical use of st-SCS for HN treatment.

Patients with syringomyelia who present with new neurological symptoms after posterior fossa decompression (PFD) are not uncommon. However, systematic reports on different pathologies are few in the literature.

Spinal cord injury (SCI) is a severe disease of the central nervous system with a very high disability rate that seriously affects the daily life of patients. Acupuncture is one of the rehabilitation therapies that has shown significant efficacy in treating post-SCI complications such as motor disorders, neuropathic pain, and neurogenic bladder. Current studies have focused on the effectiveness and mechanisms of acupuncture for SCI, but no studies are available to analyze the bibliometrics of publications related to this area.

We aimed to assess factors influencing the occurrence of delayed hyponatremia after transsphenoidal surgery in patients with Rathke's cleft cysts (RCCs).

It is widely known that carbon dioxide (CO) arc welding generates carbon monoxide (CO). However, to the best of our knowledge, no case reports have been published regarding CO poisoning in CO arc welders. Therefore, we aimed to report a case of CO poisoning-induced encephalopathy in a CO arc welder in the Republic of Korea to inform about the dangers of CO exposure among COarc welders.

Intervertebral disc degeneration (IDD) is the leading cause of low back pain (LBP). However, effective therapeutic drugs for IDD remain to be further explored. Inflammatory cytokines play a pivotal role in the onset and progression of IDD. Dihydroartemisinin (DHA) has been well reported to have powerful anti-inflammatory effects, but whether DHA could ameliorate the development of IDD remained unclear. In this study, the effects of DHA on extracellular matrix (ECM) metabolism and cellular senescence were firstly investigated in nucleus pulposus cells (NPCs) under tumor necrosis factor alpha (TNF)-induced inflammation. Meanwhile, AKT agonist sc-79 was used to determine whether DHA exerted its actions through regulating PI3K/AKT and NF-B signaling pathways. Next, the therapeutic effects of DHA were tested in a puncture-induced rat IDD model. Finally, we detected the activation of PI3K/AKT and NF-B signaling pathways in clinical degenerative nucleus pulposus specimens. We demonstrated that DHA ameliorated the imbalance between anabolism and catabolism of extracellular matrix and alleviated NPCs senescence induced by TNF. Further, we illustrated that DHA mitigated the IDD progression in a puncture-induced rat model. Mechanistically, DHA inhibited the activation of PI3K/AKT and NF-B signaling pathways induced by TNF, which was undermined by AKT agonist sc-79. Molecular docking predicted that DHA bound to the PI3K directly. Intriguingly, we also verified the activation of PI3K/AKT and NF-B signaling pathways in clinical degenerative nucleus pulposus specimens, suggesting that DHA may qualify itself as a promising drug for mitigating IDD.

Case 1, a 6-year-old, spayed female Pug, presented with severe systemic urticaria, edema, and erythema. The dog had received a famotidine injection as a treatment for repeated vomiting in another hospital. On physical examination, hyperthermia was observed. Moderate pancytopenia, hypoalbuminemia, and increased CRP and D-dimer were also observed in blood tests. Hyposthenuric proteinuria, pulmonary interstitial infiltration, and hepatomegaly were found in other tests. In the histology of the skin, dermal edema and infiltration of inflammatory cells were observed. Therefore, she was diagnosed with acute systemic hypersensitivity. Case 2, a 13-month-old, neutered male Pembroke welsh corgi, presented with severe and patchy systemic ulcerative skin lesions. The dog had a history of soft feces and pain around the anus 2 days before. Thrombocytopenia, and increased CRP and D-dimer were observed in blood tests. In histology, epidermal necrolysis, separation of the epidermis and dermis, and infiltration of inflammatory cells were observed. Therefore, he was diagnosed with an immune-mediated disease with necrolysis dermatitis. Case 3, a 12-year-old, spayed female Pomeranian, presented with severe systemic alopecia, pustule, and crust on the skin. The dog had received an infection treatment from a local hospital. Severe regenerative anemia (hematocrit 15.3%, negative saline agglutination test, negative slide agglutination test, negative Coomb's test, prominent spherocytes) elevated liver enzymes, and increased CRP and D-dimer were observed in blood tests. On histopathology of the skin, pustules, acantholytic cells, and inflammatory cells were observed in the keratin layer of the epithelium. Therefore, she was diagnosed with concurrent with immune-mediated hemolytic anemia. The 3 cases were diagnosed with fatal immune-mediated skin disease concurrently with hematological and systemic abnormalities. All the cases were treated with immune-suppressive drugs, prednisolone, and cyclosporine. In cases 2 and 3, the dogs also received human intravenous immunoglobulin as an immune modulator. The treatment was successful with significant improvements in all the 3 cases.