Doxorubicin (DOX) is a potent and broad-spectrum anthracycline chemotherapeutic agent, but dose-dependent cardiotoxic side effects limit its clinical application. This toxicity is closely associated with the generation of reactive oxygen species (ROS) radical during DOX metabolism. The present study investigated the effects of Berberine (Ber) on DOX-induced acute cardiac injury in a rat model and analysed its mechanism in cardiomyocytes in vitro. Serum creatine kinase (CK), creatine kinase isoenzyme (CK-MB) and malondialdehyde (MDA) levels were significantly increased in the DOX group compared with the control group. This increase was accompanied by cardiac histopathological injury and a decrease in cardiomyocyte superoxide dismutase (SOD) and catalase (CAT). CK, CK-MB and MDA levels decreased and SOD and CAT levels increased in the Ber-treated group compared to the DOX group. Ber ameliorated the DOX-induced increase in cytosolic calcium concentration ([Ca2+]i), attenuated mitochondrial Ca2+ overload and restored the DOX-induced loss of mitochondrial membrane potential in vitro. These results demonstrated that Ber exhibited protective effects against DOX-induced heart tissue free radical injury, potentially via the inhibition of intracellular Ca2+ elevation and attenuation of mitochondrial dysfunction.
Secukinumab is a recombinant, fully human monoclonal anti-IL-17A antibody approved to treat moderate-to-severe psoriasis and psoriatic arthritis. Its effectiveness and safety have been confirmed, but a gradual increase in the secukinumab dosing interval has not been investigated. To assess the feasibility, efficacy, and safety of gradually increasing the secukinumab dosing interval; the interval duration was determined by changes in the Psoriasis Area and Severity Index scores. Patients with moderate-to-severe plaque psoriasis received secukinumab 300 mg subcutaneously at baseline and weeks 0, 1, 2, and 3. At week 4, the improvement from baseline PASI guided the next injection time until week 36. In total, 83 patients were recruited. PASI 75 was achieved by 80%, 96%, and 95% of patients at weeks 4, 12, and 36, respectively. PASI 90 was achieved by 54%, 95%, and 84% of patients at weeks 4, 12, and 36, respectively. PASI 100 was achieved by 28%, 89%, and 68% of patients at weeks 4, 12, and 36, respectively. The average PASI score (1.05 ± 1.83) was significantly lower at week 36 than at baseline. Most patients reached PASI 75 at week 36 in our modified study. This study may provide information for future biotherapies.
Among approaches for the treatment of cutaneous squamous cell carcinoma (cSCC), complete surgical removal at the primary tumor site should be the first-line treatment when tumor characteristics (size, location, and number) allow. 1 Mohs micrographic surgery (MMS) is the gold standard for the treatment of cSCC, with a cure rate of 96%-99%. 2 Wide local excision (WLE) is another type of treatment with a cure rate of 90%-97%, and it can be used when MMS is not available or indicated. 3 No difference was found in the 5-year cure rate between MMS and WLE. 4 WLE with an interpolation flap was used F I G U R E 1 Forearm and leg rotational interpolation flap for three cases with cSCC. (A-C) Case 1 before and after WLE with a second surgery. (A). The bleeding, ulcerative tumor was in the left dorsum of the hand, and the diameter was approximately 30 mm before treatment. (B). A rotational interpolation flap was subsequently designed to incorporate a template along the proximal radial forearm. (C). Completion of the second stage. The interpolation flap survived well, and after the second surgery, the flap was used to reconstruct the defect. (D-F) Preoperative and postoperative appearance of case 2. (D). A template of the defect was made and marked along ulnar proximal skin (purple-marked line). (E). A combined rotation and interpolation flap for the treatment of neoplasms in the ulnar forearm. (F). Division of the pedicle was performed. After the secondary stage of surgery, a light skin ulcer was found in the flap. (G-J) Appearance of the two stages of case 3 in approximately one and a half months. (G). The neoplasm was in the left lower leg, and the diameter was approximately 20 mm. (H). A local rotational flap was inserted from the proximal lower leg into the defect. (I). After the second surgery, the interpolation flap survived well. (J). Ten days after the second surgery, the flap was used to reconstruct the defect. cSCC, cutaneous squamous cell carcinoma; WLE, wide local excision
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