Astragaloside IV Alleviates Doxorubicin-Induced Cardiotoxicity by Inhibiting Cardiomyocyte Pyroptosis through the SIRT1/NLRP3 Pathway.

Doxorubicin (DOX) is a powerful anthracycline antineoplastic drug used to treat a wide spectrum of tumors. However, its clinical application is limited due to cardiotoxic side effects. Astragaloside IV (AS IV), one of the major compounds present in aqueous extracts of Astragalus membranaceus, possesses potent cardiovascular protective properties, but the underlying molecular mechanisms are unclear. Thus, the aim of this study was to investigate the effect of AS IV on DOX-induced cardiotoxicity (DIC). Our findings revealed that DOX induced pyroptosis through the caspase-1/gasdermin D (GSDMD) and caspase-3/gasdermin E (GSDME) pathways. AS IV treatment significantly improved the cardiac function and alleviated myocardial injury in DOX-exposed mice by regulating intestinal flora and inhibiting pyroptosis; markedly suppressed the levels of cleaved caspase-1, N-GSDMD, cleaved caspase-3, and N-GSDME; and reversed DOX-induced downregulation of silent information regulator 1 (SIRT1) and activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in mice. The SIRT1 inhibitor EX527 significantly blocked the protective effects of AS IV. Collectively, our results suggest that AS IV protects against DIC by inhibiting pyroptosis through the SIRT1/NLRP3 pathway.

[Comparison of the effectiveness of two kinds of surgeries for treatment of flexible flatfoot combined with painful accessory navicular bone in children].

Objective: To compare the effectiveness of subtalar arthroereisis (STA) combined with modified Kidner procedure versus STA alone in the treatment of flexible flatfoot combined with painful accessory navicular bone in children. Methods: The clinical data of 33 children with flexible flatfoot combined with painful accessory navicular bone who were admitted between August 2018 and August 2021 and met the selection criteria were retrospectively analyzed. They were divided into a combination group (17 cases, treated by STA combined with modified Kidner procedure) and a control group (16 cases, treated by STA alone) according to the surgical methods. There was no significant difference in baseline data between the two groups ( P>0.05), such as gender, age, affected side of the foot, disease duration, and preoperative visual analogue scale (VAS) score, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, talus-first metatarsal angle (T1MT), talus-second metatarsal angle (T2MT), talonavicular coverage angle (TCA), talus first plantar angle (Meary angle), calcaneal inclination angle (Pitch angle), and heel valgus angle (HV). The operation time, incision length, intraoperative blood loss, number of intraoperative fluoroscopies, and perioperative complications were recorded in both groups. The anteroposterior, lateral, and calcaneal axial X-ray films for the affected feet were taken regularly, and T1MT, T2MT, TCA, Meary angle, Pitch angle, and HV were measured. The VAS score, AOFAS ankle-hindfoot score were used to evaluate pain and functional recovery before and after operation. Results: Surgeries in both groups were successfully performed without surgical complication such as vascular, nerve, or tendon injuries. Less operation time, shorter incision length, less intraoperative blood loss, and fewer intraoperative fluoroscopies were found in the control group than in the combination group ( P<0.05). One case in the combination group had partial necrosis of the skin at the edge of the incision, which healed after the dressing change and infrared light therapy, and the rest of the incisions healed by first intention. All children were followed up 12-36 months, with a mean of 19.6 months. At last follow-up, VAS score and AOFAS ankle-hindfoot score significantly improved in both groups when compared with preoperative ones ( P<0.05), and the differences of these scores between before and after operation improved more significantly in the combination group than in the control group ( P<0.05). Imaging results showed that the T1MT, T2MT, TCA, Meary angle, and HV significantly improved in both groups at last follow-up when compared with preoperative ones ( P<0.05), and the Pitch angle had no significant difference when compared with preoperative one ( P>0.05). But there was no significant difference in the difference of these indicators between before and after operation between the two groups ( P>0.05). Conclusion: Both procedures are effective in the treatment of flexible flatfoot children with painful accessory navicular bone. STA has the advantage of minimally invasive, while STA combined with modified Kidner procedure has better effectiveness.

[Feasibility study on local infiltration anesthesia for postoperative analgesia in patients with hallux valgus].

OBJECTIVE: To evaluate the clinical efficacy of local infiltration anesthesia of ropivacaine combined with compound betamethasone for postoperative analgesia in patients with hallux valgus. METHODS: From September 2019 to December 2020, 48 patients with hallux valgus were treated surgically. According to different postoperative analgesia methods, the patients were divided into combined local infiltration group and intravenous analgesia pump group. There were 24 cases, in the combined local infiltration group including 2 males and 22 females;the age ranged from 21 to 78 years old, with an average of (58.3±7.7) years old;soft tissue release and chevron osteotomy were performed in 15 cases and metatarsophalangeal joint fusion in 9 cases;immediately after operation, 20 ml of ropivacaine combined with compound betamethasone mixed diluent was used for local infiltration anesthesia once. There were 24 patients in intravenous analgesia pump group, including 3 males and 21 females;the age ranged from 23 to 81 years old, with an average of(56.8±8.3) years old;soft tissue release and Chevron osteotomy were performed in 17 cases and metatarsophalangeal joint fusion in 7 cases;immediately after operation, intravenous analgesia pump was used for analgesia. The basic flow was 2 ml / h;the self control dose was 0.5 ml;and the locking time was 15 min. Visual analogue scale (VAS) was recorded at 12, 24, 48 and 72 hours after operation;and the VAS was recorded at 24 hours after operation. The occurrence of adverse drug reactions at 0 to 12 hours, 12 to 24 hours and 24 to 48 hours after operation were recorded;and the healing of incision was recorded. RESULTS: All patients were followed up, and the duration ranged from 14 to 17 days, with a mean of (14.60±0.92) days. There was significantdifference in VAS at 12, 24 and 48 hours between the combined local infiltration group and the intravenous analgesia pump group(P<0.05). There was no significant difference in VAS between the two groups 72 hours after operation (P>0.05). There was no significant difference in the number of adverse drug reactions between the two groups at 0 to 12 hours after operation (P>0.05);there was significant difference in the number of adverse drug reactions 12 to 24 hours after operation (P<0.05). No adverse drug reactions occurred in both groups 24 to 48 hours after operation. There was no significant difference in the grade of knife edge healing between the two groups after suture removal (P>0.05). CONCLUSION: Compared with intravenous analgesia pump group, ropivacaine combined with compound betamethasone can significantly reduce postoperative wound pain without increasing adverse drug reactions, and does not increase wound infection.

Ulcerative colitis with mucosal lesions in duodenum: Two case reports.

RATIONALE: Ulcerative colitis (UC) is a chronic, nonspecific, inflammatory disease of the colon. Colorectal is the main target organ of UC, while other digestive tract involvement is rare. This report describes 2 rare cases of duodenal mucosa lesions in patients with UC after total colectomy. PATIENT CONCERNS: In case 1, a patient of 45-year-old with intermittent diarrhea and bloody mucosanguineous feces who was diagnosed as UC, revealed diffuse erosive ulcers in the descending duodenum through gastroscopy after total colectomy. In case 2, a 55-year-old Chinese female with UC, aggravated to colon cancer and received total colectomy. Eighteen months after surgery, the patient was admitted to hospital following upper abdominal pain and acid regurgitation. A gastroscopy found inflammation in the descending part of the duodenum. DIAGNOSIS: UC, duodenal mucosa lesions INTERVENTIONS:: In case 1, the patient was treated with oral mesalazine (1 g/tid) and hydrocortisone (0.3 g/d) but symptoms did not improve, and the treatment was changed to oral methylprednisolone (0.6 g/d) and a hydrocortisone enema (0.1 g/late). Finally, the patient underwent a total colectomy and ileostomy. In case 2, the patient was treated with sulfasalazine, mesalazine, and intermittent hormone enemas. A total colectomy and ileostomy were performed with the patient after diagnosed as colon cancer. After surgery, the patient received N1-(2 tetrahydrofuryl)-5-fluorouracil (FT-207), 8 g, 300 mg, and 100 mg oxaliplatin chemotherapy, and biologic therapy. OUTCOMES: In case 1, the patient presented with duodenal necrosis and died of septic shock. In case 2, the patient recovered well without recurrence by taking proton pump inhibitor. LESSONS: The occurrence of UC related ulcerative gastroduodenal mucosal lesions may be associated with progressing UC or total colitis that does not respond to hormone therapy, leading to requirement of total colectomy.