Formononetin Improves the Survival of Random Skin Flaps Through PI3K/Akt-Mediated Nrf2 Antioxidant Defense System.

Random-pattern skin flap is widely used in plastic and reconstructive surgery. However, its clinical effect is limited by ischemia necrosis occurs at the distal part of flap. Previous studies have proved that the protective effect of formononetin was associated with its antioxidant, anti-inflammatory ability. However, further research is still needed on the effect of formononetin on flap viability. The purpose of our study was to investigate the effect of formononetin on flap survival and the underlying mechanisms. Two doses (25 mg/kg, 50 mg/kg)of formononetin were administered for seven consecutive days on flap model. Flap tissues were collected on postoperative day 7. Our results revealed that formononetin promoted skin flap viability in a dose-dependent manner. Using immunohistochemical staining and western blot, we found that formononetin significantly reduced oxidative stress and inflammation. Hematoxylin and eosin (H and E) staining, laser Doppler images and immunofluorescence staining showed the enhancement of angiogenesis after formononetin treatment. Mechanistically, we demonstrated that the antioxidation of formononetin was mediated by activation and nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2), while down-regulating cytoplasmic Kelch-like ECH-associated protein 1 (Keap1) expression. Co-treatment with formononetin and LY294002 (15 mg/kg), a potent Phosphatidylinositol-3-kinase (PI3K) inhibitor, which aborted nuclear Nrf2 expression and phosphorylated Akt, indicating that formononetin-mediated Nrf2 activation was related to PI3K/Akt pathway. Overall, our findings revealed that formononetin increased angiogenesis, reduced oxidative stress and inflammation, thus promoting flap survival. We highlighted the antioxidant effects of formononetin since the Nrf2 system was activated. Therefore, formononetin might be a promising candidate drug that can enhance survival of skin flaps.

Development of a Novel Rat Intervertebral Disc Degeneration Model by Surgical Multifidus Resection-Induced Instability.

OBJECTIVE: This study aimed to investigate whether surgical resection of multifidus in rats could generate a reliable model of intervertebral disc degeneration (IVDD). METHODS: Instability of the lumbar spine in Sprague-Dawley rats was induced by multifidus resection. Longissimus changes were examined by hematoxylin and eosin staining and immunohistochemistry. Specific protein and mRNA changes in the nucleus pulposus (NP) were quantified by Western blot and reverse transcription-polymerase chain reaction. Bone alterations were assessed using X-ray imaging, and disc changes were evaluated by hematoxylin and eosin staining, immunofluorescence, and immunohistochemistry. RESULTS: Fat infiltration and increased tumor necrosis factor-α expression in the longissimus were detected following surgery. Reverse transcription-polymerase chain reaction and Western blot results demonstrated that the inflammation and catabolism in the NP were increased after the surgical intervention. Moreover, X-ray imaging showed that the disc height had decreased and bone spurs had formed at the vertebral rims. Histological analyses further revealed degeneration of the annulus fibrosus, endplate, and NP. Furthermore, in contrast to the sham group, the collagen II expression was reduced, while matrix metalloproteinase-13 was increased in the surgery group. CONCLUSIONS: Surgical resection of the multifidus in rats resulted in a reproducible IVDD model. Because the present procedure does not impart direct injury to the intervertebral disc, it can better imitate the pathological states in humans. Therefore, our rat multifidus resection model might help us further understand the intrinsic pathophysiology of IVDD.

COVID-19 May Increase the Risk of Insulin Resistance in Adult Patients Without Diabetes: A 6-Month Prospective Study.

OBJECTIVE: During the coronavirus disease 2019 (COVID-19) pandemic, exploring insulin resistance and beta-cell activity is important for understanding COVID-19‒associated new-onset diabetes. We assessed insulin sensitivity and fasting insulin secretion in patients with COVID-19 without diabetes on admission and at 3 and 6 months after discharge. METHODS: This 6-month prospective study assessed data from the records of 64 patients without diabetes diagnosed with COVID-19 at Wenzhou Central Hospital, China. Each patient was followed up at 3 and 6 months after discharge. Repeated measures analysis of variance was used to investigate differences in multiple measurements of the same variable at different times. Linear regression analysis was performed to analyze the contributor for changes in the triglyceride-glucose (TyG) index. RESULTS: Fasting C-peptide levels in patients at baseline were lower than the normal range. Compared with the baseline results, patients had significantly elevated fasting C-peptide levels (0.35 ± 0.24 vs 2.36 ± 0.98 vs 2.52 ± 1.11 µg/L; P < .001), homeostasis model assessment for beta-cell function (0.42, interquartile range [IQR] 0.36-0.62 vs 2.54, IQR 1.95-3.42 vs 2.90, IQR 2.02-4.23; P < .001), and TyG indices (8.57 ± 0.47 vs 8.73 ± 0.60 vs 8.82 ± 0.62; P = .006) and decreased fasting glucose levels (5.84 ± 1.21 vs 4.95 ± 0.76 vs 5.40 ± 0.68 mmol/L; P = .003) at the 3- and 6-month follow-up. Male gender, age, interferon-alfa treatment during hospitalization, and changes in total cholesterol and high-density lipoprotein levels were significantly associated with changes in the TyG index. CONCLUSION: Our study provided the first evidence that COVID-19 may increase the risk of insulin resistance in patients without diabetes.

Changes in perioperative hemoglobin and hematocrit in patients undergoing total knee arthroplasty: a prospective observational study of optimal timing of measurement.

OBJECTIVE: This study was performed to depict the patterns of change in the perioperative hemoglobin (Hb) concentration and hematocrit (Hct) and to identify the optimal timing of Hb and Hct measurement in patients undergoing total knee arthroplasty (TKA). METHODS: This prospective observational study involved 302 consecutive patients who underwent TKA. The patients were kept in hospital for 1 full week postoperatively. Hb and Hct measurements were performed preoperatively and on days 1 to 7 postoperatively and then during clinic visits at 1, 3, and 6 months postoperatively. RESULTS: The Hb concentration and Hct decreased during the first few days postoperatively and reached a nadir on postoperative day 4 and 3, respectively; they then recovered in the following days. Significant differences in the Hb concentration and Hct were detected between the preoperative period and day 1, between days 1 and 2, between days 2 and 3, between day 7 and 1 month, and between 1 and 3 months. A significant difference in the Hct was also detected between 3 and 6 months. CONCLUSION: The optimal timing of Hb and Hct measurement is on postoperative day 3 or 4. This timing accurately reflects ongoing hidden blood loss to better guide blood transfusions.

Influence of structured telephone follow-up on patient compliance with rehabilitation after total knee arthroplasty.

INTRODUCTION: To assess the effects of structured telephone follow-up on patient's home-exercise compliance after total knee arthroplasty (TKA). METHODS: A total of 202 elderly patients who received a unilateral TKA were enrolled in this study. The participants were randomized into two groups: the intervention group that received structured telephone follow-up after discharge and the control group that received routine health care. Pain, functional ability, quality of life, and depression survey scores were measured before and after TKA. The intergroup and intragroup differences were analyzed during the 12 months following discharge. RESULTS: There were no significant differences in the sociodemographic characteristics of both groups. The mean home-exercise time and total days in the intervention group were significantly higher than those in the control group. Variable scores differed significantly between groups. Pain, functional ability, quality of life, and depression improved significantly after TKA in both groups, and the intervention group had greater improvement in mental health and active range of motion. CONCLUSION: Undergoing a TKA can significantly reduce the patient's pain from osteoarthritis while improving the overall physical function and quality of life. Furthermore, a structured telephone follow-up can improve patient adherence to home exercise after TKA.