[This corrects the article DOI: 10.1016/j.apsb.2024.09.010.].

Objective: To investigate the inhibitory effect of curcumin(Cur) on IL-1β-induced cartilage damage and to study the relationship between the regulatory mechanisms of the DUSP1/p38 MAPK signalling pathway in the above process. Methods: Chondrocytes(C28/I2) and postoperative primary chondrocytes from osteoarthritis patients were divided into control and experimental groups, and the experimental group was treated with different concentrations of Cur(0, 10, 20, 40, 60, 80 μmol/L) after applying the inflammatory induction treatment with IL-1β(10 μg/L). The cell proliferation inhibition rate was determined by cell viability assay(CCK-8), the apoptosis rate was detected by flow cytometry assay. Real-time fluorescence quantitative PCR(qRT-PCR), Western blot, and immunofluorescence assay were used to detect type II collagen α1 chain(Collagen Ⅱ), matrix metallopeptidase 13(MMP13), interleukin-1β(IL-1β), BCL2-related X protein(Bax), B lymphocytoma-2(Bcl-2), dual-specificity phosphatase 1(DUSP1), p38 mitogen-activated protein kinase(p38), and phosphorylated p38 mitogen-activated protein kinase(p-p38) RNA and protein expression levels. The role of the DUSP1/p38 MAPK axis in the inhibition of chondrocyte oxidative stress, apoptosis and inflammation by Cur was further validated using DUSP1 interfering RNA and p38 MAPK pathway inhibitor(SB). Results: Cur significantly inhibited the IL-1β-induced decrease in chondrocyte viability and significantly reduced the levels of oxidative stress, apoptosis, and inflammation in chondrocytes; Cur inhibited the expression of MMP13, IL-1β, Bax, and p-p38 proteins, while the expression of Collagen II, Bcl-2, and DUSP1 proteins significantly increased; IL-1β and interfering RNA silencing DUSP1 activated the p38 pathway, while Cur inhibited the activation of the p38 pathway; the use of p38 MAPK pathway inhibitors reduced cellular inflammation. Conclusion Cur attenuates IL-1β-induced oxidative stress, apoptosis and inflammation in chondrocytes by promoting the expression of DUSP1 protein and inhibiting the activation of p38 MAPK pathway.

Objective:To explore the clinical efficacy of free superficial circumflex iliac artery perforator flap (SCIAPF) in reconstruction of soft tissue defects of hand and foot in children.Methods:From August 2021 to August 2023, free SCIAPFs were used to reconstruct soft tissue defects of hands and feet in 8 children at the Department of Hand and Foot Surgery, Zhoukou Huaihai Hospital. There were 6 boys and 2 girls aged between 2 and 7 years old. The sites of soft tissue defect were: 1 of metacarpophalangeal joint in the functional area of left thumb, 2 of dorsal right hand, 1 of dorsal left foot, 2 of medial malleolus of right foot, and 2 of right forefoot, and all were accompanied with tendon and bone exposure. The size of soft tissue defects ranged from 2.5 cm×3.0 cm to 6.0 cm×3.5 cm. After emergency debridement, the children received flap transfers, the flaps sized from 3.0 cm×3.5 cm to 7.0 cm×4.0 cm. Donor sites were closed by running intradermal suture. All children were included in the scheduled postoperative follow-up by visit of outpatient clinic, WeChat interviews and home visits to observe the appearance, colour, texture and sensation of the flaps, the functional recovery of the affected hands and feet, as well as the healing of donor sites.Results:After surgery, all 8 flaps survived beside 1 had a partial necrosis at the edge and healed with a scab after dressing change. Flap donor sites healed in one stage. Scheduled postoperative follow-up lasted from 7 to 22 months, with an average of 10 months. The flaps presented a slightly bloated appearance, soft texture with a restored protective sensation and satisfactory functional recovery of hands and feet. Linear scars were left at the donor sites. According to the Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association, 1 child was of excellent and 2 children of good in hand function of the 3 children with hand injury. The Maryland Foot Score revealed 3 children were of excellent and 2 of good in foot function of the 5 children with foot injury.Conclusion:Free SCIAPF is an ideal option for reconstruction of soft tissue defects of hand and foot in children, with concealed donor site, convenient flap harvesting, fewer complications and satisfactory reconstructive effect.

The adipose tissue of mammals represents an important energy-storing and endocrine organ, and its dysfunction is relevant to the onset of several health problems, including non-alcoholic fatty liver disease (NAFLD). However, whether treatments targeting adipose dysfunction could alleviate NAFLD has not been well-studied. Adrenomedullin 2 (ADM2), belonging to the CGRP superfamily, is a protective peptide that has been shown to inhibit adipose dysfunction. To investigate the adipose tissue-specific effects of ADM2 on NAFLD, adipose-specific ADM2-overexpressing transgenic (aADM2-tg) mice were developed. When fed a high-fat diet, aADM2-tg mice displayed decreased hepatic triglyceride accumulation compared to wild-type mice, which was attributable to the inhibition of hepatic de novo lipogenesis. Results from lipidomics studies showed that ADM2 decreased ceramide levels in adipocytes through the upregulation of ACER2, which catalyzes ceramide catabolism. Mechanically, activation of adipocyte HIF2α was required for ADM2 to promote ACER2-dependent adipose ceramide catabolism as well as to decrease hepatic lipid accumulation. This study highlights the role of ADM2 and adipose-derived ceramide in NAFLD and suggests that its therapeutic targeting could alleviate disease symptoms.

Objective:To investigate the efficacy of osteochondral fragment fixation using bioabsorbable pins for Hepple Ⅱ osteochondral lesions of the talus (OLT) in adolescents.Methods:Retrospective case analysis was used. The clinical data and follow-up results of 13 adolescent patients (13 feet) with Hepple Ⅱ OLT were all treated with osteochondral fragment fixation using bioabsorbable pins admitted to Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2017 to December 2021 were retrospectively analyzed. There were 7 males and 6 females, with 13 right feet. The age was (14.85±2.23) years old, ranged from 12 to 18 years old. According to the American orthopedic foot and ankle society (AOFAS) ankle-hindfoot score, visual analogue scale (VAS) and SF-36 score before operation and at the last follow-up were used to evaluate the efficacy and function of the patients. Measurement data with normal distribution were represented as mean ± standard deviation( ± s), and the comparison between groups was conducted using the t-test; The mearsurement data with skewness distribution were expressed by M( Q1, Q3), and rank-sum test was used for inter-group comparison. Results:Thirteen adolescent patients (13 feet) with Hepple Ⅱ OLT underwent surgery successfully and were followed up for (25.54±9.95) months. All wounds healed by first intention, and no complications such as wound infection and delayed healing occurred. Preoperative AOFAS ankle-posterior foot score, VAS and SF-36 score were 58.62±3.55, 7.00 (6.50, 8.00) and 68.38±4.81, respectively. At the last follow-up, the scores were 97.38±2.73, 1.00 (0.00, 1.00), 91.15±4.28, respectively, and the results were significantly improved at the last follow-up, with the difference between the two groups statistically significant( P<0.05). Conclusion:Osteochondral fragment fixation using bioabsorbable pins which can promote cartilage repair, significantly improve symptoms, and achieve better clinical satisfaction with fewer complications, is a safe and effective surgical treatment option for Hepple Ⅱ OLT in adolescents with satisfactory short-term clinical outcomes.

Objective:To compare magnetic resonance imaging (MRI)-based and computed tomography (CT)-based target volume delineation and dose coverage in partial breast irradiation (PBI) for patients with breast cancer, aiming to explore the application value of MRI localization in PBI after breast-conserving surgery.Methods:Twenty-nine patients with early breast cancer underwent simulating CT and MRI scans in a supine position. The cavity visualization score (CVS) of tumor bed (TB) was evaluated. The TB, clinical target volume (CTV), planning target volume (PTV) were delineated on CT and MRI images, and then statistically compared. Conformity indices (CI) between CT- and MRI-defined target volumes were calculated. PBI treatment plan of 40 Gy in 10 fractions was designed based on PTV-CT, and the dose coverage for PTV-MRI was evaluated.Results:The CVS on CT and MRI images was 2.97±1.40 vs. 3.10±1.40( P=0.408). The volumes of TB, CTV, PTV on MRI were significantly larger than those on CT, (24.48±16.60) cm 3vs. (38.00±19.77) cm 3, (126.76±56.81) cm 3vs. (168.42±70.54) cm 3, (216.63±81.99) cm 3vs. (279.24±101.55) cm 3, respectively, whereas the increasing percentage of CTV and PTV were significantly smaller than those of TB. The CI between CT-based and MRI-based TB, CTV, PTV were 0.43±0.13, 0.66±0.11, 0.70±0.09( P<0.001), respectively. The median percentage of PTV-MRI receiving 40 Gy dose was 81.9%(62.3% to 92.4%), significantly lower than 95.6%(95.0%~97.5%) of PTV-CT. Conclusions:The CVS between CT and MRI is not significantly different, but the MRI-based TB, CTV, PTV are significantly larger than CT-based values. The PTV-MRI is of underdose if PBI treatment plan is designed for PTV-CT. As a supplement of CT scan, MRI can enhance the accuracy of TB delineation after breast-onserving surgery.

Objective:To analyze the efficacy of chest wall boost radiotherapy in stage T 4 breast cancer patients after modified radical mastectomy. Methods:A retrospective analysis was performed on the data of 148 stage T 4 breast cancer patients who were admitted from 2000 to 2016 and received radiotherapy after modified radical mastectomy. There were 57 cases in the chest wall boost radiotherapy group and 91 cases in the conventional dose group. Radiotherapy was performed by conventional+ chest wall electron beam, three-dimensional conformal+ chest wall electron beam, intensity modulated radiotherapy+ chest wall electron beam irradiation. EQD 2 at the boost group was >50Gy. All patients received neoadjuvant chemotherapy. Kaplan-Meier method was used to analyze survival; Logrank was used to test differences; and Cox model was used to do multivariate prognostic analysis. Results:The median follow-up time was 67.2 months. The 5-year rates of chest wall recurrence (CWR), locoregional recurrence (LRR), disease-free survival (DFS), and overall survival (OS) were 9.9%, 16.2%, 58.0%, and 71.4%, respectively. The 5-year rates of CWR, LRR, DFS, and OS with and without chest wall boost radiotherapy were 14% vs. 7%, 18% vs. 15%, 57% vs. 58%, 82% vs. 65%( P>0.05), respectively. Multivariate analysis showed that chest wall boost radiotherapy had no significant effect on prognosis ( P>0.05). Among 45 patients in the recurrent high-risk group, boost radiotherapy seemed to have higher OS rate ( P=0.058), DFS rate ( P=0.084), and lower LRR rate ( P=0.059). Conclusions:Stage T 4 breast cancer patients had strong heterogeneity. Chest wall boost radiotherapy did not apparently benefit all patients. For patients with 2-3 high risk factors including positive vascular tumor embolus, pN 2-N 3, and hormone receptor negative, chest wall boost radiotherapy showed a trend of improving efficacy.

Objective:To evaluate serum complement C1q tumor necrosis factor related proteins-3 (CTRP-3) and D-dimer (D-D) in predicting hyperacute transformation after thrombolysis in patients with cerebral infarction, and their correlation with brain injury.Methods:One hundred and sixty patients with cerebral infarction admitted in our hospital from August 2016 to August 2019 were enrolled in the study. The hyperacute transformation occurred in 29 cases after intravenous thrombolysis (occurrence group) and did not occur in 131 cases (non-occurrence group). The serum CTRP-3, D-D levels and other factors that may cause hyperacute transformation were compared between the occurrence group and the non-occurrence group. Logistic regression analysis was used to analyze the risk factors of cerebral hemorrhage. The predictive values of serum CTRP-3 and D-D for hyperacute transformation in patients with cerebral infarction were analyzed with receiver operating characteristic (ROC)curve. The correlation between serum CTRP-3, D-D and brain injury was analyzed by Pearson correlation coefficient method.Results:The National Institute of Health stroke scale (NIHSS) score [(18.6±2.2) points vs. (14.0±2.1) points, t=10.62, P<0.01], proportion of infarct diameter >5 cm [69.0%(20/29) vs. 39.7%(52/131), χ 2=8.22, P<0.01], trial fibrillation rate[72.4%(21/29) vs. 44.3%(59/131), χ 2=7.52, P<0.01], and serum D-D levels [(3.02±0.31) mg/L vs. (2.24±0.23) mg/L, t=15.44, P<0.01] of the occurrence group were significantly higher than those of the non-occurrence group; while the serum CTRP-3 levels were lower than those of the non-occurrence group [(251.3±26.9) μg/L vs. (285.7±29.2) μg/L, t=5.82, P<0.01], the onset-to-needle time (OTN) was longer than that of the non-onset group [(4.61±0.43) h vs. (2.96±0.52) h, t=15.91, P<0.01]. Logistic regression analysis showed that pre-thrombosis NIHSS ( OR=1.69, 95 %CI: 1.02-2.15, P<0.01), proportion of infarct diamete r>5 cm ( OR=3.73, 95 %CI: 1.96-5.10, P=0.001), atrial fibrillation ( OR=2.14, 95 %CI: 1.25-2.96, P<0.01), OTN ( OR=3.44, 95 %CI: 1.85-5.02, P<0.01), serum DD ( OR=2.37, 95 %CI: 1.56-3.30, P<0.01) and serum CTRP-3 ( OR=2.9 d, 95 %CI: 1.91-4.25, P<0.01) were risk factors for hyperacute transformation in patients with cerebral infarction. ROC results showed that the area under the curve (AUC) of CTRP-3 and D-D for predicting hyperacute transformation in patients with cerebral infarction were 0.723 and 0.796, respectively; and the AUC of the combination of two indicators was 0.823. The anterior cerebral infarction occurred in 28 cases, the posterior cerebral infarction occured in 132 cases. The NIHSS score were(18.7±2.1)points and (14.0±1.9)points,respectively,and the modified Rankin Scale(mRS) score were(3.8±0.5)points and(3.2±0.6) points. Pearson correlation analysis showed that the serum CTRP-3 was negatively correlated with the NIHSS score of brain damage in patients with anterior circulation cerebral infarction ( r=-0.72, P<0.01), and the correlation was less strong with the NIHSS score in patients with posterior circulation cerebral infarction ( r=-0.35, P<0.01). The serum D-D was strongly positively correlated with NIHSS score of brain damage in patients with anterior circulation cerebral infarction ( r=0.88, P<0.01), and it was less strong with NIHSS score in patients with posterior circulation cerebral infarction ( r=0.24, P<0.01). The serum CTRP-3 was strongly positively correlated with brain injury mRS score ( r=0.80, P<0.01), and serum D-D was strongly negatively correlated with brain injury mRS score ( r=-0.76, P<0.01). Conclusion:The combined detection of serum CTRP-3 and D-D has a high predictive value for the occurrence of cerebral hemorrhage in hyperacute transformation after thrombolysis in patients with cerebral infarction, and two indicators have a certain correlation with brain injury of patients.

Objective: To analyze the failure patterns of locoregional recurrence (LRR) and investigate the range of radiotherapy in T_1-2N₁ breast cancer patients undergoing modified radical mastectomy. Methods: From September 1997 to April 2015, 2472 women with T_1-2N₁ breast cancer after modified radical mastectomy without neoadjuvant systemic therapy were treated in our hospital. 1898 patients who did not undergo adjuvant radiotherapy were included in this study. The distribution of accumulated LRR was analyzed. The LR and RR rates were estimated by the Kaplan-Meier method, and the prognostic factors were identified in univariate analyses with Log-rank test. Multivariate analysis was performed using Cox logistic regression analysis. Results: With a median follow-up of 71.3 months (range 1.1-194.6), 164 patients had LRR, including supraclavicular/infraclavicular lymph nodes in 106(65%), chest wall in 69(42%), axilla in 39(24%) and internal mammary lymph nodes (IMNs) in 19 patients (12%). In multivariate analysis, age (>45 years vs.≤45 years), tumor location (other quadrants vs. inner quadrant), T stage (T₁ vs. T₂), the number of positive axillary lymph nodes (1 vs. 2-3), hormone receptor status (positive vs. negative) were significant prognostic factors for both LR and RR. Conclusions In patients with T_1-2N₁ breast cancer after modified radical mastectomy, the most common LRR site is supraclavicular/infraclavicular nodal region, followed by chest wall. The axillary or IMN recurrence is rare. The prognostic factors for LR and RR are similar, which indicates that supraclavicular/infraclavicular and chest wall irradiation should be considered for postmastectomy radiotherapy.

COVID-19 and its causative pathogen SARS-CoV-2 have rushed the world into a stag-gering pandemic in a few months, and a global fight against both has been intensifying. Here, we describe an analysis procedure where genome composition and its variables are related, through the genetic code to molecular mechanisms, based on understanding of RNA replication and its feed-back loop from mutation to viral proteome sequence fraternity including effective sites on the replicase-transcriptase complex. Our analysis starts with primary sequence information, identity-based phylogeny based on 22,051 SARS-CoV-2 sequences, and evaluation of sequence variation patterns as mutation spectra and its 12 permutations among organized clades. All are tailored to two key mechanisms: strand-biased and function-associated mutations. Our findings are listed as follows: 1) The most dominant mutation is C-to-U permutation, whose abundant second-codon-position counts alter amino acid composition toward higher molecular weight and lower hydropho-bicity, albeit assumed most slightly deleterious. 2) The second abundance group includes three negative-strand mutations (U-to-C, A-to-G, and G-to-A) and a positive-strand mutation (G-to-U) due to DNA repair mechanisms after cellular abasic events. 3) A clade-associated biased muta-tion trend is found attributable to elevated level of negative-sense strand synthesis. 4) Within-clade permutation variation is very informative for associating non-synonymous mutations and viral pro-teome changes. These findings demand a platform where emerging mutations are mapped onto mostly subtle but fast-adjusting viral proteomes and transcriptomes, to provide biological and clinical information after logical convergence for effective pharmaceutical and diagnostic applica-tions. Such actions are in desperate need, especially in the middle of the War against COVID-19.