Overexpression of ETV2 in BMSCs promoted wound healing in cutaneous wound mice by triggering the differentiation of BMSCs into endothelial cells and modulating the transformation of M1 phenotype macrophages to M2 phenotype macrophages.

This study aimed to investigate the effects of E26-transformation-specific variant-2 (ETV2) overexpression on wound healing in a cutaneous wound (CW) model and clarify associated mechanisms. pLVX-ETV2 lentivirus expressing ETV2 was constructed and infected into BMSCs to generate ETV2-overexpressed BMSCs (BMSCs+pLVX+ETV2). The RT-PCR assay was applied to amplify ETV2, VE-cadherin, vWF, ARG-1, IL-6, iNOS, TGF-ß, IL-10, TNF-α. Western blot was used to determine expression of VE-cadherin and vWF. ETV2 induced differentiation of BMSCs into ECs by increasing CDH5/CD31, triggering tube-like structures, inducing Dil-Ac-LDL positive BMSCs. ETV2 overexpression increased the gene transcription and expression of VE-cadherin and vWF (P<0.01). Transcription of M1 phenotype specific iNOS gene was lower and transcription of M2 phenotype specific ARG-1 gene was higher in the RAW264.7+BMSCs+ETV2 group compared to the RAW264.7+BMSCs+pLVX group (P<0.01). ETV2 overexpression (RAW264.7+BMSCs+ETV2) downregulated IL-6 and TNF-α, and upregulated IL-10 and TGF-ß gene transcription compared to RAW264.7+BMSCs+pLVX group (P<0.01). ETV2-overexpressed BMSCs promoted wound healing in CW mice and triggered the migration of BMSCs to the wound region and macrophage activation. ETV2-overexpressed BMSCs promoted collagen fibers and blood vessel formation in the wound region of CW mice. In conclusion, this study revealed a novel biofunction of ETV2 molecule in the wound healing process. ETV2 overexpression in BMSCs promoted wound healing in CW mice by triggering BMSCs differentiation into endothelial cells and modulating the transformation of M1 pro-inflammatory and M2 anti-inflammatory macrophages in vitro and in vivo.

Association between Cu/Zn/Iron/Ca/Mg levels and cerebral palsy: a pooled-analysis.

It was well documented that macro/trace elements were associated with the neurodevelopment. We aimed to investigate the relationship between copper (Cu)/zinc (Zn)/iron/calcium (Ca)/magnesium (Mg) levels and cerebral palsy (CP) by performing a meta-analysis. We searched the PubMed, Embase, Cochrane and Chinese WanFang databases from January 1985 to June 2022 to yield studies that met our predefined criteria. Standard mean differences (SMDs) of Cu/Zn/Iron/Ca/Mg levels between CP cases and healthy controls were calculated using the fixed-effects model or the random-effects model, in the presence of heterogeneity. 95% confidence intervals (CI) were also computed. Sensitivity analysis was performed by omitting each study in turn. A total of 19 studies were involved in our investigation. CP cases showed markedly lower Cu, Zn, iron and Ca levels than those in controls among overall populations (SMD = - 2.156, 95% CI - 3.013 to - 1.299, P < 10-4; SMD = - 2.223, 95% CI - 2.966 to - 1.480, P < 10-4; SMD = - 1.092, 95% CI - 1.513 to - 0.672, P < 10-4; SMD = - 0.757, 95% CI - 1.475 to - 0.040, P = 0.038) and Asians (SMD = - 2.893, 95% CI - 3.977 to - 1.809, P < 10-4; SMD = - 2.559, 95% CI - 3.436 to - 1.683, P < 10-4; SMD = - 1.336, 95% CI - 1.807 to - 0.865, P < 10-4; SMD = - 1.000, 95% CI - 1.950 to - 0.051, P = 0.039). CP cases showed markedly lower Zn level than that in controls among Caucasians (SMD = - 0.462, 95% CI - 0.650 to - 0.274, P < 10-4). No significant differences of Cu, iron and Ca levels between CP cases and controls among Caucasians (SMD = - 0.188, 95% CI - 0.412 to 0.037, P = 0.101; SMD = - 0.004, 95% CI - 0.190 to 0.182, P = 0.968; SMD = 0.070, 95% CI - 0.116 to 0.257, P = 0.459) were observed. No marked difference of Mg level between CP cases and controls was noted among overall populations (SMD = - 0.139, 95% CI - 0.504 to 0.226, P = 0.455), Asians (SMD = - 0.131, 95% CI - 0.663 to 0.401, P = 0.629), and Caucasians (SMD = - 0.074, 95% CI - 0.361 to 0.213, P = 0.614). Sensitivity analysis did not change the overall results significantly for Cu, Zn, iron and Mg. CP cases demonstrated significantly lower levels of Cu/Zn/iron/Ca than those in healthy controls, particularly in Asians. Decreasing trend of Cu/Zn/iron/Ca levels merit attention, particularly in the population with high susceptibility to CP. Frequent monitoring and early intervention may be needed.

Suppurative tenosynovitis with chronic carpal tunnel syndrome due to corticosteroid injections: A case report.

INTRODUCTION: Steroid hormone blocking is a common treatment for tenosynovitis. However, local steroid hormone blocking requires careful attention to the local inflammatory response, as infection can cause severe local soft tissue inflammation and damage. PRESENTATION OF CASE: A 46-year-old female patient received local steroid hormone blocking treatment for tenosynovitis of the right thumb at another hospital 3 months earlier. Five days later, the patient gradually experienced redness, swelling, and pain in her right hand. By day 7, the symptoms worsened with increased swelling, wrist pain, and finger numbness. After the carpal tunnel incision, the patient's symptoms improved upon admission to the local hospital's emergency department. However, 2 weeks post-operation, she experienced recurring numbness, pain, discomfort, and local sinus exudation in her right hand, which worsened over 2 months, prompting the patient to seek outpatient treatment at our hospital. DISCUSSION: An increase in local content within the wrist joint content is a major cause of carpal tunnel syndrome. Repeated stimulation of the inflamed tissues often leads to the development of granulomatous hyperplasia. Hyperplastic granulomas often produce local compression. If located in the peripheral nerve duct, it may cause nerve entrapment and lead to peripheral nerve injury. Surgery is often required to excise the hyperplastic tissue and release the entrapped nerve. CONCLUSION: Prompt and thorough debridement is necessary for addressing local soft tissue infections caused by suppurative tenosynovitis. Failure to do so may result in recurrent local granuloma hyperplasia and the development of local compression diseases, especially in wrist median nerve compression cases.

Predictive value of bone morphogenetic protein-7, thromboxane A2, and osteoprotegerin for prognosis of patients with distal radius fractures.

OBJECTIVES: This study aims to investigate the predictive value of bone morphogenetic protein-7 (BMP-7), thromboxane A2 (TXA2), and osteoprotegerin (OPG) for the prognosis of patients with distal radius fractures. PATIENTS AND METHODS: Between January 2021 and January 2022, a total of 124 patients (71 males, 53 females; mean age: 49.8±5.1 years; range, 34 to 68 years) with distal radius fractures were included in the fracture group. Healthy volunteers receiving physical examination in our hospital in the same period were included in the control group (n=50; 29 males, 21 females; mean age: 50.1±5.4 years; range, 35 to 68 years). The expressions of BMP-7, TXA2, and OPG in the peripheral blood were detected. In the fracture group, 124 patients underwent internal fixation after inclusion and followed for six months. The prognosis was evaluated based on the Gartland & Werley scoring system for wrist joint function. The factors influencing prognosis were analyzed, and the predictive values of BMP-7, TXA2, and OPG were calculated. RESULTS: Age, fracture classification, early loss of palmar tilt, late loss of palmar tilt, time to return to exercise after surgery, BMP-7, TXA2, and OPG were all factors influencing the prognosis (p<0.05). For predicting the prognosis, the area under the ROC curve of BMP-7 + TXA2 + OPG (0.928) was significantly larger than those of BMP-7 (0.810), TXA2 (0.856) and OPG (0.823) alone, and BMP-7 + TXA2 + OPG had the highest predictive efficiency. The BMP-7 was negatively correlated with TXA2 (r=-0.471), but positively correlated with OPG (r=0.437). CONCLUSION: The combined detection of BMP-7, OPG, and TXA2 is highly valuable for predicting the prognosis of patients with distal radius fractures.

SOX9 Inhibits the Progression of Osteonecrosis of the Femoral Head via the Activation of the Wnt/Beta-Catenin Pathway.

Background: In this study, we aimed to explore whether the SRY-box transcription factor 9 (SOX9) can play protective roles against the occurrence and development of osteonecrosis of the femoral head (ONFH) by regulating the proliferation, apoptosis, and osteogenic differentiation of human bone marrow stromal cells (hBMSCs) via the Wnt/ß-catenin pathway.Methods: We used 1600 mg of glucocorticoid (GC) to induce hBMSCs to establish an ONFH cell model and performed various experiments. Reverse transcription-quantitative polymerase chain reaction and western blotting assays were used to determine the expression levels of SOX9 and osteoblast markers, such as the RUNX family transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osterix, Wnt3a, and ß-catenin. An ALP detection kit was used to measure the ALP activity. Flow cytometry and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays were performed to determine the cell viability.Results: GC treatment decreased the expression levels of RUNX2, ALP, and osterix, suppressed ALP activity, and inhibited SOX9 expression. SOX9 overexpression promoted GC-induced cell proliferation and decreased cell apoptosis. Additionally, hBMSCs were transfected with SOX9-small interfering RNA in GC treatment, and SOX9 knockdown was found to suppress the osteogenic differentiation of cells and decrease their viability.Conclusion: Our results revealed that SOX9 is related to the Wnt/ß-catenin pathway in ONFH. Moreover, SOX9 participated in ONFH development by activating the Wnt/ß-catenin pathway.

A novel modified Winograd surgical tricks and tips with a "bird flap" for the treatment of ingrown toenails.

BACKGROUND: The Winograd technique is the most commonly used surgical treatment for ingrown toenails. We describe a novel modified approach, more effective and simpler to perform with a better cosmetic outcome. METHODS: We retrospectively included 45 and 39 patients with 67 and 58 ingrown toenails who underwent our modified Winograd technique and the Winograd technique, respectively, from July 2017 to June 2020, and obtained data after 3, 6, and 12 months of follow-up. RESULTS: No significant differences in the postoperative time taken to return to regular activities in the modified Winograd and traditional Winograd groups (p = 0.103) and regarding the recurrence in both groups (p = 0.055) were found. The extent of proximal germinal matrix exposure with the modified Winograd technique was significantly more clearly revealed than in the traditional Winograd method contextually (p < 0.05). The postoperative appearance satisfaction rate was significantly higher in the modified Winograd group than in the traditional Winograd group (p = 0.029). CONCLUSION: The modified Winograd technique is effective in treating ingrown toenails.

Exhausting circ_0136474 and Restoring miR-766-3p Attenuate Chondrocyte Oxidative Injury in IL-1ß-Induced Osteoarthritis Progression Through Regulating DNMT3A.

Circular RNA circ_0136474 is a new contributor of human osteoarthritis (OA) by suppressing chondrocyte proliferation. However, its role and mechanism in OA chondrocyte injury remain ill defined. Herein, we performed real-time quantitative PCR to detect RNA expression of circ_0136474, microRNA (miR)-766-3p, and DNA methyltransferase 3A (DNMT3A) and utilized Western blotting to measure protein expression of DNMT3A, matrix metalloproteinase-1 (MMP1), MMP13, collagen II, proliferating cell nuclear antigen (PCNA) and B cell lymphoma (Bcl)-2, and Bcl-2-associated X protein (Bax). Direct interaction between miR-766-3p and circ_0136474 or DNMT3A was confirmed by bioinformatics algorithms, dual-luciferase reporter assay, and RNA immunoprecipitation. Functional experiments including cell counting kit-8 assay, flow cytometry, and special assay kits were employed to measure oxidative injury in interleukin (IL)-1ß-induced OA-like chondrocytes. First, IL-1ß administration induced cell viability inhibition, collagen II suppression, and promotion of MMP1 and MMP13 in human chondrocyte CHON-001 cells. Expression of circ_0136474 and DNMT3A was upregulated, and miR-766-3p was downregulated in human OA cartilages and IL-1ß-induced CHON-001 cells. Functionally, both blocking circ_0136474 and upregulating miR-766-3p could rescue cell viability and levels of PCNA, Bcl-2, reduced glutathione (GSH), and total superoxide dismutase (SOD), and attenuate apoptosis rate and levels of Bax, reactive oxygen species (ROS), and lipid peroxidation malondialdehyde (MDA). Mechanically, circ_0136474 served as miR-766-3p sponge to govern miR-766-3p-targeted DNMT3A expression. Accidently, restoring DNMT3A counteracted the miR-766-3p upregulation role, and silencing miR-766-3p weakened circ_0136474 knockdown effect in IL-1ß-induced CHON-001 cells. In conclusion, exhausting circ_0136474 could mitigate OA chondrocyte oxidative injury through regulating miR-766-3p/DNMT3A axis.

Association between leptin level and renal cell carcinoma susceptibility and progression: A meta-analysis.

OBJECTIVES: It is well-documented that obesity participated in the development of renal cell carcinoma (RCC). Leptin is closely associated with obesity. This study is aimed to investigate the relationship between leptin level and RCC susceptibility and progression. METHODS: A meta-analysis was conducted to explore the association between leptin level and RCC susceptibility and progression. The studies were retrieved from electronic databases during January 1990-September 2017 with keywords. The qualified studies were screened with inclusion and exclusion criteria. A random effects model was applied to calculate the pooled standard mean differences and the corresponding confidence intervals. RESULTS: Ten studies were finally included in this meta-analysis. The serum leptin level in male RCC was significantly lower than that of in female RCC in overall populations, Asians, and Caucasians while no marked difference was noted between genders in the plasma samples. Plasma leptin level in Stage I-II RCC was significantly higher than that in the Stage III-IV. In addition, no significant difference was observed between following parameters, including RCC and non-RCC, clear and non-clear RCC, Grade I-II and Grade III-IV RCC, M0 and M1 RCC, N0 and N1 RCC, and size <4 cm and size >4 cm RCC. No evidence of publication bias was observed. CONCLUSIONS: Our findings indicated that serum leptin level was lower in men with RCC than in women with RCC. Leptin level may not be related to the risk and progression of RCC. However, more studies should be performed in the future.