Application of Modified Kite Flap in Reconstruction of Facial Wounds After Operation and Case Series.

Our team used a new kite flap preparation method to repair wounds after the removal of a benign facial tumor with satisfactory aesthetic results. Thus, this modified kite flap has significant value in facial trauma repair.

Research on the correlation between the renal resistive index, renal microvessel density, and fibrosis.

BACKGROUND: This study was designed to investigate the relationship between the renal resistive index (RRI), renal microvessel density (RMD), and fibrosis in patients with chronic kidney disease (CKD). METHODS: A total of 73 CKD patients were included in the study. Prior to kidney biopsy, we recorded the RRI of the interlobar artery and the estimated glomerular filtration rate (eGFR). Immunohistochemical analysis was performed to assess CD34 expression, and Masson staining was used to evaluate histopathological specimens for RMD and the degree of fibrosis. The percentage of the positive area (PPA) was recorded. Subsequently, we investigated the correlation between RRI, RMD, and kidney fibrosis. RESULTS: RMD (CD34 PPA-total and CD34 PPA-peritubular capillary) showed a slight increase in early CKD stages (1-2) and gradually declined from CKD stages 2 to 5. No correlation was observed between the RRI and RMD or between the RRI and fibrosis across CKD stages 1 to 5. However, across CKD stages 2 to 5, RRI negatively correlated with CD34 PPA-glomerulus (r = -0.353, p = 0.022), but no correlation was found with CD34 PPA-total, CD34 PPA-peritubular capillary, or kidney fibrosis. eGFR showed a positive correlation with RMD (CD34 PPA-total, CD34 PPA-peritubular capillary, and CD34 PPA-glomerulus) across CKD stages 2 to 5, while no correlation was found from CKD stages 1 to 5. CONCLUSION: There was no correlation between RRI and RMD or between RRI and fibrosis across CKD stages 1 to 5 (RRI ≤ 0.7).

IL1R2 is a Novel Prognostic Biomarker for Lung Adenocarcinoma.

AIMS: The aim of this study is to figure out the role of IL1R2 in LUAD (lung adenocarcinoma). BACKGROUND: IL1R2, a special member of IL-1 receptor family, binds to IL-1 and plays an important role in inhibiting IL-1 pathway, which seems to be involved in tumorigenesis. Emerging studies demonstrated higher IL1R2 expression levels in several malignancies. OBJECTIVE: In the present study, we assessed the expression of IL1R2 in LUAD tissues with immunohistochemistry and explored various databases to determine whether it could be a potential prognostic biomarker and therapeutic target. METHODS: The expression level of IL1R2 in lung adenocarcinoma was analyzed by Immunohistochemistry and UALCAN database. The correlation between IL1R2 expression and the patient prognosis was identified by Kaplan-Meier plotter. The correlation of IL1R2 expression with immune infiltrates was clarified by TIMER database. The protein-protein interaction network and gene functional enrichment analysis were constructed and performed by STRING and Metascape database. RESULTS: Immunohistochemistry showed that the expression of IL1R2 was higher in tumor tissues of LUAD patients and that patients with lower IL1R2 level have a better prognosis than their counterparts. We validated our findings in several online databases and found that IL1R2 gene was also positively correlated with B cells and neutrophils and biomarkers of CD8+ T cells and exhausted T cells. PPI network and gene enrichment analyses showed that expression of IL1R2 was also associated with complex functionspecific networks involving IL-1 signal, NF-KappaB transcription factors. CONCLUSION: According to these findings, we demonstrated that IL1R2 was involved in the progression and prognosis of LUAD and the underlying mechanism needs further investigation.

Utility of shear wave-based ultrasound elastography in chronic kidney disease and related pathological quantitative analysis.

OBJECTIVES: The purpose of this study was to investigate the effects of tissue fibrosis and microvessel density on shear wave-based ultrasound elastography (SWUE) of chronic kidney disease (CKD). In addition, we were looking to see whether SWUE could predict stage of CKD, correlating with the histology on kidney biopsy. METHODS: Renal tissue sections from 54 patients diagnosed with suspected CKD were subjected to immunohistochemistry (CD31 and CD34), and the degree of tissue fibrosis was assessed using Masson staining. Before renal puncture, both kidneys were examined using SWUE. Comparative analysis was used to assess the correlation between SWUE and microvessel density, and between SWUE and the degree of fibrosis. RESULTS: Fibrosis area according to Masson staining (p < 0.05) and integrated optical density (IOD) (p < 0.05) were positively correlated with CKD stage. The percentage of positive area (PPA) and IOD for CD31 and CD34 were not correlated with CKD stage (p > 0.05). When stage 1 CKD was removed, PPA and IOD for CD34 were negatively correlated with CKD stage (p < 0.05). Masson staining fibrosis area and IOD were not correlated with SWUE (p > 0.05), PPA and IOD for CD31 and CD34 were not correlated with SWUE (p > 0.05) and, finally, no correlation between SWUE and CKD stage was found (p > 0.05). CONCLUSION: The diagnostic value of SWUE for CKD staging was very low. The utility of SWUE in CKD was affected by many factors and its diagnostic value was limited. KEY POINTS: • There was no correlation between SWUE and the degree of fibrosis, or between SWUE and microvessel density among patients with CKD. • There was no correlation between SWUE and CKD stage and the diagnostic value of SWUE for CKD staging was very low. • The utility of SWUE in CKD is affected by many factors and its value was limited.

Spontaneous Disappearance of Filar Cysts Diagnosed by Transabdominal Ultrasonography: A Report of Three Cases.

Filar cysts (FCs) can be detected using ultrasound before or after delivery. They usually present as anechoic structures with a clear boundary just caudal to the lower end of the conus medullaris. They are generally considered a physiological variation and do not affect health. Some studies have pointed out that FCs in children can disappear spontaneously, as identified by ultrasound or magnetic resonance imaging. Three cases of FCs diagnosed by prenatal transabdominal ultrasound were reported in this study, and it was observed that FCs could disappear spontaneously in utero. The shortest time of disappearance was 4 weeks.

Basic Pan-Cancer Analysis of the Carcinogenic Effects of Cyclin-Dependent Kinase 4 (CDK4) in Human Surface Tumors.

Although the evidence based on current human, animal, or molecular biology can explain some of the relationships between CDK4 and cancer, there is no pan-cancer analysis of the gene CDK4 in human skin tumors. Therefore, the potential carcinogenic effects of CDK4 in 33 tumors were initially explored in the datasets of the GEO (Gene Expression Omnibus) and the CGA (Cancer Genome Atlas). We found that CDK4 was highly expressed in most cancers and that CDK4 performance levels significantly correlated with the prognosis of cancer patients. These were found in our preliminary exploration. In addition, we used the dataset in tumors such as cutaneous melanoma or lung adenocarcinoma and found increased levels of phosphorylation of r24 l/C/h/s. In addition, fibroblast infiltration associated with CDK4 cancer was observed in head and neck, sarcoma, and melanoma skin. Using this pan-cancer study, our group has provided a comprehensive preliminary demonstration of the oncogenic effects of the CDK4 gene on different human skin tumors.

Induction of notochordal differentiation of bone marrow mesenchymal­derived stem cells via the stimulation of notochordal cell­rich nucleus pulposus tissue.

The degeneration of intervertebral disc (IVD) tissue, initiated following the disappearance of notochordal cells (NCs), is characterized by the decreased number of nucleus pulposus (NP) cells (NPCs) and extracellular matrix. Transplanting proper cells into the IVD may sustain cell numbers, resulting in the synthesis of new matrix; this represents a minimally invasive regenerative therapy. However, the lack of cells with a correct phenotype severely hampers the development of regenerative therapy. The present study aimed to investigate whether porcine NC­rich NP tissue stimulates bone marrow­derived mesenchymal stem cell (BM­MSC) differentiation toward NC­like cells, which possess promising regenerative ability, for the treatment of disc degeneration diseases. BM­MSCs were successfully isolated from porcine femurs and tibiae, which expressed CD90 and CD105 markers and did not express CD45. Differentiation induction experiments revealed that the isolated cells had osteogenic and adipogenic differentiation potential. When co­cultured with NC­rich NP tissue, the BM­MSCs successfully differentiated into NC­like cells. Cell morphological analysis revealed that the cells exhibited an altered morphology, from a shuttle­like to a circular one, and the expression of NC marker genes, including brachyury, keratin­8, and keratin­18, was enhanced, and the cells exhibited the ability to generate aggrecan and collagen II. Taken together, the findings of the present study demonstrated that the primarily isolated and cultured BM­MSCs may be stimulated to differentiate into NC­like cells by porcine NC­rich NP explants, potentially providing an ideal cell source for regenerative therapies for disc degeneration diseases.

Retracted: Expression of Lymphocyte-Activation Gene 3 (LAG-3) Immune Checkpoint Receptor Identifies a Tumor-Reactive T Cell Population in the Peripheral Blood of Patients with Colorectal Cancer.

This article is retracted due to authors' claims in regards to errors in data and statistical analyses. Authors' message: We greatly regret to inform you that we just discovered some fatal errors in the statistical analysis, in which we mistakenly used the cultured cells TCR sequencing data as the results of CD8+ LAG3+ and CD8 LAG3-T cells. Therefore, the current results and data have serious defects and do not accurately represent the sorted cells. On behalf of all the contributing authors of the manuscript, we have decided to immediately retract the manuscript titled "LAG-3 receptor identifies a higher tumor-reactive cell population in the peripheral blood of colorectal cancer patients" to avoid further problems.

Expression of Lymphocyte-Activation Gene 3 (LAG-3) Immune Checkpoint Receptor Identifies a Tumor-Reactive T Cell Population in the Peripheral Blood of Patients with Colorectal Cancer.

BACKGROUND The use of adoptive T cell therapy has proven to be effective in some advanced malignancies. This study aimed to investigate the effects of lymphocyte-activation gene 3 (LAG-3) immune checkpoint receptor in the enrichment of tumor antigen-specific CD8⁺ T lymphocytes derived from peripheral blood mononuclear cells (PBMCs) in patients with colorectal cancer. MATERIAL AND METHODS Peripheral blood samples were obtained from 20 patients with colorectal cancer and apheresis was performed with enrichment and cell sorting to obtain CD8⁺LAG-3⁺ T cells, which were expanded using high-dose interleukin-2 (IL-2). T cell subsets were detected using fluorescence-activated cell sorting (FACS), and T cell receptor (TCR) sequencing was used to determine specific clone types. Interferon-γ (IFN-γ) enzyme-linked immunospot (ELISpot) and cell counting kit-8 (CCK-8) assays were used to measure cell avidity and cytotoxicity. RESULTS The cultured cells increased in number over time and had the greatest proliferative activity at 15 days, at which time the percentage of CD3⁺, CD3⁺CD8⁺, and CD8⁺CD28⁺ reached maximal levels. High purity CD8⁺LAG-3⁺ T cells were isolated by FACS and at 15 days. TCR sequencing showed that CD8⁺LAG-3⁺ T cells were oligoclonal, ELISpot identified increased production of tumor-specific IFN-γ, and the CCK-8 assay showed increased cytotoxicity when compared with pre-cultured CD8⁺LAG-3⁻ T cells. CONCLUSIONS In patients with colorectal cancer, CD8⁺LAG-3⁺ T cells showed more specific anti-tumor activity following cell culture in vitro, which supported the potential role for the LAG-3 immune checkpoint receptor in enriching tumor-specific T cells in patients with cancer.

Caveolin­1 regulates oxidative stress­induced senescence in nucleus pulposus cells primarily via the p53/p21 signaling pathway in vitro.

Previous studies have indicated that cellular senescence is a critical underlying mechanism of intervertebral disc degeneration. However, the precise mechanism by which cellular senescence accelerates disc degeneration has not been fully elucidated. Caveolin­1 has recently emerged as an important regulator of cellular senescence. Therefore, the aim of the present study was to investigate whether caveolin­1 is involved in nucleus pulposus (NP) cellular senescence during oxidative stress. PCR was used to detect caveolin­1 mRNA expression and protein expression was detected by western blotting. Caveolin­1 expression at the mRNA and protein levels was markedly increased following treatment with tert­butyl hydroperoxide, and an increase in premature senescence was observed, as determined by senescence­associated ß­galactosidase staining and the decline of cellular proliferative ability. In addition, caveolin­1 gene expression was successfully knocked down by lentivirus­mediated RNA interference, which exerted a protective effect against the cellular senescence induced by oxidative stress. Notably, p53 and p21 protein expression, though not p16 protein expression, decreased with caveolin­1 silencing. The results suggested that caveolin­1 may be involved in NP cellular senescence during oxidative stress in vitro, mainly via the p53/p21 signaling pathway. Thus, caveolin­1 may represent a novel therapeutic target for the prevention of intervertebral disc degeneration.

Isoflurane promotes glucose metabolism through up-regulation of miR-21 and suppresses mitochondrial oxidative phosphorylation in ovarian cancer cells.

Ovarian cancer is one of the most lethal gynecologic malignancies in women. Isoflurane is one of the volatile anesthetics used extensively for inhalational anesthesia and gynecological surgery. However, the effects of isoflurane on ovarian cancer have not been fully elucidated. It is widely studied that one of the biochemical fingerprints of cancer cells is the altered energy metabolism which is characterized by preferential dependence on glycolysis for energy production in an oxygen-independent manner. In the present study, we explored the roles of isoflurane in the regulation of cellular metabolism of ovarian cancer cells. We observed the glucose uptake, lactate production and extracellular acidification of two ovarian cancer cell lines, SKOV3 and TOV21G were significantly stimulated by isoflurane treatments at 1 and 2 h. The glycolysis enzymes, HK2, PKM2, and LDHA were up-regulated by isoflurane. We report that miR-21 was induced by isoflurane treatments in ovarian cancer cells, leading to the elevated AKT phosphorylation and up-regulation of glycolysis enzymes. In contrast, the mitochondrial functions were suppressed by isoflurane treatments: the oxygen consumption, mitochondrial membrane potential (MMP), and activities of complex I, II, and IV on the electron transport chain were significantly decreased under isoflurane treatments. Importantly, ovarian cancer cells become hypersensitive to glycolysis inhibitors with isoflurane pretreatments. The present study demonstrates that isoflurane treatments drive a metabolic switch of ovarian cancer cells and contributes to the discovery and development of clinical therapeutic agents against ovarian cancer.

Comparison of contrast-enhanced ultrasonography with virtual touch tissue quantification in the evaluation of focal liver lesions.

PURPOSE: To evaluate the diagnostic efficacy of virtual touch tissue quantification (VTQ) and contrast-enhanced ultrasonography (CEUS), separately and in combination, in diagnosing malignant focal liver lesions (FLLs). METHODS: Forty-six patients with 55 FLLs (28 benign and 27 malignant) underwent both VTQ and CEUS. The diagnostic values of VTQ and CEUS, alone and in combination, were compared. RESULTS: The diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of CEUS were 92.6% (25/27), 96.4% (27/28), 94.5% (52/55), 96.2% (25/26), and 93.1% (27/29), respectively. The diagnostic sensitivity, specificity, accuracy, PPV, and NPV of VTQ with a cutoff of 2.22 m/s were 51.9% (14/27), 85.7% (24/28), 69.1% (38/55), 77.8% (14/18), and 64.9% (24/37), respectively. The diagnostic sensitivity, specificity, accuracy, PPV, and NPV of VTQ and CEUS combined were 96.3% (26/27), 82.1% (23/28), 89.1% (49/55), 83.9% (26/31), and 95.8% (23/24), respectively. Comparing the accuracies of the three methods, the diagnostic values of CEUS and of the combination of CEUS with VTQ were significantly higher than those of VTQ alone (p ≤ 0.01). There was no significant difference between the combination of CEUS with VTQ and CEUS (p = 0.49). CONCLUSIONS: CEUS is superior to VTQ in diagnosing malignant FLLs. Adding VTQ to CEUS did not improve the diagnosis of FLLs. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:347-353, 2016.

Effects of CCN3 on rat cartilage endplate chondrocytes cultured under serum deprivation in vitro.

The presence of apoptotic cells and loss of extracellular matrix (ECM) are common characteristics of degenerated cartilage endplates (CEPs). In addition, therapeutic efficacy is hampered by an incomplete understanding regarding the mechanisms underlying CEP homeostasis and degeneration. The CCN proteins have recently emerged as important regulators of cell­ECM interactions, and have been identified as key mediators of nucleus pulposus ECM composition and tissue homeostasis. However, whether CCN3 is associated with CEP homeostasis has yet to be elucidated. The present study aimed to investigate the effects of CCN3 on the apoptosis and ECM synthesis of CEP cells cultured under serum deprivation. Rat CEP cells were confirmed to be of the chondrocytic phenotype by toluidine blue staining. The mRNA expression levels of CCN3 were markedly increased, and a dose­dependent increase of apoptotic rate was detected under serum deprivation conditions following treatment with recombinant CCN3, whereas CCN3 did not exert a proapoptotic effect on cells cultured under normal conditions. Furthermore, CCN3­treated cells exhibited a decrease in the expression levels of aggrecan and collagen II in both groups. These results suggested that CCN3 may act as a regulator, rather than an initiator, of serum deprivation­induced cellular apoptosis, and that CCN3 has a catabolic effect on the mediation of ECM synthesis under both normal and serum deprivation conditions. Therefore, CCN3 may represent a novel therapeutic target for the prevention of CEP degeneration.

Heregulin-1β Promotes the Synergistic Effect Between Allogenic Skin-Derived Precursor Differentiated Schwann Cells (SKP-SC) and Acellular Nerve Allograft (ANA) in Peripheral Nerve Regeneration Through Inhibiting Mir-21

Previous studies in our lab found that heregulin-1β with SKP-SCs (neurons and Schwann cells differentiated from SKPs) / ANA (acellular nerve allograft) transplantation represented a powerful therapeutic approach, and facilitates the efficacy of ANA in peripheral nerve injury. In this study, our purpose is to explore the mechanism between them. Firstly we transplanted ANA + SKP-SC + heregulin-1β into rats with right sciatic nerve injury and then detected the miR-21 and SOX2 (SRY-like HMG box 2) levels. Then we transfected miR-21 inhibitor in SCs (Schwann cells) which induced in hypoxic condition before harvesting. Then we detected expression of miR-21 and SOX2 using real time-PCR and western blot assay. Results in vivo showed that the expression of miR-21 in rats was inhibited after transplantation of ANA + SKP-SC + heregulin-1β with induced SOX2 accordingly. Then we found miR-21 was increased time dependently in hypoxic SCs with decreased SOX2 accordingly. After miR-21 inhibitor transfection, miR-21 level was reduced and SOX2 was up-regulated. Meanwhile it was also showed that the miR-21 inhibitor induced the hypoxic SCs growth, decreased the apoptosis with cell cycle changing. In conclusion miR-21 and its target gene SOX2 played important role in peripheral nerve injury. Heregulin-1β may increase the synergistic effect between SKP-SC and ANA through inhibiting miR-21 in vivo.

Treatment of stiff thoracic scoliosis by thoracoscopic anterior release combined with posterior instrumentation and fusion.

BACKGROUND: Thoracoscopic anterior release has been shown that it can effectively improve spinal flexibility in animal and human cadaveric studies, and has been advocated for use in patients with scoliosis. This prospective case series aims to investigate the improvement of the spinal flexibility and the effectiveness in deformity correction by anterior thoracoscopic release and posterior spinal fusion. METHODS: Eleven patients with stiff idiopathic thoracic scoliosis underwent anterior thoracoscopic release followed by posterior instrumentation. The average number of discs excised was five. Spinal flexibility was assessed by the fulcrum bending technique. Cobb angle before and after the anterior release was compared. RESULTS: The patients were followed for an average of 5.6 years (range 2.2 to 8.1 years). Fulcrum bending flexibility was increased from 39% before the thoracoscopic anterior spinal release to 54% after the release. The average Cobb angle before anterior release was 74 degrees on the standing radiograph and 45 degrees with the fulcrum-bending radiograph. This reduced to 34 degrees on the fulcrum-bending radiograph after the release, and highly corresponded to the 31 degrees measured at the post-operative standing radiograph. CONCLUSION: It was demonstrated in patients with stiff idiopathic thoracic scoliosis that thoracoscopic anterior spinal release can effectively improve the spinal flexibility and increase the correction of the spinal deformity.