[Curative effects of bi-pedicled deep inferior epigastric perforator flap in repairing large soft tissue defects in the lower limbs].

Objective: To investigate the curative effects of bi-pedicled deep inferior epigastric perforator (DIEP) flap in repairing large soft tissue defects in the lower limbs. Methods: A retrospective observational study was conducted. From February 2016 to June 2020, 16 patients with large soft tissue defects in the lower limbs caused by trauma or after tumor/scar resection were admitted to the Department of Hand Surgery of the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, including 9 males and 7 females, aged 25-58 years, with the area of soft tissue defects ranging from 14.0 cm×8.0 cm to 32.0 cm×18.0 cm. Using the abdomen as the donor site, the conjoined abdominal wall flap, i.e., the bi-pedicled DIEP flap (with an area ranging from 15.0 cm×9.0 cm to 32.0 cm×20.0 cm) carrying two sets of the trunk of the deep inferior epigastric artery was designed and resected to repair the wound. The donor site wound was sutured directly. The flap survival and wound healing in the donor and recipient areas were observed after operation. The curative effect was evaluated during the follow-up. At the last follow-up, the American Knee Society score and lower extremity functional scale were used to assess the functions of knee joint and lower limb, respectively. Results: The flaps of 15 patients survived after operation; the flap of one patient had partial infection at the edge after operation but healed after debridement and dressing change. The wounds in the donor and recipient areas of 16 patients all healed well. Follow-up of 16-28 months showed that the recipient area had a good shape and pliable texture, and there was no obvious swollen appearance, hyperpigmentation, or abnormal hair growth; the donor site had linear scar only, with no complications such as abdominal hernia or hyperplastic scar; the functions of knee joint and lower limb were well reconstructed, with no recurrence of tumor. At the last follow-up, among the 4 patients with knee joint injury, 3 cases were excellent and 1 case was good in the evaluation of knee joint function; among the 12 patients with lower limb injury, 9 cases were excellent and 3 cases were good in the evaluation of lower limb function. Conclusions: The donor site of bi-pedicled DIEP flap is concealed with abundant tissue and large area for resection, with which can be used to repair large soft tissue defects in the lower limbs, achieving good short-term results of appearance and function restoration.

[The association between the frequency of prenatal care in childbearing aged women and risk of small for gestational age among neonatal twins in Shaanxi Province].

Objective: To explore the association between the frequency of prenatal care in childbearing aged women and risk of small for gestational age (SGA) among neonatal twins in Shaanxi Province. Methods: From July to December 2013, a total of 30 027 childbearing aged women, who were pregnant from January 2010 to November 2013 and had definite outcomes, were selected from 30 districts (counties) of Shaanxi Province by using the multi-stage random sampling method. The questionnaires with a face-to-face survey method were used to retrospectively collect demographic information, pregnancy history, lifestyle during pregnancy, disease history, nutritional supplements, and health care during pregnancy. Information on the gestational age and birth weight of the newborn were obtained by consulting the medical certificate of birth and were registered as twin A and twin B by birth order. Finally, 356 childbearing aged women and their twin babies with complete data were included in the analysis. A generalized estimation equation model was used to analyze the association between the frequency of prenatal care and the risk of SGA among neonatal twins. Results: The age of childbearing aged women was (27.44±4.68) years old, of which 79.49% (283 women) were rural residents and 44.38% (158 women) had seven or more times prenatal care. The gestational age and birth weight were (37.64±2.51) weeks and (2 510±497) g, respectively. The prevalence of SGA was 51.40% (183/356) for twin A and 53.37% (190/356) for twin B, respectively. The prevalence of SGA was 44.30% (70/158) for twin A with seven or more times prenatal care and 42.41% (67/158) for twin B with seven or more times prenatal care, which was lower than that for twins with less than seven times prenatal care, respectively [57.07% (113/198) and 62.12% (123/198)] (P values were 0.017 and <0.001). The results of generalized estimation equation model suggested that compared to those with less than seven times prenatal care, after adjusting for parity, birth order, place of residence, maternal age, occupation, education, family wealth index, passive smoking, pregnancy-induced hypertension syndrome, folic acid, and iron supplement during perinatal period, and gender of the newborn, the OR (95%CI) of risk of SGA among childbearing aged women with seven or more times prenatal care was 0.60 (0.40-0.91). Conclusion: Seven or more times prenatal care could reduce the risk of SGA among neonatal twins in Shanxi Province.

Long noncoding RNA LINC00511 involves in breast cancer recurrence and radioresistance by regulating STXBP4 expression via miR-185.

OBJECTIVE: The aim of this study was to explore the molecular function of long intergenic noncoding RNA 00511 (LINC00511) and its target proteins in recurrent breast cancer after breast-conserving surgery followed by radiotherapy. PATIENTS AND METHODS: LINC00511 expression in tissues was measured by quantitative polymerase chain reaction (qPCR). The association between LINC00511 expression and the clinicopathological features of breast cancer was analyzed by Chi-square tests. The impact of LINC00511 on overall survival was evaluated by the log-rank test. MDA-MB-231/MDA-MB-436 cell lines transfected with short hairpin RNA (shRNA) were used to investigate the influence of LINC00511 silencing on tumor growth and radiosensitivity in vitro and in vivo. A series of experiments including cell apoptosis assay, cell colony formation assay, and mouse xenograft models were applied to test those transfected cell lines. MicroRNA (miRNA) targets of LINC00511 were identified by bioinformatics analysis and further validated by dual luciferase reporter assay, qPCR, and Western blot analysis. RESULTS: LINC00511 expression was significantly increased in breast cancer tissues and correlated with recurrence and poor survival after breast-conserving surgery followed by radiotherapy. LINC00511 knockdown by shRNA restricted cell proliferation, promoted cell apoptosis, and enhanced radiosensitivity in vitro, and inhibited tumor growth with an increased response to radiation in vivo. In addition, elevated LINC00511 was found to increase syntaxin-binding protein 4 (STXBP4) expression through competitive binding to miR-185, while silencing LINC00511 decreased STXBP4 expression and increased radiosensitivity. CONCLUSIONS: LINC00511 inhibition impairs its competitive binding to miR-185, resulting in increased STXBP4 expression and improved radiation response in breast cancer. Our study results suggest that the LINC00511/miR-185/STXBP4 axis may be a promising therapeutic target for improving the prognosis of breast cancer.

Long noncoding RNA FAM201A involves in radioresistance of non-small-cell lung cancer by enhancing EGFR expression via miR-370.

OBJECTIVE: The aberrant expression of long noncoding RNAs (lncRNAs) is involved in the molecular regulation of non-small cell lung cancer (NSCLC). This study aims to investigate the biological interaction of lnc-FAM201A and its downstream factors and their impacts on the radiotherapy response of NSCLC. PATIENTS AND METHODS: Quantitative Polymerase Chain Reaction (qPCR) was used to determine the expression of FAM201A in NSCLC tissues. The Chi-square tests explored the association between FAM201A level and the poor clinicopathological characteristics (including radioresistance) of NSCLC. Univariate and multivariate Cox proportional hazards regression analyses were used to evaluate various prognostic factors for overall survival (OS). The effect of FAM201A on OS was tested by the log-rank test. A549/SK-MES-1 cell lines transfected with short hairpin RNA (shRNA) were used to verify the promoting effects of FAM201A on radiotherapy resistance in vitro and in vivo. Cell apoptosis (analyzed by flow cytometry), cell proliferation (determined by Cell Counting Kit-8), and mice xenograft models were performed to confirm the results. The downstream targets of FAM201A were predicted by bioinformatics tools. Additionally, the Dual-luciferase reporter assay, qPCR, and Western blotting were performed to confirm their interaction. RESULTS: FAM201A was significantly upregulated in tissues obtained from NSCLC patients resistant to radiotherapy. Increased FAM201A expression was strongly associated with radioresistance and inferior survival in NSCLC, as demonstrated by clinical data. The silence of FAM201A could inhibit cell proliferation and further cell apoptosis of NSCLC cells under X-ray irradiation both in vitro and in vivo. Moreover, by competitively targeting miR-370, FAM201A elevated the epidermal growth factor receptor (EGFR) and the hypoxia-inducible factor 1alpha (HIF-1α) levels. After FAM201A knockdown, EGFR and HIF-1α were repressed with enhanced radiosensitivity. CONCLUSIONS: The interference of FAM201A impairs its suppression of miR-370, resulting in the upregulation of EGFR and HIF-1α and enhancement of radiosensitivity in NSCLC patients. Collectively, our results indicated that this regulatory axis might serve as a potential therapeutic target to increase the sensitivity of radiotherapy in NSCLC patients.

Primary spinal melanoma of extramedullary origin: a report of three cases and systematic review of the literature.

STUDY DESIGN: A review of the literature and three case reports. OBJECTIVES: Primary spinal melanoma (PSM) of extramedullary origin is a rare malignant condition with limited current literature in regards to its clinical course, magnetic resonance imaging (MRI) findings, treatment strategies and prognosis. We reported here three cases of PSM of extramedullary origin. SETTING: China, Guangzhou. METHODS: We report three cases of PSM of extramedullary origin. The clinical and radiological findings of these cases were retrospectively analyzed. RESULTS: The three cases were all of males aged 39, 47 and 76 years, respectively. The duration of their symptoms was 3 weeks, 2 months and 11 months respectively. The extramedullary tumors were all well-defined solitary tumors and were located at C4-5, L2-3 and T9-10, respectively. In one case, involvement of the intervertebral foramen was found. Preoperative MRI showed hyperintense T1W signals and hypointense T2W signals in all three cases and all tumors were clinically misdiagnosed as schwannomas. The patients received total or subtotal resection surgery without radiotherapy or chemotherapy. Patients were alive at 18 months, 27 months and 36 months postoperative follow-up, respectively. CONCLUSION: PSM of extramedullary origin is a rare malignant tumor that shows characteristic findings on MRI. Surgical resection is the preferred treatment strategy.

AXL receptor kinase is a mediator of YAP-dependent oncogenic functions in hepatocellular carcinoma.

Yes-associated protein (YAP) is a downstream effector of the Hippo signaling pathway, which controls organ expansion and tissue development. We have recently defined the tumorigenic potential and clinical significance of the YAP1 oncogene in human hepatocellular carcinoma (HCC). The present study aims to define the tumorigenic properties of YAP in HCC and elucidate the related downstream signaling mechanism. In a gain-of-function study, we demonstrated that ectopic increased expression of YAP in the immortalized non-tumorigenic hepatocyte cell line MIHA confers tumorigenic and metastatic potentials, as evidenced by (1) enhanced aptitudes in cell viability, anchorage-independent growth, migration and invasion; (2) tumor formation in a xenograft mouse model; and (3) induction of HCC biomarker α-fetoprotein and activation of mitogen-activated protein kinase. Furthermore, we have identified AXL, a receptor tyrosine kinase, as a key downstream target that drives YAP-dependent oncogenic functions. RNAi-mediated knockdown of AXL expression decreased the ability of YAP-expressing MIHA cells and of the primary HCC cell line to proliferate and invade. These results indicate that AXL is a mediator of YAP-dependent oncogenic activities and implicates it as a potential therapeutic target for HCC.

Forkhead box P3+ T cells express interleukin-17 in nasal mucosa of patients with both allergic rhinitis and polyposis.

The pathogenesis of nasal polyposis remains unclear; it severely affects patients' quality of life and complicates inflammation in adjacent organs such as sinusitis and asthma. Aberrant immune regulatory function in these patients is proposed. The present study aims to examine the regulatory T cells (T(reg) ) in nasal mucosa of patients with allergic rhinitis (AR) and nasal polyposis (NP). Patients with AR or AR/NP were treated with inferior turbinectomy for their inferior turbinate hyperplasia. Surgically removed nasal mucosa was collected to examine the T(reg) by immunohistochemistry and flow cytometry. The results showed that more forkhead box P3 (FoxP3)(+) cells were found in AR with polyps than in those with AR alone. Further studies revealed that these FoxP3(+) T cells from AR/NP group also expressed interleukin (IL)-17. In vitro study showed that staphylococcal enterotoxin B (SEB) induced CD4(+) FoxP3(+) T cells to become FoxP3(+) IL-17(+) cells via facilitating the expression of IL-6, that in synergy with transforming growth factor-beta, induce the expression of IL-17 in FoxP3(+) cells. We conclude that FoxP3(+) IL-17(+) T cells were localized in the nasal mucosa of patients with AR and NP. SEB may play a role in converting FoxP3(+) T(reg) to FoxP3(+) IL-17(+) T cells. The presence of IL-17(+) FoxP3(+) T cells may play a role in the remodelling of the nasal airways in certain people who develop polyps, irrespective of whether or not they are atopic.

Role of muscarinic receptor activation in regulating immune cell activity in nasal mucosa.

BACKGROUND: The prevalence of airway inflammatory disorders keeps rising; its pathogenic mechanism is still not fully understood. OBJECTIVE: The present study aimed to investigate the role of muscarinic receptor (M receptor) in regulating the immune cell activity in nasal mucosa by using surgical removed nasal mucosa from patients with nasal polyposis (NP) as a study platform. METHODS: Human nasal mucosal sample was collected from inferior turbinectomy of 86 patients with NP or/and allergic rhinitis. Expression of tumor necrosis factor alpha (TNF-alpha), M receptor, OX40 ligand was measured in nasal mucosa by enzyme-linked immunosorbent assay, flow cytometry, and Western blotting assay. RESULTS: When compared with non-NP (nNP) nasal mucosa, contents of TNF-alpha and TNF-alpha+ cells markedly increased in NP nasal mucosa; immune staining colocalized M3 receptor+ and TNF-alpha+ cells in NP nasal mucosa; exposure of isolated CD4+ T cells to methacholine induced the release of TNF-alpha. We also found CD11c+/M3 receptor+ cells in NP nasal mucosa. Methacholine increased the expression of OX40L in dendritic cells. Staphylococcal (S) aureus and S. enterotoxin B (SEB) were detected in NP nasal mucosa. Exposure of dendritic cells or naïve CD4+ T cells to SEB initiated the expression of M3 receptor at mRNA and protein levels. CONCLUSIONS: The present data demonstrate that parasympathetic activity has the capacity to activate dendritic cells to release OX40 ligand, the latter induces CD4+ T cells to produce IL-4 and TNF-alpha that may further contribute to the pathogenesis of NP.

Kimura disease: a case report and review of the Chinese literature.

BACKGROUND: Kimura disease, often accompanied by nephrotic syndrome, is a rare, chronic inflammatory disorder of unknown cause. In this report, the clinical and histopathological characteristics of 20 Chinese patients with Kimura disease-associated nephrotic syndrome were retrospectively evaluated. METHODS: We report a case of Kimura disease that was diagnosed recently in our ward, with steroid-responsive but recurrent minimal-change nephrotic syndrome. Meanwhile, we also used three powerful Chinese journal search engines (Cqvip.com, Wanfang.data and ScienceChina) to search the cases reported in Chinese from 1984 to 2007. RESULTS: The nephrotic syndrome of our patient occurred 20 months after the onset of Kimura disease. Renal biopsy revealed minimal-change lesions. The patient was responsive to the steroid, but proteinuria recurred. In most of the 19 other cases, the onset of nephrotic syndrome occurred after subcutaneous masses. Renal biopsy in 13 cases showed mesangial proliferative glomerulonephritis in 9, minimal change disease in 2 and membrane nephropathy in 2 cases. Serum creatinine levels were elevated in 5 patients. CONCLUSION: Normally, Kimura disease-associated nephrotic syndrome patients are sensitive to prednisone therapy but are likely to relapse. In patients with recurrent nephrotic syndrome, renal insufficiency is not uncommon.

An aqueous extract of the popular Chinese nutraceutical Kwei Ling Ko (Tortoise shell-Rhizome jelly) activates the PPARgamma pathway and down-regulates the NFkappaB activity.

It is generally believed that the popular nutraceutical 'Kwei Ling Ko' (KLK; Tortoise shell-Rhizome jelly) has antiinflammatory effects, but the mechanism by which its effects are manifested remains unknown. Peroxisome proliferation-activated receptors (PPARs) are members of the nuclear hormone receptor/transcription factor superfamily with multiple roles in adipocyte differentiation, glucose homeostasis, immunomodulation and antiinflammatory regulation. As PPAR is required for adipocyte induction, we used adipogenesis as a possible screen for the activation of the PPAR pathway. Interestingly, an aqueous extract of KLK (sKLK) was able to induce the adipocyte differentiation of fibroblast cell lines. Adipogenesis was confirmed by flow cytometric analysis using a fluorescent lipid stain. Up-regulation of PPARgamma transcripts during adipogenesis was also demonstrated by reverse transcription-polymerase chain reaction (RT-PCR). The sKLK-induced adipogenesis was similar to that elicited by insulin. The activity of nuclear factor-kappaB (NFkappaB), a transcription factor responsible for the regulation of proinflammatory genes, was also down-regulated in response to sKLK. Luciferase reporter gene assays further demonstrated that sKLK inhibited both basal and tumor necrosis factor-alpha-stimulated NFkappaB activation. The activities reported in this study support an immunomodulatory effect for sKLK. As activation of PPAR pathway has a dual role in adipogenesis and anti-inflammation, our observations are consistent with the notion that KLK possesses antiinflammatory properties.

Thanatophoric dysplasia type I.

Thanatophoric dysplasia is a sporadic, nearly always lethal congenital skeletal dysplasia. It is characterized by shortening of the limbs, a severely small thorax, macrocephaly, and platyspondyly. There are two major subtypes: a short, curved femur characterizes type I, and a straighter femur with cloverleaf skull characterizes type II. Recently, mutations in the fibroblast growth factor receptor 3 (FGFR-3) gene have been identified in both subtypes, which suggest that thanatophoric dysplasia is a genetically homogenous skeletal disorder. Most affected neonates die of respiratory failure, due to narrow thorax with pulmonary hypoplasia. Antenatal sonographic diagnosis is feasible in the second trimester of pregnancy, but differentiating thanatophoric dysplasia from non-lethal skeletal disorders is very important. At the present time, however, prenatal genetic screening seems unpractical.

Use of electron microscopic evaluation for the diagnosis of adrenal cortical carcinoma in fine needle aspiration cytology: a case report and review of the literature.

Bilateral adrenal tumors were detected in a 72-year-old man who had a history of hepatic inflammatory pseudotumor. Computet tomography (CT)-guided fine needle aspiration cytology (FNAC) of the adrenal glands was performed. The cytologic findings were similar to the previous diagnosis of "inflammatory pseudotumor" in the liver. However, the origin of some aggregated large atypical cells observed in the adrenal FNAC specimens was not known. Immunocytochemically, these large atypical cells were positive for vimentin and negative for cytokeratin and chromogranin A. An electron-microscopic study showed that these large atypical cells contained mitochondria with tubulovesicular cristae and smooth endoplasmic reticulum arranged in whorled and laminated patterns, and these findings confirmed diagnosis of primary adrenal cortical carcinoma. The histopathological diagnosis of the resected bilateral adrenal tumor was adrenal cortical carcinoma. The patient died 7 months after surgery, with recurrence of the bilateral adrenal cortical carcinoma and extensive metastases. A diagnosis of primary adrenal cortical carcinoma with extensive metastases was finally demonstrated by autopsy. Retrospectively, the previous liver tumor was determined to be a metastatic lesion.

Ultrastructural characteristics of myocardial and coronary microvascular lesions in Kawasaki disease.

Kawasaki disease (KD) is an acute febrile mucocutaneous lymph node syndrome with multisystemic vasculitis affecting mainly infants and children. Although several studies on cardiovascular lesions in KD have been done at the light microscopic level, the ultrastructural characteristics and incidences of these lesions have not been well defined. In order to investigate the myocardial and coronary microvascular sequelae in KD, we performed an ultrastructural study on endomyocardial biopsy specimens obtained during follow-up from 54 patients who had typical clinical manifestations of KD, of whom 47 had associated coronary aneurysms as demonstrated by coronary arteriography (CAG) or two-dimensional echocardiography in the acute or healed stage. The average age of onset was 2.2 years old and the duration of illness was from 2 months to 23 years. Follow-up CAG showed that the coronary aneurysms persisted in 33 of the 47 patients (8 with associated stenosis) and resolved in the remaining 14 patients. Ultrastructurally, the myocardial changes revealed hypertrophy, various degrees of degeneration, proliferation and abnormality of mitochondria, infiltration of a small number of lymphocytes, and fibrosis. The coronary microvascular lesion was characterized by microvascular dilatation, endothelial cell injury, platelet aggregation with thrombosis, and stenotic lumen with thickened walls in the small arterioles. It persisted after convalescent stage even up to 23 years and closely correlated with the myocardial sequelae. Moreover, significantly increased incidences of myocardial and coronary microvascular lesions were found in patients with coronary artery lesion. These findings suggest the coronary microvascular lesion as a possible underlying factor of persistent sequelae in KD.

Childhood MELAS syndrome presenting with seizure and cortical blindness: a case report.

An 11-year-old boy presented with seizure and cortical blindness. A T1 weighted magnetic resonance image of the brain showed high signal intensity in the bilateral corpus striatum and long T1 and T2 changes in the bilateral occipital and cerebellar hemispheric regions. Increased cerebrospinal fluid lactate concentration of 56.7 mg/dl and blood lactate concentration of 34.2 mg/dl were also noted. A muscle biopsy obtained from the quadriceps femoris muscle showed the presence of ragged red fibers and mitochondrial DNA (mtDNA) analysis showed an A-->G mutation at nucleotide position 3243. MtDNA analysis of the patient's mother revealed the same mutation. These findings indicated MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes).

Central core disease associated with scoliosis: report of one case.

A 13 year-old girl with scoliosis and central core disease is reported. She was noted to have mild psychomotor developmental delay since early infancy. Scoliosis with minimal muscle weakness was noted at about five years old. The neurological examination disclosed absent knee jerk. The spine MRI showed no significant finding. The serum CK revealed 518 U/L. The muscle biopsy obtained from the quadriceps femoris muscle showed Type 1 fiber atrophy and predominance, as is commonly seen in congenital myopathies. Under nicotinamide adenine dinucleotide dehydrogenase (NADH) and succinate dehydrogenase (SDH) stains, core structures were identified and the diagnosis of central core disease (CCD) was made. Since kyphoscoliosis usually becomes prominent as muscle weakness progresses to loss of ambulation in other myopathies, the disproportionate spinal involvement in central core disease appears to be a striking feature. We suggest that all patients with idiopathic scoliosis deserve a thorough neurological evaluation if congenital myopathies are suspected. Muscle biopsy should also be recommended for a confirmatory diagnosis even if only minimal muscle weakness present. Besides, early detection of CCD helps us to identify the population who are at a higher risk for malignant hyperthermia.

Reconstruction of sheath with fascial graft in flexor tendon repair. An experimental study.

Using chicken's toes as an experimental model, we compared the healing process and function recovery of partially injured flexor tendons when the sheath was repaired with fascial graft, sheath patch or was left as a defect. Post-operatively, the toes were immobilised or mobilised immediately. Histological study and the measurement of tendon sliding revealed that the sheath reconstruction and mobilised groups were better than the sheath defect or immobilised groups. We also found the fascial graft was superior in the reconstruction of tendon sheath and may become synovial-like tissue under the sliding pressure of the tendon.