Elaiophylin triggers paraptosis and preferentially kills ovarian cancer drug-resistant cells by inducing MAPK hyperactivation.

Finely tuned mitogen-activated protein kinase (MAPK) signaling is important for cancer cell survival. Perturbations that push cells out of the MAPK fitness zone result in cell death. Previously, in a screen of the North China Pharmaceutical Group Corporation's pure compound library of microbial origin, we identified elaiophylin as an autophagy inhibitor. Here, we demonstrated a new role for elaiophylin in inducing excessive endoplasmic reticulum (ER) stress, ER-derived cytoplasmic vacuolization, and consequent paraptosis by hyperactivating the MAPK pathway in multiple cancer cells. Genome-wide CRISPR/Cas9 knockout library screening identified SHP2, an upstream intermediary of the MAPK pathway, as a critical target in elaiophylin-induced paraptosis. The cellular thermal shift assay (CETSA) and surface plasmon resonance (SPR) assay further confirmed the direct binding between the SHP2 and elaiophylin. Inhibition of the SHP2/SOS1/MAPK pathway through SHP2 knockdown or pharmacological inhibitors distinctly attenuated elaiophylin-induced paraptosis and autophagy inhibition. Interestingly, elaiophylin markedly increased the already-elevated MAPK levels and preferentially killed drug-resistant cells with enhanced basal MAPK levels. Elaiophylin overcame drug resistance by triggering paraptosis in multiple tumor-bearing mouse models resistant to platinum, taxane, or PARPi, suggesting that elaiophylin might offer a reasonable therapeutic strategy for refractory ovarian cancer.

[Visual analysis of literature knowledge structure and acupoint matching rules of acupuncture for depression].

OBJECTIVE: To analyze the literature knowledge structure and acupoint matching rules of acupuncture for depression. METHODS: The articles regarding acupuncture for depression published from January 1 of 1984 to October 19 of 2020 were searched in CNKI database. CiteSpace5.7.R2 software was used to import the literature data, and the keyword cluster analysis, emergence analysis and time-zone analysis of articles and acupoints were conducted, and the map of scientific knowledge was draw. RESULTS: A total of 3524 articles were included to the knowledge structure analysis, while 601 articles into the acupoint matching rules analysis. There were 13 keyword clusters of acupuncture for depression, with "post-stroke depression" and "electroacupuncture treatment" as high-frequency keywords, and "electroacupuncture treatment" and "Hamilton depression scale" had high centrality, and "electroacupuncture treatment" had the highest emergence intensity. The keywords such as "electroacupuncture treatment" and "Hamilton depression scale", etc. appeared the earliest, followed by "post-stroke depression", "fluoxetine" and "auricular point therapy", etc. According to traditional Chinese medicine theory, acupoint keywords were divided into four clusters: ①core acupoint, ②replenishing-spleen and dispelling phlegm, dispersing-liver and relieving depression, reinforcing qi and nourishing blood, ③back-shu points, five-zhi points, ④inducing-resuscitation and opening-closes. CONCLUSION: The main knowledge structure of acupuncture for depression includes five parts: treatment method, depression type, TCM-related diseases, literature type and curative effect index. Clinical acupoint matching should adhere to the principle of "focusing the disease before syndrome" and "combination of disease and syndrome", and treatment should be modified for the syndromes of phlegm stagnation blocking, liver-stagnation and qi-stagnation, and deficiency of both qi and blood.

Efficacy and safety of endovascular coiling vs surgical clipping for patients with ruptured carotid-ophthalmic aneurysm: A protocol for systematic review and meta-analysis.

BACKGROUND: Carotid-ophthalmic aneurysms are relatively rare, and represent 1% of all intracranial aneurysms. Generally, endovascular coiling and surgical clipping are the 2 most commonly used methods to treat ruptured carotid-ophthalmic aneurysms, it provides the most favorable outcome for a patient. This study aims to assess the efficiency and safety of endovascular coiling vs surgical clipping for patients with a ruptured carotid-ophthalmic aneurysm. METHODS: A comprehensive systematic literature review was done in PubMed, EMBASE, Cochrane Library, Web of Science, Scopus, China National Knowledge Infrastructure (CNKI), and WanFang databases. Only randomized trials that compared endovascular coiling with surgical clipping in patients with ruptured carotid-ophthalmic aneurysm was included. Data was extracted independently by 2 review authors. Moreover, the quality of study and bias risk was evaluated by utilizing an appropriate method. Triallists will be contacted to acquire missing information. The data is presented as risk ratio and mean difference, or standardized mean difference with 95% confidence intervals. RESULTS: The results from the present research shall be published in a peer-reviewed journal. CONCLUSION: The present study summarizes the direct and in-direct evidence to judge the efficiency and safety of these 2 methodologies to treat ruptured carotid-ophthalmic aneurysms and attempt to find the most efficiency and safety therapeutical method. ETHICS AND DISSEMINATION: The present study is a meta-analysis based on published evidence. As a result, ethics approval and patient consent are not needed.

Truncated Bid Regulates Cisplatin Response via Activation of Mitochondrial Apoptosis Pathway in Ovarian Cancer.

Refractoriness to conventional chemotherapy is a major challenge in the treatment of advanced ovarian cancer (OC). There is increasing evidence that mitochondrial priming correlates with cisplatin response in various cancers. Notably, Bim and Bid, two of the proapoptotic BH3-only proteins, are recognized as the most effective inducers of mitochondrial priming in OC. In this study, we constructed two tumor-specific oncolytic adenoviruses (Ads) coding for Bim (Ad-Bim) or truncated Bid (Ad-tBid), respectively, and performed gain-of-function assays in nine OC cell lines. Ad-tBid exhibited significant antitumor efficacy than the controls. On addition of Ad-tBid pretreatment, mito-primed cells displayed more sensitivity to cisplatin both in vitro and ex vivo. We also found that Ad-tBid induced mitochondrial apoptosis in a Bak-dependent manner. Furthermore, a combined cisplatin plus Ad-tBid therapy markedly inhibited tumor growth in a subcutaneous xenotransplanted tumor model. In mice bearing peritoneal disseminated OC, intraperitoneal administration of Ad-tBid potentiated the antitumor effect of cisplatin. Our findings suggest that Ad-tBid enhances cisplatin response in OC cells, establishing the potential treatment of advanced OC via a combination of cisplatin and Ad-tBid.

CD36- and obesity-associated granulosa cells dysfunction.

Emerging evidence indicates that obesity impairs granulosa cell (GC) function, but the underlying mechanisms remain unclear. Gene expression profiles in GC of non-polycystic ovary syndrome (PCOS) obese (NPO), PCOS obese (PO), PCOS normal weight (PN) and non-PCOS normal weight (NPN) patients were analysed by microarray analysis. Compared with the NPN group, there were 16, 545 and 416 differently expressed genes in the NPO, PO and PN groups respectively. CD36 was the only intersecting gene, with greater than two fold changes in expression between the NPO versus NPN and PO versus NPN comparisons, and was not present in the PN versus NPN comparison. In addition, levels of CD36 protein were higher in GC from obese than normal weight patients. Furthermore, CD36 overexpression in a GC line inhibited cell proliferation, as determined by the cell counting kit-8 (CCK8) test, promoted cell apoptosis, as determined by flow cytometry, and inhibited the secretion of oestradiol by depositing triglyceride in cells and increasing cellular lipid peroxide levels. These adverse effects were reduced by sulfo-N-succinimidyloleate, a specific inhibitor of CD36. Together, the findings of this study suggest that obesity with and without PCOS should be regarded as separate entities, and that CD36 overexpression in GC of obese patients is one of the mechanisms by which obesity impairs GC function.

Long noncoding RNA-antisense noncoding RNA in the INK4 locus accelerates wound healing in diabetes by promoting lymphangiogenesis via regulating miR-181a/Prox1 axis.

BACKGROUND: Slow lymphangiogenesis is one crucial reason for the impaired wound healing process in diabetes. Accumulative evidence showed that long noncoding RNA-antisense noncoding RNA in the INK4 locus (ANRIL) could influence lymphangiogenesis. Besides, miR-181a has been reported to regulate Prox1 that is essential for lymphangiogenesis. However, the relationship between ANRIL and miR-181a as well as the definitive function of ANRIL in lymphangiogenesis is not clear. METHODS: The diabetic mouse model was set up to assess the wound healing rate in vivo. Quantitative real-time polymerase chain reaction was performed to measure the expressions of ANRIL, miR-181a, and Prox1. Western blot analysis was used to assess the expressions of vascular endothelial growth factor receptor-3, lymphatic vessel hyaluronan receptor-1, Prox1, and epithelial-mesenchymal transition (EMT)-related proteins. Flow cytometry was used to assess the cell apoptosis. Wound healing assay was used to determine the effect of ANRIL on cell migration. Tube-formation assay and immunofluorescence staining were performed to determine tube-formation capacity of human dermal lymphatic endothelial cells (LECs). RESULTS: ANRIL and Prox1 were downregulated, whereas miR-181a was upregulated in the diabetic wound healing mouse model and high glucose (HG)-induced LECs. The wound healing rate and EMT were inhibited during the diabetic wound healing process. Dual-luciferase assay proved that miR-181a could bind Prox1 to repress its expression, whereas ANRIL could sponge miR-181a to recover Prox1 expression. Overexpression of ANRIL or inhibition of miR-181a rescued the impairments of survival, migration, EMT formation, and tube formation of LECs caused by HG. CONCLUSION: ANRIL could promote lymphangiogenesis during the diabetic wound healing process via sponging miR-181a to enhance Prox1 expression, which might help design new therapy to improve the wound healing efficacy for diabetes.

Diagnosis and Differential Diagnosis of Desmoplastic Fibroblastoma by Clinical, Radiological, and Histopathological Analyses.

BACKGROUND: Desmoplastic fibroblastoma (collagenous fibroma) is an uncommon benign soft-tissue tumor, rarely involving bone. It shares some overlapping features with other infiltrate tumors, such as desmoid-type fibromatosis, neurofibroma, and low-grade fibromyxoid sarcoma. The misdiagnosis may cause unnecessary surgical overtreatment, especially for those involving bone. In order to deepen the understanding of the diagnosis and differential diagnosis of desmoplastic fibroblastoma, we planned to analyze the clinical, radiological, and histopathological features and the outcome of desmoplastic fibroblastoma on the basis of case analysis and literature review. METHODS: Sixteen cases were retrieved from the surgical pathology records from May 2011 to April 2016 in the Department of Pathology in Beijing Jishuitan Hospital. Formalin-fixed, paraffin-embedded specimens of 16 cases of desmoplastic fibroblastoma were collected. Hematoxylin and eosin stain and immunohistochemistry were used to observe the histological features of desmoplastic fibroblastoma of soft tissue and bone. The images for diagnosis obtained from the ultrasonic examination, X-ray, magnetic resonance imaging, and computed tomography were used to observe the radiological features. Related literatures were retrieved from the PubMed and CNKI databases. RESULTS: Sixteen cases of desmoplastic fibroblastoma of soft tissue were located in the hand (n = 7), foot (n = 4), upper arm (n = 1), shoulder (n = 1), forearm (n = 2), and one case occurred in the proximal femur. Age ranged from 32 to 82 years (median age: 58 years). There were six females and ten males. Histologically, the lesions of soft tissue appeared as well-circumscribed masses with abundant collagenous matrix and low vascularity. Tumor cells were stellate- or spindle-shaped and uniformly distributed within the extracellular matrix. In five cases, the desmoplastic fibroblastoma were found to have infiltrated into the skeletal muscle tissue. In one case of desmoplastic fibroblastoma of bone, radiographs revealed osteolytically well-defined lesion. Immunohistochemistry stain showed that vimentin and smooth muscle actin were positive in all cases of desmoplastic fibroblastoma. CONCLUSIONS: Desmoplastic fibroblastoma (collagenous fibroma) has prominent clinical, histopathological, and radiological features. Before the differential diagnosis from other tumors is obtained by thorough analysis and comparison of the similar and different characteristics, the appropriate surgical management and accurate prognosis evaluation could not be delivered to the patient.

Early laparotomy and timely reconstruction for patients with abdominal electrical injury: Five Case Reports and Literature Review.

INTRODUCTION: High-tension electricity can cause devastating injuries that may result in abdominal wall loss, visceral damage, and sometimes major threat to life. The visceral organ may be exposed after debridement and require flap cover, but the tensile strength of abdominal wall may be lack even if flap transplanted. METHODS: From April 2007 through May 2015, 5 patients with severe abdominal electrical injury were treated at our hospital. Exploratory laparotomy was performed based on their clinical manifestations and debridement findings of abdominal wall at early stage, and decision regarding technique for reconstruction of abdominal wall was based on an assessment of the location and extent of the defect. Medical records were reviewed for these data. RESULTS: Clinical evaluation and debridement findings of the abdomen revealed 4 patients with suspicious visceral damage. Laparotomy was performed in 4 cases, and revealed obvious lesion in 3 cases, including segmental necrosis of small intestine, partial necrosis of diaphragm, left liver and gastric wall, and greater omentum. Five patients underwent abdominal wall reconstruction using island retrograde latissimus dorsi myocutaneous flap or free/island composite anterolateral thigh myocutaneous flap. All flaps survived, abdominal bulging occurred in 3 cases after follow-up of 12 to 36 months. CONCLUSIONS: The clinical manifestations and wound features of abdomen collectively suggest a possible requirement of laparotomy for severe abdominal electrical burns. Retrograde latissimus dorsi myocutaneous flap or composite anterolateral thigh myocutaneous flap is an effective option for reconstruction of abdominal wall loss, the long-term complication of abdominal bulging, however, remains a significant clinical challenge.

Tumor-associated Lymphatic Endothelial Cells Promote Lymphatic Metastasis By Highly Expressing and Secreting SEMA4C.

PURPOSE: Lymphatic vessels are mainly regarded as passive conduits for the dissemination of cancer cells. In this study, we investigate whether and how the tumor-associated lymphatic vessels may play an active role in tumor metastasis. EXPERIMENTAL DESIGN: In situ laser capture microdissection of lymphatic vessels followed by cDNA microarray analysis was used to determine the expression profiling of lymphatic endothelial cells (LEC). Gene expression levels and activity of signaling pathways were measured by real-time RT-PCR, ELISA, or immunoblotting. Lymphangiogenesis was assessed by IHC. Lymph node metastasis was measured using fluorescence imaging. The effects of SEMA4C on lymphangiogenesis in vitro were evaluated using migration assay and tube-formation assay of LECs. RESULTS: Tumor-associated LECs are molecularly and functionally different from their normal counterparts. In addition to expressing high levels of membrane-bound SEMA4C, tumor-associated LECs also produced soluble SEMA4C (sSEMA4C). Increased serum sSEMA4C was detected in patients with breast cancer and cervical cancer. Patients with metastasis had much higher levels of serum sSEMA4C. sSEMA4C promoted lymphangiogenesis by activating PlexinB2-ERBB2 signaling in LECs, and promoted the proliferation and migration of tumor cells by activating PlexinB2-MET signaling, thus promoting lymphatic metastasis. Although the SEMA4C signaling pathways differ between LECs and tumor cells, RHOA activation was necessary for the effects of SEMA4C in both types of cells. CONCLUSIONS: Tumor-associated LECs produce sSEMA4C to promote lymphatic metastasis of tumors. Our results suggest that SEMA4C and RHOA might be potential therapeutic targets, and that higher serum sSEMA4C could be a marker for breast cancer and cervical cancer. Clin Cancer Res; 23(1); 214-24. ©2016 AACR.

Role of glucose-regulated protein 78 in early brain injury after experimental subarachnoid hemorrhage in rats.

Early brain injury (EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage (SAH). This study investigated the role of glucose-regulated protein 78 (GRP78) in EBI after SAH. Male Sprague-Dawley rats (n=108) weighing 260±40 g were divided into control, sham-operated, and operated groups. Blood was injected into the prechiasmatic cistern of rats in the operated group. Neurological scores, ultrastructures of neurons, apoptosis, and GRP78 expression in the hippocampus were examined using Garcia scoring system, transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling, and Western blotting at 1, 6, 12, 24, 48, and 72 h after SAH, respectively. The results showed that neurological scores were significantly decreased in the operated group as compared with those in control and sham-operated groups at 12, 24, 48, and 72 h. Metachromatin, chromatin pyknosis at the edge, endoplasmic reticulum swelling, and invagination of nuclear membrane were observed at 24 h in the operated group, indicating the early morphological changes of apoptosis. The number of apoptotic cells was significantly increased in the operated group as compared with that in control and sham-operated groups at 6, 12, 24, 48, and 72 h. The GRP78 protein expression levels in the operated group were significantly elevated at all time points and reached the peak at 12 h. GRP78 expression was positively associated with apoptosis cells and negatively with neurological scores. In conclusion, EBI was demonstrated to occur after SAH and GRP78 was involved in the development of EBI after SAH.

An epidemiological analysis of paediatric burns in urban and rural areas in south central China.

OBJECTIVE: This study aims to analyse the epidemiology of paediatric burns in south central China, illustrate the differences between rural and urban areas, and discern prevention measures to reduce paediatric burns. METHODS: Data were obtained from all paediatric patients admitted to Department of Burns unit of Xiangya Hospital during 2009-2012. A retrospective review was performed, including cause of burn, pre-hospital treatment, place of burn occurrence, anatomical areas involved, extent of burn, date of injury, number of operations, complications, length of hospital stay, hospitalisation cost and cure rate. RESULTS: A total of 278 hospitalised paediatric patients were admitted in this study. The majority (56.47%) were 1-3 years old. Rural patients accounted for 67.99% in total; the ratio of boys to girls was 2.05. Scalding with hot fluids was the most common cause of burns in children (62.59%), followed by flame (17.63), fireworks (9.71%), electricity (5.76%) and other factors such as contact and chemical (4.32%). The living room was the location with the highest frequency of burns in children (53.24%). Burns were more likely to happen in winter and the upper extremities were the most involved anatomic site (53.24%). Total burn surface area (TBSA) ranging from 0% to 9% accounted for 55.4% in total. Rural patients underwent more operations and had longer and costlier hospital stays than urban patients. CONCLUSION: Compared with treatment in urban areas, rural burn patients received less first-aid treatment, underwent more surgery, had more complications and longer and more costly hospital stays. This finding strongly suggests that it is necessary to make more efforts to prevent burns, especially in rural areas.

[Pay emphasis on the use of perforator flaps in burn surgery].

This article presents the anatomical basis, different kinds of perforator flaps and the distribution regularity of perforator vessels, principle of terminology, range of application, and their advantages and disadvantages. The procedure in harvesting and transplantation of perforator flaps are also discussed, in order to promote clinical application of perforator flaps, and to provide a more efficacious way to reconstruct the deep burn wound.

[Repair of wound on hand or foot due to electrical burn using free lateral upper arm perforator flap].

OBJECTIVE: To observe the effect of free lateral upper arm perforator flap in repairing wound on hand or foot due to electrical burn. METHODS: Six patients with full-thickness wounds on hand or foot resulting from electrical burn were hospitalized from June 2010 to June 2013. The wounds ranged from 6.0 cm ×4.0 cm to 8.5 cm×7.5 cm in area. Free lateral upper arm perforator flaps were used to repair these defects, with flap area ranging from 9 cm ×4 cm to 12 cm × 9 cm. The donor sites in five cases were closed by suturing; the other one donor site was closed by transplantation of full-thickness skin from abdomen. RESULTS: One flap used to repair the wound in middle finger failed due to failure of venous return, and it was repaired with full-thickness skin harvested from abdomen after dressing change. The other five flaps survived resulting in good elasticity and matched appearance of the recipient area without obvious bulkiness. Patients were followed up for 6 to 24 months. The function of the injured hands or feet recovered well, and the results of function evaluation of five hands were excellent in 2 cases, good in 2 cases, and poor in 1 case. Little scar formation with no contraction or function impairment was observed on donor site, and the result was satisfactory. CONCLUSIONS: Free lateral upper arm perforator flap, with long vessel and less adipose tissue, is suitable for repairing small but deep wound on hand or foot due to electrical burn.

[Effects of antisense p38 α mitogen-activated protein kinase on myocardial cells exposed to hypoxia and burn serum].

OBJECTIVE: To study the effects of antisense p38α mitogen-activated protein kinase (hereinafter referred to as p38α) on myocardial cells exposed to hypoxia and burn serum. METHODS: Thirty adult SD rats were inflicted with 40% TBSA full-thickness burn on the back to obtain burn serum. The myocardial cells were isolated from 80 neonatal SD rats and cultured, then they were divided into 4 groups according to the random number table: normal control group (N, ordinary culture without any treatment), hypoxia+burn serum group (HB, exposed to hypoxia after being treated with 10% burn rat serum), hypoxia+burn serum+infection group (HBI, exposed to hypoxia and 10% burn rat serum after being infected with antisense p38α gene-carrying adenovirus), hypoxia+burn serum+empty vector infection group (exposed to hypoxia and 10% burn rat serum after being infected with adenovirus empty vector). At post hypoxia hour (PHH) 1, 3, 6, and 12, mRNA and protein expression levels of p38α in the latter 3 groups were determined by RT-PCR and Western blotting, cell viability was determined by methylthianolyldiphenyl-tetrazolium bromide assay, and lactate dehydrogenase (LDH) activity was assayed at the same time point. At PHH 1, 6, and 12, apoptosis rate of myocardial cells was assessed by annexin V staining method. The indexes of group N were determined with the methods mentioned-above. Three wells were set at each time point in each group. Data were processed with one-way analysis of variance and LSD- t test. RESULTS: (1) At PHH 1, 3, and 6, the p38α mRNA level was higher in group HB than in group N and group HBI (with t values from 2.725 to 4.375, P values all below 0.05). (2) At PHH 1, 3, and 6, the p38α protein level was higher in group HB than those in group N and group HBI (with t values from 5.351 to 7.981, P values all below 0.01). (3) At PHH 3, 6, and 12, the cell viability in group HB (0.115 ± 0.007, 0.104 ± 0.006, 0.094 ± 0.005) was lower than that in group N (0.141 ± 0.014) and group HBI (0.136 ± 0.009, 0.124 ± 0.010, 0.112 ± 0.007, with t values from 2.357 to 6.812, P values all below 0.05). (4) The LDH activity was up-regulated in group HB as compared with that in group N and group HBI at each time point (with t values from 22.753 to 201.273, P values all below 0.01). (5) At PHH 1, 6, and 12, the apoptosis rate of myocardial cells in group HB [(5.4 ± 0.7)%, (8.7 ± 1.1)%, (13.6 ± 1.7)%] was higher than that of group N [(3.1 ± 0.3)%] and group HBI [(4.3 ± 0.5)%, (5.1 ± 0.7)%, (7.2 ± 0.9)%, with t values from 2.345 to 9.700, P < 0.05 or P < 0.01]. CONCLUSIONS: Antisense p38α can protect the myocardial cells from the injury of hypoxia and burn serum.

[Small cell malignant tumors of bone: comparison between diagnosis using core needle biopsies and surgical specimens].

OBJECTIVE: To compare the pathologic diagnosis and immunohistochemistry of small cell malignant tumors (SCMT) of bone using both core needle biopsy and surgical specimen. METHODS: Seventy-seven cases of SCMT with core needle biopsies and surgical specimens available were respectively analyzed by histologic examination and immunohistochemical study, with literature review. RESULTS: The male-to-female ratio was 48:29. The age of the patients ranged from 6 to 73 years. The tumors studied included Ewing sarcoma/PNET (n = 38), myeloma (n = 23), lymphoma (n = 10), small cell osteosarcoma (n = 2), small cell carcinoma (n = 2) and mesenchymal chondrosarcoma (n = 2). The tumors involved limbs, axial skeleton and flat bones. Microscopically, the tumors shared similar histology, with small round cells and spindly cells arranged in diffuse sheets. The pathologic diagnosis by core needle biopsies correlated with that by surgical specimens in 84.4% (65/77) of the cases. CONCLUSIONS: SCMT represents a heterogeneous group of malignancy. Correlations with clinicoradiologic findings and application of ancillary investigations including immunohistochemistry and molecular study are important for definitive diagnosis. Pathologic diagnosis using core needle biopsies shows good results and provides useful information for surgical planning.

[Clinicopathologic features of primary osteosarcoma in elderly patients].

OBJECTIVE: To study the clinical manifestations, radiologic findings, pathologic diagnosis and differential diagnosis of primary osteosarcoma in elderly patients. METHODS: Twelve cases of primary osteosarcoma occurring in patients older than 60 years were encountered during the period from 1985 to 2010. The clinical manifestations, radiologic features and pathologic findings were studied and the follow-up data were analyzed. RESULTS: The sites of involvement included long bones (number = 7), ilium (number = 1), craniofacial bones (number = 2) and soft tissue (number = 2). Radiologic examination showed a mixture of osteosclerotic and osteolytic lesions in 10 patients, soft tissue lesions with high-density areas in 2 patients and soft tissue lesions with periosteal reaction in 8 patients. Histologically, most cases showed features of conventional osteosarcoma. There were 2 cases of malignant fibrous histiocytoma-like osteosarcoma, 2 cases of chondroblastic osteosarcoma and 1 case of well-differentiated intraosseous osteosarcoma. Immunohistochemical study played little role in pathologic diagnosis. Ten patients had undergone amputation, including one patient who had received adjuvant chemotherapy beforehand. Nine patients had follow-up information available. Three of them died of lung metastasis and 1 died of cardiovascular disease. CONCLUSIONS: Primary osteosarcoma rarely occurs in elderly patients and can easily be missed. Correlation with clinical, radiologic and histologic features is important for arriving at a correct diagnosis.

[Regulation of peroxisome proliferator-activated receptor ß by epidermal growth factor in wound tissue of mice with full-thickness skin defect].

OBJECTIVE: To study the effect of freeze-dried mouse epidermal growth factor (mEGF) on the expression of peroxisome proliferator-activated receptor ß (PPAR-ß) in mice during wound healing. METHODS: Full-thickness skin defect with area of 1.5 cm × 1.5 cm was reproduced on both sides of the back of 70 BALB/c mice (2 wounds in each mouse). The wound on the left side in each mouse was treated with 5 µg/mL mEGF solution (experiment group), and that on the right side in each mouse was treated with saline (control group). On post injury day (PID) 7, 11, and 16, 20 mice were used for determination of wound healing rate at each time point. On PID 1, 3, 7, 11, 14, and 18, specimens of wound edge were harvested for determination of protein and gene expression of PPAR-ß with immunohistochemical staining and in situ hybridization, with 10 specimens at each time point (denoted as integral absorbance value). Data were processed with t test. RESULTS: (1) Wound healing rate. The wound healing rate in experiment group on PID 7, 11, and 16 was respectively higher than that in control group (with t value respectively 3.03, 6.05, 11.9, P values all below 0.01). (2) Immunohistochemical observation. In both groups, the PPAR-ß proteins highly expressed in fibroblasts of wound granulation tissues and nuclei of keratinocytes located in wound edge at early stage after injury, and they highly expressed in newly formed epidermis and their fibroblasts in the lower layer after wound epithelization. The expression of PPAR-ß protein was gradually decreased after wound healing. The expression of PPAR-ß protein at each time point in experiment group was respectively higher than that in control group (with t values from 2.15 to 7.37, P < 0.05 or P < 0.01). The expression of PPAR-ß protein peaked on PID 3 in experiment group [(3.46 ± 1.33) × 10(3)], which was (2.35 ± 1.09) × 10(3) in control group. (3) In situ hybridization. The expression levels of PPAR-ß mRNA in both groups were up-regulated after injury, which were mainly observed in fibroblasts of wound and cytoplasm of KC in wound edge, but they were down-regulated after wound epithelization. The expression of PPAR-ß mRNA at each time point in experiment group was respectively higher than that in control group (with t values from 2.35 to 6.64, P < 0.05 or P < 0.01). The expression of PPAR-ß mRNA in both groups peaked on PID 3 [(7.3 ± 2.6) × 10(6), (4.5 ± 3.0) × 10(6), respectively]. CONCLUSIONS: mEGF can up-regulate the expression of PPAR-ß in wound tissue of mice and promote wound healing.

[Study on adenovirus mediated antisense p38α fragment gene in suppressing apoptosis of the myocardium of neonatal rat by burn serum and hypoxia].

OBJECTIVE: To investigate the relationship between the activation of p38 mitogen-activated protein kinase (p38MAPK) in the myocardium and the apoptosis in the presence of burn serum and hypoxia. METHODS: Ventricular myocardium isolated from neonatal rats were employed in this study, and they were divided into three groups as the normal control group, with the myocardium grew naturally; burn serum+ hypoxia group, in which the myocardium was stimulated by the serum collected from the rat 6 hours after burn injury involving 40% of total body surface area (TBSA), and at the same time exposed to 1%O(2), 5%CO(2), and 94%N(2); antisense blocking group, in which rats were pretreated by AD-antisense (AS) p38α, then exposed to the same conditions as burn serum+hypoxia group. The phosphorylation of p38 in the myocardium was determined by Western blotting. The level of myocardium apoptosis was determined by DNA ladder and flow cytometry. RESULTS: Compared with normal control group, the level of phosphorylation of p38 (gray value) was markedly increased (8.68±0.14 vs. 3.21±0.05, P<0.01) after being exposed to burn serum and hypoxia, and at the same time myocardium apoptosis was strikingly increased [(50.367±0.451)% vs. (2.063±0.111)%, P<0.01]. When the myocardium was transfected by AD-ASp38α, the phosphorylation of p38 (gray level) was decreased remarkably (5.46±0.16 vs. 8.68±0.14, P<0.01), the rate of the apoptosis was lowered remarkably [(13.200±0.121)% vs. (50.367±0.451)%, P<0.01]. CONCLUSION: Burn serum combined with hypoxia can induce apoptosis of the myocardium by activating p38MAPK; blockage of p38MAPK signal transduction pathway may lessen the damage of the myocardium in early period of severe burn.

[Anatomic basis of the accompanying pattern of the superficial temporal arterial branches and veins and its clinical application].

OBJECTIVE: To study the course of branches of the superficial temporal artery (BSTA) and the accompanying pattern of their veins in order to provide anatomic basis for flap design. METHODS: Head and facial part of ten adult corpses (19 sides) were dissected and photographed. The coordinate system was set up with external auditory foramen as the point of origin, aided by the graph analysis software Digimizer. The course of the frontal branch and parietal branch of the superficial temporal artery (STA), and the accompanying pattern between the BSTA and the veins were measured and analyzed. The STA and its branches were located by Ultrasonic Doppler, and the corresponding branches of the superficial temporal vein (BSTV) were disclosed by bowing patient's head with breath holding or cerclaging the basement of the patient's skull. And then 10 sides of transposition (fascia) flaps with axis at the angular bisector between BSTA and BSTV were devised to repair wounds of 9 patients that hospitalized from February 2008 to December 2009. Data were processed with test of variance homogeneity. RESULTS: Frontal BSTV absence was found in 6 head sides, and the maximum distance between artery and vein was (2.1 ± 1.2) cm. Parietal BSTV absence was found in 3 head sides, and the maximum distance was (1.4 ± 0.7) cm. The distance between frontal BSTA and BSTV was larger than that between parietal BSTA and BSTV, and the dispersion degree of the former was higher than that of the latter (F = 0.0404, P = 0.0475). All the (fascia) flaps survived without congestion or necrosis. CONCLUSIONS: When branch of the superficial temporal vessel was selected as the axial vessel of flap, the flap design shall depend on the accompanying pattern of BSTV to avoid the flap necrosis due to poor venous return after surgery. The superficial temporal vein and its branches can be well disclosed by bowing head or cerclaging skull. The approach is simple, useful, safe, and reliable.