Systematic analysis of the expression and prognostic value of ITPR1 and correlation with tumor infiltrating immune cells in breast cancer.

BACKGROUND: ITPR1 is a key gene for autophagy, but its biological function is still unclear, and there are few studies on the correlation between ITPR1 gene expression and the occurrence and development of breast cancer. METHODS: Analyze the expression of ITPR1 through online databases such as Oncomine and TIMER. Kaplan-Meier plotter and other databases were used to evaluate the impact of ITPR1 on clinical prognosis. The expression of ITPR1 in analysis of 145 cases of breast cancer and 30 cases of adjacent normal tissue was detected by Immunohistochemistry. Statistical analysis was used to evaluate the clinical relevance and prognostic significance of abnormally expressed proteins. And the Western Blot was used to detect the expression of ITPR1 between breast cancer tissues and cells. The TIMER database studied the relationship between ITPR1 and cancer immune infiltration. And used the ROC plotter database to predict the response of ITPR1 to chemotherapy, endocrine therapy and anti-HER2 therapy in patients with breast cancer. RESULTS: Compared with normal breast samples, ITPR1 was significantly lower in patients with breast cancer. And the increased expression of ITPR1 mRNA was closely related to longer overall survival (OS), distant metastasis free survival (DMFS), disease specific survival (DSS) and relapse free survival (RFS) in breast cancer. And the expression level of ITPR1 was higher in patients treated with chemotherapy than untreated patients. In addition, the expression of ITPR1 was positively correlated with related gene markers of immune cells in different types of breast cancer, especially with BRCA basal tissue breast cancer. CONCLUSION: ITPR1 was lower expressed in breast cancer. The higher expression of ITPR1 suggested favorable prognosis for patients. ITPR1 was related to the level of immune infiltration, especially in BRCA-Basal patients. All research results indicated that ITPR1 might affect breast cancer prognosis and participate in immune regulation. In short, ITPR1 might be a potential target for breast cancer therapy.

The structure of blood-tumor barrier and distribution of chemotherapeutic drugs in non-small cell lung cancer brain metastases.

BACKGROUND: Brain metastasis is an important cause of increased mortality in patients with non-small cell lung cancer (NSCLC). In brain metastasis, the blood-brain barrier (BBB) is frequently impaired, forming blood-tumor barrier (BTB). The efficacy of chemotherapy is usually very poor. However, the characteristics of BTB and the impacts of BTB on chemotherapeutic drug delivery remain unclear. The present study investigated the structure of BTB, as well as the distribution of routine clinical chemotherapeutic drugs in both brain and peripheral tumors. METHODS: Bioluminescent image was used to monitor the tumor load after intracranial injection of lung cancer Lewis cells in mice. The permeability of BBB and BTB was measured by fluorescent tracers of evans blue and fluorescein sodium. Transmission electron microscopy (TEM), immunohistochemistry and immunofluorescence were performed to analyze structural differences between BBB and BTB. The concentrations of chemotherapeutic drugs (gemcitabine, paclitaxel and pemetrexed) in tissues were assayed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). RESULTS: Brain metastases exhibited increased BTB permeability compared with normal BBB detected by fluorescence tracers. TEM showed abnormal blood vessels, damaged endothelial cells, thick basement membranes, impaired intercellular endothelial tight junctions, as well as increased fenestrae and pinocytotic vesicles in metastatic lesions. Immunohistochemistry and immunofluorescence revealed that astrocytes were distributed surrounded the blood vessels both in normal brain and the tumor border, but no astrocytes were found in the inner metastatic lesions. By LC-MS/MS analysis, gemcitabine showed higher permeability in brain metastases. CONCLUSIONS: Brain metastases of lung cancer disrupted the structure of BBB, and this disruption was heterogeneous. Chemotherapeutic drugs can cross the BTB of brain metastases of lung cancer but have difficulty crossing the normal BBB. Among the three commonly used chemotherapy drugs, gemcitabine has the highest distribution in brain metastases. The permeability of chemotherapeutic agents is related to their molecular weight and liposolubility.

Clinical utility and effectiveness of a training programme in the application of a new classification of narrow-band imaging for vocal cord leukoplakia: A multicentre study.

OBJECTIVE: To analyse the application of a new narrow-band imaging (NBI) classification in the diagnosis of vocal cord leukoplakia by laryngologists with different levels of laryngoscopic experience and to explore the impact of NBI training programmes on laryngologists' identification of benign and malignant leukoplakia. DESIGN: Prospective multicentre study. SETTING: Tertiary hospitals. PARTICIPANTS: Sixteen laryngologists were divided into less-experienced and experienced groups and received NBI training course. Thirty cases of vocal cord leukoplakia were investigated. MAIN OUTCOME MEASURES: Diagnostic accuracy and interobserver agreement under white light imaging (WLI), before and after NBI training, were analysed among doctors with varying levels of experience. RESULTS: The accuracy in the less-experienced group was significantly lower than that of experience group (0.59 vs 0.69) under WLI. There was no significant difference in the diagnostic accuracy between the less-experienced group and the experienced group before NBI training (0.75 vs 0.74) and after NBI training (0.79 vs 0.83). NBI training could improve the interobserver agreement from fair or moderate to good agreement. CONCLUSION: The new NBI diagnostic classification is helpful for identifying benign and malignant vocal cord leukoplakia. In addition, the NBI training programme can improve the diagnostic accuracy and interobserver agreement of less-experienced doctors to the level of experienced laryngologists.

Pd-Pt Alloy with Coral-Like Nanostructures Showing High Performance for Oxygen Electrocatalytic Reduction.

Three-dimensional (3D) Pd-Pt alloy with coral-like nanostructures were synthesized via bubble dynamic templated electrodeposition method at room temperature. The morphology of the as-prepared nanostructures was characterized using scanning electron microscopy (SEM), EDS, high-resolution transmission electron microscopy (HRTEM), respectively. Cyclic voltammetry method was adopted to evaluate the electrocatalytic activities of the synthesized electrodes toward oxygen reduction in KCl solution. The electrochemical results indicated that the Pd-Pt alloy with coral-like nanostructures hold the high performance for oxygen reduction.

Clinical Characteristics and Long-Term Outcomes following Surgery Combined with Adjuvant Radiotherapy for Patients with Frontal Sinus Malignancies.

Objectives Primary frontal sinus malignancies (FSMs) are the rarest sinonasal cancers. This study aimed to determine clinicopathologic characteristics of primary FSMs and provide long-term survival outcomes. Design This study is a retrospective review. Setting The study was conducted at a tertiary medical center. Participants Patients who participated in this study were diagnosed with primary FSMs. Main Outcome Measures Median survival time is the primary outcome measure of this study. Results In this series, the median age was 48 years (30-53 years) and all patients were male. There were five cases with squamous cell carcinoma and one with osteosarcoma. All cases presented with locally advanced disease without regional lymphatic metastasis, including five cases of stage III and one case of stage II. The two most common pathways of tumor invasion were as follows: local tumor broke posteriorly through bone wall and invaded dura mater, followed by frontal lobe; local tumor infiltrated downward through the floor of frontal sinus into ethmoid sinus, thereafter invaded laterally orbit and orbital contents. All patients received surgery followed by postoperative radiotherapy at the total doses of 50 to 75.95 Gy. Among them, only one patient underwent R0 resection, the rest of patients underwent R1/R2 resection. With a median survival time of 56 months (32-76 months), two patients receiving R1/R2 resection developed treatment failure and died within 5 years, including one case with local recurrence and one with local recurrence, thereafter distant metastasis. Conclusion The majority of FSMs presented with peripherally invasive progression lesions which led to a high ratio of R1/R2 resection. Surgery combined with postoperative radiotherapy might result in satisfactory efficacy.

QSPR models for the physicochemical properties of halogenated methyl-phenyl ethers.

Halogenated methyl-phenyl ethers (anisoles) are ubiquitous organic compounds in the environment. In the present study, geometrical optimization and electrostatic potential calculations have been performed for 134 halogenated anisoles at the HF/6-31G* level of theory. A number of statistically based parameters have been obtained. Linear relationships between sub-cooled liquid vapor pressures (lgp(L)), n-octanol/water partition coefficient (lgK(ow)) and aqueous solubilities (-lgS(w,L)) of halogenated anisoles and the structural descriptors have been established by multiple regression method. The result shows that the quantities derived from electrostatic potential V(min), V(s,max), summation operatorV(s)(+), summation operatorV(s)(-), V(s,av)(-) and nu, together with the molecular volume (V(mc)) and E(HOMO) can be well used to express the quantitative structure-property relationships of halogenated anisoles, which proves the general applicability of this parameter set to a great extent. Good predictive capabilities have also been demonstrated. Based on these excellent equations, the predicted values have been presented for those halogenated anisoles whose experimentally determined physicochemical properties are unavailable.

[DDP-sensitivity-related genes in 10 lung cancer cell lines].

OBJECTIVE: To search for genes related to cisplatin (DDP) sensitivity in small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) cell lines. METHODS: The sensitivity of 4 SCLC lines and 6 NSCLC lines to DDP was evaluated by MTT assay. The expression of 1291 genes related to DDP-sensitivity in the 10 cell lines was measured by cDNA macroarray and the relationship between genes and DDP-sensitivity was analyzed. RESULTS: 20 genes were negatively related to DDP-sensitivity in the SCLC and NSCLC cell lines, including Metallothionein, Cathepsin B, TIMP1, TNF-R1, TGF beta-induced 68 000, Cathepsin L, Galectin-1, Annexin 11, PAI-1, IGFBP4, UPAR, Jagged, CD13, alpha 1 A-AR, EphA2 (Eck), APC, RhoC, Fibromodulin, GATA-6 and HSC 70, while only procoagula and MDM2 were positively related to DDP-sensitivity in the SCLC and NSCLC cell lines. 10 genes were negatively related to DDP-sensitivity in the SCLC cell lines, including VHL, MMP-7, Elongin A, GSK-3 beta, SLC, Galectin-3, integrin beta 5, moesin, IKK beta, and ETV 1, while only AT2 was positively related to DDP-sensitivity in the SCLC cell lines. 10 genes were negatively related to DDP-sensitivity in the NSCLC cell lines, including Clusterin, FG FR-2, Thrombospondin 1, HSP 32, Lactate dehydrogenase A, P300, Thymosin beta l0, CD81, C/EBP gamma, Rak, while only CaMKK and TPA were positively related to DDP-sensitivity in the NSCLC cell lines. CONCLUSION: There were 45 genes related to DDP-sensitivity in 10 lung cancer cell lines. There were 22 co-expressed genes in both SCLC and NSCLC cell lines, and only 11 and 12 genes expressed in the SCLC and NSCLC cell lines, respectively.

[Extraction of praeruptorin A from Radix Peucedani by supercritical fluid extraction-CO2].

OBJECTIVE: To extract praeruptorin A from Radix Peucedani by supercritical fluid extraction (SFE)-CO2. METHODS: After preliminary experiment, three main factors were acquired that could influence the result of SFE-CO2, including the time, pressure and temperature of the extraction. The optimal extraction process was carried out on orthogonal design, and SFE-CO2 was compared with the traditional methods. RESULTS: In the extraction of the praeruptorin A, the best extraction conditions were 60 degrees C, 20 MPa, and duration for three hours. As cosolvent alcohol was added, the amount of extraction of the praeruptorin A increased, and the amount of SFE-CO2 extraction was higher than those of decoction and heating reflux. CONCLUSION: The SFE-CO2 in extracting praeruptorin A from Radix Peucedani is feasible and reliable.

Community analysis of ammonia and nitrite oxidizers in start-up of aerobic granular sludge reactor.

A lab-scale sequencing batch reactor (SBR) was set-up and the aerobic granular sludge was successfully incubated using anaerobic granular sludge as seed sludge. Nitrogen was partially removed by simultaneous nitrification and denitrification (SND) via nitrite with free ammonia (FA) of about 10 mg/L. The denaturing gradient gel electrophoresis (DGGE) method was used to investigate community structure of alpha-Proteobacteria, beta-Proteobacteria, ammonia oxidizing bacteria (AOB), and Nitrospira populations during start-up. The population sizes of bacteria, AOB and Nitrospira were examined using real-time PCR method. The analysis of community structure and Shannon index showed that stable structure of AOB population was obtained at day 35, while the communities of alpha-Proteobacteria, beta-Proteobacteria, and Nitrospira became stable after day 45. At stable stage, the average cell densities were 1.1 x 10(12), 2.2 x 10(10) and 1.0 x 10(10) cells/L for bacteria, AOB and Nitrospira, respectively. The relationship between characteristics of nitrifying bacteria community and nitrogenous substrate utilization constant was discussed by calculating Pearson correlation. Certain correlation seemed to exist between population size, biodiversity, and degradation constant. And the influence of population size might be greater than that of biodiversity.

FAT10 is associated with the malignancy and drug resistance of non-small-cell lung cancer.

Lung cancer has become one of the leading causes of cancer mortality worldwide, and non-small-cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases. Currently, platinum-based chemotherapy drugs, including cisplatin and carboplatin, are the most effective treatment for NSCLC. However, the clinical efficacy of chemotherapy is markedly reduced later in the treatment because drug resistance develops during the treatment. Recently, a series of studies has suggested the involvement of FAT10 in the development and malignancy of multiple cancer types. In this study, we focused our research on the function of FAT10 in NSCLC, which has not been previously reported in the literature. We found that the expression levels of FAT10 were elevated in quick chemoresistance NSCLC tissues, and we demonstrated that FAT10 promotes NSCLC cell proliferation, migration, and invasion. Furthermore, the protein levels of FAT10 were elevated in cisplatin- and carboplatin-resistant NSCLC cells, and knockdown of FAT10 reduced the drug resistance of NSCLC cells. In addition, we gained evidence that FAT10 regulates NSCLC malignancy and drug resistance by modulating the activity of the nuclear factor kappa B signaling pathway.

Role of PGI2 in the formation and maintenance of hyperdynamic circulatory state of portal hypertensive rats.

AIM: To investigate the role of prostacyclin (PGI(2)) and nitric oxide (NO) in the development and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats. METHODS: Ninety male Sprague-Dawley rats were divided into three groups: intrahepatic portal hypertension (IHPH) group by injection of CCl(4), prehepatic portal hypertension (PHPH) group by partial stenosis of the portal vein and sham-operation control (SO) group. One week after the models were made, animals in each group were subdivided into 4 groups: saline controlled group (n = 23), Nomega-nitro-L-arginine (L-NNA) group (n = 21) group, indomethacin (INDO) group (n = 22) and high-dose heparin group (n = 24). The rats were administrated 1 mL of saline, L-NNA (3.3 mg/kg.d) and INDO (5 mg/kg.d) respectively through gastric tubes for one week, then heparin (200 IU/Kg/min) was given to rats by intravenous injection for an hour. Splanchnic and systemic hemodynamics were measured using radioactive microsphere techniques. The serum nitrate/nitrite (NO(2)(-)/NO(3)(-)) levels as a marker of production of NO were assessed by a colorimetric method, and concentration of 6-keto-PGF1alpha, a stable hydrolytic product of PGI(2), was determined by radioimmunoassay. RESULTS: The concentrations of plasma 6-keto-PGF1alpha (pg/mL) and serum NO(2)(-)/NO(3)(-) (micromol/L) in IHPH rats (1123.85+/-153.64, 73.34+/-4.31) and PHPH rats (891.88+/-83.11, 75.21+/-6.89) were significantly higher than those in SO rats (725.53+/-105.54, 58.79+/-8.47) (P<0.05). Compared with SO rats, total peripheral vascular resistance (TPR) and spanchnic vascular resistance (SVR) decreased but cardiac index (CI) and portal venous inflow (PVI) increased obviously in IHPH and PHPH rats (P<0.05). L-NNA and indomethacin could decrease the concentrations of plasma 6-keto-PGF1alpha and serum NO(2)(-)/NO(3)(-) in IHPH and PHPH rats (P<0.05). Meanwhile, CI, FPP and PVI lowered but MAP, TPR and SVR increased (P<0.05). After deduction of the action of NO, there was no significant correlation between plasma PGI(2) level and hemodynamic parameters such as CI, TPR, PVI and SVR. However, after deduction of the action of PGI(2), NO still correlated highly with the hemodynamic parameters, indicating that there was a close correlation between NO and the hemodynamic parameters. After administration of high-dose heparin, plasma 6-keto-PGF(1alpha) concentrations in IHPH, PHPH and SO rats were significantly higher than those in rats administrated vehicle (P<0.05). On the contrary, levels of serum NO(2)(-)/NO(3)(-) in IHPH, PHPH and SO rats were significantly lower than those in rats administrated Vehicle (P<0.05). Compared with those rats administrated vehicle, the hemodynamic parameters of portal hypertensive rats, such as CI and PVI, declined significantly after administration of high-dose heparin (P<0.05), while TPR and SVR increased significantly (P<0.05). CONCLUSION: It is NO rather than PGI(2) that is a mediator in the formation and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats.

ß-Adrenergic Receptors : New Target in Breast Cancer.

BACKGROUND: Preclinical studies have demonstrated that ß-adrenergic receptor antagonists could improve the prognosis of breast cancer. However, the conclusions of clinical and pharmacoepidemiological studies have been inconsistent. This review was conducted to re-assess the relationship between beta-adrenoceptor blockers and breast cancer prognosis. MATERIALS AND METHODS: The literature was searched from PubMed, EMBASE and Web of Nature (Thompson Reuters) databases through using key terms, such as breast cancer and beta- adrenoceptor blockers. RESULTS: Ten publications met the inclusion criteria. Six suggested that receiving beta- adrenoceptor blockers reduced the risk of breast cancer-specific mortality, and three of them had statistical significance (hazard ratio (HR)=0.42; 95% CI=0.18-0.97; p=0.042). Two studies reported that risk of recurrence and distant metastasis (DM) were both significantly reduced. One study demonstrated that the risk of relapse- free survival (RFS) was raised significantly with beta-blockers (BBS) (HR= 0.30; 95% CI=0.10-0.87; p=0.027). One reported longer disease-free interval (Log Rank (LR)=6.658; p=0.011) in BBS users, but there was no significant association between overall survival (OS) and BBS (HR= 0.35; 95% CI=0.12-1.0; p=0.05) in five studies. CONCLUSIONS: Through careful consideration, it is suggested that beta-adrenoceptor blockers use may be associated with improved prognosis in breast cancer patients. Nevertheless, larger size studies are needed to further explore the relationship between beta-blocker drug use and breast cancer prognosis.

[The effect of PGI2 on formation and development of hyperdynamic circulatory state in portal hypertensive rats].

OBJECTIVE: To investigate the effects of prostacyclin (PGI(2)) and nitric oxide (NO) in the development of hyperdynamic circulatory state on chronic portal hypertensive rats. METHODS: Sixty-six male SD rats were divided into three groups, namely intrahepatic portal hypertension (IHPH) by injection of CCl(4), prehepatic portal hypertension (PHPH) by partial stenosis of the portal vein for 2 weeks and sham-operated controls (SO). Animals in each group were divided further into 3 subgroups and received N(omega)-nitro-L-arginine (L-NNA), indomethacin and saline (as control), respectively. Splanchnic and systemic hemodynamics was measured using radioactive microsphere techniques. The NO concentration in serum was determined by nitrates-nitrites which were measured using a colorimetric method, and concentration of PGI(2) was determined using specific radioimmunoassay for its stable hydrolytic product, 6-keto-PGF(1 alpha). RESULTS: The concentrations of plasma 6-keto-PGF(1 alpha) and serum nitrates + nitrites in IHPH rats (1 123.85 +/- 153.64; 73.34 +/- 4.31) and in PHPH rats (891.88 +/- 83.11; 75.21 +/- 6.89) were significantly higher than those of SO rats (725.53 +/- 105.54;58.79 +/- 8.47). L-NNA and indomethacin could decrease the concentrations of plasma 6-keto-PGF(1 alpha) and serum nitrates + nitrites in IHPH and PHPH rats (P < 0.05). At the same time, CI, FPP and PVI were lowered while MAP, TPR and SVR were increased (P < 0.05). After deduction of NO action, there were no significant correlation between plasma PGI(2) level and hemodynamic parameters such as CI, TPR, PVI and SVR. However, after deduction of PGI(2) action, NO was still correlated highly with those hemodynamic parameters. CONCLUSION: It is NO rather then PGI(2) that is a mediator in the formation and development of hyperdynamic circulatory state in chronic portal hypertensive rats.

[Dominant perforator neurocutaneous flaps for one-staged reconstruction of defects caused by high energy at lower legs, ankles and feet].

OBJECTIVE: To evaluate the therapeutic effect of dominant perforator neurocutaneous flaps for one-staged reconstruction of defects caused by high energy at lower legs, ankles and feet. METHODS: From July 2003 to Feb. 2011, 39 cases, with defects caused by high energy at lower legs, ankles and feet, were retrospectively studied. The defects were covered primarily by one or two perforator neurocutaneous flaps (free or pedicled) which were based on a dominant perforator arising from the posterior tibial or peroneal artery (including the lateral supramalleolar perforating artery which is also from the peroneal vessel) respectively through sural, saphenous and superficial peroneal neurocutaneous vascular axis. RESULTS: 39 cases with 44 defects were treated by 32 sural neurocutaneous flaps based on the peroneal perforator (5 free and 27 pedicled), 6 saphenous neurocutaneous flaps on the posterior tibial perforator (1 free and 5 pedicled) and 6 superficial peroneal ones on the lateral supramalleolar perforating artery. The largest flap size was 22 cm x 10 cm. All flaps were survived successfully without necrosis. The average in-hospital time was 23 days ( ranged from 12-36 days). CONCLUSIONS: The three kinds of dominant perforator neurocutaneous flaps have reliable blood supply with a relatively large size. They can be chosen and designed individually for all kinds of defects over the lower leg, ankle and foot. There are many advantages in a primary procedure, such as easier dissection, better vessel status in or around recipient areas, less secondary necrosis and lower risk of chronic infection. Moreover, the reduction of granulation and scar tissues benefit functional rehabilitation.

[Superficial peroneal neurocutaneous vascular axial adipofascial-cutaneous flap pedicled with lateral supramalleolar perforator for coverage of donor site defects at foot dorsum].

OBJECTIVE: To report the operative techniques and clinical results of modified superficial peroneal neurocutaneous propeller adipofascial-cutaneous flap for reconstruction of donor site defects at foot dorsum. METHODS: A propeller adipofascial flap with a skin pedicle (4-6 cm in width) based on the lateral superamalleolar perforating artery which vascularized the flap through the nutrient vessel chain of the superficial peroneal nerve was designed to repair defects after harvesting of foot pedicled dorsal flap. The defects at donor site of the leg was closed directly and split-thickness skin grafting was performed on the adipofascial surface of the flap primarily or secondarily. RESULTS: From May 2007 to Oct. 2011, 7 cases were treated. All flaps were transplanted successfully with satisfactory cosmetic and functional results. The flaps size ranged from 19 cm x 8 cm to 30 cm x 11 cm. CONCLUSIONS: The flap has reliable blood supply with a relatively large vascularized area, long rotation are and minimum donor-site cosmetic morbidity. It' s a simple and safe procedure which is suitable for covering donor sites defects after harvesting foot pedicled dorsal flap.

[Modified sural neurocutaneous vascular flap based on single dominant perforator arising from peroneal artery for coverage of defects over Achilles tendon].

OBJECTIVE: To report the operative techniques and clinical results of specially designed sural neurocutaneous vascular flap pedicled on a dominant perforator (the diameter > or = 0.8 mm) of the peroneal artery for coverage of soft tissue defects overlying the Achilles tendon. METHODS: An approximately rectangular sural neurocutaneous vascular flap pedicled on the lowest dominant perforator arising from the peroneal artery was designed and harvested to repair defects over the Achilles tendon. The pedicle was located at a certain part of the flap, which divided the flap into the distal and the proximal parts. After the tendon was repaired, the flap was rotated 180 degrees based on the perforator and the position of the distal and proximal parts of the flap was changed to cover the defects and part of the donor site respectively. In most cases, skin graft was not needed. RESULTS: The modified flaps were applied in 15 cases. All flaps (ranged from 13 cm x 15 cm - 18 cm x 9 cm ) were transplanted successfully without necrosis, and no vascular problems occurred. Following up for 10-17 months showed both satisfactory functional and cosmetic results. CONCLUSIONS: The modified flap has reliable blood supply and the special design provides nearly normal outline of the ankle which favorites shoe wearing. It' s an excellent option for covering defects overlying the Achilles tendon.

[Modified superficial peroneal neurocutaneous flap pedicled with lateral supramalleolar artery arising from peroneal artery for forefoot defect].

OBJECTIVE: To report the operative techniques and clinical results of modified distally based superficial peroneal neurocutaneous flap for skin defect of the forefoot. METHODS: A reversed superficial peroneal neurocutaneous flap pedicled with the lateral superamalleolar perforating artery or its descending branch, which vascularized the flap through the nutrient vessel chain of the nerve, which linked vascular territories of superamalleolar perforating artery, cutaneous branches of the anterior tibial artery and superficial peroneal artery, was designed to repair skin defects in the forefoot. RESULTS: The modified flaps were applied in 17 cases. All flaps were survived successfully with no complication. The largest size of the flap was 20 cm x 8 cm. The flap could reach as far as the proximal end of the second and third toes or weight-bearing areas under the fifth metatarsal caput. CONCLUSIONS: The modified flap has reliable blood supply with a relatively large size and long rotation arc. It is a simple and safe for covering medium to large defects in the forefoot.

[Study of distribution of dominant perforators arising from peroneal artery with color Doppler flow imaging and its clinical significance for sural neurocutaneous flap].

OBJECTIVE: To study the distribution of the dominant perforators (the diameter > or = 0.8 mm) of the peroneal artery with color Doppler flow imaging (CDFI) for the purpose of anatomical preparations for the perforator sural neurocutaneous flap. METHODS: The dominant perforators of the peroneal artery (DPPA) were studied with CDFI on bilateral legs of 20 healthy volunteers. The numbers, diameters and locations of the perforators were recorded for a statistical analysis. From Jan. 2005 to Jan. 2009, 51 free or pedicled sural neurocutaneous flaps supplied by a single DPPA were designed and harvested to repair the defects near the ankle (n=22), at the leg (n=15) and the forefoot or hand dorsum (n=14). The perforators were located preoperatively with CDFI and accuracy of CDFI was evaluated intraoperatively. The causes of false results were analysed to improve examining techniques. RESULTS: The average number of DPPA was 4.2 with the average diameter of (1.13 +/- 0.24) mm (0.80-1.90 mm). They were located in the second to ninth segment of the line from the fibular caput to the tip of lateral malleolus which was equally divided into nine segments. The largest DPPA was (1.43 +/- 0.29) mm (1.00-1.90 mm) in diameter and most of them were located in the third to fifth segment (80.4%). The average diameter of the lowest DPPA was (1.02 +/- 0.16) mm( 0.80-1.30 mm) and they were located between the sixth to ninth segment. The total 169 DPPA as well as the largest ones mostly appeared in the middle third of the leg. All of the 51 flaps were transplanted successfully without necrosis, and no vascular problems occurred. Preoperative CDFI examination had a 93.6% true-positive rate and an 88.0% positive predictive value. What should be demonstrated was that if just considered the cases after Dec. 2007, the true-positive rate was 97%, and the positive predictive value was 93.9%. CONCLUSIONS: According to the distribution characteristics of DPPA, a sural neurocutaneous flap pedicled with one of this relatively large perforator can be designed and harvested to repair skin defects of leg and around ankle, but can not be utilized for that of forefoot. With anastomosis of the perforator, the flap based on the largest DPPA can be used as a free flap to cover defect anywhere. CDFI is reliable in preoperative location of DPPA, which makes the surgical procedures easier.

Stat1 mediates an auto-regulation of hsp90beta gene in heat shock response.

We have reported earlier that a heat shock element in the first intron of human hsp90beta gene (iHSE) acts as an intronic enhancer to bind the heat shock factor (HSF1) and activates hsp90beta gene under heat shock. Here, we show that, in addition to the HSF1, Stat1 phosphorylation is indispensable in the event. We show that Jak2, a Janus kinase specifically associated with the beta subunit of IFNgamma receptor, and PKCepsilon an isoform of the atypical PKC family, are the two dominant kinases responsible for the heat shock induced phosphorylation on Y701 and S727 of Stat1. However, the activation of these kinases under heat shock requires the association of chaperone proteins of the Hsp90 family, in particular, the Hsp90beta under heat shock. Furthermore, Brg1, an ATPase subunit of the SWI/SNF chromatin remodeling complex is likely recruited by HSF1 and Stat1 at the iHSE under heat shock. Brg1 further confers an open chromatin conformation at the promoter region that is pivotal to the heat shock induced fully activation of the hsp90beta gene in Jurkat cells. This is a novel example of how multiple activation steps occur under heat shock, first on the kinases and then the Stat1 and the SWI/SNF chromatin remodeling complex that follows to conduct an auto-regulation based fully activation of the gene.

[Free peroneal artery perforator sural neurocutaneous flap for hand and foot defects].

OBJECTIVE: To report the operative techniques and clinical results of the free peroneal artery perforator sural neurocutaneous flaps. METHODS: Free sural neurocutaneous flap with a single unit of perforating veins and artery arising from the peroneal artery was designed to repair skin defects of hand or from the ankle to distal end of the foot. After the flap was transposed to the defect, the perforating artery was anastomosed with a branch of a nearby artery, and the small saphenous vein was anastomosed with the cephalic vein or the great saphenous vein to establish the flap's circulation. An alternative way was to anastomose the perforating vessels only. The sural nerve was anastomosed to innervate the flap. RESULTS: From Jan 2005 to Dec 2007, 12 cases were treated with the flaps with no flap necrosis. The size of the flaps ranged from 12 cm x 7 cm to 18 cm x 11 cm. The follow-up period was 7 to 27 months. Both the cosmetic and functional results were satisfactory. Two point discrimination was 7 to approximately 12 mm. CONCLUSIONS: The flap has all the advantages of the free flap, the perforator flap and the neurocutaneous flap. It is easily performed with reliable blood supply. It's a good choice for repairing the skin defects of hands and feet.