[Repair methods of complex facial defect wounds involving paranasal sinuses and their clinical effectiveness].

Objective: To explore the repair methods of complex facial defect wounds involving paranasal sinuses and their clinical effectiveness. Methods: A retrospective observational study was conducted. From January 2020 to May 2022, 5 patients admitted to the Department of Burns and Plastic Surgery of Xiangya Hospital of Central South University and 4 patients admitted to the Department of Burns and Plastic Surgery of Chenzhou First People's Hospital with complex facial defect wounds involving paranasal sinuses met the inclusion criteria, including 6 males and 3 females, aged 35-69 years, including 4 patients with titanium mesh exposure combined with paranasal sinuses injury and 5 patients with tumor involving paranasal sinuses. After an adequate assessment of the damage by a multiple discipline team, titanium mesh removal, paranasal sinus debridement, and paranasal sinus mucosa removal were performed in patients with exposed titanium mesh, and radical tumor resection was performed in patients with tumors, with postoperative skin and soft tissue defects areas of 5.0 cm×2.5 cm to 18.0 cm×7.0 cm, anterior paranasal sinus wall defects/absence areas of 3 cm×2 cm to 6 cm×4 cm, and sinus cavity depths of 1 to 4 cm. Depending on the perforator course of the descending branch of the lateral circumflex femoral artery, the anterolateral femoral chimeric flap or anterolateral femoral myocutaneous flap (with flap area of 9 cm×4 cm to 19 cm×8 cm, muscle size of 5 cm×3 cm×3 cm to 11 cm×6 cm×3 cm) was transplanted to repair the defect, and the donor site wound was sutured directly. The type of tissue flap transplanted, the blood vessel of the recipient area, and the vascular anastomosis way during the operation, the recovery of the donor and recipient areas and the occurrence of complications after operation were observed. The appearance and blood supply of the recipient area and the recurrence of ulcers and tumors were followed up. Results: The anterolateral femoral myocutaneous flap transplantation was performed in 6 patients, and the anterolateral femoral chimeric flap transplantation was performed in 3 patients. The blood vessels in recipient areas were facial arteries and veins in 3 cases and superficial temporal arteries and veins in 6 cases. The superficial temporal arteries and veins were bridged with blood vessels in tissue flaps by flow-through way in 2 patients, and end-to-end anastomosis of blood vessels in donor and recipient areas was performed in 7 patients. After operation, all the tissue flaps survived, and the facial defect wounds were well repaired without cerebrospinal fluid leakage or paranasal sinus secretion leakage, no intracranial infection occurred, and the wounds in donor areas were healed well. Follow-up of 6-35 months after operation showed that all the patients had good blood supply in the recipient area, and the shape was acceptable; 4 patients with exposed titanium mesh had no recurrence of ulceration, and 5 patients with tumor had no local tumor recurrence or metastasis. Conclusions: Based on an adequate assessment of the extent of paranasal sinuses involved in the facial wound and the nature of the defect, good clinical effects can be achieved by using the anterolateral femoral muscle flap or the anterolateral femoral chimeric flap transplantation to repair complex facial defect wounds with open paranasal sinuses.

[Repair methods and clinical effects of full-thickness burn wounds deep to tendon or even bone in fingers].

Objective: To explore the repair methods and clinical effects of full-thickness burn wounds deep to tendon or even bone in fingers. Methods: A retrospective non-randomized controlled trial was conducted on the 98 patients with full-thickness finger burns deep to tendon or even bone who met the inclusion criteria and were hospitalized in Xiangya Hospital of Central South University from January 2010 to December 2019. Among the 98 patients, there were 81 males and 17 females, aged from 1 to 72 years, with 160 fingers involved. The wound area of each of affected fingers ranged from 2.0 cm×1.5 cm to 12.0 cm×3.5 cm, and the maximum wound area after merging the affected fingers was 12.0 cm×10.0 cm. For adult hands with multiple full-thickness burn wounds deep to tendon or even bone in multiple fingers or children with full-thickness finger burns deep to tendon or even bone, pedicled abdominal flaps were selected. For adults with single or two fingers with full-thickness burns deep to tendon or even bone, the pedicled internal hand flaps and free tissue flaps were selected. The free tissue flap repair requires good vascular conditions in the recipient area with arteries and veins available for anastomosis. For thumb nail burns deep to tendon or even bone or partial absence of the thumb after burns, the thumbs were reconstructed with the first toenail flap or dorsal foot flap with the second toe. In this study, 45 pedicled abdominal flaps were used to repair the wounds in 91 fingers, 37 pedicled internal hand flaps were used to repair the wounds in 37 fingers, 26 free tissue flaps were used to repair the wounds in 28 fingers, 3 first toenail flaps were used to reconstruct 3 patients' thumb nails and to repair hand wounds, and 1 dorsal foot flap with the second toe was used to reconstruct 1 patient's thumb and to repair hand and wrist wounds. The tissue flap area was from 2.0 cm×1.5 cm to 20.0 cm×10.0 cm. The wound in the donor site was repaired by direct suture or full-thickness skin grafting from the medial upper arm of the affected limb or split-thickness skin grafting from the outer thigh. The postoperative survival of the tissue flap, postoperative complications, and appearance and function of the flap donor site were observed. For the patients who were followed up, their finger functions were evaluated at the last follow-up using the trial criteria for replantation function evaluation of the amputated finger issued by the Hand Surgery Society of the Chinese Medical Association, and the satisfaction of the patients was investigated using the Efficacy Satisfaction Scale. Data were statistically analyzed with Kruskal-Wallis H test and Nemenyi test. Results: Of the 112 tissue flaps, 104 tissue flaps survived completely and had good blood circulation; 1 pedicled thumb dorsal ulnar reverse island flap, 1 pedicled finger artery cutaneous branch reverse island flap, and 1 free grafted anterolateral thigh perforator flap were slightly necrotic at the end, which were repaired with outer thigh split-thickness skin graft after dressing change and granulation tissue growth; 2 free grafted tarsal external artery flaps and 1 pedicled thumb dorsal ulnar reverse island flap suffered from postoperative venous return obstruction, which survived after partial suture removal and heparin saline cleansing of the wound; 1 pedicled modified dorsal metacarpal artery retrograde island flap and 1 free grafted peroneal artery perforator flap were necrotic, which were repaired by a pedicled abdominal flap and a lateral upper arm flap free transplantation respectively in stage Ⅱ. After transplantation, the tissue flaps had good shape, soft texture, and good elasticity, without bloating. There was no functional disorder in the flap donor site, and only slight scar remained. A total of 117 fingers of the 72 patients received 3-24 months of outpatient or telephone follow-up. At the last follow-up, the excellent and good rates of function evaluation of fingers repaired with pedicled abdominal flap, pedicled internal hand flap, and free tissue flap were respectively 77.3% (51/66), 96.3% (26/27), and 95.8% (23/24). The function of fingers repaired with free tissue flap and pedicled internal hand flap was significantly better than that with pedicled abdominal flap (P<0.01). The satisfaction of patients with fingers repaired by free tissue flaps was significantly higher than that by pedicled abdominal flap (P<0.05). Conclusions: According to the specific situation of full-thickness burn wounds deep to tendon or even bone in fingers, the pedicled abdominal flap is used to repair the multiple full-thickness burn wounds deep to tendon or even bone in multiple fingers of adult or the full-thickness burn wounds deep to tendon or even bone in fingers of children, the pedicled internal hand flap or free tissue flap is used to repair the full-thickness burn wounds deep to tendon or even bone in single or two fingers of adult patients, and the first toenail flap or the dorsal foot flap with the second toe is used to reconstruct the thumbs with full-thickness burn deep to tendon or even bone, with high postoperative tissue flap survival rate and few complications. The functional recovery of the affected finger is better after repair with free tissue flap and pedicled internal hand flap, and the patients' satisfaction is the highest after free tissue flap repair.

[Clinical effects of axillary propeller flaps in reconstructing the axillary fold scar contracture].

Objective: To explore the clinical effects of axillary propeller flaps in reconstructing the axillary fold scar contracture. Methods: A retrospective cohort study was conducted. From July 2016 to January 2020, 11 patients with anterior axillary fold or anterior and posterior axillary fold scar contractures after burns were admitted to Xiangya Hospital of Central South University, including 7 males and 4 females, aged 8 to 48 years. The lesions involved unilateral axilla in 9 cases and bilateral axilla in 2 cases, with the joint abduction angle of the affected shoulder ranging from 25 to 100°. The axillary fold contracture scars were excised and released, resulting in wound of 8 cm×5 cm-24 cm×20 cm. According to the condition of the residual normal skin in axilla, 2, 3, and 4-leaf propeller flaps with area of 5 cm×3 cm-24 cm×10 cm were designed to repair the wounds after scar excision and release. The donor site wound was closed by suturing directly, and the residual wound that could not be completely sutured was transplanted with free full-thickness skin grafts from the inner thigh or abdomen. The application of 2, 3, and 4-leaf propeller flaps, the joint abduction angle of the affected shoulder immediately after operation, and the survival of the flaps and skin grafts after operation were recorded. The recurrence of scar contracture, the appearance of the flaps, the joint abduction angle of the affected shoulder, and the functional recovery of the affected shoulder joint and upper arm were observed through a follow-up. Results: Among the 13 axillary propeller flaps transplanted in the 11 patients in this group, there were 9 double-leaf propeller flaps, two 3-leaf propeller flaps, and two 4-leaf propeller flaps. The joint abduction angle of the affected shoulder reached 110-165° immediately after operation. All the flaps survived after operation. Nine flap donor sites were repaired with free skin grafts, with skin grafts survived in 7 flap donor sites after operation. Scar erosion in incision and small area of skin graft necrosis developed in 2 flap donor sites. One of the wounds was debrided and repaired by transplantation of split-thickness skin grafts from inner thigh, and the other wound was healed after dressing changes. A follow-up of 6 to 24 months was conducted after surgery, and all the patients had no recurrence of axillary scar contracture; the color of the flap matched the receiving area; the elasticity of flap was good; the joint abduction angle of the affected shoulder reached 120-165°, and the joint pronation and supination, upper arm lifting and circular rotation of the affected shoulder were all good. Conclusions: Reconstruction of the axillary fold scar contracture with axillary propeller flaps has good result, with better flap appearance and recovery of the shoulder joint activity and upper arm function after operation.

[Establishment and test results of an artificial intelligence burn depth recognition model based on convolutional neural network].

Objective: To establish an artificial intelligence burn depth recognition model based on convolutional neural network, and to test its effectiveness. Methods: In this evaluation study on diagnostic test, 484 wound photos of 221 burn patients in Xiangya Hospital of Central South University (hereinafter referred to as the author's unit) from January 2010 to December 2019 taken within 48 hours after injury which met the inclusion criteria were collected and numbered randomly. The target wounds were delineated by image viewing software, and the burn depth was judged by 3 attending doctors with more than 5-year professional experience in Department of Burns and Plastic Surgery of the author's unit. After marking the superficial partial-thickness burn, deep partial-thickness burn, or full-thickness burn in different colors, the burn wounds were cut according to 224×224 pixels to obtain 5 637 complete wound images. The image data generator was used to expand images of each burn depth to 10 000 images, after which, images of each burn depth were divided into training set, verification set, and test set according to the ratio of 7.0∶1.5∶1.5. Under Keras 2.2.4 Python 2.8.0 version, the residual network ResNet-50 of convolutional neural network was used to establish the artificial intelligence burn depth recognition model. The training set was input for training, and the verification set was used to adjust and optimize the model. The judging accuracy rate of various burn depths by the established model was tested by the test set, and precision, recall, and F1_score were calculated. The test results were visualized to generate two-dimensional tSNE cloud chart through the dimensionality reduction tool tSNE, and the distribution of various burn depths was observed. According to the sensitivity and specificity of the model for the recognition of 3 kinds of burn depths, the corresponding receiver operator characteristics (ROC) curve was drawn, and the area under the ROC curve was calculated. Results: (1) After the testing of the test set, the precisions of the artificial intelligence burn depth recognition model for the recognition of superficial partial-thickness burn, deep partial-thickness burn, or full-thickness burn were 84% (1 095/1 301), 81% (1 215/1 499) and 82% (1 395/1 700) respectively, the recall were 73% (1 095/1 500), 81% (1 215/1 500) and 93% (1 395/1 500) respectively, and the F1_scores were 0.78, 0.81, and 0.87 respectively. (2) tSNE cloud chart showed that there was small overlapping among different burn depths in the test results for the test set of artificial intelligence burn depth recognition model, among which the overlapping between superficial partial-thickness burn and deep partial-thickness burn and that between deep partial-thickness burn and full-thickness burn were relatively more, while the overlapping between superficial partial-thickness burn and full-thickness burn was relatively less. (3) The area under the ROC curve for 3 kinds of burn depths recognized by the artificial intelligence burn depth recognition model was ≥0.94. Conclusions: The artificial intelligence burn depth recognition model established by ResNet-50 network can rather accurately identify the burn depth in the early wound photos of burn patients, especially superficial partial-thickness burn and full-thickness burn. It is expected to be used clinically to assist the diagnosis of burn depth and improve the diagnostic accuracy.

[Clinical effectiveness of simultaneous reconstructions of multiple joint scar contracture deformity of limb].

Objective: To explore the clinical effects of simultaneous reconstruction of multiple joint scar contracture deformity of limb. Methods: From January 2010 to June 2018, 24 patients with multiple joint scar contracture deformity of the same limb were reconstructed in simultaneous operations in Xiangya Hospital of Central South University, including 16 males and 8 females, aged 3-42 years, with 15 patients having deformities in the upper limbs and 9 patients having deformities in the lower limbs. One operation was performed to repair contracture deformity of axillary fossa and elbow in 3 patients, cubital fossa and palmar of wrist in 4 patients, cubital fossa and hand in 5 patients, palmar of wrist, palm, and palmar of finger in 3 patients, groin and medial knee in 2 patients, popliteal fossa and posterior ankle in 1 patient, and anterior ankle and dorsum of foot in 6 patients. After the release of various joint scar contractures, the area of skin defect was 140 to 580 cm(2). Autologous full-thickness skin grafts were used in 7 patients, autologous medium-thickness skin grafts were used in 4 patients, autologous full-thickness skin grafts combined with local skin flaps were used in 9 patients, and allogeneic acellular dermal matrix and autologous thin skin grafts were used in 4 patients. Comprehensive measures for rehabilitation were taken and the survival of the skin graft was observed after operation. Six months to eight years after the operation, all the patients were followed up for the functions of the affected limbs, among which the functions of the upper limbs were evaluated according to the trial standard for the evaluation of the functions of the upper limbs of the Hand Surgery Society of the Chinese Medical Association. The joint mobility, walking, and squatting function of lower extremity were examined after operation. Recurrence of contractures in all the affected limbs and reoperation were recorded. Results: The grafts survived after operation in 22 patients. Two patients had necrosis in small full-thickness skin area, of which one was healed by skin grafting after debridement, and the other one was healed after dressing changes. The deformity of scar contracture at each repaired joint was completely or partially corrected. During a follow-up for 6 to 96 months, the upper limb functions of 15 patients were rated excellent in 12 patients and good in 3 patients. Among the 9 patients of lower limb scar contractures, except for one 3-year-old child who experienced recurrence of medial knee scar contracture and underwent surgical release and skin grafting 5 years later, the remaining 8 patients basically recovered normal joint functions with pretty good outcomes. Conclusions: For continuous scar contracture deformity of multiple joints of the same limb, simultaneous surgical release and skin grafting can reduce operation frequency and obtain better outcomes of surgical operation.

[Clinical characteristics and repair effect of 136 patients with electric burns of upper limb].

Objective: To analyze clinical characteristics and wound repair methods and effects of patients with upper limb electric burns. Methods: Medical records of 136 patients with upper limb electric burn who met the inclusion criteria and hospitalized in our unit from January 2015 to March 2019 were retrospectively analyzed. Proportion in patients with electric burns in the same period, gender, age, admission time, categories, injury causes, injury voltage, burn area and depth of upper limb, simultaneous injury of both upper limbs, and early wound treatment measure of patients with upper limb electric burn were recorded. The main repair methods of each affected limb were classified and recorded. The overall efficacy of the patients was recorded, including postoperative wound complications and healing condition. The patients repaired with distal pedicled flaps and those with free flaps were followed up for 3 to 6 months. The survival rate of flaps were recorded, the function of affected limbs after operation was evaluated, and the satisfaction degree of patients was investigated by Curative Effect Score Table. The amputation rate, age, and burn area of upper limbs of patients caused by high-voltage and low-voltage electricity were compared. Data were processed with Wilcoxon rank sum test, chi-square test, or Fisher's exact probability test. Results: (1) The number of upper limb electric burn patients accounted for 88.3% of 154 patients with electric burns hospitalized in the same period, including 117 males and 19 females, aged 1 year and 2 months to 72 years [(34±18) years], admitted 1 h to 48 d after injury, including 51 electricians, 32 rural migrant workers, 31 students and preschool children, and 22 patients belonging to other categories. Patients of the first two categories were mainly injured by work accidents, and those of the latter two categories mainly suffered from touching power source or power leakage. Among all the patients, 75 cases were injured by high-voltage electric burn, and 61 cases were injured by low-voltage electric burn, with burn area of upper limb from 0.2% to 16.0% [2% (1%, 5%)] total body surface area (TBSA) and area of wounds deep to bone from 0.2% to 15.0% [2% (1%, 5%)] TBSA. Two upper limbs in 54 cases were simultaneously injured, accounting for 39.7%. Early fasciotomy was performed for 73 limbs. (2) Thirteen affected limbs were treated with dressing change, 2 affected limbs were sutured directly after debridement, 56 affected limbs were repaired by skin grafting, 12 affected limbs were repaired by local flap, 45 affected limbs were repaired by distal pedicled flap, 22 affected limbs were repaired by free flap, and 40 affected limbs were amputated (accounting for 21.1%). (3) One case died of pulmonary infection, sepsis, and multiple organ failure after operation, and the rest patients were all cured. One case with avulsion of abdominal flap was repaired by skin grafting after dressing change. The anterolateral thigh flap in one case necrotized after transplantation, which was replaced by pedicled abdominal flap. Seven cases had small erosion on the pedicle or margin after transplantation of abdominal flap and were healed by dressing change. Six cases had local bruising at the distal end after transplantation of abdominal flap and were healed after conservative treatment such as hyperbaric oxygen. The other flaps survived well. (4) The survival rate of distal pedicled flap grafting was 97.8% (44/45), which was close to that of free flap grafting (95.5%, 21/22, P>0.05). The function recovery of affected limb after free flap grafting was better than that of distal pedicled flap grafting (Z=-3.054, P<0.01), but their satisfaction degree of patients was similar (Z=-0.474, P>0.05). (5) Patients with high-voltage electric burn had higher amputation rate, older age, and larger upper limb burn area than those with low-voltage electric burn (χ(2)=4.743, Z=-2.801, -6.469, P<0.05 or P<0.01). Conclusions: Upper extremity electric burn often occurs in children, electricians, and rural migrant workers with high rate of amputation. Teachers and parents should strengthen safety education for children and manage power source of life well. Workers should improve safety awareness and operate standardly. Fasciotomy for relaxation should be performed for electric burn wound as soon as possible, and flap grafting can effectively repair wound after early debridement. The function recovery of affected upper limb repaired with free flap grafting is better.

[Clinical application of negative pressure dressing in the full-thickness skin grafting].

Objective: To investigate the effect of different negative pressure of wound negative pressure dressing (NPD) on the survival of full-thickness skin grafts of patients. Methods: One hundred and eleven patients who need skin grafting, conforming to the inclusion criteria were hospitalized in our unit from August 2012 to March 2017, and their clinical data were retrospectively analyzed. Forty-seven patients hospitalized from August 2012 to October 2015 were assigned into traditional treatment group. Sixty-four patients hospitalized from November 2015 to March 2017 were divided into -9.975 kPa negative pressure treatment group (n=34) and -13.300 kPa negative pressure treatment group (n=30). Patients in traditional treatment group received conventional dressing after full-thickness skin grafting. Patients in -9.975 kPa and -13.300 kPa negative pressure treatment groups received -9.975 kPa and -13.300 kPa NPD based on traditional treatment after vacuum sealing, respectively. Dot necrosis area of skin grafts and erosion and escharosis of graft edges of patients in the three groups on post operation day 10 were observed. The percentage of dot necrosis area of skin grafts and occurrence rate of erosion and escharosis of skin graft edges were calculated, respectively. Data were processed with chi-square test, Fisher's exact test, and Kruskal-Wallis H test. Results: Percentages of dot necrosis area of skin grafts of patients in traditional treatment group and -9.975 kPa and -13.300 kPa negative pressure treatment groups were 17.81%, 3.20%, and 3.00%, respectively. Percentage of dot necrosis area of skin grafts of patients in traditional treatment group was significantly higher than that in -9.975 kPa and -13.300 kPa negative pressure treatment groups (Z=-5.770, -4.690, P<0.001). Percentages of dot necrosis area of skin grafts of patients in -9.975 kPa and-13.300 kPa groups were close (Z=-0.619, P>0.05). The occurrence rates of erosion and escharosis of skin graft edges of patients in traditional treatment group and -9.975 kPa and -13.300 kPa negative pressure treatment groups were 78.7% (37/47), 32.4 (11/34), and 36.7% (11/30), respectively. Erosion and escharosis of skin graft edges of patients in -9.975 kPa and -13.300 kPa negative pressure treatment groups were better than those in traditional treatment group (P<0.001). Erosion and escharosis of skin graft edges of patients in -9.975 kPa and -13.300 kPa negative pressure treatment groups were close (P>0.05). Conclusions: The use of -9.975 kPa and -13.300 kPa NPD in skin grafts after full-thickness skin grafting significantly diminishes the occurrence rates of dot necrosis area of skin grafts and erosion and escharosis of graft edges.

[Effects of improved V-Y advancement flap with major artery perforator on repairing skin and soft tissue defects].

Objective: To explore the effect of improved V-Y advancement flap with major artery perforator on repairing several skin and soft tissue defects in whole body. Methods: From March 2015 to June 2017, 4 cases with pressure ulcer in sacrococcygeal region, 4 cases with pressure ulcer at ischial tuberosity, 2 cases with scalp and skull defects at occiput, 1 case with secondary wound after tumor resection in axillary region, and 2 cases with skin and soft tissue defects caused by other trauma were hospitalized, with disease duration ranging from 1 week to 6 months. Bones, blood vessels, or nerves were exposed in wounds of 11 cases. After debridement, wounds with area ranging from 5 cm×4 cm to 15 cm×12 cm were repaired by improved V-Y advancement flap with major artery perforator including occipital artery perforator, arteria glutaea perforator, intercostal artery perforator, and peroneal artery perforator, and the area of flap ranged from 11 cm×5 cm to 35 cm×20 cm. Distal end of flaps additionally carried 1 major artery perforator in 4 cases. Results: All flaps survived well without hemodynamic disorder, and wounds and donor sites healed well. During the follow-up for 3 to 18 months, the flaps were good in appearance with similar color and texture to normal skin around wound and without recurrence of rupture. Conclusions: Compared with traditional V-Y advancement flap, the improved V-Y advancement flap with major artery perforator has the advantages of larger repair area, longer advance distance without tension, simple operation, and good appearance after operation, which is beneficial to clinical application.

Effect of Ginkgo biloba extract on matrix metalloproteinase-3 expression in a rat model of chondrocyte injury.

A rat model with cartilage chondrocyte injury was established using interleukin-1ß (IL-1ß) to investigate the effect of Ginkgo biloba extract (EGb) on matrix metalloproteinase-3 (MMP-3) expression. Rat chondrocytes were extracted and randomly divided into six groups: control group, IL-1ß (model) group, IL-1ß + dexamethasone group, and IL-1ß + EGb group (both high and low dose groups). Reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay were used to detect MMP-3 expression. Compared to the MMP-3 mRNA level in the control group, MMP-3 mRNA level significantly increased in the model group (P < 0.05). The application of dexamethasone or EGb significantly decreased the MMP-3 mRNA level (P < 0.05). MMP-3 mRNA and protein levels decreased in the EGb-treated group, especially in the high-dose group, compared to those in the dexamethasone group (P < 0.05). EGb may reduce MMP-3 production during IL-1ß-induced chondrocyte damage and protect chondrocytes to some extent, with better efficacy at high doses.

Hypoxia triggers a Nur77-ß-catenin feed-forward loop to promote the invasive growth of colon cancer cells.

BACKGROUND: ß-Catenin is a potent oncogenic protein in colorectal cancer (CRC), but the targets and regulation of this important signalling molecule are not completely understood. Hypoxia is a prominent feature of solid tumours that contributes to cancer progression. METHODS: Here, we analysed the regulation between Nur77 and ß-catenin under hypoxic conditions. Cell proliferation, migration, and invasion assays were performed to assess functional consequences. RESULTS: We showed that hypoxia stimulated co-upregulation of ß-catenin and Nur77 in a number of human CRC cell lines. Interestingly, expression of ß-catenin and Nur77 by hypoxia formed a mutual feedback regulation circuits that conferred aggressive growth of CRC. Overexpression of ß-catenin increased Nur77 transcription through hypoxia-inducible factor-1α rather than T-cell factor. Nur77-mediated activation of ß-catenin by hypoxia was independent of both DNA binding and transactivation. Further, we showed that hypoxic activation of ß-catenin was independent of the classical adenomatous polyposis coli and p53 pathways, but stimulated by phosphatidylinositol 3-kinase/Akt in a Nur77-dependent manner. Under hypoxic conditions, enhanced ß-catenin and Nur77 expression synergistically stimulated CRC cell migration, invasion, and epithelial-mesenchymal transition. CONCLUSION: These findings provide a novel molecular mechanism for hypoxic CRCs that may contribute to tumour progression, and its targeting may represent an effective therapeutic avenue.

RXR agonists inhibit high glucose-induced upregulation of inflammation by suppressing activation of the NADPH oxidase-nuclear factor-κB pathway in human endothelial cells.

An inflammatory response induced by high glucose is a cause of endothelial dysfunction in diabetes and is an important contributing link to atherosclerosis. Diabetes is an independent risk factor of atherosclerosis and activation of retinoid X receptor (RXR) has been shown to exert anti-atherogenic effects. In the present study, we examined the effects of the RXR ligands 9-cis-retinoic acid (9-cis-RA) and SR11237 on high glucose-induced inflammation in human umbilical endothelial vein endothelial cells (HUVECs) and explored the potential mechanism. Our results showed that the inflammation induced by high-glucose in HUVECs was mainly mediated by the activation of nuclear factor-B (NF- κB). High glucose-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were in comparison, significantly decreased by treatment with RXR. The effect of RXR agonists was mainly due to the inhibition of NF-κB activation. Using pharmacological inhibitors and siRNA, we confirmed that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was an upstream activator of NF-κB. Furthermore, RXR agonists significantly inhibited high glucose-induced activation of NADPH oxidase and significantly decreased the production of reactive oxygen species (ROS). To explore whether the rapid inhibitory effects of RXR agonists were in fact mediated by RXR, we examined the effect of RXR downregulation by RXR siRNA. Our results showed that RXR siRNA largely abrogated the effects of RXR agonists, suggesting the requirement of RXR expression. Therefore, we have shown that RXR is involved in the regulation of NADPH oxidase- NF-κB signal pathway, as the RXR ligands antagonized the inflammatory response in HUVECs induced by high glucose.

Inhibition of ß-catenin signaling by nongenomic action of orphan nuclear receptor Nur77.

Dysregulation of ß-catenin turnover due to mutations of its regulatory proteins including adenomatous polyposis coli (APC) and p53 is implicated in the pathogenesis of cancer. Thus, intensive effort is being made to search for alternative approaches to reduce abnormally activated ß-catenin in cancer cells. Nur77, an orphan member of the nuclear receptor superfamily, has a role in the growth and apoptosis of cancer cells. Here, we reported that Nur77 could inhibit transcriptional activity of ß-catenin by inducing ß-catenin degradation via proteasomal degradation pathway that is glycogen synthase kinase 3ß and Siah-1 independent. Nur77 induction of ß-catenin degradation required both the N-terminal region of Nur77, which was involved in Nur77 ubiquitination, and the C-terminal region, which was responsible for ß-catenin binding. Nur77/ΔDBD, a Nur77 mutant lacking its DNA-binding domain, resided in the cytoplasm, interacted with ß-catenin, and induced ß-catenin degradation, demonstrating that Nur77-mediated ß-catenin degradation was independent of its DNA binding and transactivation, and might occur in the cytoplasm. In addition, we reported our identification of two digitalis-like compounds (DLCs), H-9 and ATE-i2-b4, which potently induced Nur77 expression and ß-catenin degradation in SW620 colon cancer cells expressing mutant APC protein in vitro and in animals. DLC-induced Nur77 protein was mainly found in the cytoplasm, and inhibition of Nur77 nuclear export by the CRM1-dependent nuclear export inhibitor leptomycin B or Jun N-terminal kinase inhibitor prevented the effect of DLC on inducing ß-catenin degradation. Together, our results demonstrate that ß-catenin can be degraded by cytoplasmic Nur77 through their interaction and identify H-9 and ATE-i2-b4 as potent activators of the Nur77-mediated pathway for ß-catenin degradation.

[Bioconversion of hemicellulose hydrolysates for xylitol production].

Xylitol has attracted much attention because of its many applications in the food, medicine and chemical industries. However the use has been limited by its high price. This coast is a result of the extensive purification steps needed for the preparation of a pure xylose solution, which is essential for the chemical process. The fermentative process of xylitol is an interesting alternative to conventional chemical process, since it does not require initial xylose purification. The present review describes the advantage of xylitol production by fermentation, xylitol-producting microorganisms, metabolic pathway of xylose in yeasts, detoxification of hemicellulose hydrolysates and fermentative conditions affecting xylitol production.

[Expression of single-chain Fv antibody for anti-beet necrotic yellow vein virus in Escherichia coli].

The heavy chains variable region gene (VH) of monoclonal antibody against beet necrotic yellow vein virus (BNYVV) was amplified from total DNA extracted from anti-BNYVV hybridoma cells by PCR. Sequencing showed that the VH belongs to mouse subgroup II(A) and contains 360 bp, which code one hundred and twenty amino acids. The VH and VL genes were inserted into a plasmid which contains a linker sequence for constructing scFv gene. The new vector named pTC scFv. The scFv was produced in Escherichia coli and appeared binding activity with BNYVV antigen by ELISA method.

[Comparative study of pulmonary magnetic resonance angiography (MRA)].

Imaging was performed using a 1.0 Tesla superconducting MR system with a body coil. Two-dimensional(2D) turbo FLASH sequence and/or three-dimensional(3D) FISP sequence were carried out in 46 volunteers with 113 pulmonary MRA. The total MRAs were divided into 4 groups and analysed. The results showed: After Gd-DTPA was injected, the signal-to-noise ratio(SNR) of pulmonary 2D- and 3D-TOF MRA was increased in 46 normal pulmonary MR angiography cases(P < 0.01); the number of left and right pulmonary artery divisions identified was much greater than that before Gd-DTPA injection both in 2D- and 3D-MOF(except lingual segment of left lobe). It is suggested that Gd-DTPA may markedly promote the efficiency of pulmonary MRA.

Lack of inhibition of clomethiazole metabolism by cimetidine: model experiments in the dog.

The disposition of clomethiazole was studied in six dogs subjected to pretreatment with cimetidine or saline according to a cross-over design. Pretreated dogs received approximately 20 mg/kg of cimetidine p.o. for 4 days and 30 mg/kg i.v. immediately before an intraduodenal infusion of clomethiazole (117 mumol/kg clomethiazole base within 90 min). Compared to controls, cimetidine had no effect on peak plasma concentrations and on areas under the plasma concentration time curves of clomethiazole or of its metabolite 5-acetyl-4-methylthiazole (P greater than 0.05). Identical pretreatment of the same dogs resulted in a 50% inhibition of aminopyrine demethylation (P less than 0.001) as revealed by the aminopyrine breath test. Clomethiazole may be metabolized in the dog through metabolic routes which cannot be inhibited by cimetidine.