Objective To investigate the effects of 5-Aza-CdR( methylation transferase inhibitor) on the expression levels of leptin gene in chondrocytes and methylation states of leptin promoter region between osteoarthritis (OA) group and control. Methods The chondrocytes in osteoarthritis group were treated with 5-Aza-CdR with different doses and time-points, and the expression level of leptin was detected by real-time polymerase chain reaction for picking up the optimum dose and time-point. Next, the chondrocytes in 5 osteoarthritis patients and 5 control patients (amputation due to severe trauma) were treated with 5-Aza-CdR. Lastly, leptin mRNA expression levels in the four groups osteoarthritis and control chondrocytes treated with/without 5-Aza-CdR were measured by real-time PCR and the methylation state of promoter region ( - 280- + 79) was detected by epityper quantitative DNA methylation analysis. Results ( 1 ) After treating the chondrocytes in OA groups with 10 μmol/L 5-Aza-CdR for 72 h, the mRNA expression levels of leptin were increased significantly. ( 2 ) The mRNA expression levels of leptin were significantly different among the four groups ( P ＜ 0. 05 ), and the chondrocytes in osteoarthritis groups treated with 5-Aza-CdR showed a marked induction of leptin mRNA expression. (3) Analysis of quantitative methylation data using an unsupervised hierarchical clustering algorithm, showed that methylation patterns of leptin promoter was different between control and osteoarthritis chondrocyte treated with/without 5-Aza-CdR. Conclusion Demethylation of leptin promoter might up-regulate leptin gene expression level and it might contribute to osteoarthritis.

Objective To discuss clinical curative effects of using Forehead skin expansion combine with auricular cartilage for repairing nose alar full-thickness defects.Methods From August 2010 to August 2010,36 patients with nose alar full-thickness defects in the second affiliated hospital of kunmin medical university,The defect range exceed 1.5 cm× 1.2 cm.50-80 ml expander was implanted in forehead and injected saline water to expand in order to acquire extra skin.We Turn around the skin of defect as the lining of nose,harvest ipsilateral auricular cartilage for nose ala framework,Expanded forehead pedicle flap was transferred to cover framework.The donor area was sutured directly.The pedicle of flap was cut and trimmed after 2 months.Results Follow-up time of 3-18 months after the operation,All flaps are survive,nose alar defects are repaired successfully.Some cases were performed second surgery,postoperative,nose alar color,thickness,nostril size and shape the same with the contralateral side.Donor site healed with linear scar.Conclusions This method could be easy to obtain excess skin,for repairing large sides nose alar full-thickness defect.Frontal scar is not obvious,It is a practical.

Objective To investigate the effects of CD147/MMP-9 pathway on early left ventricular remodeling Methods 30 healthy eight-week male SHR were divided into 3 groups (n = 10 for each group). SHR group received tail vein injections of normal saline weekly; CD147 group received CD147 of 600 ng·kg-1 weekly; and CD147+DOX group received CD147 of 600 ng/kg weekly and intragastric administration of DOX ( doxycycline ) of 30 mg/kg daily . 10 healthy eight-week male Wistar-Kyoto rats (WKY group) were treated as SHR group. Echocardiography, myocardial sections microscopy examination (HE and VG stain), and Western blot (for assessing levels of MMP-9, TIMP-1, CD147, and collagen I and Ⅲin myocardial tissues) were performed on day 56. Left ventricular weight index (LVWI)was measured and calculated. Collagen volume fractions (CVF) were obtained by image analysis. Results As compared with WKY group , levels of CD147 , MMP-9 , and MMP-9/TIMP-1 were lower but TIMP-1 and collagenⅠand Ⅲ were significantly higher in SHR group. The abundance of CD147 and MMP-9 protein and the ratio of MMP-9/TIMP-1 were obviously increased in CD147 group than in SHR group (P < 0.05). Levels of CD147, MMP-9, and MMP-9/TIMP-1 did no differ between CD147+DOX group and CD147 group. LVWI and contents of collagenⅠand Ⅲ were obviously declined in CD147 group as compare with SHR group. Cardiomyocyte hypertrophy , partial myocardial fibre rupture , myocyte dissolution and fuzzy myocardial fibre boundaries , more abundant of collagen fibers, and higher CVF were found in SHR group. Cardiac fibrosis was significantly improved after CD147 intervention, but the action was suppressed as DOX was administrated simultaneously. Conclusions Early ventricular remodeling may be involved in the inhibition of CD147/MMP-9 pathway in SHR. Input of CD147 to upregulate the pathway can improve the remodeling.

Objective To evaluate the efficacy of accelerated partial breast irradiation ( APBI ) and whole breast irradiation ( WBI ) with simultaneous integrated boost ( SIB ) from the perspective of economics, and provide a reference for postoperative adjuvant therapy mode selection for early-stage breast cancer after breast-conserving surgery. Methods A total of 355 early-stage breast cancer patients who underwent APBI or WBI-SIB after breast-conserving surgery were evaluated on efficacy and cost-effectiveness, of which 177 patients received APBI, and 178 patients received WBI-SIB. Survival analysis was done according to treatment received. NCI-CTC 3.0 was used to score the toxicities. Breast aesthetic outcome were evaluated with Harris standards. Results Median follow-up was 42 months ( 5.8 -92.7 months) . The 3-year locoregional recurrence free survival( LRFS) rates in APBI group and WBI-SIB group were 98.2％ and 97.6％, distant metastasis free survival( DMFS) were 94.3％ and 93.7％, disease-free survival ( DFS) were 93.1％ and 91.6％, and overall survival 95.5％ and 94.3％, respectively, without statistically significant differences(P>0.05). Compared with WBI-SIB group, the acute reaction rates in APBI group decreased from 5. 6％ to 3.4％(χ2 =6.044, P <0. 05), and late reactions from 5.6％ to 2.3％ (χ2 =6.149, P<0. 05), while the cosmetic outcome improved from 88.8％ to 93.8％(χ2 =5.22, P<0. 05). Moreover, the processing average time was shortened by 26.5 d (χ2 =40.76, P<0. 05). Conclusions After breast-conserving surgery, the efficacy of APBI showed no difference from WBI-SIB with respect to 3-year local control, disease-free survival, and overall survival, but displayed a significantly better toxicity profile and cost-effectiveness ratio for early breast cancer patients. It can be used as a good radiotherapy model after breast-conserving surgery in early-stage breast cancer.

Objective:To investigate the regulatory effect of deoxycytidine kinase (dCK) on ionizing radiation (IR) induced ferroptosis in triple-negative breast cancer (TNBC).Methods:TNBC cell line MDA-MB-231 was used to establish dCK knockdown and different phosphorylation phenotypes cell models, and were treated with ferroptosis activator Erastin and / or ferroptosis inhibitor ferrostatin-1 (Fer-1) combined with / without X-ray irradiation. Cell viability was detected by MTT assay. The level of reactive oxygen species (ROS) was measured by 2′,7′-dichlorofluorescin diacetate (DCFH-DA) staining. The expression levels of dCK, transferrin, transferrin receptor (TfR1), ferroportin (FPN) and ferritin heavy chain 1 (FTH1) were detected by Western blot. Statistical analysis was performed by SPSS 17.0 and Origin 2021 software. Measurement data with normal distribution were expressed by Mean ±SD. The comparison between two groups was conducted by Student t-test. The comparison among three or more groups was performed by one-way analysis of variance. Results:In MDA-MB-231 cells, IR induced cell death was observed and Erastin significantly promoted radiation induced cell death, while Fer-1 was able to reverse radiation induced cell death. Compared with the control group, IR induced cell death was increased, the level of ROS was suppressed in the dCK knockdown group. Erastin combined with IR induced reduced cell death and weakened ROS level. Fer-1 reduced the degree of IR induced cell death, and it could not inhibit the induction of ROS by IR.Compared with the control cells, the rate of cell death was decreased induced by IR, the level of ROS was decreased, the expression of FTH1 was down-regulated after IR in the dCK wild-type (dCK-WT ) or dCK hyperphosphorylated (dCK-S74E) MDA-MB-231 cells. In addition, Erastin promotes IR induced cell death and increased ROS levels, while Fer-1 significantly enhances the degree of reversal of IR induced ROS and cell death in these cells. Conclusions:dCK phosphorylation increases ferroptosis induced by IR in TNBC cells. Targeting dCK may be a novel therapeutic approach to overcome radioresistance in TNBC treatment.

In October 2016, a male patient attacked by a black bear was treated in the Department of Plastic Surgery, the Second Affiliated Hospital of Kunming Medical University.The patient had facial skin and soft tissue defects, and zygomatic arch and buccal damage. The patient received three operations, including debridement, scapular free skin flap transplantation, and reconstruction of zygomatic arch. The facial appearance recovered well after 6-months follow-up.

Objective To investigate the consensus and controversies on the delineation of radiotherapy target volume for patients with locally advanced non-small cell lung cancer (LA-NSCLC).Methods Questionnaires including 15 questions on the delineation of radiotherapy target volume of NSCLC were sent to 12 radiation departments in China in November 2015.A patient with LA-NSCLC was selected by Fudan University Shanghai Cancer Center, and simulation CT images and medical history data were sent to the 12 radiation departments.Twelve radiation oncologists from the 12 radiation departments showed and explained the delineation of radiotherapy target volume of their own, and the patient was discussed by all experts in the sixth multidisciplinary summit forum of precise radiotherapy and chemotherapy for tumor and lung cancer.Results All receivers of the questionnaire answered the questions.The standard lung window width/level for the delineation of lung cancer was 800-1600/-600 to-750 HU, and the mediastinum window was 350-400/20-40 HU.Respiratory movement was measured by stimulator, 4D-CT, and stimulator+4D-CT with 2-5 mm expansion based on experience.The primary clinical target volume (CTV) was defined as gross target volume (GTV) plus 5-6 mm for squamous carcinoma/5-8 mm for adenocarcinoma.The metastatic lesion of mediastinal lymph nodes was delineated as 5 mm plus primary lesion in 6 departments and as primary lesion in another 6 departments.Of the 12 departments, 10 applied 5 mm of set-up error, 1 applied 3 mm, and 1 applied 4-6 mm.For V20 of the lungs, 10 departments defined it as<30%, 1 as<35%, and 1 as 28%.Nine departments defined the radiation dose of concurrent chemoradiotherapy (CCRT) for LA-NSCLC as 60 Gy in 30 fractions, 62.7 Gy in 33 fractions in 1 department, 50-60 Gy in 25-30 fractions in 1 department, and 60-70 Gy in 25-30 fractions in 1 department.For the delineation of target volume for the LA-NSCLC patient treated with CCRT, the primary planning target volume (PTV) was defined as GTV plus organ movement (IGTV) and set-up error (GTV→IGTV→PTV) in 3 departments, as CTV plus organ movement (ITV) and set-up error (GTV→CTV→ITV→PTV) in 8 departments, and as CTV plus set-up error/IGTV plus 5-6 mm for squamous carcinoma/5-8 mm for adenocarcinoma (CTV) and set-up error (GTV→CTV→PTV/GTV→IGTV→CTV→PTV) in 1 department.For the delineation of PTV in the mediastinal lymph node, GTV→IGTV→PTV was performed in 3 departments, GTV→CTV→ITV→PTV in 8 departments, and GTV→CTV→PTV in 1 department.For 10%-100% patients with LA-NSCLC, the radiation field needed to be replanned when 38-50 Gy was completed.There was no unified standard for the optimal standardized uptake value (SUV) of positron emission tomography (PET)-computed tomography (CT) simulation and delineation.Seven departments had applied magnetic resonance imaging (MRI) simulation and 10 departments had applied stereotactic body radiation therapy (SBRT) for the treatment of early-stage NSCLC.For the delineation of PTV for early-stage NSCLC (T1-2N0M0), GTV→IGTV→PTV was performed in 5 departments, IGTV→PTV in 3 departments, and GTV→CTV→ITV→PTV in 2 departments.In all the 12 departments, peripheral early-stage NSCLC was given 6.0-12.5 Gy/fraction, 3-12 fractions and central early-stage NSCLC was given 4.6-10.0 Gy/fraction, 5-10 fractions.The results of discussion on the delineation of target volume for the patient were as follows:respiratory movements should be measured by 4D-CT or simulator;the lung window width/level is 1600/-600 HU and the mediastinal window width/level is 400/20 HU;the primary controversy is whether the involved-field irradiation or elective nodal irradiation should be used for the delineation of CTVnd in the mediastinal lymph node.Conclusions Basic consensus is reached for the delineation of target volume in LANSCLC in these aspects:lung window width/level, respiratory movements and set-up error, primary lesion delineation, the radiation dose in CCRT, and the optimal time for replanning the radiation field.There are controversies on the optimal SUV in the delineation of target volume based on PET-CT simulation, the optimal dose fractionation in SBRT for early-stage NSCLC, and the delineation of CTVnd.

Objective: To explore the effects of anteriolateral thigh perforator flap and fascia lata transplantation in combination with computed tomography angiography (CTA) on repair of electrical burn wounds of head with skull exposure and necrosis. Methods: Seven patients with head electrical burns accompanied by skull exposure and necrosis were admitted to our burn center from March 2016 to December 2017. Head CTA was performed before the operation. The diameters of the facial artery and vein or the superficial temporal artery and vein were measured, and their locations were marked on the body surface. Preoperative CTA for flap donor sites in lower extremities were also performed to track the descending branch of the lateral circumflex femoral artery with the similar diameter as the recipient vessels on the head, and their locations were marked on the body surface. Routine wound debridement and skull drilling were performed successively. The size of the wounds after debridement ranged from 12 cm×8 cm to 20 cm×12 cm, and the areas of skull exposure ranged from 8 cm×6 cm to 15 cm×10 cm. Anteriolateral thigh perforator flaps with areas from 13 cm×9 cm to 21 cm×13 cm containing 5-10 cm long vascular pedicles were designed and dissected accordingly. The fascia lata under the flap with area from 5 cm×2 cm to 10 cm×3 cm was dissected according to the length of vascular pedicle. The fascia lata was transplanted to cover the exposed skull, and the anteriolateral thigh perforator flap was transplanted afterwards. The descending branch of the lateral circumflex femoral artery and its accompanying vein of the flap were anastomosed with superficial temporal artery and vein or facial artery and vein before the suture of flap. The flap donor sites were covered by intermediate split-thickness skin graft collected from contralateral thigh or abdomen. Results: The descending branch of the lateral circumflex femoral artery and its accompanying vein were anastomosed with superficial temporal artery and vein in six patients, while those with facial artery and vein in one patient. All the flaps survived after the operation, and no vascular crisis was observed. Wound healing was satisfactory. One patient was lost to follow up. Six patients were followed up for 6 to 10 months. The patients were bald in the head operation area with acceptable appearance. No psychiatric symptom such as headache or epileptic seizure was reported. The flap donor sites were normal in appearance. The muscle strength of the lower extremities all reached grade V. The sensation and movement of the lower extremities were normal. Conclusions Anterolateral thigh perforator flap with fascia lata transplantation can effectively repair electrical burn wounds of head with skull exposure and necrosis. The fascia lata can be used to protect the vascular pedicle of flaps, which is beneficial to the survival of the flap. Preoperative head and lower extremities CTA can provide reference for intraoperative vascular exploration in donor site and recipient area, so as to shorten operation time.

BACKGROUND:Gut microbiota is closely related to host energy balance and metabolism.The metabolites of intestinal flora can regulate the occurrence and development of obesity and can be a new target for the prevention and treatment of obesity. OBJECTIVE:To summarize the interaction between the intestinal flora and obesity,as well as the specific mechanism underlying regulation of obesity by metabolites of intestinal flora,thereby providing a new reference and basis for the prevention and treatment of obesity. METHODS:"Intestinal microbiota,intestinal bacteria,intestinal microbiota metabolites,short-chain fatty acids,bile acids,ipopolysaccharide,trimethylamine N-oxide,medium-chain fatty acids,tryptophan derivatives,obesity"were used as search terms in Chinese and English.Literature related to obesity from 1990 to 2022 was retrieved in PubMed and CNKI databases.According to inclusion and exclusion criteria,88 articles were finally selected. RESULTS AND CONCLUSION:Intestinal flora is closely related to the occurrence and development of obesity.For example,changes in the Firmicutes to Bacteroidetes ratio can be used as a biomarker for the diagnosis of obesity,and the occurrence of obesity can be delayed by the colonization of probiotics such as Bifidobacterium breve,Lactobacillus and Akkermansia.Intestinal flora is mainly mediated by the metabolites of intestinal flora to participate in the regulation of obesity.For example,short-chain fatty acid can regulate adipogenesis by regulating signaling pathways such as G protein-coupled receptors 41,43 and peroxisome proliferator-activated receptor γ,thus delaying the occurrence and development of obesity.Bile acids can increase insulin sensitivity and body energy expenditure by promoting the activation of G protein-coupled receptor 5 and farnesol X receptor.In addition,lipopolysaccharide,trimethylamine oxide,medium-chain fatty acids and tryptophan derivatives are also widely involved in the occurrence and development of obesity through various signaling pathways.Further studies have found that metabolites of the same bacterial community exert heterogeneous effects in the specific process of regulating obesity via different signaling pathways.For example,under the influence of high-fat diet,acetic acids can activate the parasympathetic nervous system,leading to hyperphagia and liver insulin resistance and thus accelerating the physiological course of obesity.

BACKGROUND:Intestinal flora and its metabolites can participate in the pathological process of osteoporosis and play an important role in the diagnosis and treatment of osteoporosis.In addition,exercise can regulate the intestinal flora and thus affect the occurrence and development of osteoporosis. OBJECTIVE:To summarize the effects and mechanism of intestinal flora on osteoblasts,osteoclasts,and bone marrow mesenchymal stem cells,and the potential role of exercise-mediated intestinal flora in regulating osteoporosis. METHODS:"Intestinal flora,intestinal bacteria,metabolites of intestinal flora,bone metabolism,osteoporosis,exercise"were selected as keywords.Literatures from 1990 to 2023 were retrieved from PubMed and CNKI databases. RESULTS AND CONCLUSION:Changes in the abundance and diversity of intestinal flora and changes in the levels of intestinal flora metabolites such as trimethylamine oxide and bile acid can be used as biomarkers for the diagnosis of osteoporosis.The imbalance of intestinal flora can lead to intestinal barrier dysfunction and excessive production of lipopolysaccharides and trimethylamine oxide,induce the secretion of tumor necrosis factor-α and other inflammatory cytokines,activate the nuclear factor κB signaling pathway and aggravate oxidative stress,thus promoting osteoclast differentiation,inducing osteoblast apoptosis and affecting bone marrow mesenchymal cell migration.Remodeling intestinal flora homeostasis can inhibit inflammatory response,downregulate oxidative stress,inhibit osteoclast differentiation,promote osteoblast differentiation,and regulate the osteogenic migration of bone marrow mesenchymal cells to prevent and treat osteoporosis.Exercise can regulate intestinal flora homeostasis,improve intestinal barrier function,promote the secretion of short-chain fatty acids and bile acids,down-regulate serum lipopolysaccharide level,reduce oxidative stress,and then inhibit osteocyte apoptosis,inhibit osteoclast differentiation,promote osteoblast differentiation,and regulate osteocyte nutrient metabolism to exert the potential of preventing and treating osteoporosis.