Objective:To analyze clinicopathological characteristics of trauma-related melanoma and their relationship with the prognosis of patients.Methods:Clinical data were collected from 87 cases of trauma-related melanomas in Department of Dermatology, Xijing Hospital, the Fourth Military Medical University from 2009 to 2020, and their clinicopathological characteristics were retrospectively analyzed. Mann-Whitney test was used to analyze the difference in Breslow thickness of tumors between patients of different ages or genders; Spearman rank correlation analysis was used to analyze the correlation between the time from trauma to the notice of melanoma and Breslow thickness, Kaplan-Meier survival analysis and Log-Rank test were employed to analyze the relationship between clinicopathological characteristics of melanoma and the prognosis of patients; Cox regression model was used to analyze risk factors for survival duration of patients with trauma-related melanoma.Results:Among the 87 patients with trauma-related melanoma, 47 (54.02%) were males and 40 (45.98%) were females. Among them, melanoma occurred in 50 (57.47%) cases after sharp injuries, and in 37 (42.53%) after blunt injuries. In addition, 31 (35.63%) cases presented with primary lesions on the hands, and 48 (55.17%) on the feet. The Breslow thickness of the primary tumors was significantly higher in the group aged > 55 years than in the group aged ≤ 55 years ( U= 623.500, P= 0.010) , but there was no significant difference between patients of different genders ( P= 0.138) . The time from trauma to the notice of melanoma was negatively correlated with the Breslow thickness of tumors ( r=-0.203, P= 0.037) . The age of patients, Breslow thickness of tumors, Ki67 proliferation index and genetic background of tumor significantly affect the survival duration of patients with trauma-related melanoma ( P= 0.011, 0.031, 0.002 and 0.031, respectively) ; the gender, type of trauma and ulceration of tumor mass did not significantly affect the survival duration of patients ( P= 0.618, 0.114 and 0.379, respectively) . Cox regression model analysis showed that the Ki67 proliferation index and Breslow thickness were independent risk factors affecting the prognosis of trauma-related melanoma (risk ratio [ RR] and 95% confidence interval [ CI] were 1.946 (1.234, 4.217) and 1.839 (1.014, 3.332) , P= 0.039 and 0.045, respectively) . Conclusion:The Breslow thickness of trauma-related melanoma is related to the age of patients and time from trauma to the notice of melanoma; the age, Breslow thickness of tumors, Ki67 proliferation index and genetic background of tumor all affect the survival duration of patients with melanoma, and Ki67 proliferation index and Breslow thickness are independent risk factors affecting prognosis.

OBJECTIVETo study the molecular mechanism of TAp63gamma-induced cell apoptosis.

METHODSTranscription and protein expression of apoptosis inducing factor and p63 were investigated by immunohistochemistry and RT-PCR in human esophageal squamous carcinoma cell line EC9706 respectively. Twenty-four hours after transfection with pcDNA3.1-TAp63gamma, the apoptosis and translocation of apoptosis inducing factor in EC9706 cells were studied by flow cytometry, laser confocal microscopy and mitochondrial/cytosol/nuclear extraction analysis respectively. Down-regulation of apoptosis inducing factor protein was achieved by RNAi and pretreatment with caspase inhibitor zVAD.fmk of EC9706 cells.

RESULTSPresence of protein expressions of apoptosis inducing factor and absence of TAp63gamma was observed in the cytoplasm of untransfected cells. RT-PCR verified the subtype of p63 in EC9706 cells was DeltaNp63. After 24 hours of transfection, both nuclear and cytoplasmic expression of apoptosis inducing factor protein were observed in cells transfected with TAp63gamma and p53 expression vectors, but not in cells transfected with control vector. Cell apoptosis rates were 1.37%, 13.64%, 4.52%, 4.03% and 1.91% in the pcDNA3.1 transfection group, pcDNA3.1-TAp63gamma transfection group, apoptosis inducing factor siRNA and pcDNA3.1-TAp63gamma transfection group, zVAD.fmk treatment group, and the group receiving apoptosis inducing factor siRNA, plus zVAD.fmk treatment and pcDNA3.1-TAp63gamma transfection, respectively.

CONCLUSIONSApoptosis inducing factor of EC9706 cells is released from mitochondria into both the cytoplasm and nucleus during TAp63gamma induced apoptosis. Down-regulation of apoptosis inducing factor inhibits TAp63gamma-induced apoptosis. Overall, TAp63gamma-induced apoptosis is dependent on the expression of apoptosis inducing factor and caspase.

Amino Acid Chloromethyl Ketones ; pharmacology ; Apoptosis ; Apoptosis Inducing Factor ; genetics ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Caspase Inhibitors ; Cell Line, Tumor ; Cell Nucleus ; metabolism ; Cytoplasm ; metabolism ; Down-Regulation ; Esophageal Neoplasms ; metabolism ; pathology ; Humans ; Mitochondria ; metabolism ; Plasmids ; Protein Transport ; RNA Interference ; RNA, Small Interfering ; genetics ; Trans-Activators ; genetics ; metabolism ; Transcription Factors ; Transfection ; Tumor Suppressor Proteins ; genetics ; metabolism

OBJECTIVETo investigate the association of AKR1B10 expression in gastric cancer tissues with clinicopathologic features and prognosis of gastric cancer patients.

METHODSReal-time polymerase chain reaction (RT-PCR) was conducted to detect AKR1B10 mRNA expression in gastric cancer and adjacent gastric mucosa tissues (n=36). AKR1B10 protein expression was measured by immunohistochemistry in primary gastric cancer tissues (n=100) and non-tumorous gastric mucosa tissues (n=70).

RESULTSRT-PCR results confirmed that AKR1B10 was significantly down-regulated in gastric cancer tissues compared with that in paired adjacent mucosa [8.3% (3/36) vs. 91.7% (33/36), P=0.000]. Immunohistochemistry revealed that the percentage of AKR1B10 positive specimens in gastric carcinoma was lower than that in normal specimens [33.0% (33/100) vs. 92.9% (65/70), P=0.000]. The frequencies of positive AKR1B10 in patients was significantly correlated with tumor size (P=0.000), invasive depth (P=0.004), lymph node metastasis (P=0.028), distant metastasis (P=0.031) and TNM stages (P=0.000). The 5-year survival rate of positive AKR1B10 group was significantly higher as compared to negative group (60.6% vs. 32.8%, P<0.01).

CONCLUSIONThe down-regulation of AKR1B10 expression in gastric cancer may be associated with the progress of gastric cancer is suggestive of poor prognosis.

Adult ; Aged ; Aged, 80 and over ; Aldehyde Reductase ; genetics ; metabolism ; Female ; Gastric Mucosa ; enzymology ; pathology ; Humans ; Male ; Middle Aged ; Prognosis ; RNA, Messenger ; genetics ; Stomach Neoplasms ; diagnosis ; enzymology ; pathology

Objective To investigate the role of mitochondrial calcium uptake 1 (MICUI) in myocardial hypertrophy of mice and underlying mechanism.Methods The model of myocardial hypertrophy was established via incubation of mouse cardiac myocytes (MCM) with 300nmol/L angiotensin Ⅱ (Ang Ⅱ) for 48 hours in vitro.After that,MICU1 specific small interfering RNA (siRNA) was delivered to knockdown MICU1 levels in MCM.On the other hand,adenovirus-mediated over-expression of MICU 1 was transfected into MCM.Accordingly,the expressions of ANP and BNP in myocardial cells were measured by qRT-PCR.Mitochondrial membrane potential and ATP contents were detected byJC-1 assay kit and ATP assay kit,respectively.Then,Western blotting and qRT-PCR were used to detect the levels of MICU1 in myocardial cells.The mitochondrial Ca2+ contents were measured via atomic absorption flame spectroscopy.The size of myocardial cells was determined by α-actinin staining.Results Mitochondrial membrane potential and ATP contents in hypertrophic cardiomyocytes induced by Ang Ⅱ were both decreased.Meanwhile,myocardial hypertrophy significantly increased mitochondrial Ca2+ contents but decreased MICU1 levels.With the method of genetic intervention,we found that MICUI deficiency exacerbated mitochondrial Ca2+ overload,increased cell surface and elevated the expression of BNP.Conversely,the overexpression of MICU1 obviously decreased mitochondrial Ca2+ overload,cell surface of MCM and expressions of ANP and BNP.Conclusion MICU1 alleviates Ang Ⅱ-induced myocardial hypertrophy via inhibiting mitochondrial Ca2+ overload.

OBJECTIVE: To evaluate the effect of uncemented total hip arthroplasty(THA) on treatment of traumatic arthritis caused by intramedullary nailing interfixation of intertrochanteric fractures. METHODS: Total of 22 patients treated with THA due to traumatic arthritis caused by intramedullary nailing interfixation of intertrochanteric fractures from January 2012 to January 2017 were studied retrospectively, including 10 males and 12 females with a mean age of (72.5±9.8) years old ranging from 61 to 84 years old. Initial internal fixation method:14 patients were treated with Gamma nails and 8 patients were treated wit PFNA.The time from internal fixation surgery to THA was 10 to 68 months with an average of (32.2±21.3) months.Harris scores of the hip joint before and after surgery were compared, and the position of the prosthesis through postoperative imaging at 3, 6, 12 months and the last follow-up were evaluated. RESULTS: One patient was died due to heart failure 1 year after operation. Two patients was died to advanced tumor 2 years after operation. The other 19 patients were followed up for 36 to 64 months with an average of (48.5±11.9) months. At final follow up, 14 patients regained the ability to walk independently, 4 patients needed support of a cane, 1 patient needed assistance of a walker. No serious complications such as joint dislocation, periprosthetic fracture and deep venous thrombosis occurred during follow-up. There were no signs of loosening and subsidence of the prosthesis at the final follow-up. Mean Harris hip score increased from (29.2±12.9) points preoperatively to (74.2±11.2) points at the final follow up(P<0.05);the score was excellent in 9 patients, good in 7 and fair in 3. CONCLUSION Uncemented total hip arthroplasty for traumatic arthritis after intramedullary nail fixation of femoral intertrochanteric fracture can significantly improve hip function and effectively avoid bone cement implantation syndrome. The medium-term effect is satisfactory.
Male ; Female ; Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Hip/methods* ; Follow-Up Studies ; Treatment Outcome ; Retrospective Studies ; Bone Nails ; Hip Fractures/surgery* ; Fracture Fixation, Intramedullary/adverse effects* ; Arthritis/surgery*

Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L

OBJECTIVETo determine whether additional Chinese medicine (CM) could prolong survival and improve the quality of life (QOL) in patients with advanced non-small cell lung cancer (NSCLC) compared with Western medicine (WM) alone.

METHODSThis was a multicenter, prospective cohort study. A total of 474 hospitalized patients with stage III-IV NSCLC were recruited and divided into 2 groups. Patients in the WM group received radiotherapy, chemotherapy, and optimal supportive therapy according to the National Comprehensive Cancer Network (NCCN) guidelines. In the integrative medicine (IM) group, individualized CM (Chinese patent medicines and injections) and WM were administered. The primary end point was overall survival, and the secondary end points were time to disease progression, adverse events, and QOL. Follow-up clinical examinations and chest radiography were performed every 2 months.

RESULTSThe median survival was 16.60 months in the IM group and 13.13 months in the WM group (P<0.01). The incidences of loss of appetite, nausea, and vomiting in the IM group were significantly lower than those in the WM group (P<0.05). The QOL based on Functional Assessment of Cancer Therapy-Lung in the IM group was markedly higher than that in the WM group at the fourth course (P<0.05).

CONCLUSIONSAdditional CM may prolong survival and improve the QOL patients with NSCLC. The adverse effects of radio- and chemotherapy may be attenuated as CM is used in combination with conventional treatments.

OBJECTIVE: To investigate the effects of melatonin (MT) on bone mass and serum inflammatory factors in rats received ovariectomy (OVX) and to investigate the effects of MT on the levels of inflammatory factors in culture medium and osteogenic ability of bone marrow mesenchymal stem cells (BMSCs) stimulated by lipopolysaccharide. METHODS: Fifteen 12-week-old Sprague Dawley (SD) rats were randomly divided into 3 groups. The rats in Sham group only received bilateral lateral abdominal incision and suture, the rats in OVX group received bilateral OVX, and the rats in OVX+MT group received 100 mg/(kg·d) MT oral intervention after bilateral OVX. After 8 weeks, the levels of serum inflammatory factors [interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α)] were detected using ELISA assay. Besides, the distal femurs were detected by Micro-CT to observe changes in bone mass and microstructure, and quantitatively measured bone volume fraction, trabecular thickness, and trabecular number. The BMSCs were extracted from the femurs of three 3-week-old SD rats using whole bone marrow culture method and passaged. The 3rd-5th passage BMSCs were cultured with different concentrations of MT (0, 1, 10, 100, 1 000 µmol/L), and the cell viability was then detected using cell counting kit 8 (CCK-8) to select the optimal concentration of MT for subsequent experiments. Cells were devided into osteogenic induction group (group A) and osteogenic induction+1/5/10 μg/mL lipopolysaccharide group (group B-D). The levels of inflammatory factors (IL-1β, IL-6 and TNF-α) in cell culture medium were detected using ELISA assay after corresponding intervention. According to the results of CCK-8 method and ELISA detection, the cells were intervened with the most significant concentration of lipopolysaccharide for stimulating inflammation and the optimal concentration of MT with osteogenic induction, defining as group E, and the cell culture medium was collected to detect the levels of inflammatory factors by ELISA assay. After that, alkaline phosphatase (ALP) staining and alizarin red staining were performed respectively in groups A, D, and E, and the expression levels of osteogenic related genes [collagen type Ⅰ alpha 1 chain (Col1a1) and RUNX family transcription factor 2 (Runx2)] were also detected by real time fluorescence quantitative PCR (RT-qPCR). RESULTS: ELISA and Micro-CT assays showed that compared with Sham group, the bone mass of the rats in the OVX group significantly decreased, and the expression levels of serum inflammatory factors (IL-1β, IL-6, and TNF-α) in OVX group significantly increased (P<0.05). Significantly, the above indicators in OVX+MT group were all improved (P<0.05). Rat BMSCs were successfully extracted, and CCK-8 assay showed that 100 µmol/L was the maximum concentration of MT that did not cause a decrease in cell viability, and it was used in subsequent experiments. ELISA assays showed that compared with group A, the expression levels of inflammatory factors (IL-1β, IL-6, and TNF-α) in the cell culture medium of groups B-D were significantly increased after lipopolysaccharide stimulation (P<0.05), and in a concentration-dependent manner. Moreover, the expression levels of inflammatory factors in group D were significantly higher than those in groups B and C (P<0.05). After MT intervention, the expression levels of inflammatory factors in group E were significantly lower than those in group D (P<0.05). ALP staining, alizarin red staining, and RT-qPCR assays showed that compared with group A, the percentage of positive area of ALP and alizarin red and the relative mRNA expressions of Col1a1 and Runx2 in group D significantly decreased, while the above indicators in group E significantly improved after MT intervention (P<0.05). CONCLUSION MT may affect the bone mass of postmenopausal osteoporosis by reducing inflammation in rats; MT can reduce the inflammation of BMSCs stimulated by lipopolysaccharide and weaken its inhibition of osteogenic differentiation of BMSCs.
Female ; Rats ; Animals ; Tumor Necrosis Factor-alpha ; Osteogenesis ; Rats, Sprague-Dawley ; Core Binding Factor Alpha 1 Subunit ; Melatonin/pharmacology* ; Interleukin-6/genetics* ; Lipopolysaccharides/pharmacology* ; Coloring Agents ; Inflammation