Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress / 国际口腔科学杂志·英文版

C18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma. However, the function of ceramide synthase 1, a key enzyme in C18 ceramide synthesis, in oral squamous cell carcinoma is still unclear. The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer. In this study, we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines. In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide, ceramide synthase 1 knockout was associated with the severity of oral malignant transformation. Immunohistochemical studies showed significant upregulation of PCNA, MMP2, MMP9, and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area. In addition, ceramide synthase 1 knockdown promoted cell proliferation, migration, and invasion in vitro. Overexpression of CERS1 obtained the opposite effect. Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation. Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation. In addition, mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance. Taken together, our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.

Diagnosis, treatment and prognosis of human major exocrine ductal carcinoma / 国际肿瘤学杂志

Exocrine ductal carcinoma is an important part of malignant tumors of exocrine glands, including invasive breast ductal carcinoma, salivary duct carcinoma, pancreatic ductal adenocarcinoma and cholangiocarcinoma. Most of these diseases are aggressive, highly malignant and endanger human health. Early detection and diagnosis are the key to a good prognosis for exocrine ductal carcinoma. Different exocrine ductal carcinomas also have certain connections, and their molecular biological characteristics, pathological characteristics and molecular mechanisms have similarities. Surgical resection combined with adjuvant radiotherapy and chemotherapy is currently a common treatment method for exocrine ductal carcinoma. At the same time, its related targeted therapy and immunotherapy sites can also learn from each other. Human epidermal growth factor receptor-2 (HER-2) and the family markers have become breast ductal carcinoma and salivary duct carcinoma targeted therapy sites, and immunotherapy at programmed death ligand 1 (PD-L1) sites has also been involved in many studies, but there is no clear conclusion yet.

Perforated maxillofacial defect repaired by anteromedial thigh flap instead of anterolateral thigh flap: a case report / 华西口腔医学杂志

Anterolateral thigh flap is perfect for reconstructing maxillofacial soft tissue defects. This tissue has been widely used by clinicians, but often causes operation difficulties because of vascular variation. In this paper, we report a case where anteromedial thigh was used as new donor site when the vascular anatomic variation of anterolateral thigh perforator flap induced a failure in the flap harvest. Moreover, this paper discusses the anatomy and application of anteromedial thigh flap.

Systematic review of magnetic resonance imaging in diagnosing mandibular invasion caused by oral cancers / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the diagnostic value of magnetic resonance (MR) imaging in the diagnosis of mandibular invasion caused by oral cancers.</p><p><b>METHODS</b>Medline, EMBASE, SIGLE, and Chinese biomedical literature database were searched electronically. Manual searching for 19 relevant Chinese journals was also performed. Two reviewers evaluated the literature and extracted the data. Meta-Disc 1.4 was chosen to conduct the sensitivity (SEN), specificity (SPE), and 95% confidence interval (95%CI).</p><p><b>RESULTS</b>Twelve studies with a total of 476 patients, namely, 5 prospective studies and 7 retrospective studies, were included. All the studies had unclear risk of bias. Meta-analysis result showed that the combination of SEN of MR in diagnosing mandibular invasion was 0.779 (95%CI: 0.719-0.831), combination of SPE was 0.823 (95%CI: 0.767-0.870), positive likelihood ratio was 3.442 (95%CI: 2.181-5.431), negative likelihood ratio was 0.286 (95%CI: 0.181- 0.451), and diagnostic odds ratio was 25.702 (95%CI: 13.406-49.273). The area under curve was 0.903 9 and Q* was 0.835 4. Meta-analysis was not processed when diagnosing mandibular medullary invasion because only two studies with 55 patients had been reported. The SEN was 0.838, and the SPE was 0.722.</p><p><b>CONCLUSION</b>MR is efficient and has clinical value in the diagnosis of mandibular invasion caused by oral cancer.</p>

Central adenoid cystic carcinoma of the mandible: a case report / 华西口腔医学杂志

Central malignant salivary gland tumor of the mandible is rarely observed with adenoid cystic carcinoma, which only comprises a small proportion of cancer patients. In this study, a patient with central adenoid cystic carcinoma of the mandible is presented, and relevant literature is reviewed.

Increased invasion ability mechanism of salivary adenoid cystic carcinoma through elevated interstitial fluid pressure in vitro / 华西口腔医学杂志

<p><b>OBJECTIVE</b>Through a simulation of interstitial fluid pressure (IFP), we developed an in vitro model to explore the change law of biological characteristics of adenoid cystic carcinoma (ACC) under different IFP.</p><p><b>METHODS</b>A pressure cooker was refitted into a controllable pressure device. Cultured ACC-2 cells were subdivided into different groups, namely, negative control (untreated ACC-2) and experimental group (stressed for 3, 6, 12, 24 h under pressure of 7.551, 7.649, 7.747 kPa). CCK-8 and immunofluorescence of Ki67 were used to reflect proliferation ability. Transwell chamber assay was performed to observe the invasion ability of cells.</p><p><b>RESULTS</b>The proliferation ability was positively correlated with treatment time, and the peak value was obtained after the cells were subjected to 7.649 kPa of stress for 24 h. The invasion ability of ACC-2 cells was upregulated under stress.</p><p><b>CONCLUSION</b>We successfully developed an in vitro model of IFP and found that high IFP can stimulate cell proliferation ability and upregulate invasion ability.</p>

The molecular mechanism between interstitial fluid pressure and malignant phenotype of salivary adenoid cystic carcinoma / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To explore the effects of stress imposed on adenoid cystic carcinoma (ACC), therefore to clarify the molecular basis and mechanism of ACC's malignant phenotype under the elevated tumor interstitial fluid pressure.</p><p><b>METHODS</b>ACC cells were cultured under pressure (103.74 kPa), and were divided into four groups (3 h group, 6 h group, 12 h group, 24 h group) according the pressure time. Untreated ACC2 was as negative control group, untreated ACCM was as positive control group. The level of epidermal growth factor receptor (EGFR) was detected by semiquantitative analysis of immunochemistry. Matrix metalloproteinase 9 (MMP9) and EGFR mRNA expression were assessed by reverse transcriptase polymerase chain reaction. EGFR, phosphorylation epidermal growth factor receptor (P-EGFR), MMP9, keratinocyte growth factor (KGF) and phosphorylation extracellular signal-regulated kinase (P-ERK) protein expressions were assessed by Western blot.</p><p><b>RESULTS</b>As the extension of pressure time, the expression of EGFR, P-EGFR, MMP9, KGF, P-ERK in ACC2 gradually increased, which were positive correlation with pressure time, and were higher than that of negative control group.</p><p><b>CONCLUSION</b>Under the stimulation of pressure, the mRNA and protein levels of adhesion molecules and metastatic relative molecules in ACC2 were sharply elevated.</p>

Differential proteomics research on exosomes derived from tongue squamous cell carcinoma cells and normal mucosa cells / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study aimed to explore further the mechanisms of tongue squamous cell carcinoma (TSCC) cell recurrence, metastasis, and diffusion, as well as to establish the experimental basis for the molecular biology research on TSSC. We intend to complete our objective through differential proteomics and preliminary analysis protein expression of exosomes derived from TSCC and normal mucosa cells.</p><p><b>METHODS</b>We acquired cultured supernatant fluid in vitro in the laboratory by culturing TSCC (tongue cancer Tca8113 cell line) and human normal mucosa cells (HOK cell line). The exosomes were separated and purified through differential centrifugation. Furthermore, the different protein expressions were identified through dielectrophoresis and mass spectrometry. The functions of the different protein expressions were identified through an online database search.</p><p><b>RESULTS</b>TSCC and human normal mucosa cells secrete a large amount of capsule bubble structure substances in vitro, as confirmed by electron microscopy and surface markers heat shock protein-70 and major histocompatibility complex class 1. A total of 16 oral cancer cell-derived exosomes that expressed quantity more than two times, twelve that increased their expression levels, and four that cut their expressions were identified through the differential proteomics research on the two groups.</p><p><b>CONCLUSION</b>Differential proteins that were verified through the online database serve an important function in exosome formation and in the progress of cancer.</p>

Effect of EDA-A1 gene mutant on proliferation and cell cycle distribution of cultured human umbilical vein endothelial cell ECV304 / 重庆医学

Objective To investigate the effect of ectodysplasin A (EDA‐A1) gene of hypohidrotic ectodermal dysplasia on pro‐liferation and cell cycle of human umbilical vein endothelial cell (ECV304). Methods Recombinant eukaryotic expression vectors pcDNA3. 1(‐)‐EDA‐A1‐M /W (mutant, M and wild, W) containing the coding sequence were transected into ECV304 cells. EDA‐A1 gene was amplified by reverse transcription polymerase chain reaction (RT‐PCR), and the protein was detected by Western blot. Cell viability and cycle distribution were invested by MTT and Flow cytometry (FCM ). Results The EDA‐A1 gene and pro‐tein were detected respectively by RT‐PCR and Western blot in ECV cells transfected with pcDNA3. 1(‐)‐EDA‐A1‐M /W, but not in ECV cells transfected with plasmid pcDNA3. 1(‐) and cells without transection. And also, compared with control groups, EDA‐A1 gene mutant significantly decreased proliferation of ECV cells and its inhibition rate was 45. 70% ( P 0. 05). A significant increase of the G0 /G1 and S fraction was seen in the ECV cells of mutant group, compared with wild group with an accumulation in S phase and a concomitant decrease in G2 /M phase population (P< 0. 05). Conclusion Mutant and wild EDA‐A1 gene may have distinct biological functions on proliferation and cell cycle distribution of cultured human umbilical vein endothelial cell.

Experience of guiding the innovative experiment programs in preclinical medicine / 中华医学教育探索杂志

The innovative experiment programs are important teaching reform for improving the students' innovating spirit and practical ability.The innovative experimental studies for medical students in preclinical stage include scientific research topic selection,information retrieval,experimental study and manuscript preparation.The innovative experiments stimulated the research interests,improved the comprehensive quality and promoted the learning of preclinical theories.However,the supporting rules,the assessment methods and the quality of teachers remain to be further improved in order to execute the programs more successfully.

Systematic review on control of swelling and trismus after extraction of impacted mandibular third molar by dexamethasone pericoronal injection / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To assess the efficacy of Dexamethasone (DM) pericoronal injection for the control of swelling and trismus caused by impacted mandibular third molars extraction.</p><p><b>METHODS</b>Cochrane, PUBMED, EMBASE and CBM were searched for eligible studies. Hand-searching included references of the included studies and Chinese dental journals. Risk of bias of the included studies was assessed by two reviewers independently using Cochrane Collaboration's tool, and data extraction was done by them. Meta-analysis was delivered with Revman 5.1.</p><p><b>RESULTS</b>Seven randomized controlled trials, involving 684 participants, were included. Six of them had moderate risk of bias and one had high risk of bias. Meta-analysis showed that DM pericoronal injection could relieve trismus by 6.77 mm (P=0.02) within 1-2 days after the surgery. It could also reduce 51% of the risk of moderate-severe trismus(P<0.000 01) and could significantly control facial swelling (P<0.05). There was no differences between 4 mg and 8 mg DM (P>0.05).</p><p><b>CONCLUSION</b>Periodontal injection of 4-5 mg DM could control facial swelling and trismus following impacted mandibular third molar extraction. But more randomized controlled trials are needed.</p>

A study on hyperthermia and endurance in adolescents and adults with hypohidrotic ectodermal dysplasia / 重庆医学

Objective To evaluate exertional overheating and endurance during and after physical exercise on individuals with hypohidrotic ectodermal dysplasia(HED) ,to assess protective effects of skin cooling device ,and to provide theoretical basis for ex-ternal cooling devices .Methods 12 HED patients and 12 age-matched healthy controls were studied during standardized exercise on a treadmill at ambient temperatures of 25 ℃ and 30 ℃ .Body core temperature ,performance ,heart rate ,respiratory rate ,blood pres-sure and serum lactate were investigated during and after exercise .Results HED subjects experienced a significantly greater rise in body temperature after cycling than healthy controls ,and their body temperature remained elevated longer(P<0 .05) .HED subjects had a lower endurance time(F=9 .985 ,P=0 .005) and increasing speed value(F=7 .158 ,P=0 .014) .However ,serum lactate value of the HED subjects found to be higher than the controls (F=5 .204 ,P=0 .033) .Maximum heart rates ,respiratory rate and blood pressure did not differ significantly between HED and the control groups .However ,compared with controls ,body temperature and endurance time of HED patients equipped with skin cooling device had no statistical significance .Conclusion HED subjects showed a significantly greater rise of body temperature during exercise than the control groups ,and their body temperature remained elevat-ed longer than in healthy subjects ,and had a lower performance .External evaporative skin cooling attenuates exertional overheating in HED patients and may facilitate their participation in athletic activities and professional life .

Research on induced apoptosis of recombinant human adenovirus-p53 injection in patients with oral leukoplakia / 肿瘤研究与临床

Objective To probe the biological effect of multiple intraepithelial injections of recombinant adenovirus-p53(rAd-p53)on inducing the apoptosis in patients with dysplastic oral leukoplakia.Methods 18 patients clinically and histopathologically diagnosed as dysplastic oral leukoplakia were recruited for this study.Intraepithelial injections of rAd-p53 were administered.Immunohistochemistry was used to examine the protein expression of p53 and bcl-2.TUNEL was performed to detect apoptotic cells.Results In the post-treatment patients,p53 protein expression were significantly enhanced(100 ％,18/18),yet bcl-2 protein presented low expression(17 ％,3/18).Statistical analysis revealed the expression of p53 protein had a negative correlation with that of bcl-2 protein(r =-0.837,P ＜ 0.01).15 post-treatment samples (83 ％)were detected obvious apoptotic cells,especially in the samples that were strong p53-positive(r =0.684,P ＜ 0.01).Conclusion Intraepithelial injections of rAd-p53 can induce apoptosis for patients with dysplastic oral leukoplakia.It may be a promising treatment for oral leukoplakia.

Biological effect of micro ribonucleic acid-21 on human tongue squamous cell carcinoma lines / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To detect the biological influence to human tongue squamous cell carcinoma (TSCC) cells of micro ribonucleic acid-21 (miR-21).</p><p><b>METHODS</b>Referring to mature miR-21 sequence, the sense and antisense oligonucleotide (sense-miR-21 and AS-miR-21) modified by 2'O-Me were designed to transfect into TSCC cells (Tca8113 and high metastasis cells) by liposome transfection technology, in order to establish an in vitro TSCC cell model. The expression changes of miR-21 in the transfected cells were detected with real-time fluorescence quantitative polymerase chain reaction (real-time PCR). The changes of cell proliferation, cell cycle, cell early apoptosis, cell migration and invasion capabilities were detected respectively by the technologies of methyl thiazolyl tetrazolium (MTT), flow cytometry, Annexin V cell early apoptosis assay, scratch assay and Transwell assay, to check AS-miR-21's effect on the biological characteristics of human TSCC cell lines.</p><p><b>RESULTS</b>For the TSCC cells, the antisense oligonucleotide of targeting miR-21 could effectively inhibit cell proliferation, promoted cell apoptosis, and inhibited the capability of cell's migration and invasion.</p><p><b>CONCLUSION</b>The expressions of miR-21 decrease after AS-miR-21 transfected into TSCC cells, and miR-21 can affect biological behavior of TSCC cells.</p>

In vivo study on antisense-micro ribonucleic acid-21 oligonucleotide inhibiting tongue squamous cell carcinoma growth / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To detect antisense-micro ribonucleic acid-21 oligonucleotide (AS-miR-21)'s inhibiting effect to tongue squamous cell carcinoma.</p><p><b>METHODS</b>Living image and TUNEL experiments were performed, based upon the xenograft animal models set up by introduction of Tca8113-luc cells which were stably transfected with pGL6 luciferase report gene plasmid into nude mice, while the tumors were injected with AS-miR-21.</p><p><b>RESULTS</b>Tca8113-luc cell line which steadily expressed luciferase activity was constructed by transfecting pGL6 report gene plasmid. The subcutaneous tumor formation rate was much higher in nude mice introduced with the cells, and the tumors grew well. After injection of AS-miR-21 into mice tumors, it was obviously viewed that tumors grew slower, the volume of the tumors was smaller, the photon number in live body imaging was getting less, the necrosis in the tumor specimens was rare, cell nuclei was getting smaller, dyeing color was lighter, heteromorphism and new vessels were decreased, micro ribonucleic acid-21 expression in tumor cells was considerably lower, and apoptotic index was increased.</p><p><b>CONCLUSION</b>All the results indicate that the injection of AS-miR-21 can inhibit growth of tongue squamous cell carcinoma in nude mice model, and effectively promote cell apoptosis of tongue squamous cell carcinoma.</p>

Drainage for the control of complications after extraction of impacted mandibular third molar: a systematic review / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To assess the efficacy and safety of drainage for the control of the complications following impacted mandibular third molar extraction.</p><p><b>METHODS</b>To retrieve randomized controlled trials assessing the efficacy and safety of drainage for the control of the complications following impacted mandibular third molar extraction, bibliographic databases including MEDLINE, Cochrane Controlled Trials Register, EMBASE, OPEN SIGLE and China Biology Medicine Database (CBM) were searched on August 23th 2011. References of the included studies and Chinese dental journals were hand-searched. The risk of bias were used by Cochrane Collaboration's tool and the data were extracted. Meta-analysis was done with Revman 5.1.</p><p><b>RESULTS</b>Nine articles met the eligibility criteria and were included, seven randomized controlled trials and 2 quasi-randomized controlled trials. Seven of these studies had unclear risk of bias and 2 had high risk of bias. Drainage could significantly increase 4.44 mm of the post-operative maximal mouth opening (P = 0.003), relief facial swelling (P < 0.05) and reduce post-operative complications (P = 0.008). But no evidence showed that drainage had a positive effects on post-operative pain (P = 0.09).</p><p><b>CONCLUSION</b>Drainage could probably control the complications following impacted mandibular third molar extraction; but more randomized controlled trials are needed to reinforce the conclusion.</p>

Hyaluronate sodium treatment for internal derangement of temporomandibular joint: a systematic review based on randomized controlled trials / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To assess the efficacy and safety of hyaluronate sodium (HS) for internal derangement of temporomandibular joint by means of systematic review on relevant randomized controlled trials.</p><p><b>METHODS</b>After identifing the study question of the efficacy and safety of HS for internal derangement of temporomandibular joint, Medline, Cochrane Controlled Trials Register, EMBASE, OPEN SIGLE and CBM were searched electronically till October 3rd 2010. Hand-searching covering 19 dental journals in Chinese were also performed. Risk of bias assessment, with Cochrane Collaboration's tool, and data extraction of included studies were conducted by two reviewers in duplicate. Meta analysis was done with Revman 5.0.23 and the quality of evidence was evaluated by GRADE.</p><p><b>RESULTS</b>10 randomized controlled trials met the eligibility criteria and were included. All these studies had unclear risk of bias. When compared with negative control, HS showed a significant advantage on maximal mouth opening in short and long-term (P < 0.05), and clinical overall assessment in short-term (P < 0.05), but its effect on pain control and long-term effect on clinical overall assessment had no extra benefit (P > 0.05). Additionally, when compared with glucocorticoids, the participants who received HS injection would get a better clinical overall assessment in short-term and less adverse drug reactions (P < 0.05), but presented a similar temporomandibular joint pain relief and maximal mouth opening (P > 0.05).</p><p><b>CONCLUSION</b>To a certain extent, HS had good efficacy and better safety than controls when treating internal derangement of temporomandibular joint. However, as the quality of some included studies were limited, more randomized controlled trials are needed to reinforce the conclusion.</p>

Training of medical students' critical thinking ability in pathophysiology teaching / 中华医学教育探索杂志

Carrying out the training of critical thinking in pathophysiology teaching is appropriate, and the medical students critical thinking ability can be achieved via construction of the awareness, and diverse teaching methods which include questioning, exploration and discussion.

Effects of tetrazanbigen on the protein expression in human hepatocellular carcinoma cell line QGY-7701 / 华中科技大学学报（医学）（英德文版）

Tetrazanbigen (TNBG) is a novel synthetic antitumor drug with significant antitumor effects on common solid tumors in vitro and in vivo. It may lead to death of cancer cells through a tumor-associated lipoidosis mechanism, and result in lipid droplets (LDs) accumulation at the cytoplasm. In this study, the effects of TNBG on protein expression in human hepatocellular carcinoma cell line QGY-7701 were studied for elucidating its antitumor mechanism. The proteins extracted from TNBG-treated human hepatocellular carcinoma cell line QGY-7701 were analyzed and compared with control cells by two-dimensional gel electrophoresis. The differential proteins were identified by matrix-associated laser desorption ionization time-of-flight mass (MALDI-TOF-MS) spectrometry. Two proteins of interest, the levels of which were significantly increased in TNBG-treated cells, were further characterized by Western blot analysis. The results showed a total of 846+/-23 spots in control cells and 853+/-30 spots in TNBG-treated cells. Twenty-six up-regulated or down-regulated proteins were found by analyzing differential proteomic 2-DE map. Eleven of them were identified by mass spectrometry. They were protein disulfide-isomerase precursor, 94 kD glucose-regulated protein, heat shock protein (HSP) 90-alpha, ATP-citrate lyase, HMG-CoA reductase, glucose-6-phosphate 1-dehydrogenase, very-long-chain specific acyl-CoA dehydrogenase, squalene synthetase, sterol regulatory element-binding protein 1, fructose-bisphosphate aldolase A, and peroxiredoxin-1. These up-regulated or down-regulated proteins are mostly related to lipid metabolism. The TNBG antitumor mechanism is probably to influence tumor lipid metabolism, resulting in accumulation of LDs in tumor cells.

The effect of immune reaction induced by alginate on parotid acinar cells in vitro / 实用口腔医学杂志

Objective: To explore the effect of immune reaction induced by alginate on parotid acinar cells in vitro. Methods: Rabbits were immunized from the conjugated alginate- BSA (1.0 mg/kg) by 40-days routine immunity method. ELJSA method was used to examine the titration (valence) of anti-alginate serum. Five groups (group A: contrast, group B: BSA, group C; alginate, group D: anti-alginate serum, group E; alginate + anti-alginate serum) were examined by MTT method at four time points( 1, 6,12 and 24 h). The growth and morphology of parotid acinar cells were observed under inverted phase contrast microscope and scanning electron microscope. Results: Antibody-serum was acquired by routine immunity method, and the titration (valence) of anti-alginate serum was 1: 400. MTT results showed that the proliferation of parotid acinar cells had been limited at 24 h( P <0.05), the other three time points showed no difference. Under inverted phase contrast microscope, a few of acinar cells whose membranes were destroyed after 12 h, some cell contents leaked out. The holes in membrane could be seen early at 6h under scanning electron microscope. Most of the acinar cells were broken at 24 h. Conclusion: The antibody-serum to alginate and immunized rabbit was acquired by routine immunity method. The immune reaction induced by alginate can destroy parotid acinar cells in vitro.