The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC cells.We found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro.RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy.Further,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC cells.Mechanistically,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of ATF4.In summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth.Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.

Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS (HR=1.069, 95%CI: 1.005-1.137, P=0.035) and ΔLVEF (HR=0.935, 95%CI: 0.878-0.995, P=0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 (P=0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P=0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P=0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.
Humans ; Male ; Middle Aged ; Aged ; Coronary Artery Disease/diagnostic imaging* ; Stroke Volume ; Myocardial Perfusion Imaging ; Retrospective Studies ; Ventricular Function, Left ; Myocardial Ischemia

Objective:To evaluate the curative efficacy of a buttress plate combined with Kirschner wires for treatment of Regan-Morrey type Ⅱ coronoid fracture after elbow terrible triad injury.Methods:A retrospective study was conducted of the 20 patients who had been surgically treated for Regan-Morrey type Ⅱ coronoid fracture after elbow terrible triad injury from August 2014 to August 2018 at Department of Pelvic Trauma, Henan Luoyang Orthopedic-Traumatological Hospital. They were 12 men and 8 women, aged from 18 to 60 years (average, 39 years), with 6 left and 14 right sides affected. All the coronoid fractures were fixated with Kirschner wires plus a buttress plate through the anterior approach, the radial head and lateral collateral ligaments (LCL) were repaired through the posterolateral approach, and the medial collateral ligament (MCL) was repaired or fixated with a hinged external fixator if necessary. The curative efficacy was evaluated at the last follow-up by range of motion (ROM) of the elbow, Mayo elbow performance score (MEPS), American Shoulder and Elbow Surgeons Scale (ASES) and radiographs of the elbow. Complications were also recorded.Results:The mean follow-up time was 18 months (from 12 to 24 months) and the mean healing time 5 months. At the last follow-up, ROM in flexion and extension of the affected elbow joint averaged 132.5°, ROM in elbow pronation-supination 150°, MEPS 88, and ASES 87. No subluxation or dislocation occurred after elbow surgery. The fracture of coronoid process was slightly displaced in one case but eventually healed without affecting any elbow function; fat liquefaction occurred around the posterolateral incision in 2 cases but healed after debridement; traumatic arthritic changes occurred in 5 patients but no significant dysfunction of the elbow was observed.Conclusion:A buttress plate combined with Kirschner wires can lead to fine curative efficacy for Regan-Morrey type Ⅱ coronoid fracture after elbow terrible triad injury.

Objective:To compare the curative effects between anatomic locking plate and common reconstruction plate in the treatment of acetabular posterior wall fracture.Methods:The 50 patients with acetabular posterior wall fracture were retrospectively analyzed who had been admitted to Department of Pelvic Trauma Surgery, Luoyang Orthopaedic Hospital of Henan Province from February 2015 to February 2020. They were assigned into 2 groups according to different internal fixation methods. In the reconstruction plate group of 24 patients whose fractures were fixated by a common reconstruction plate from February 2015 to June 2017, there were 21 males and 3 females with an age of (38.9±10.9) years. In the anatomical plate group of 26 patients whose fractures were fixated by an anatomic locking plate between July 2017 and February 2020, there were 20 males and 6 females with an age of (38.0±10.0) years. The 2 groups were compared in terms of operation time, intraoperative blood loss, reduction quality, hip function and complications at the last follow-up.Results:There was no significant difference in the preoperative general data between the 2 groups, indicating the 2 groups were comparable ( P>0.05). The 50 patients were followed up for 18 to 26 months (mean, 22 months). The operation time [(132.8±8.6) min] and intraoperative blood loss [(357.0±14.7) mL] in the anatomic plate group were significantly less than those [(177.2±5.9) min and (492.0±17.6) mL] in the reconstruction plate group( P<0.05). Postoperative CT examination showed that 96.2% (25/26) of the patients in the anatomical plate group and 91.7% (22/24) of the patients in the reconstruction plate group had a fracture step ≤3 mm, showing no significant difference ( P>0.05). At the last follow-up, the excellent and good rate by Harris hip score was 92.3% (24/26) in the anatomic plate group, significantly higher than that (66.7%, 16/24) in the reconstruction plate group ( P<0.05). The incidence of complications was 3.8% (1/26) in the anatomic plate group, significantly lower than that [29.2% (7/24)] in the reconstruction plate group ( P<0.05). Conclusion:Anatomical locking plate is better than common reconstruction plate in the treatment of acetabular posterior wall fracture.

BACKGROUNDTransforming growth factor-beta 1 (TGF-β1) and gene variants have been extensively studied in various human diseases. For example, TGF-β1 polymorphisms were associated with fibrosis and pneumoconiosis, but the data remained controversial. The aim of this meta-analysis was to assess the association between TGF-β1 -509 C>T [rs1800469], +869 T>C [rs1800470], and +915 G>C [rs1800471] polymorphisms and pneumoconiosis.

METHODSA comprehensive literature search was conducted through searching in PubMed, Embase, the Chinese Biomedical Database, and the Wei Pu (Chinese) Database by the end of April 2016. Eleven publications with 21 studies were included in this meta-analysis, covering a total of 4333 patients with pneumoconiosis and 3478 controls. Study quality was assessed, and heterogeneity and publication bias were measured. All statistical analyses were performed using STATA version 12.0 (StataCorp, College Station, TX, USA) software.

RESULTSThe data showed significant associations between TGF-β1 -509 C>T polymorphism and the risk of pneumoconiosis development (T vs. C, odds ratio [OR] = 1.35, 95% confidence interval [CI]: 1.00-1.81, P = 0.046); between TGF-β1 +915 G>C polymorphism and the pneumoconiosis risk (C vs. G, OR = 1.69, 95% CI: 1.19-2.40, P = 0.004; CG vs. GG, OR = 1.79, 95% CI: 1.23-2.60, P = 0.002; CC+CG vs. GG, OR = 1.80, 95% CI: 1.24-2.61, P = 0.002). In addition, the subgroup analysis of ethnicity versus pneumoconiosis types indicated a significant association of silicosis among Asian populations but not that of coal workers' pneumoconiosis in Caucasian populations. In contrast, no significant association was exhibited between TGF-β1 +869 T>C polymorphism and risk of pneumoconiosis.

CONCLUSIONThe polymorphisms of both TGF-β1 -509 C>T and +915 G>C are associated with increased risk of pneumoconiosis.

Asian Continental Ancestry Group ; European Continental Ancestry Group ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Pneumoconiosis ; genetics ; Polymorphism, Genetic ; genetics ; Transforming Growth Factor beta1 ; genetics

Adult ; Altitude ; Craniotomy ; methods ; Follow-Up Studies ; Humans ; Male ; Young Adult

Objective To analyze the causes of severe adverse reaction after painless abortion and to offer some advices for prevention and cure.Methods Clinical files and results of 3 patients with severe adverse re-action after painless abortion were analyze.Results Total of 130-140 mg· kg -1 propofol intravenous injection and oxytocin 10 u intramuscular injection was used in three patients underwent painless abortion.Three patients have the symptoms of chills , fever , nausea , vomiting , low blood pressure , damages of multiple organs and elevation of peripheral white blood cell and neutrophilic granulocyte.The shock occurred within 0.5-4 h after operation.Conclusion The symptoms of severe adverse reac-tion after transfusion are very serious.Early diagnosis and rational man-agement are the key to the successful salvage.

Objective To understand the distribution,molecular characteristics and virulence genes of the O1 and O139 Vibrio cholerae isolates from the Pearl River Estuary water.Methods Vibrio cholerae isolates collected from the Pearl River estuary waters from January 2009 to December 2010,were tested by PCR for eight virulence-related genes,including cholera toxin(ctxA),zonula occludens toxin(zot),accessory cholera enterotoxin(ace),hemolysin(hlyA),toxin-coregulated pilus (tcpA),outer membrane protein(ompU),and the regulatory protein genes(tcpⅠ,toxR).Genetic relation was assessed by pulsed-field gel electrophoresis(PFGE)and the patterns were clustered by BioNumerics.Results From 1152 aquatic samples,69 isolates were identified,including 41 Inaba,18 Ogawa and 10 O139.All the isolates showed ctxA negative,while the hlyA and toxR genes were positive in all the isolates.34.15％(14/41)of the Inaba strains were hlyA + toxR + ompU + ace + zot + tcpI+,while 66.67％(12/18)belonged to Ogawa strains and 70％(7/10)of the O139 strains were hlyA + toxR+.Through PFGE analysis,the O1 isolates formed three clusters in this study.The patterns of O1 isolates differed widely,with the similarity as 72.8％-100.0％,while the patterns of O139 isolates having the similarity of 69.9％-95.5％.Conclusion The non-toxigenic O1 and O139 V.cholerae had a wide distribution in the environment of Pearl River estuary water during the nonepidemic period of cholera.All the aquatic isolates presented diversities on the related virulent genes.

Objective To understand the phenotypic characteristics of foodbome Vibrio parahaemolyticus in Guangdong province through carrying out a comprehensive comparison including pulse field gel electrophoresis,ribotyping and serotyping.Methods 74 different Vibrio parahaemolyticus strains isolated from seafood and cases due to food poisoning in Guangdong province were under serotyping and susceptibility testing,in addition to the testing of direct heat hemolysin(tdh)and the heat hemolysin-related hemolysin hormone(trh)via PCR.Ribosomal genotyping(ribotyping)with EcoR Ⅰ restriction enzyme was utilized on 74 different Vibrio parahaemolyticus isolates,whereas pulsed-field gel electrophoresis(PFGE)with the Not Ⅰ restriction enzyme was used on 74 different Vibrio parahaemolyticus isolates.BioNumerics software was used to compare the isolates from different sources,times and places in order to elicit the correlation between different strains.Results Although Vibrio parahaemolyticus was 100.00％ sensitive to chloramphenicol,it still presented different levels of resistance against 13 other antibiotics.Among the 74 different strains of Vibrio parahaemolyticus under testing,24.32％ showed positive for the tdh virulence gene,whereas 4.05％ positive for trh.74 different Vibrio parahaemolyticus strains were found to belong to 26 serotypes,where the O5:K17 and O2:K28 serotypes were dominant in those isolates that causing seafood-poisoning.The O3:K6 serotype was found to be the dominant of those isolates that causing food-poisoning.Based on ribosomal genotyping,the 74 Vibrio parahaemolyticus isolates were divided into 62 different ribotypes,whereas the 74 strains of Vibrio parahaemolyticus were divided into 67 different PFGE types,thus exhibiting considerable genetic diversities of the strains.Conclusion Majority of the isolates causing food-poisoning carried tdh virulence gene.PFGE was shown to have the highest resolution,followed by ribotyping with serotyping being the lowest,where the combination of the three could improve the resolution.

OBJECTIVEThrough systematic monitoring of the number and strain types of O1 and O139 Vibrio cholerae in the Pearl River estuary waters to analyze it's relevance with the temperature of environment, and the relevance between strains in water and isolates during outbreaks and epidemics as well as to estimate the methods used for environmental water detection and the potential role in cholera surveillance program.

METHODSTwenty-four stations along the Pearl River were selected and the water samples were collected monthly from March 2006 to February 2007. V. cholerae O1 and O139 strains were isolated from the samples. Real-time PCR established in our laboratory was used to detect V. cholerae O1 and O139. Air temperature and water temperature were collected during sampling. Pulsed field gel electrophoresis (PFGE) was applied in molecular typing of the isolates.

RESULTS862 water samples were collected during the study period. A total number of 77 O1 and O139 V. cholerae were isolated in 67 water samples and the positive rates were 7.77% for isolation and 26.33% for real-time PCR. Seasonal trend of positive rates by month were approximately coincident with the change of water temperature. The positive rates in the stations in urban area were higher than those in other areas. Toxigenic O139 strains were found in one station located in downstream of a marine market. Most of the O1 and O139 isolates were non-toxigenic. No trend of seasonal variation of the strains was noticed. Within these 75 isolates, 49 PFGE patterns were identified and the patterns differed widely with the similarity of 57.4% - 100%.

CONCLUSIONV. cholerae existed as the natural habitat in estuary water of the Pearl River and showed obvious genetic diversity. Data from monitoring waters might show the separation of strains with certain seasonal association. But the crowd did not show the relationship between the infections. Results from water surveillance program might provide indicators on the appearance of cholera pathogen which might be used in assessing the environmental risk of cholera epidemics as well as the alert of cholera.

Electrophoresis, Gel, Pulsed-Field ; Environmental Monitoring ; Phylogeny ; Polymerase Chain Reaction ; Seasons ; Temperature ; Vibrio cholerae O1 ; classification ; genetics ; isolation & purification ; Vibrio cholerae O139 ; classification ; genetics ; isolation & purification