OBJECTIVES: The phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is one of the main signaling pathways related to autophagy. Autophagy plays a key role in the formation of silicosis fibrosis. The phenotypic transformation of lung fibroblasts into myofibroblasts is a hallmark of the transition from the inflammatory phase to the fibrotic phase in silicosis. This study aims to investigate whether the PI3K/Akt/mTOR pathway affects the phenotypic transformation of silicosis-induced lung fibroblasts into myofibroblasts via mediating macrophage autophagy. METHODS: The human monocytic leukemia cell line THP-1 cells were differentiated into macrophages by treating with 100 ng/mL of phorbol ester for 24 h. Macrophages were exposed to different concentrations (0, 25, 50, 100, 200, 400 μg/mL) and different times (0, 6, 12, 24, 48 h) of SiO₂ dust suspension. The survival rate of macrophages was measured by cell counting kit-8 (CCK-8) method. Enzyme linked immunosorbent assay (ELISA) was used to measure the contents of transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) in the cell supernatant. The co-culture system of macrophages and HFL-1 cells was established by transwell. A blank control group, a SiO₂ group, a LY294002 group, a SC79 group, a LY294002+SiO₂ group, and a SC79+SiO₂ group were set up in this experiment. Macrophages in the LY294002+SiO₂ group were pretreated with LY294002 (PI3K inhibitor) for 18 hours, and macrophages in the SC79+SiO₂ group were pretreated with SC79 (Akt activator) for 24 hours, and then exposed to SiO₂ (100 μg/mL) dust suspension for 12 hours. The expression of microtubule-associated protein 1 light chain 3 (LC3) protein in macrophages was detected by the immunofluorescence method. The protein expressions of PI3K, Akt, mTOR, Beclin-1, LC3 in macrophages, and collagen III (Col III), α-smooth muscle actin (α-SMA), fibronectin (FN), matrix metalloproteinase-1 (MMP-1), tissue metalloproteinase inhibitor-1 (TIMP-1) in HFL-1 cells were measured by Western blotting. RESULTS: After the macrophages were exposed to SiO₂ dust suspension of different concentrations for 12 h, the survival rates of macrophages were gradually decreased with the increase of SiO₂ concentration. Compared with the 0 μg/mL group, the survival rates of macrophages in the 100, 200, and 400 μg/mL groups were significantly decreased, and the concentrations of TGF-β1 and TNF-α in the cell supernatant were obviously increased (all P<0.05). When 100 μg/mL SiO₂ dust suspension was applied to macrophages, the survival rates of macrophages were decreased with the prolonged exposure time. Compared with the 0 h group, the survival rates of macrophages were significantly decreased (all P<0.05), the concentrations of TGF-β1 and TNF-α in the cell supernatant were significantly increased, and the protein expression levels of Beclin-1 and LC3II were increased markedly in the 6, 12, 24, and 48 h groups (all P<0.05). Immunofluorescence results demonstrated that after exposure to SiO₂ (100 μg/mL) dust for 12 h, LC3 exhibited punctate aggregation and significantly higher fluorescence intensity compared to the blank control group (P<0.05). Compared with the blank control group, the protein expressions of Col III, FN, α-SMA, MMP-1, and TIMP-1 in HFL-1 cells were up-regulated in the SiO₂ group (all P<0.05). Compared with the SiO₂ group, the protein expressions of PI3K, Akt, and mTOR were down-regulated and the protein expressions of LC3II and Beclin-1 were up-regulated in macrophages (all P<0.05), the contents of TNF-α and TGF-β1 in the cell supernatant were decreased (both P<0.01), and the protein expressions of Col III, FN, α-SMA, MMP-1, and TIMP-1 in HFL-1 cells were down-regulated (all P<0.05) in the LY294002+SiO₂ group. Compared with the SiO₂ group, the protein expressions of PI3K, Akt, and mTOR were up-regulated and the protein expressions of LC3II and Beclin-1 were down-regulated in macrophages (all P<0.05), the contents of TNF-α and TGF-β1 in the cell supernatant were increased (both P<0.01), and the protein expressions of Col III, FN, α-SMA, MMP-1, and TIMP-1 in HFL-1 cells were up-regulated (all P<0.05) in the SC79+SiO₂ group. CONCLUSIONS Silica dust exposure inhibits the PI3K/Akt/mTOR pathway, increases autophagy and concentration of inflammatory factors in macrophages, and promotes the phenotype transformation of HFL-1 cells into myofibroblasts. The regulation of the PI3K/Akt/mTOR pathway can affect the autophagy induction and the concentration of inflammatory factors of macrophages by silica dust exposure, and then affect the phenotype transformation of HFL-1 cells into myofibroblasts induced by silica dust exposure.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Silicon Dioxide/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Matrix Metalloproteinase 1/metabolism* ; Tissue Inhibitor of Metalloproteinase-1 ; Sirolimus ; Beclin-1/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Dust ; TOR Serine-Threonine Kinases/metabolism* ; Lung/metabolism* ; Fibroblasts/metabolism* ; Silicosis/metabolism* ; Macrophages/metabolism* ; Autophagy

【Objective】 To investigate the relationship between ABO blood types and the risk of malignant tumors in Chaoshan area, Guangdong. 【Methods】 Chi-square test was used to analyze the distribution of ABO blood types between 45 890 patients with malignant tumors from the Cancer Hospital of Shantou University Medical College and 42 465 healthy blood donors from Shantou Central Blood Bank. 【Results】 Among the main types of malignant tumors, the distributions of ABO blood types in patients with esophageal cancer or head and neck cancer were significantly different from that in the normal population (χ²=11.16, P<0.05; χ²=74.36, P<0.05; respectively). People with type B were identified with high risk of esophageal cancer and head and neck cancer (OR=1.09, 95% CI=1.03-1.15, P<0.05; OR=1.46, 95% CI=1.34-1.60, P<0.05), whereas those with type A or O were identified with low risk of head and neck cancer (OR=0.87, 95% CI=0.79-0.96, P<0.05; OR=0.83, 95% CI=0.76-0.90, P<0.05). 【Conclusion】 ABO blood type distribution in patients with esophageal cancer or head and neck cancer in Chaoshan area may be different from that in normal population, suggesting that different ABO blood types may be associated with the risk of esophageal cancer and head and neck cancer.

Objective:To explore the role of insulin-like growth factor binding protein 1 (IGFBP1) in the diagnosis and prognosis of nasopharyngeal carcinoma (NPC), and to search for molecular markers that can be used for the diagnosis of NPC.Methods:A retrospective analysis was conducted on 150 NPC patients (treated from April 2014 to May 2015) at the Cancer Hospital Affiliated to Shantou University Medical School, and clinical baseline data were collected from 143 healthy individuals (normal control group) during the same period. The serum IGFBP1 concentration was detected using enzyme-linked immunosorbent assay (ELISA) in 112 nasopharyngeal carcinoma patients and 109 normal controls in the training cohort, and was validated in the validation cohort (38 nasopharyngeal carcinoma patients and 34 normal controls). The diagnostic value of serum IGFBP1 in nasopharyngeal carcinoma was evaluated using the receiver operating characteristic curve (ROC).Results:Compared to the normal control group, the expression level of serum IGFBP1 in nasopharyngeal carcinoma patients was higher in the training and validation queues (all P<0.05). In the training queue, the area under the ROC curve was 0.768 (95% CI: 0.706-0.830), with diagnostic specificity and sensitivity of 90.83% and 48.21%, respectively. In the validation queue, the area under the ROC curve was 0.798 (95% CI: 0.697-0.899), with diagnostic specificity and sensitivity of 97.06% and 31.58%, respectively. The predictive values for positive cases in both cohorts were greater than 80%, while the predictive values for negative cases were greater than 50%. The diagnostic threshold for serum IGFBP1 in both cohorts was 1 077 ng/ml. Conclusions:IGFBP1 has practical value as a molecular marker for the diagnosis of nasopharyngeal carcinoma.

Objective:To understand the genetic characteristics of subgenus C human adenovirus (HAdV-C) strain isolated in Hunan in 2014.Methods:An HAdV-C strain named Hunan2014-s024 was isolated from throat swab collected from a child with severe acute respiratory infection in Changsha city of Hunan province in 2014. The whole genome sequence (WGS) was obtained by segmented amplification and sequence splicing. Database of HAdV-C was constructed with the strain from this study and the HAdV-C representative strains from GenBank. The whole genome characteristics was analyzed by using bioinformatics software.Results:Strain Hunan2014-s024 has the highest homology with the HAdV-C strain (MK041244-CHN-2006) isolated from stool sample of a healthy child in Shanxi province in 2006, and the genome of strain MK041244-CHN-2006 was used as the backbone, and penton based gene was replaced by gene fragment from MK041246-chn-2012 strain isolated from a child with acute lower respiratory tract infection in Hunan province in 2012.Conclusions:Our result indicated that 2014 Hunan strain(Hunan2014-s024)is a recombinant virus of 2006 Shanxi strain(MK041244-CHN-2006)and 2012 Hunan strain(MK041246-CHN-2012). Due to the change of pathogenicity, it is necessary to strengthen the molecular epidemiological surveillance of HAdV-C to understand its potential disease burden and public health significance.

OBJECTIVE: To investigate the potential risk of approach-related complications at different access angles in minimally invasive lateral lumbar interbody fusion.METHODS: Eighty-six axial magnetic resonance images were obtained to analyze the risk of approach-related complications. The access corridor were simulated at different access angles and the potential risk of neurovascular structure injury was evaluated when the access corridor touching or overlapping the corresponding structures at each angle. Furthermore, the safe corridor length was measured when the corridor width was 18 and 22 mm.RESULTS: When access angle was 0°, the potential risk of ipsilateral nerve roots injury was 54.7% at L4–L5. When access angle was 45°, the potential risk of abdominal aorta, contralateral nerve roots or central canal injury at L4–L5 was 79.1%, 74.4%, and 30.2%, respectively. The length of the 18 mm-wide access corridor was largest at 0° and it could reach 44.5 mm at L3–L4 and 46.4 mm at L4–L5. While the length of the 22 mm-wide access corridor was 42.3 mm at L3–L4 and 44.1 mm at L4–L5 at 0°.CONCLUSION: Changes in the access angle would not only affect the ipsilateral neurovascular structures, but also might adversely influence the contralateral neural elements. It should be also noted to surgeons that alteration of the access angle changed the corridor length.
Aorta, Abdominal ; Magnetic Resonance Imaging ; Surgeons

Objective:To assess the safety and efficacy of induction chemotherapy with cisplatin and docetaxel followed by radia-tion concurrent with weekly cisplatin for unresectable, locally advanced esophageal cancer. Methods: Thirty-three patients with T3N0M0 to T4N2M0 thoracic esophageal squamous cell carcinoma without celiac lymph node metastasis were included in the study. They were treated with cisplatin (75 mg/m2 d1, d22) and docetaxel (75 mg/m2 d1, d22) neoadjuvant chemotherapy followed by three-dimensional conformal radiotherapy (60Gy/30F/6w) concurrent with cisplatin (30 mg/m2 d1, 8, 15, 22, 29, 36 from the beginning of radiation). Results:Grade 4 hematological toxicities were observed in 13.33%(4/33) of the patients after the neoadjuvant chemother-apy. No grade 3 or above hepatic or renal toxicities were found. During concurrent chemoradiation, the highest grade 3 hematological toxicities were observed in the erythrocyte, granulocyte, and macrophage at 21.21%(7/33), 15.15%(5/33), and 3.01%(1/33), respec-tively. No grade 2 or above hepatic or renal toxicities were observed. Grade 3 radiation esophagitis was observed in 9.1%(3/33) of the patients, whereas grade 3 and above radiation esophagitis or grade 1 and above acute radiation pneumonitis did not occur. The evalua-tion results after treatment completion were 84.85%(28/33), 12.12%(4/33), and 3.03%(1/33) for CR+PR, SD, and PD , respectively. Two months after treatment completion, the results changed to 75.76%(25/33), 9.10%(3/33), and 15.15%(5/33), respectively. Overall, 15 patients died. The one-year survival rate was 66.4%. Local failure was approximately 46.67%(7/15), whereas the local+distant fail-ure was approximately 26.67%(4/15). Therefore, local failure is the main pattern of failure in esophageal cancer. Conclusion:The re-sults indicate that neoadjuvant chemotherapy with cisplatin and docetaxel followed by radiotherapy concurrent with weekly cisplatin for locally advanced esophageal cancer is safe. Local failure remains the main pattern of failure in esophageal cancer.

Objective To analyze the prevalence status and the genetic characterizations of influenza B viruses isolated in Hunan Province after pandemic influenza A (H1N1) 2009,and to explore possible reasons for the prevalence.MethodsThroat swabs were collected from outpatients with influenza-like illness in 23 sentinel hospitals of Hunan Province in 2010.Influenza viruses were isolated with Madin-Darby canine kidney (MDCK) cells and identified by haemagglutination inhibition test.The genomes of 10 selected influenza B viruses were sequenced and analyzed for phylogenetic and molecular characterization.ResultsWith the reduction of isolation of pandemic influenza A (H1N1)2009 viruses,influenza B virus became the predominant isolated strain in the first half of 2010.Epidemic viruses mainly belonged to the B/Victoria lineage,and both two lineages co-circulated.Seven out of 11 influenza outbreaks caused by type B.Ten strains were filled into 2 branches of BV and BY which were classified by their lineage types in polymerase (PB2,PB1,PA),hemagglutinin (HA),neuraminidase (NA),NB,membrane protein (M1),influenza B virus membrane protein M2 (BM2),and non-structural protein (NS1,NS2) phylogenetic trees except the NP phylogenetic tree in which 10 strains were all in the BY branch.Compared with World Health Organization (WHO) vaccine strains,the amino acid identity of 11 proteins of the 10 strains was high (97.2％-100.0％).However,some amino acid point mutations were found.No mutation was found in drug resistance mutation sites.Some mutations in NA,NB,PB1,PB2 and NS2 molecules were found in 2 strains isolated from outbreaks compared with strains from sentinel surveillance.Conclusions The point mutations,insertions and genetic reassortment indicate viruses sustaining evolution,which is probably the reason for predominant influenza B viruses after pandemic influenza A (H1N1) 2009 in Hunan Province.