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The choline-binding proteins play essential roles in pneumococcal colonization and virulence. It has been suggested that the choline-binding protein J (termed CbpJ; encoded by the gene sp_0378) from Streptococcus pneumoniae TIGR4 involves in the colonization in host and contributes to evasion of neutrophil killing. Here we report the 2.0 A crystal structure of CbpJ in complex with choline. CbpJ consists of an N-terminal putative functional domain (N-domain) followed by a C-terminal choline-binding domain (CBD). The N-domain harbors four degenerated choline-binding repeats (CBRs) that lose the capacity of binding to choline, whereas the CBD is composed of seven typical CBRs. Further functional assays showed that the CBD contributes to the pneumococcal adhesion to human lung epithelial cell A549. These findings provide insights into the pneumococcal pathogenesis and broaden our understanding on the functions of choline-binding proteins.

Objective To analyse the application of a new narrow-band imaging (NBI) classification in the diagnosis of vocal cord leukoplakia by laryngologists with different levels of laryngoscopic experience and to explore the impact of NBI training programmes on laryngologists' identification of benign and malignant leukoplakia. Design Prospective multicentre study. Setting Tertiary hospitals. Participants Sixteen laryngologists were divided into less-experienced and experienced groups and received NBI training course. Thirty cases of vocal cord leukoplakia were investigated. Main outcome measures Diagnostic accuracy and interobserver agreement under white light imaging (WLI), before and after NBI training, were analysed among doctors with varying levels of experience. Results The accuracy in the less-experienced group was significantly lower than that of experience group (0.59 vs 0.69) under WLI. There was no significant difference in the diagnostic accuracy between the less-experienced group and the experienced group before NBI training (0.75 vs 0.74) and after NBI training (0.79 vs 0.83). NBI training could improve the interobserver agreement from fair or moderate to good agreement. Conclusion The new NBI diagnostic classification is helpful for identifying benign and malignant vocal cord leukoplakia. In addition, the NBI training programme can improve the diagnostic accuracy and interobserver agreement of less-experienced doctors to the level of experienced laryngologists.

The current study presents a convenient, rapid and effective simultaneous extraction/derivatization (SEDP) strategy for effective pretreatment of catecholamines (CAs). Commercial zirconium oxide (ZrO2) nanoparticles were employed for the selective capturing of cis-diol containing CAs to remove the biological interferences and phenyl isothiocyanate (PITC) was used for derivatization to improve the ionization and to improve the chromatographic separation. The extraction and derivatization procedures were integrated into one step to simplify the sample pretreatment. Excessive derivatization reagents were removed as well, reducing the degree of contaminations in mass spectrometry. The factors affecting the SEDP process were optimized and the results showed that the detection sensitivity and chromatographic separation of CAs greatly improved compared with underivatized CAs, during LC-MS/MS analysis. Combined with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), quantifying the concentration of norepinephrine (NE), epinephrine (E) and dopamine (DA) in biological fluids was validated in ranges of 1-200.0 ng/mL with a satisfactory correlation coefficient (R2 > 0.997). The obtained recoveries were in the range of 91.0-109.5% with RSDs less than 9.4%. Finally, significant changes in CAs levels in urine samples of healthy people and pheochromocytoma patients were detected. The developed method offers comparative advantages in terms of sensitivity, specificity and selectivity.

BACKGROUND Stromal and immune cells play important roles in hepatocellular carcinoma (HCC) development and progression. However, tools for predicting the prognosis of patients with HCC based on stromal and immune scores are not well established. We aimed to develop nomograms that predicted the disease-free survival (DFS) and overall survival (OS) of patients after radical surgery. METHODS Basic information of 251 patients were retrieved from The Cancer Genome Atlas. Multivariate Cox analyses identified variables predicting the prognosis of patients. DFS and OS nomograms were constructed based on the stromal and immune scores of the training group and verified in the well-matched test group. RESULTS An intermediate stromal score (hazards ratio [HR] = 3.177; P

Background/Aims: Erinacine, which is extracted from the medicinal mushroom Hericium erinaceus, is known to play anticancer roles in human cancers. The following study aims to investigate the role of erinacine in the opening of the mitochondrial permeability transition pore (MPTP) in hepatocellular carcinoma (HCC) through the PI3K/Akt/GSK-3β signaling pathway and highlights the applicability of erinacine in HCC treatments. Methods: HCC and paracancerous tissues were obtained from 85 HCC patients who’ve undergone surgical resection. Immunohistochemistry was adopted to detect positive expression of PI3K, Akt, and GSK-3β. Treatment of HepG-2 with LY294002 (an inhibitor of the PI3K/Akt/GSK-3β signaling pathway) and different concentration of erinacine was performed to determine the involvement of LY294002 in erinacine action. The expressions of PI3K, Akt, GSK-3β, CyclinD1, Vimentin, β-catenin, Bcl-2, E-cadherin, Bax, and caspase-9 were determined by RT-qPCR and Western blot analysis. Cell viability, colony formation rate, migration, invasion, cycle, and apoptosis were detected by MTT, colony formation, wound healing assay, Transwell assay, and flow cytometry, respectively. The size and weight of xenograft tumors were observed in nude mice. Mitochondrial membrane potential in HepG-2 was determined using laser scanning confocal microscopy following JC-1 staining. Mitochondrial Ca2+ indicator Rhod-2, AM was used to detect the changes of mitochondrial Ca2+, while western blot analysis was employed to detect the presence levels of cytochrome C (cyt-C). Results: The results revealed that PI3K, Akt, and GSK-3β were up-regulated in HCC tissues. Erinacine or LY294002 led to a decrease in mitochondrial membrane potential, increase in intracellular mitochondrial Ca2+, and the release of cyt-C in mitochondria. In addition, Erinacine was found to decrease the mitochondrial membrane potential, expression of PI3K, Akt, GSK-3β, CyclinD1, Vimentin, β-catenin, and Bcl-2, cell proliferation, colony formation ability, migration, invasion, and xenograft tumor size, while E-cadherin, Bax, and caspase-9 expression, and cell apoptosis were elevated in a dose-dependent manner. Erinacine also stimulated the effects of LY294002 on the HCC. Following the addition of 500 μM Erinacine and MPTP opening inhibitor CsA, we found that the mitochondrial membrane potential level increased, while mitochondrial Ca2+ and Cyt-C decreased from the mitochondria. Conclusion: The results from the study demonstrated that erinacine induced MPTP opening, facilitates the release of cyt-C, and inhibited cell proliferation, migration, and invasion, while it promotes apoptosis by inactivating the PI3K/Akt/GSK-3β signaling pathway, preventing the progression of HCC.

The research by Liao et al.(1) showed that postdiagnosis aspirin use improved the mortality of various subtypes of biliary tract cancer (BTC). The results were impressive, with the adjusted hazard ratios of mortality ranging from 0.51 to 0.58, and all subgroup analyses were statistically significant. However, we think that some other aspects should be discussed.

Supplemental Digital Content is available in the text, Background: The role of fruit and vegetables (FVs) consumption in decreasing gallstone disease risk remains contradictory. We performed a meta-analysis to analyze this potential correlation, followed by investigation of dose-response relationship of FVs consumption with gallstone disease. Materials and methods: PubMed, Embase, as well as Web of Science were searched to determine all published researches about the connection of FVs consumption with gallstone disease before March 2018. Relative risks (RRs) or odds ratios (ORs) along with corresponding 95% confidence intervals (CIs) was pooled utilizing random effect models, aiming at examining the correlation of FVs consumption with gallstone disease risk. Results: One cross-sectional study, our case-control studies as well as nine cohort studies were enrolled, covering approximately 33,983 patients with gallstone disease and 1,53,3752 participants. In a pooled analysis, vegetables consumption was significantly related to a decreased gallstone disease risk, (RR = 0.83, 95% CI, 0.74–0.94, I2 = 91.1%), and for fruits consumption, RR was similar (RR = 0.88, 95%CI, 0.83–0.92, I2 = 0.01%). This inverse correlation of FVs consumption with gallstone disease risk was solid in most subgroup analysis. The nonlinear dose-response correlation indicated that gallstone risk was reduced by 4% (RR = 0.96, 95%CI, 0.93–0.98) and 3% (RR = 0.97, 95%CI, 0.96–0.98) for every 200 g per day increment in vegetables consumption (P = .001) and fruits consumption (P = .001), respectively. Conclusion: This study suggests vegetables and fruits consumption is correlated with a significantly reduced risk of gallstone disease.

AIM To investigate the prognostic value of the combination of preoperative plasma fibrinogen and CA199 in patients with gallbladder carcinoma (GBC). METHODS The clinicopathological data of 154 GBC patients were retrospectively reviewed after surgery. A receiver operating characteristic (ROC) curve was plotted to verify the optimum cut-off values for plasma fibrinogen and CA199. Univariate and multivariate survival analyses were performed to identify the factors associated with GBC prognosis. Based on the HRs calculated via multivariate survival analyses, patients with elevated plasma fibrinogen and CA199 levels were allocated a score of 2.1; those with an elevated plasma fibrinogen level only were allocated a score of 1, those with an elevated CA199 level only were allocated a score of 1.1, and those with neither of these abnormalities were allocated a score of 0. RESULTS ROC curve analysis showed that the optimum cut-off values for preoperative plasma fibrinogen and CA199 were 3.47 g/L and 25.45 U/mL, respectively. Multivariate analysis indicated that elevated preoperative plasma fibrinogen and CA199 levels were significantly correlated with worse overall survival (OS) (HR = 1.711, 95%CI: 1.114-2.627, P = 0.014, and HR = 1.842, 95%CI: 1.111-3.056, P = 0.018). When we combined these two parameters, the area under the ROC curve increased from 0.735 (for preoperative plasma fibrinogen only) and 0.729 (for preoperative CA199 only) to 0.765. When this combined variable was added to the multivariate analysis, the combination of plasma fibrinogen and CA199 (P < 0.001), resection margin (P < 0.001) and TNM stage (P = 0.010) were independent prognostic factors for GBC. CONCLUSION The combination of plasma fibrinogen and CA199 may serve as a more efficient independent prognostic biomarker for postoperative GBC patients than either parameter alone.

Introduction: Hashimoto’s thyroiditis (HT) can present as focal nodular disease. This study aimed to determine the distinguishing sonographic features of nodules in biopsy-proven focal HT. Materials and Methods: The study included 388 thyroid nodules from 310 patients who underwent ultrasound-guided fine-needle aspiration biopsy (FNAB). There were 28 focal HT, 27 malignant and 333 other benign nodules. Sonographic features of focal HT nodules on prebiopsy ultrasound were compared with malignant nodules and other benign nodules using multinomial logistic regression adjusting for the correlation between multiple nodules obtained from the same patient. Results: Most focal HT nodules were purely solid (92.8%), iso-hyperechoic (70.4%), had regular margins (75.0%) and central vascularity (85.7%). Hypoechogenicity (29.6% vs 42.3%; P = 0.017) and microcalcifications (3.6% vs 44.4%; P = 0.003) were significantly less common in focal HT than malignant nodules. None of the focal HT nodules demonstrated marked hypoechogenicity, irregular margins or cervical lymphadenopathy, which are traditionally associated with malignancy. Compared to other benign nodules, focal HT nodules were significantly more likely to be purely solid (92.8% vs 49.0%; P = 0.016), ill-defined (25.0% vs 7.0%; P = 0.004) and lack comet-tail artefacts (92.9% vs 66.1%; P = 0.012), which in combination were 17.9% sensitive and 94.6% specific for focal HT. Conclusion: Awareness of the above-described sonographic appearances of focal HT may aid in differentiating them from malignant nodules and risk-stratify for FNAB. While there is substantial overlap with other benign nodules, a combination of the above-mentioned 3 ultrasound features is highly specific for focal HT and can prompt further serological evaluation in clinically unsuspected HT. Key words: FNAB, Ultrasound-guided thyroid biopsy

The PI3K/Akt/mTOR and JAK/STAT3 signaling pathways are important for regulating apoptosis, and are frequently activated in cancers. In this study, we targeted STAT3 and mTOR in human hepatocellular carcinoma Bel-7402 cells and examined the subsequent alterations in cellular apoptosis. The expression of STAT3 was silenced with small interfering RNA (siRNA)-expressing plasmid. The activity of mTOR was inhibited using rapamycin. Following treatment, Annexin V/propidium iodide staining followed by flow cytometry and Hoechst33258 immunofluorescence staining was used to examine cellular apoptosis. JC-1 staining was used to monitor depolarization of mitochondrial membrane (ΔΨm). Furthermore, the expression of activated caspase 3 protein was analyzed by Western blotting. Compared to non-treated or control siRNA-transfected cells, significantly higher levels of apoptosis were detected in siSTAT3-transfected or rapamycin-treated cells (P < 0.05), which was further enhanced in cells targeted for both molecules (P < 0.05). The pro-apoptotic effects were accompanied with concomitant depolarization of mitochondrial membrane and up-regulation of activated caspase 3. Combined treatments using rapamycin and STAT3 gene silencing significantly increases apoptosis in Bel-7402 cells, displaying more dramatic effect than any single treatment. This study provides evidence for targeting multiple molecules in cancer therapy.

Rationale: Lymphoepithelioma-like cholangiocarcinoma (LEL-CC) is a rare variant of intrahepatic cholangiocarcinoma (ICC), which is characterized by the better outcome than normal ICC. There is no report about the treatment for the metastasis of the LEL-CC. Here, we describe a rare case of LEL-CC of the liver and report the treatment for metastasis of it. Patient concerns: A 38-year-old woman with a chronic hepatitis B infection was referred to the department of liver surgery in our hospital with a mass in the liver. Diagnoses: A past ultrasound examination had revealed a 28 mm × 16 mm nodular lesion in the right posterior lobe of the liver in May 2013. She had undergone partial resection of the thyroid gland for papillary carcinoma 1 year earlier. Intervention: Suspicious of the metastasis from thyroid cancer, she underwent surgery with liver segmentectomy. The pathologic diagnosis of the lesion was LEL-CC. After surgery, she regularly got checked in our hospital, and in the 6 months after surgery, there was enlargement of lymph node before the inferior vena cava in CT. The doctor did not detect the enlargement of the lymph node until June 2017. The PET-CT was done in June of 2017, which showed the lymph node was hypermetabolic. Outcomes: The patient got her second surgery for lymph node three years after the first surgery, which was proved that the lymph node was metastasis from LEL-CC. The patient was free from recurrence 9 months after surgery. Lessons: We report the first case of surgery for metastasis from LEL-CC in the liver that was diagnosed 3 years after hepatectomy. Our findings suggest that surgery could be an effective way of treating lymph node metastasis of LEL-CC and early PET-CT can help to identify metastasis.

To establish the digital model about sagittal split ramus osteotomy and discuss the stress and displacement of 3 different fixation methods.Three-dimensional reconstruction software Mimics and Geomagic were used to establish the three-dimensional entity model of mandible, and simulated sagittal split ramus osteotomy and fixation. Three-dimensional finite element model was established by mesh generation through ANSYS. After boundary constraint the occlusal load of 132N on the bilateral lower first molars was applied.Three-dimensional finite element models of sagittal split ramus osteotomy and 3 different fixation methods were established, and the biomechanical character of stress and displacement after occlusal load preoperatively and after splitting mandibles were found.As the stress distribution tends to uniformity and the displacement at split area is the least one, the fixation by bicortical screws in inverted-L position after sagittal split ramus osteotomy is the stablest of the 3 fixation methods. Supported by Natural Science Foundation of Guangdong Province (S2011010003872) and Science and Technology Projects of Guangzhou City (7421165457455).

To evaluate the effect of fenestration and suction drainage in the treatment of large odontogenic mandibular cystic lesions.From 2005 to 2009, 24 cases of large odontogenic mandibular cystic lesions were treated with fenestration and suction drainage. The clinical symptoms and radiographical findings were evaluated before the operation and at 1 month and 6 months after suction drainage.Follow-up for 1-3 years showed that all the cystic lesions disappeared without recurrence, and the clinical symptoms were resolved.Fenestration and suction drainage can reduce the cystic size and rapidly correct the deformity to serve as a useful modality for primary management of large odontogenic mandibular cystic lesions.

To investigate the method and effect of treatment of complex scapular body fractures by locking reconstructive plate through modified posterior approach.From August 2005 to November 2009, 27 patients with complex scapula body fractures were treated by locking reconstruction bone plate fixation,including 19 males and 8 females with an average age of 36 years old ranging from 16 to 64 years. The time after injury was 0.5 hours to 11 days (averaged 3 days). Of all the patients, 9 cases were associated with ipsilateral clavicle fracture, 2 cases were associated with acromioclavicular joint dislocation,16 cases were associated with multiple rib fractures, 1 case were associated with humeral shaft fractures, 5 cases were associated with pleural effusion, atelectasis, lung contusion etc. After operating,shoulder functional recovery were followed up.Twenty-four patients were followed up from 2 to 35 months with an average of 19 months. According to Hardegger shoulder function,the results were excellent in 15 cases, good in 7 cases, general in 2 cases.This method had the advantage of less trauma and clear exposure, firm and reliable fixation, and early activities.

This paper presents a scientific strategy for cycling induced by the functional electrical stimulation. In order to simulate the FES-cycling movement produced by human body, a neuro-musculo-skeletal model containing 16 segments and 186 muscles is developed, which can simulate human movements precisely. This model contains mathematical model of electrically stimulated skeletal muscles. Having known the kinematics and dynamics of the model, we design an FES-cycling control system based on the central pattern generator (CPG), which can produce rhythm stimulus to produce desired torque and generate rhythm cycling movements. And an approach to control multiple muscles is proposed. In the end of this paper, the simulation results are provided.

To evaluate the effectiveness of Tension-band Laminoplasty (TBL) as a management for cervical ossification of posterior longitudinal ligament (OPLL).Forty-six patients with cervical OPLL and undergone TBL in our department were chosen for the present study, including 33 male and 13 female. The mean age was 59 years (36 - 77 years). These OPLLs were confirmed as following types: 4 cases of single spinal level, 20 cases of continuous and 22 cases of mixed type. C(3) or/and C(2) levels were involved in 16 cases. All the patients underwent C(2 - 7) TBL, to which C(1) laminectomy was added for the cases with C(3) and/or C(2) involved. The neurological effect was evaluated by using Japanese Orthopedic Association (JOA) scoring criteria for cervical myelopathy. The anatomical effect was analyzed by comparing the pre- and post-operatively roentgenograms and MRIs. Wilcoxon's rank test was used for the statistics study.For 42 (91.3%) patients, the JOA scores were improved for approximately 2 points after the operation, posterior shift of the spinal cord was obtained, while the diameters of dural sleeves and spinal cords were enlarged, yet the spinal alignments were not significantly interrupted.TBL was proved an effective treatment for cervical OPLL and it could be expanded to include C(1) laminectomy if the spinal levels upper than C(4) were involved.