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BACKGROUND: Glioblastoma is the most common and most aggressive type of primary brain tumor. OBJECTIVE: The aim of this study was to investigate the efficacy and safety of intranasal granulocyte-macrophage colony stimulating factor (GM-CSF) administration combined with chemoradiotherapy in patients with glioblastoma who underwent surgery. METHODS: Ninety-two patients were randomly divided into two groups: a control group (n= 46), who received radiotherapy with adjuvant local delivery of nimustine hydrochloride (ACNU) and systemic administration of temozolomide, and an intervention group (n= 46), who received intranasal GM-CSF prior to each cycle of adjuvant chemotherapy in addition to the treatment of the control group. Karnofsky performance status (KPS) scores, progression-free survival (PFS), overall survival (OS), and adverse effects were calculated and compared between the two groups. RESULTS: Compared with the control group, the intervention group had longer PFS (7.8 vs. 6.9 months, P= 0.016) and OS (19.2 vs. 17.1 months, P= 0.045, without adjustment for interim analyses). The KPS scores were also higher in the intervention group than in the control group after 6 months (84.35 ± 8.86 vs. 80.65 ± 7.72; t= 4.552, P= 0.036). Furthermore, the patients in the intervention group had lower incidence of neutropenia and thrombocytopenia (8.7% vs. 29.5%, P= 0.012; 8.7% vs. 18.2%, P= 0.186). Other adverse events were similar in both groups, and most adverse events were grade I/II and resolved spontaneously. CONCLUSION: Intranasal GM-CSF enhances the efficacy of the local ACNU administration combined with oral temozolomide chemotherapy. The survival and performance status were significantly improved in patients with glioblastoma after surgery. Additionally, the GM-CSF therapy was able to reduce the occurrence of chemotherapy-related neutropenia and thrombocytopenia.

Renal cell carcinoma (RCC) has the highest mortality rate among urological cancers and tumor angiogenesis that plays a critical role in RCC progress. Epidermal growth factor-like domain multiple 7 (EGFL7) has been recently identified as a regulator in RCC tumor angiogenesis and progression. Long noncoding RNA (LncRNA) HOTAIR has been considered as a pro-oncogene in multiple cancers, but its precise mechanism of tumor angiogenesis has rarely been reported. MicroRNA-126 (miR-126) functions as a tumor suppressor in RCC. However, the underlying tumor angiogenesis mechanism of HOTAIR/miR-126 axis in RCC has not been studied. The proliferation, migration, angiogenesis, and expression of EGFL7 and related proteins in extracellular signal-regulated kinase (ERK)/activators of transcription 3 (STAT3) signal pathway were determined to examine the effect and mechanism of HOTAIR and miR-126 on RCC progress. The regulatory relationship of HOTAIR and miR-126, as well as miR-126 and EGFL7 were tested using dual-luciferase reporter assay. Aenograft RCC mice model was used to examine the effect of HOTAIR on RCC tumor growth and metastasis in vivo. HOTAIR knockdown and miR-126 overexpression suppressed the proliferation, migration, and angiogenesis of RCC cells. HOTAIR regulated EGFL7 expression by competitively binding to miR-126. Knockdown of HOTAIR significantly suppressed the RCC tumor progression and lung metastasis in vivo. These findings suggest that lncRNA HOTAIR regulate RCC angiogenesis through miR-126/EGFL7 axis and provide a new perspective on the molecular pathways of angiogenesis in RCC development, which might be potential therapeutic targets for RCC treatment.

Primary malignant melanoma of the esophagus (PMME) is a rare malignant disease and has not been well characterized in terms of clinicopathology and survival.To investigate the clinical features and survival factors in Chinese patients with PMME.The clinicopathological findings of ten cases with PMME treated at Henan Provincial People's Hospital were summarized. Moreover, the English- and Chinese-language literature that focused on Chinese patients with PMME from 1980 to September 2021 was reviewed and analyzed. Univariate and multivariate analyses were employed to investigate the clinicopathologic factors that might be associated with survival.A total of 290 Chinese patients with PMME, including ten from our hospital and 280 from the literature were enrolled in the present study. Only about half of the patients (55.8%) were accurately diagnosed before surgery. Additionally, 91.1% of the patients received esophagectomy, and 88 patients (36.5%) received adjuvant therapy after surgery. The frequency of lymph node metastasis (LNM) was 51.2% (107/209), and LNM had a positive rate of 45.3% even when the tumor was confined to the submucosal layer. The risk of LNM increased significantly with the pT stage [The correct diagnosis of PMME before surgery is low, and physicians should pay more attention to avoid a misdiagnosis or missed diagnosis. Extended lymph node dissection should be emphasized in surgery for PMME even though the tumor is confined to the submucosal layer. Both the LNM and pT stage are independent prognosis factors for OS, and the pT stage is the prognosis factor for DFS in patients with PMME.

Objective The aim of this study was to evaluate the predictive factors of central lymph node metastasis (CLNM) and BRAFV600E mutation in Chinese patients with papillary thyroid carcinoma (PTC). Methods A total of 943 PTC patients who underwent thyroidectomy from 2014 to 2016 at our hospital were enrolled. Those patients were divided into PTC > 10 mm and papillary thyroid microcarcinoma (PTMC) groups by tumor size. The BRAFV600E mutation was examined by quantitative real-time PCR. Univariate and multivariate analyses were used to examine risk factors associated with CLNM and the BRAFV600E mutation. Results The frequency of CLNM was 53% (505/943). Both univariate and multivariate analyses suggested that the risk factors for CLNM in PTC patients were male, younger age, and larger tumor size (P < 0.05). Coexistent Hashimoto thyroiditis (HT) was an independent protective factor against CLNM when the tumor was > 10 mm (P = 0.006). Stratified analysis revealed that male, age ≤ 30 years, and tumor size > 5 mm were independent risk factors for CLNM. The BRAFV600E mutation rate was 85%. Multivariate logistic regression analysis revealed that age (P < 0.001) and coexistent HT (P = 0.005) were independent predictive factors of BRAFV600E mutation in PTC patients. Only age was a risk factor for the BRAFV600E mutation when the tumor was > 10 mm (P = 0.004). In the PTMC group, the BRAFV600E mutation was significantly correlated with tumor size (P < 0.001) and coexistent HT (P = 0.03). Stratified analysis revealed that age > 30 years and tumor size > 5 mm were independent predictive factors of BRAFV600E mutation. Furthermore, the incidence of CLNM was significantly higher in BRAFV600E mutation-positive patients (P = 0.009) when the tumor was ≤ 5 mm. Conclusion The factors male, younger age (≤ 30 years), large tumor size (> 5 mm), and coexistent HT are independent predicative factors for CLNM. The BRAFV600E mutation is associated with both large size and without HT in PTMC patients, age > 30 years in the PTC > 10 mm group. The BRAFV600E mutation was an independent risk factor for CLNM when the tumor was ≤ 5 mm. For optimal management, these features should be comprehensively evaluated to determine the initial surgical approach for PTC patients.

Objective:The aim of the study is to evaluate the association of the BRAFV600E mutation with the clinicopathologic characteristics in Chinese population with papillary thyroid carcinoma (PTC).MethodsA total of 943 PTC patients who underwent thyroidectomy from 2014 to 2016 at Henan Provincial People’s Hospital were included in the present study. The BRAFV600E mutation was examined in each resected specimen by quantitative Real-time PCR (qRT-PCR) technique. Results The PTC patients were subclassified into the overall, PTC>10mm and papillary thyroid microcarcinoma(PTMC) groups. The positive rate of BRAFV600E mutation was 85.4% in Chinese patients with PTC. In both overall PTC and PTC> 10mm groups, the BRAFV600E mutation was much more frequently detected in elderly patients and patients at T1 stage (P< 0.05). In addition, the positive rate of BRAFV600E mutation was significantly higher in PTC patients without concomitant Hashimoto’s thyroiditis in overall PTC and PTMC groups (P< 0.05). Furthermore, logistic regression analysis suggested that the risk of having a larger tumor diameter was increased by 6-fold when BRAFV600E mutation in the PTMC group. No association between the BRAFV600E mutation and other clinicopathologic factors was observed. ConclusionThe BRAFV600E mutation was significantly associated with patients age and T stage. Furthermore, the risk of having a larger tumor size was significantly increased when BRAFV600E mutation in the PTMC group. which suggests that BRAFV600E mutation might play an important role in the activation of early thyroid carcinogenesis, the effect might weaken in the progression of PTC.

Background: Glioma is highly heterogeneous. Real-time tumor markers in vivo can most truly reflect the clonal evolution of glioma, and can accurately monitor postoperative minimal residual disease (MRD) and early tumor DNA relapse. The histological and molecular markers of resected tumor could not represent the characteristics of recurrent tumor, and the reference basis of postoperative clinical treatment plan should be adjusted. Methods: This retrospective cohort analyzed 32 patients with glioma from January 1, 2018 to January 31, 2020. Samples of tumor tissue, tumor fluid in situ and cerebrospinal fluid were collected, and next-generation tumor DNA sequencing was performed. Findings: Adequate tumor DNA was detected in TISF. The consensus rate of shared mutations at tumor progression was 45.8%, the variant allele fractions (VAFs) for TISF mutations were between 0.1% and 84.3%. VAF and cfDNA concentrations increased as the tumor progressed. At tumor progression, 100% (15/15) of tumor DNA was positive in TISF, CSF-ctDNA was detected in only 4 patients (26.7%, 4/15). The concentration of cfDNA in TISF samples ranged from 0.9-346.5ng/ mL, while that in CSF was only 0.55-16.23ng/mL. The level of shared mutation VAF was higher than that of CSF in TISF. High concentration of cfDNA in early postoperative TISF indicates high residual disease in early postoperative TISF, which is an early recurrence risk ( 600 days Patients (p = 0.006). Interpretation: Tumor DNA derived from TISF can find the molecular information of MRD before tumor recurrence, which cannot be detected by imaging and CSF-ctDNA. It can provide accurate glioma genomic information in real-time in vivo, and can monitor tumor MRD, clonal evolution, early tumor DNA relapse, and provide clinical treatment strategies. Funding Statement: Science and Technology Tackle Program of Henan Province and Joint Project of Medical Science and Technology Tackling Plan of Henan Province (Grants no. 192102310126 and 201601016) Declaration of Interests: Authors declare that they have no competing interest. Ethics Approval Statement: Approval was obtained from the Ethics Committee and Institutional Review Committee of the People’s Hospital of Henan Province.

Long noncoding RNAs (lncRNAs) function through a diverse array of mechanisms that are not presently fully understood. Here, we sought to find lncRNAs differentially regulated in cancer cells resistant to either TNF-related apoptosis-inducing ligand (TRAIL) or the Mcl-1 inhibitor UMI-77, agents that act through the extrinsic and intrinsic apoptotic pathways, respectively. This work identified a commonly up-regulated lncRNA, ovarian adenocarcinoma-amplified lncRNA (OVAAL), that conferred apoptotic resistance in multiple cancer types. Analysis of clinical samples revealed OVAAL expression was significantly increased in colorectal cancers and melanoma in comparison to the corresponding normal tissues. Functional investigations showed that OVAAL depletion significantly inhibited cancer cell proliferation and retarded tumor xenograft growth. Mechanically, OVAAL physically interacted with serine/threonine-protein kinase 3 (STK3), which, in turn, enhanced the binding between STK3 and Raf-1. The ternary complex OVAAL/STK3/Raf-1 enhanced the activation of the RAF protooncogene serine/threonine-protein kinase (RAF)/mitogen-activated protein kinase kinase 1 (MEK)/ERK signaling cascade, thus promoting c-Myc-mediated cell proliferation and Mcl-1-mediated cell survival. On the other hand, depletion of OVAAL triggered cellular senescence through polypyrimidine tract-binding protein 1 (PTBP1)-mediated p27 expression, which was regulated by competitive binding between OVAAL and p27 mRNA to PTBP1. Additionally, c-Myc was demonstrated to drive OVAAL transcription, indicating a positive feedback loop between c-Myc and OVAAL in controlling tumor growth. Taken together, these results reveal that OVAAL contributes to the survival of cancer cells through dual mechanisms controlling RAF/MEK/ERK signaling and p27-mediated cell senescence.

Background: Glioblastoma (GBM) is one of the worst cancers with bad prognosis despite systemic chemotherapy and radiotherapy after surgery. Methods: In this study, 71 patients with GBM were enrolled and randomly assigned to two groups: Receiving radiotherapy with concomitant and adjuvant temozolomide (TMZ) (TMZ, standard therapy) after surgery, or receiving radiotherapy with concomitant and adjuvant local delivery of nimustine (ACNU) rendezvousing with oral TMZ (rendezvous therapy). In the follow-up of all patients and the progression-free survival (PFS), overall survival (OS), Karnofsky performance score (KPS) and toxicities were recorded. Results: For the whole cohort, the median OS was 18.0 months, and the median PFS was 7.8 months. A significantly longer OS was observed in patients received rendezvous therapy than those who receiving standard therapy (18.5 months vs. 16.0 months; P = 0.014), as well as PFS (8.8 months vs. 7.0 months; P = 0.008). The KPS ≥70 rates were 81.8%, 40.9%, 20.5% in 1, 2, and 3 years for the rendezvous therapy group, significantly superior to standard therapy group. The most common toxicities were tolerable gastrointestinal reaction, liver dysfunction, and hematological toxicities, which were relieved with symptomatic treatment. Grade 3 or 4 toxicity was documented in 8 (18.3%) patients in rendezvous therapy group, while it was observed in 6 (22.2%) patients in standard therapy group during whole treatment process. Conclusions: Compared to standard therapy, the antitumor effects of rendezvous therapy were more effective in GBM patients without increasing the toxicities.

The boring and trepanning association (BTA) deep hole drilling is a typical self-guiding machining method. The drilling force and its distribution laws along the cutting radius directly affect the stability of drilling and the quality of machined hole. Based on the oblique cutting theory, a novel drilling force model is developed to predict the thrust and torque for staggered teeth BTA deep hole drill with variable geometries. Using the constraint relationships between the cutting force components and cutting angles, combined with the measured drilling force during the drill entrance, the parameters of the model including normal shear angle, normal friction angle and shear stress involved in the cutting force coefficients along the cutting radius, and the axial and circumferential friction coefficients between the guide pads and the hole wall are obtained. The model-predicted drilling force is validated by experimental results.

Under the concept of precision or targeted vibration suppression, a novel approach is developed to reduce the vibration of drilling tool system in deep-hole drilling process. The concept is to suppress the dominant vibration upon its emergence by variable damping or to force the harmful vibration morph into less harmful by different damper position. A magneto-rheological (MR) fluid damper is designed with adjustable damping capability to counteract emerging vibration. A series of experimental investigations are carried out on the BTA deep hole drilling process. The experimental results show that the adjustable MR damping brings down the vibration in all applications with different suppression effect. A relative optimal suppression can always be found. The suppressed vibration experiences a frequency shift which sheds light on the possible avoidance of matching of unwelcome frequency. Different damper locations have different but consistent suppression results which foresee a possibility of forcing the mode of vibration into less harmful one. A potential precision or targeted suppression of vibration upon its emergence is thus possible.

The problem of chip breaking and evacuation is the key point of staggered teeth boring and trepanning association (BTA) drilling. The factors that influence chip breaking with staggered teeth BTA deep hole drilling are analyzed by using the chip bending deformation mechanism for chip formation and flow through the rake face and chip breaker. This study investigated the distribution and variation of chip deformation and breaking along drilling conditions, with respect to drilling radius, drilling process parameters, tool wear, and chip breaker geometric parameters. The results show that the tool-chip contact length is about 1.65 times the chip thickness in staggered teeth BTA drilling. The cutting radius of the teeth has a considerable influence on the chip thickness. Compared with the drilling speed, the feed has a greater impact on chip deformation and breaking, and the chip thickness and strain increase with increased feed. Increased drilling depth and tooth wear aggravates the friction state between the chip and the rake face, augments chip thickness and tool-chip contact length, and increases the chip&rsquo, s strain increment. As the width of chip breaker decreases and the height increases, the chip strain increases and the breaking conditions are improved.

Melanotic neuroectodermal tumor of infancy is a rare melanin-containing neoplasm with locally aggressive and rapid expansile growth, usually involving the maxilla, skull, and mandible of early infancy. Radical surgery is critical for a long-term outcome. We present a case of 14-month-old girl with rapid-growing subcutaneous mass arising in the right temporal bone and extending intracranially on computed tomographic scan. Radical surgery was performed. A brownish-black tumor composed of large pigmented epithelioid cells, positive for cytokeratins and HMB-45, and nests of small neuroblast-like cells positive for neuron-specific enolase and synaptophysin, was diagnosed as melanotic neuroectodermal tumor of infancy. The patient remained well without evidence of recurrence for 1 year after surgery. Clinicopathological features, management alternatives and outcome were discussed.

Dysembryoplastic neuroepithelial tumors are rare, surgically curable, neuronal-glial neoplasms affecting young patients with intractable epilepsy. Its recognition is needed to avoid unnecessary adjuvant therapy. The authors reviewed the records of 15 patients with dysembryoplastic neuroepithelial tumors who underwent epilepsy surgery using intraoperative electrocorticography monitoring, including 8 males and 7 females (mean age, 15.8 years). Neuroimaging showed a predominantly intracortical location, the presence of septations, a triangular pattern of distribution, a lack of contrast enhancement, and an absence of peritumoral edema. Eleven cases were classified as complex type, 3 as simple type, and 1 as “nonspecific” type. Associated cortical dysplasia was found in 5 cases and leptomeningeal involvement in 1 case. Its immunophenotype suggested a pluripotential neuroepithelial origin. The mean follow-up was 37.5 months; 2 patients had tumor recurrence. Although they are generally benign neoplasms, recurrences sometimes occur. Complete resection of the tumor with the epileptogenic zone is important for a favorable outcome.

The vibration characteristics of the tendon-based parallel robot for processing are presented. Firstly, the free vibration equations of the robot on the stable position and orientation were modeled, and secondly the natural frequencies were deduced from the transformation of principal coordinates into modal coordinates. Next, cutting-force model was introduced and the solutions of the forced vibration equations were obtained from the Runge-Kutta method, where the minimum natural frequency was taken as basis of the time step that was important for computation convergence. Lastly, the algorithm was verified by simulations, also including solution transformation of time domain into frequency domain by Fast Fourier Transformation (FFT). The vibration properties could be manifested clearly by the solutions in frequency domain. The results show that the eccentricity and the mass of the moving platform are the important factors to make system instable in certain excitation frequency.

miR-34a is an important molecule that can inhibit the tumor growth. This study aimed to investigate the functional role of miR-34a in hepatocellular carcinoma (HCC) and explore the interaction between miR-34a and histone deacetylase 1 (HDAC1). RT-qPCR was employed to detect the mRNA expression of miR-34a and HDAC1 in 60 HCC tissues. Results showed miR-34a expression in HCC tissues was significantly lower than in normal tissues (P

MicroRNAs (miRNA) play important regulatory roles in the occurrence and development of cancers. This study aimed to investigate the effects of miR-26a on the proliferation and apoptosis of ovarian cancer cells and explore the potential mechanism. qRT-PCR was performed to measure the miR-26a expression in 46 ovarian cancer tissues, and results showed miR-26a expression reduced significantly when compared with normal ovarian tissues (P

Papillary glioneuronal tumor (PGNT) is a rare, recently described distinct low-grade brain neoplasm. This study was performed to characterize the clinicopathologic and neuroradiologic features of PGNTs. We reviewed the medical records of 16 patients with PGNT who underwent surgery, including 11 males and five females (median age 27 years). The clinical, neuroradiologic, histopathologic, and immunohistochemical findings were documented. Headache was the principal presentation. Neuroimaging showed contrast-enhancing, cystic-solid or cystic masses with a mural nodule, mostly involved the frontal or parietal lobes. Histologically, the tumors were characterized by glial fibrillary acidic protein (GFAP)-positive small cuboidal cells lining hyalinized vascular pseudopapillae and synaptophysin and/or NeuN-positive interpapillary neuronal elements. Other findings included small angiomatous areas in ten, small islands of neuropil and rosettes in seven, and microvascular proliferation and/or nuclear atypia in six. Mitoses or necrosis were absent. All lacked isocitrate dehydrogenase 1 (IDH1) R132H protein expression. Low expression of p53 was observed in three cases. Ki67 labeling index ranged from less than 1 to 3 %. All but one was totally resected. Median follow-up was 65 months, and one patient had tumor recurrence. PGNTs display distinct clinicopathologic and imaging characteristics and indicate a favorable prognosis. However, recurrences sometimes occur. Immunohistochemistry facilitates the appropriate diagnosis of these tumors. Complete resection of the tumor is important for a favorable outcome.

In this article, the nonlinear dynamic responses of drilling shaft system with hydrodynamic forces of cutting fluid were analyzed in deep slot hole drilling. A numerical method is presented to observe the states of the drilling shaft system. Using the proposed method, the periodic orbit of the drilling shaft motion and its period are calculated when the design parameters of drilling shaft system are subject to change, then the stability for dynamic responses of the drilling shaft system can be determined by the Floquet theory. According to the physical character of cutting fluid, the variational constraint approach is introduced to continuously revise the variational form of Reynolds equation at every step of iteration process. The nonlinear hydrodynamic forces of cutting fluid and their Jacobian are solved simultaneously without the increasing of computing efforts. The numerical examples show that the scheme of this study saves computing efforts but also is good precision, and can make a good reference for the dynamic design of drilling shaft system in deep slot hole drilling.

Background Our previous works have demonstrated that Helicobacter pylori (Hp) infection can alter histone H3 serine 10 phosphorylation status in gastric epithelial cells. However, whether Helicobacter pylori-induced histone H3 serine 10 phosphorylation participates in gastric carcinogenesis is unknown. We investigate the expression of histone H3 serine 10 phosphorylation in various stages of gastric disease and explore its clinical implication. Materials and methods Stomach biopsy samples from 129 patients were collected and stained with histone H3 serine 10 phosphorylation, Ki67, and Helicobacter pylori by immunohistochemistry staining, expressed as labeling index. They were categorized into nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, and intestinal-type gastric cancer groups. Helicobacter pylori infection was determined by either 13 C-urea breath test or immunohistochemistry staining. Results In Helicobacter pylori-negative patients, labeling index of histone H3 serine 10 phosphorylation was gradually increased in nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia groups, peaked at low-grade intraepithelial neoplasia, and declined in high-grade intraepithelial neoplasia and gastric cancer groups. In Helicobacter pylori-infected patients, labeling index of histone H3 serine 10 phosphorylation followed the similar pattern as above, with increased expression over the corresponding Helicobacter pylori-negative controls except in nonatrophic gastritis patient whose labeling index was decreased when compared with Helicobacter pylori-negative control. Labeling index of Ki67 in Helicobacter pylori-negative groups was higher in gastric cancer than chronic atrophic gastritis and low-grade intraepithelial neoplasia groups, and higher in intestinal metaplasia group compared with chronic atrophic gastritis group. In Helicobacter pylori-positive groups, Ki67 labeling index was increased stepwise from nonatrophic gastritis to gastric cancer except slightly decrease in chronic atrophic gastritis group. In addition, we noted that histone H3 serine 10 phosphorylation staining is accompanied with its location changes from gastric gland bottom expanded to whole gland as disease stage progress. Conclusions These results indicate that stepwise gastric carcinogenesis is associated with altered histone H3 serine 10 phosphorylation, Helicobacter pylori infection enhances histone H3 serine 10 phosphorylation expression in these processes; it is also accompanied with histone H3 serine 10 phosphorylation location change from gland bottom staining expand to whole gland expression. The results suggest that epigenetic dysregulation may play important roles in Helicobacter pylori-induced gastric cancer.

Background and Objective: Gastroesophageal reflux disease (GERD) has been linked to a number of extra-esophageal symptoms and disorders, primarily in the respiratory tract. Current animal models of reflux esophagitis are adapted to diseases of the digestive system, rather than to reflux-associated respiratory symptoms. The aim of this study was to evaluate a novel external esophageal perfusion model to induce esophageal, tracheal and pneumonic histological injury similar to that associated with GERD. Methods: Twenty guinea pigs were randomized to the acid-treated or PBS-treated group. Esophageal catheters were used to perfuse the esophageal lumen of guinea pigs with hydrochloric acid containing 1 g/l pepsin or PBS for 14 days. The total cell number and cell differential counts in bronchoalveolar lavage fluid (BALF) were determined 24 h after the last perfusion. Histological changes in the esophageal, tracheal and pneumonic tissues were observed by hematoxylin-eosin staining. Results: The numbers of lymphocytes, eosinophils and total inflammatory cells in the BALF were significantly higher in acid-perfused than PBS-perfused animals. Histological evidence suggested esophageal and pneumonic inflammations were prominent in acid-treated animals. Conclusion: Repetitive, acid-perfused, esophageal events copied the animal models of reflux esophagitis, and elicited inflammatory responses in the airways and lungs of guinea pigs.

The stability and nonlinear dynamic behavior of drilling shaft system in copper stave deep hole drilling were analyzed. The effects of the fluctuation of the cutting force, the mass eccentricity and the hydrodynamic forces of cutting fluid could be taken into consideration in the model of drilling shaft system. Based on the isoparametric finite element method, the variational form of Reynolds equation in hydrodynamic fluid was used to calculate nonlinear hydrodynamic forces and their Jacobian matrices simultaneously. In the stability analysis, a new shooting method for rapidly determining the periodic orbit of the nonlinear drilling shaft system and its period was presented by rebuilding the traditional shooting method and changing the time scale. Through the combination of theories with experiment, the correctness and effectiveness of the above methods are verified by using the Floquet theory. The results show that the mass eccentricity can inhibit the whirling motion of drilling shaft to some extent.

Nonlinear dynamic behaviors of drilling shaft system in boring and trepanning association deep hole drilling are investigated. The effects of the mass eccentricity and the cutting force fluctuating can be taken into consideration in the model of drilling shaft system. Nonlinear hydrodynamic forces are adopted to increase the numerical accuracy. Based on the isoparametric finite element with eight nodal points method, the nonlinear hydrodynamic forces and their Jacobian matrices of compatible accuracy are calculated simultaneously. To solve the nonlinear dynamic orbit of drilling shaft system, the period T of the periodic orbit of the nonlinear drilling shaft system is drawn into the governing equation of the system explicitly by changing the time scale. Then, the period T is taken as a parameter in the iterations of the shooting method. The periodic orbit and its period of the drilling shaft system are determined rapidly by generalized shooting method. The local stability and dynamic behaviors of periodic motion with the change of the drilling shaft design parameters value are obtained by the Floquet theory. The numerical results indicate the rich and complex dynamic behaviors of the drilling shaft system, such as periodic, quasiperiodic, jumped solution, and coexistence of multisolution and can make a good reference for the dynamic design of drilling shaft system in deep hole drilling.

Objective: This study aimed to investigate expression level of FOXC2 and its relationship to clinical pathological features of renal cell carcinoma (RCC). Methods: The expression levels of FOXC2 in RCC tissues and normal renal tissues (62 samples, respectively) were detected by immunohistochemistry and PCR Array. Statistics analyses were done with SPSS to compare the differences between RCC tissues and normal renal tissue, and to explore the relationship between the expression level of FOXC2 and the clinical pathological features of RCC. Results: Expression level of FOXC2 in RCC tissues was significantly higher than in normal renal tissues, and other related cancer genes also highly expressed in RCC tissues. FOXC2 expression was positively associated with clinical stage and pathological grade (P < 0.05), but not significantly related to the gender and age (P > 0.05). Conclusion: The expression of FOXC2 in renal cell carcinoma was significantly higher than that in normal renal tissues. It is suggested that FOXC2 might play a crucial role in the occurrence and development of RCC and could be an important prognostic indicator for clinical therapy.

To investigate the prevalence of occupational asthma, airway inflammation and analyze the risk factors for workers exposed to isocyanates.A cross-sectional study was applied. Totally 429 isocyanates exposed workers were surveyed and the prevalence of occupational asthma and airway inflammation situation were examined by questionnaire, physical examination and laboratory tests. Multivariate logistic regression was applied to analyze the possible risk factors of isocyanate-induced occupational asthma.(1) A total of 366 patients with complete data were included in the study, and finally 11 cases were diagnosed as isocyanate-induced occupational asthma with a prevalence of 3.0%. (2) Neutrophil percentage in the induced sputum of occupational asthma increased significantly [42.00% (34.00%-55.00%) before work and 59.00% (51.00%-70.00%) after work (Z = -2.940. P0.05)]. (3) Length of service (OR = 3.096, P = 0.025) and rhinitis (OR = 1.901, P = 0.008) were independent dangerous factors, and protective measures (OR = 0.074, P = 0.015) was protective factors to isocyanate-induced occupational asthma.Neutrophilic inflammation can be triggered by isocyanate exposure. Regular health examinations, effective protective measures can reduce the prevalence of isocyanate-induced occupational asthma.

To study the clinicopathologic features, radiologic findings, treatment options and prognosis of dysembryoplastic neuroepithelial tumor (DNT).The clinicopathologic and radiologic features were retrospectively analyzed in 10 cases of DNT.Intractable partial seizure was the main presenting symptom in all patients. The tumor was located in temporal lobe (number = 5), frontal lobe (number = 3) or parietal lobe (number = 2). CT scan displayed a hypodense lesion. MRI scan revealed the tumor was non-enhancing T1WI hypointense and T2WI hyperintense, with internal septation and hyperintense ring around the tumor seen on FLAIR image. There was neither peritumoral edema nor mass effect. Histologically, the tumor showed the presence of glioneuronal element, with oligodendrocyte-like cells, floating neurons, astrocytes and associated microcystic changes. Immunohistochemical study demonstrated positivity for NeuN and synaptophysin in the neurons and some oligodendrocyte-like cells. Olig2 and S-100 protein were also expressed in the oligodendrocyte-like cells. Ki-67 index were lower than 1% in all cases. Nine cases were treated by complete surgical excision and the remaining case was subtotally excised. No post-operative chemotherapy or radiotherapy was given. One of the 10 cases recurred on follow up.Correct diagnosis of DNT requires correlation with clinicopathologic, radiologic and immunohistochemical findings. Complete resection of the tumor and epileptogenic foci is the mainstay of treatment for DNT, with intraoperative EEG monitoring. Post-operative chemotherapy or radiotherapy is not required.

To constitute a correlation with the subjective indicators by investigation of the causes and clinical features in patients with chronic cough.Totally 100 patients with chronic cough were recruited followed a diagnostic program. Airway responsiveness [by methacholine challenge test (MCT)], Leicester cough questionnaire (LCQ), visual analogue scale (VAS), cough score, age, gender and disease duration were all recorded for analysis.The top five causes of chronic cough in these patients were variant asthma, post infectious cough, atopic cough, eosinophilic bronchitis and upper airway cough syndrome. LCQ total score was negatively correlated with age and the VAS score (r = -0.239 and -0.470 respectively, all P0.05), while no difference was found among patients with different causes of disease or gender (F = 1.233, t = 1.918, all P0.05) and no correlation was found with BMI (r = -0.029, P0.05). The physiological and psychological field score in female patients significantly reduced (t = 2.174, 1.990, P0.05), and LCQ total score of MCT positive patients obviously reduced than negative ones (t = -2.22, P0.05). After the treatment of two weeks, LCQ three component field and total score could be improved significantly (all P0.01).Gender and age may have some impact on the quality of life in patients with chronic cough. LCQ, VAS and cough score should be used to assess cough severity and evaluate therapeutic effect in patients with chronic cough.

To observe sputum cytology counts, the levels of nerve growth factor (NGF) and IL-4 in cough variant asthma (CVA) patients and the change of their levels after using glucocorticoids combined with β(2)-adrenergic agonists one month, and to investigate CVA's characteristics of airway inflammation.Totally 36 patients with untreated CVA were selected, as well as 23 healthy controls. Coughed up sputum cells were obtained and HE strained for differential cell counting in each enrolled patient. In induced sputum's supernatant, the levels of NGF and IL-4 were determined by ELISA.Before treatment, CVA patients had a median eosinophils (EOS) percentage of 8%, which was significantly higher than that after treatment (2%, P0.05) and in healthy control group (1%, P0.001). The levels of NGF and IL-4 in induced sputum of CVA group were (9.50 ± 1.69) ng/L and (257.37 ± 53.57) ng/L. After treatment, they were (8.78 ± 1.02) ng/L and (228.60 ± 52.93) ng/L in CVA group, (6.98 ± 0.69) ng/L and (166.44 ± 24.75) ng/L in healthy control group. The levels of NGF and IL-4 before and after treatment in the CVA group, as compared with the healthy control group, had statistically significant differences (all P0.001). In CVA group before and after treatment, the level of NGF and IL-4 paired difference was significant (P0.001). The percentage of induced sputum EOS correlated with sputum supernatant concentrations of NGF and IL-4 (P0.01). In induced sputum supernatant, the concentrations of NGF and IL-4 were significant correlated (P0.01).Glucocorticoid joint long-term β(2) agonist inhaled treatment significantly reduced NGF, IL-4 and EOS levels and reduced eosinophilic inflammation, which are closely related with the nerve-immune mechanism, NGF as well as IL-4 participated the inflammation. Induced sputum examination is non-invasive, economical, simple, easily accepted by patients, and repeatable, widely used in clinical.

To observe the expression of substance P (SP) in the airway mucosa of guinea pigs with repetitive esophageal stimulation by hydrochloric acid (HCL).Twenty adult guinea pigs were randomly divided into 2 groups (n = 10 each): (1) The HCL model group: On the day of experimentation, guinea pigs were maintained under ketamine anesthesia. A 5F catheter was inserted orally into the lumen of the middle and lower esophagus. The esophagus of each animal was perfused with HCl-P for 20 min/d for 14 d. (2) The PBS control group: The esophagus of each animal was perfused with PBS instead. The bronchial responsiveness to Ach given intravenously with increasing doses (3.125, 6.25, 12.5, 25, 50, 100 microg/kg) was measured after the last perfusion. The left lung was isolated for pathological examination. Lung sections were stained with hematoxylin and eosin, and other sections were prepared for immunohistochemistry using monoclonal antibodies against SP.In response to increasing doses of ACh, all guinea pigs showed dose-dependent increases in R(L). However, when the dose of ACh was increased to 25 microg/kg, the airway responsiveness increased significantly in the HCl-P model animals compared with the PBS control group (t values = 43.057, 51.410, 57.359 respectively, all P0.01). The mean gray values of SP decreased significantly in the tracheal epithelia and the distal airway walls of the model group compared with the PBS control group (t values = 3.44, 2.16 respectively, all P0.01).There was airway neurogenic inflammation in guinea pigs with repetitive esophageal stimulation by HCL, which maybe closely related to the pathogenesis of gastro-esophageal reflux disease.

To investigate the changes and significance of cell apoptosis, Fas/FasL and P53 protein in epithelial cells from patients with idiopathic pulmonary fibrosis (IPF).Cell apoptosis and the expressions of Fas/FasL and P53 protein in lung tissues from 12 patients with IPF (IPF group) and 10 normal controls (control group) were detected by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) and immunohistochemistry.Compared with the control group (0/10), the percentage of apoptosis in alveolar epithelial cells and bronchial cells of the IPF group (12/12) was higher. The percentage of Fas, FasL and P53 protein expressions (12/12, 12/12, 11/12) in alveolar epithelial cells of the IPF group were higher than those of the control group (5/10, 2/10, 0/10); and the percentage of Fas, FasL and P53 protein expressions (12/12, 12/12, 11/12) in bronchial cells of the IPF group were also higher than those of the control group (6/10, 3/10, 0/10). There was a significant correlation between the percentage of apoptosis and Fas/FasL and P53 protein expression (r=0.625-0.839, all P0.01). The correlation of the Fas/FasL and P53 protein expression was also significant (r=0.571-0.760, all P0.01).The apoptosis percentage of epithelial cells and the expression of Fas/FasL and P53 protein are up-regulated in lung tissues of IPF, which may play an important role in the development of the disease.

To study ultrastructured change and neuron apoptosis after focal cerebral ischemia/reperfusion (I/R) in the aged rats.The aged SD rats (20-21 months) and the young (4-5 months) were subjected to 3 hours of middle cerebral artery occulsion with the intraluminal filament technique, followed by reperfusion for 3 hours, 6 hours, 12 hours, 24 hours, 72 hours. The ultrastructure of brain, infarct zone and neuron apoptosis were observed.The cerebral infarct zone increased in the aged rats with ischemia for 3 hours and I/R for 12 hours compared with those in the young. The brain injury was obviously deteriorated with I/R time longer, which was serious in the aged than that in the young. The neuron apoptosis increase with I/R time longer, and showed earlier and lasted longer in the aged.The cerebral injury is serious and neuron apoptosis increase shows early and lasts longer.

To evaluate the efficacy and safety of cefditoren pivoxil in treatment of respiratory infections.199 cases of respiratory infection confirmed by etiological and clinical examinations were treated with cefditoren pivoxil tablets taken orally. Therapeutic evaluation was conducted among 196 cases and safety evaluation was conducted among 199 cases.The total effective rate was 94.9%, and the causative bacteria -elimination rate was 96.7%. Clinical adverse events, including moderate diarrhea, mild nausea and vomiting, and stomach discomfort, were seen in 9 cases with an incidence rate of 4.5%. Laboratory adverse events, including increase of with an incidence rate of 3.5%.Cefditoren pivoxil is effective and safe in treatment of mild and moderate respiratory infections. The resistance rate to cefditoren pivoxil of pathogens of respiratory infections and the efficacy of cefditoren pivoxil show no difference from those tested 7 years ago.