Salvage endoscopic surgery for skull base osteoradionecrosis in nasopharyngeal carcinoma patients: A prospective, observational, single-arm clinical study.

BACKGROUND: Postradiation skull base osteoradionecrosis (ORN) is a severe complication that occurs after radiotherapy in patients with nasopharyngeal carcinoma (NPC) that can severely affect quality of life (QOL) and be life threatening. Only 13.4% - 28.6% of patients can be cured by traditional repeated endoscopic debridement. Here, we introduced salvage endoscopic surgery for skull base ORN patients and evaluated its clinical efficacy. METHODS: This was a prospective, observational, single-arm clinical study. Clinical data from 18 skull base ORN patients who underwent radical endoscopic necrectomy followed by reconstruction using a septal pedicled mucosal flap or temporal muscle flap were included in the study. The endpoint was an overall survival (OS) of 2 years. The numeric rating scale (NRS) scores for pain and foul odor were analyzed to determine the efficacy and safety of this surgery. RESULTS: A total of 21 patients were recruited, 18 of whom completed the study and were analyzed. All surgeries were successfully performed. During the 2-year study, the OS rate of the entire cohort was 75%. The median NRS score for pain decreased from 6.44 +- 2.62 to 0.50 +- 0.71, and the NRS score for foul odor decreased from 1.89±1.08 to 1 after surgery. CONCLUSIONS: Salvage endoscopic necrectomy followed by construction using a septal pedicled mucosal flap or temporal muscle flap is a novel, safe, and effective treatment for ORN in patients with NPC. CLINICAL TRIAL REGISTRATION: This study was approved by the independent ethics committee of the Eye, Ear, Nose and Throat Hospital of Fudan University (IEC No. 2019095-1). Written informed consent was obtained from all patients. The study was registered with the Chinese Clinical Trial registry (ChiCTR2000029327).

[Genetic analysis of 45 patients with suspected Lynch syndrome using next-generation sequencing].

Objective: To evaluate the value of next generation sequencing (NGS) in the genetic testing of Lynch syndrome. Methods: Immunohistochemical method was used to detect the expressions of DNA mismatch repair (MMR) proteins, including MutL homolog 1 (MLH1), PMS1 homolog 2 (PMS2), MutS homolog 2 (MSH2) and MutS homolog 6 (MSH6) in colorectal cancer, gastric cancer and endometrial cancer tissues collected from Shandong Provincial Hospital between 2016 and 2018. The genomic DNA of 45 patients who were suspected with Lynch syndrome was extracted from non-cancerous tissue paraffin samples, which were postoperatively confirmed by microscope. The mutations of 12 genes including MLH1 and MSH2 were detected using NGS. The germline mutant sites and significance were analyzed by bioinformatics technology and further confirmed by using Sanger sequencing. Results: The immunohistochemical results showed that the 45 cases of suspected Lynch syndrome included 22 cases of MLH1 and PMS2 deficient expression, 16 cases of MLH2 and MSH6 deficient expression, and 7 cases of MMR proteins normal expression. The NGS result showed that 28 cases of adjacent sample from colon cancer patients included 4 cases of MLH1 pathogenic mutation, 1 case of suspected MLH1 mutation, 2 cases of MLH2 pathogenic mutation, 2 cases of suspected MLH2 mutation. No MMR gene mutation was found in adjacent samples of 6 cases of rectal cancer, 6 cases of gastric cancer and 7 cases of colorectal cancer with MMR normal expression. One case of MLH1 or MHL2 pathogenic mutation and one case of MLH1 suspected mutation was detected in adjacent samples of 5 cases of endometrial cancer. Moreover, NGS also detected many other genes mutations and unreported gene mutation sites. Pathogenic and suspected MLH1 and MSH2 mutations were verified by Sanger sequencing. Conclusions: High-throughput NGS is a quick, accurate and reliable technique to identify gene variants in suspected Lynch syndrome patients. It has a wide application prospect for gene testing of tumors associated with Lynch syndrome.

[Long-term efficacy and safety of simultaneous integrated boost radiotherapy in non-operative esophageal squamous cell carcinoma: a multicenter retrospective data analysis (3JECROG R-05)].

Objective: To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients. Methods: The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1∶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed. Results: The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively (P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively (P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm(3), the median survival time of SIB and No-SIB group was 34.7 and 30.3 months (P=0.155), respectively. In the patients whose GTV volume>50 cm(3), the median survival time of SIB and No-SIB group was 16.1 and 20.1 months (P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group (P<0.001). Conclusions: The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.

[Prognostic analysis of definitive radiotherapy for early esophageal carcinoma(T1-2N0M0): a multi-center retrospective study of Jing-Jin-ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group].

Objective: To evaluate the prognostic factors of T1-2N0M0 esophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy. Methods: The clinical data of 196 patients with T1-2N0M0 ESCC who were treated with definitive radiotherapy in 10 hospitals were retrospectively analyzed. All sites were members of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG). Radiochemotherapy were applied to 78 patients, while the other 118 patients received radiotherapy only. 96 patients were treated with three-dimensional conformal radiotherapy (3DCRT) and 100 treated with intensity-modulated radiotherapy (IMRT). The median dose of plan target volume(PTV) and gross target volume(GTV) were both 60 Gy. The median follow-up time was 59.2 months. Log rank test and Cox regression analysis were used for univariat and multivariate analysis, respectively. Results: The percentage of normal lung receiving at least 20 Gy (V(20)) was (18.65±7.20)%, with average dose of (10.81±42.05) Gy. The percentage of normal heart receiving at least 30 Gy (V(30)) was (14.21±12.28)%. The maximum dose of exposure in spinal cord was (39.65±8.13) Gy. The incidence of radiation pneumonia and radiation esophagitis were 14.80%(29/196) and 65.82%(129/196), respectively. The adverse events were mostly grade 1-2, without grade 4 toxicity. Median overall survival (OS) and progression-free survival (PFS) were 70.1 months and 62.3 months, respectively. The 1-, 3- and 5-year OS rates of all patients were 75.1%、57.4% and 53.2%, respectively. The 1-, 3- and 5-year PFS rates were 75.1%、57.4% and 53.2%, respectively. Multivariate analysis demonstrated that patients'age (HR=1.023, P=0.038) and tumor diameter (HR=1.243, P=0.028)were the independent prognostic factors for OS, while tumor volume were the independent prognostic factor for PFS. Conclusions: Definitive radiotherapy is a promising therapeutic method in patients with T1-2N0M0 ESCC. Patients' age, tumor diameter and tumor volume may impact patients' prognosis.

[Efficacy analysis of the radiotherapy and chemotherapy in patients with stage â £ esophageal squamous carcinoma: a multicenter retrospective study of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG R-01F)].

Objective: To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation. Methods: The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed. Results: The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups (P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy (P<0.05). Multivariate analysis demonstrated that PGTV dose (OR=0.693, P=0.004), radiation esophagitis (OR=0.867, P=0.038), and radiation pneumonia (OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions: For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.

[The study of self-constructed brainstem fiber bundle by neurosurgeon through using 3D-Slicer software].

Objective: To explore the methods and appliaction value for self-constructing brainstem fiber bundles by neurosurgeon through 3D-Slicer software in neurosurgical preoperative planning. Methods: The DCIOM format imaging data of 31 patients with neurosurgical brainstem lesions were collected who admitted to Neurosurgery Department at the First Affiliated Hospital of Chongqing Medical University from June 2018 to May 2019 and imported into the 3D-Slicer software system. The neurosurgery specialists independently constructed the fiber bundles to generate two-dimensional Fraction Anisotropy maps, Directionally Encoded Color maps and three-dimensional fiber bundle tracing maps. Building a preopertive virtual pathological anatomical imaging system and understanding the three-dimensional pathological anatomical relationship between lesions and brain stem fiber bundles to develop an accurate surgical approach and simulate surgicalprocedures before surgery. Results: All cases were reconstructed by neurosurgeon, and the self-constructed 3D virtual images were used to develop the surgical plan. All the operations were successfully completed under the assistance of microsurgical techniques and neuroendoscopy while avoiding fiber bundles as much as possible, and the total or subtotal tumor was achieved without damage to the fiber bundle. After operation, the symptoms of new brainstem fiber bundle injury were mild. 31 patients were followed up 3 months after operation without obvious symptoms of brainstem fiber bundle injury, and 31 patients were followed up 6 months after operation without obvious symptoms of brainstem fiber bundle injury. Conclusions: Constructing brainstem fiber bundles by neurosurgeon can accurately and purposefully reconstruct the shape of brainstem fiber bundles, so that neurosurgeons can more accurately understand the three-dimensional pathological anatomical relationship between tumor and brain stem fiber bundles. In order to formulate the surgical plan in a more reasonable way, choose the optimal surgical approach, understand the location of the "relative safe area" , and be more confident to avoid damage to the brain stem fiber bundle while achieving subtotal or total resection of the tumor,also the nerve function of the patient is preserved as much as possible.

[Neuroendoscopy assisted microneurosurgery for posterior cranial fossa lesion].

Objective: To study the value of neuroendoscopy assisted microneurosurgery technique in the treatment of posterior cranial fossa lesion. Methods: Clinical data of 36 patients with posterior fossa lesions who accepted neuroendoscopy assisted microneurosurgery (NEAM group) in the department of neurosurgery of the First Affiliated Hospital of Chongqing Medical University, from January 2014 to December 2016, were retrospectively enrolled. A total of 113 cases diagnosed with the same lesions and accepted conventional microneurosurgery (non-NEAM group) in the same period were analyzed as control group. The total tumor resection rate, postoperative leakage of cerebrospinal fluid, intracranial infection, operating time and the recovery of facial nerve function were compared between the two groups. Results: Ninety-three patients with acoustic neuroma were analyzed, which were divided into non-NEAM group 78 cases (removed posterior lip of internal auditory canal in different degrees) and NEAM group 15 cases (not removed posterior lip of internal auditory canal). The total tumor resection rate and postoperative facial nerve function had no significant statistical differences between two groups. The operating time of NEAM group was longer than that of non-NEAM group (P=0.048, P<0.05), but the rate of leakage of cerebrospinal fluid and intracranial infection did not increase. Twenty-seven cases were diagnosed with cerebellopontine angle cholesteatoma. These cases were divided into two groups, 17 cases in non-NEAM group and 10 cases in NEAM group. NEAM group have higher total tumor resection rate (P=0.014, P<0.05), better short-term postoperative facial nerve function (P=0.039, P<0.05), and longer operating time (P=0.015, P<0.05), compared with non-NEAM group. No significant statistical differences were observed on long-term postoperative facial nerve function and postoperative complications. Of the 16 cases diagnosed tentorial meningioma, 10 cases were in non-NEAM group and 6 cases in NEAM group. Six cases in non-NEAM group and 4 cases in NEAM group were total removal. For the mean operating time, non-NEAM group was (6.6±1.0) hours and NEAM group was (7.1±0.7) hours. Thirteen cases were with fourth ventricular cholesteatoma, which all were totally resected, and 8 cases were in non-NEAM group and 5 cases in NEAM group. For non-NEAM group, 5 cases dissected cerebellar vermis and the mean operating time is (6.0±0.7) hours. However, NEAM group all did not dissect cerebellar vermis and the mean operating time is (6.4±0.4) hours. Conclusions: Neuroendoscopy assisted microneurosurgery for cranial fossa lesions was benefit to totally resect tumor and reduce unnecessary injury. It needed longer operating time, but not increase postoperative intracranial infection.

[Dynamic retraction microneurosurgery for the treatment of medial tentorial meningiomas].

Objective: To investigate the effectiveness and clinical significance of dynamic retraction microneurosurgery for the treatment of medial tentorial meningiomas. Methods: From January 2011 to December 2016, a cohort of 28 patients with medial tentorial meningiomas were treated by microneurosurgery at the First Affiliated Hospital of Chongqing Medical University. Patients who treated intraoperatively with dynamic retraction surgery from January 2014 to December 2016 were assigned into dynamic retraction group, and those with fixed retractors intraoperatively from January 2011 to December 2013 were assigned into retractor group. The surgical approaches tailored in our patients were based on predominant direction of tumor extension. The extent of tumor resection was scored according to the Simpson's classification scale. Comparisons of tumor size, operation time, hospitalization time, retraction-related injury, tumor Simpson resection grade and Karnofsky Performance Scale(KPS) score six months after surgery were also made between two groups. Results: A total of 12 patients(retractor group) were treated with the use of self-retaining brain retractors intraoperatively and dynamic retraction surgical procedure was performed intraoperatively in 16 patients(dynamic retraction group). The difference between two groups with regard to sex, age, tumor size, operation time and tumor Simpson resection grade was not statistically significant(all P>0.05). The mean duration of hospital time was shorter in the dynamic retraction group than that in the retractor group(18.3 d±1.8 d vs 20.2 d±1.3 d, P=0.004). The dynamic retraction group had lower incidence of retraction-related injury compared with the retractor group(1/16 vs 6/12), P=0.022]. The dynamic retraction group had better neurological recovery rate with KPS >80 evaluated six months after surgery compared with the retractor group(14/16 vs 5/12, P=0.017). Conclusions: Dynamic retraction microneurosurgery for the treatment of medial tentorial meningiomas is feasible, which can obviate or reduce the amount of brain retraction needed, and may be of help in lowering the risk of postoperative neurological deficits and complications and leading to reduced hospitalization cost and improved surgical outcomes.

[LincRNA-ROR functions as a ceRNA to regulate Oct4, Sox2, and Nanog expression by sponging miR-145 and its effect on biologic characteristics of colonic cancer stem cells].

Objective: To investigate the impact of lincRNA-ROR, a ceRNA by binding miR-145 on the expression of the downstream genes Oct4, Sox2 and Nanog, and related biological characteristics of colon cancer stem cells, and to elucidate the clinical significance of this molecular regulatory network. Methods: Fifty-two cases of colorectal cancer tissue and adjacent tissue were collected at Nanyang City Central Hospital and Nanyang Second Hospital, Henan Province, from 2014 to 2016. Real-time quantitative polymerase chain reaction (qPCR) was used to detect the expression of lincRNA-ROR and miR-145 in colorectal cancer tissue and isolated colon cancer cells. The correlation between the expression of lincRNA-ROR, miR-145 and the clinicopathologic features of colon cancer was performed. CD44(-)CD133(-) and CD44(+) CD133(+) cells were isolated from SW1116 by using flow cytometry. The expression of CD44, CD133, Oct4, Sox2, Nanog, lincRNA-ROR and miR-145 in cells were detected by qPCR. The relationship between lincRNA-ROR, miR-145, Oct4, Sox2 and Nanog was analyzed by bioinformatics, dual luciferase reporter assay, qPCR and Western blot. The effects of silencing lincRNA-ROR on the proliferation and chemosensitivity of colon cancer stem cells were detected by MTT, colony formation. Results: LincRNA-ROR was frequently up-regulated and inversely correlated with miR-145 down-regulation in the colon cancer specimens(P<0.05). LincRNA-ROR was related to tumor size, lymph node involvement and distant metastasis(P<0.05), and miR-145 was found related to tumor size and tumor location(P<0.05). CD44(+) CD133(+) cells were successfully isolated from SW1116 by flow cytometry. The levels of CD44, CD133, Oct4, Sox2, Nanog, lincRNA-ROR in CD44(+) CD133(+) cells were significantly increased, while miR-145 was decreased compared with CD44(-)CD133(-)cells(P<0.05). The levels of CD44, CD133, lnc-ROR in CD44(+) CD133(+) cells were significantly reduced upon cell adherence, while miR-145 was significantly increased(P<0.05). Bioinformatics analysis revealed that lincRNA-ROR shared miRNA response elements with core transcription factors Oct4, Sox2 and Nanog. MiR-145 significantly inhibited the expression of lincRNA-ROR, Oct4, Sox2 and Nanog. Silencing lincRNA-ROR significantly inhibited colon cancer stem cells proliferation and increased the sensitivity to chemotherapy. Conclusions: Linc-ROR functions as a key ceRNA to prevent core TFs, e. g., Oct4, Sox2, Nanog, from miR-145-mediated suppression in colon cancer stem cells and regulates cell proliferation and chemosensitivity.The data may provide insights into the pathophysiological interactions of the components of genetic networks in the development of colon cancer and may lead to new therapies in the future.

[PAHs exposure and occupational health risk assessment of workers in coal tar pitch factory].

Objective: To Investigation of industrial sites involving coal tar pitch to detect PAHs in the occupational environment and to assess their occupational health risks to workers. Methods: Taking coal tar pitch enterprises as the research object, and making the occupational health field investigation and inspection. Detecting the 16 PAHs in the samples by high performance liquid chromatography (HPLC) , analyze the PAHs exposed dose of the workers in the place, and using cumulative toxic equivalent quantity method, loss of life expectancy method and carcinogenic risk factor method to assessment worker's occupational health risk. Results: In the 15 posts involved, Some workers' exposed to the total concentration of PAHs is higher than others, the maximum exposure concentration is 1931.45ng/m3. There are different hazard risk levels in different working post due to different processes.The lifetime risk of workers is significantly higher than the acceptable range. Some workers has higher carcinogenic risk and workers' life expectancy loss is up to 1033.95 hours. Conclusion: Part of the coal tar pitch workers exposed to higher concentrations of PAHs, and beyond the occupational exposure limits.And there is a high occupational health risk due to high exposure to PAHs.

Efficacy and safety of fosaprepitant in the prevention of nausea and vomiting following highly emetogenic chemotherapy in Chinese people: A randomized, double-blind, phase III study.

The prevention of chemotherapy-induced nausea and vomiting was one of the most challenging supportive care issues in oncology, especially to highly emetogenic chemotherapy (HEC). A total of 645 patients were randomized into fosaprepitant group (fosaprepitant/placebo 150 mg d1 in combination with granisetron and dexamethasone) or aprepitant group (aprepitant/placebo 125 mg d1; 80 mg d2-d3 plus granisetron and dexamethasone).The primary endpoint was the percentage of patients who had a complete response (CR) over the entire treatment course (0-120 hr, overall phase [OP]). It was assessed by using a non-inferiority model, with a non-inferiority margin of 10%. The difference of the CR rate was compared between two groups with chi-square analysis. Six hundred and twenty-six patients were included in the per protocol analysis. The percentage of patients with a CR in the fosaprepitant group was not inferior to that in the aprepitant group (90.85% versus 94.17%, p = .1302) during OP. Whether the cisplatin-based chemotherapy or not, the CR rate of the fosaprepitant group was not inferior to that of the aprepitant group. Both regimens were well tolerated. The most common adverse event was constipation. Fosaprepitant provided effective and well-tolerated control of nausea and vomiting associated with HEC in Chinese patients.

[Research of relationship between occupational exposure to coal tar pitch workers and cytogenetic damage].

Objective: To investigate the effect of coal tar pitch occupational exposure on the cytogenetic damage. Methods: In July 2015, 691 workers exposed to coal tar pitch were selected as contact group. The administrative and the support crew 201 cases were selected as control group. Detect the tail DNA% and tail moment in peripheral blood lymphocyte as DNA damage degree by single cell gel electrophoresis (SCGE) . Detect the concentration of the metabolic product in urine by HPLC/MC as exposure levels. Results: The contact group were significantly higher than the control group in tail DNA% (contact group14.44%, control group 11.17%) and olive tail moment (contact group 2.85 µm, control group 1.95 µm) . The smoking one (contact group18.51%, control group13.43%) were significantly higher than the group not smoking (contact group12.69%, control group 11.71%) in tail DNA%. The coal tar pitch content in the air of workplace have correlation with worker, stail DNA% (r(s)=0.10) and olive tail moment (r(s)=0.11) . Conclusion: Occupational exposure to coal tar pitch and smoking can cause cytogenetic damage to workers.

[Investigation and analysis on occupational hazards in a carbon enterprise].

Objective: To explore occupational-disease-inductive in a carbon enterprise workplace and personnel occupational health examination, providing the basis for occupational disease prevention and control of the industry. Methods: Field occupational health survey and inspection law were used to study the the situation and degree of occupational disease hazards in carbon enterprise from 2013 to 2015.Occupational health monitoring was used for workers, physical examination, detection of occupational hazard factors and physical examination results were analyzed comprehensive. Results: Dust, coal tar pitch volatiles, and noise in carbon enterprise were more serious than others. Among them, the over standard rate of coal tar pitch volatiles was 76.67%, the maximum point detection was 1.06 mg/m(3), and the maximum of the individual detection was 0.67 mg/m(3). There was no statistical difference among the 3 years (P>0.05) . There were no significant differences in the incidence of occupation health examination, chest X-ray, skin audiometry, blood routine, blood pressure, electrocardiogram between 3 years (P>0.05) , in which the skin and audiometry abnormal rate was higher than 10% per year. Conclusion: Dust, coal tar, and noise are the main occupational hazard factors of carbon enterprise, should strengthen the corresponding protection.

[A association of genetic polymorphisms of XRCC1 and damage levels in workers exposed to coal tar pitch].

Objective: To study the relationship between XRCC1 gene polymorphism and DNA damage in peripheral blood lymphocytes of workers exposed to coal tar pitch. Methods: 203 coal tar asphalt device operation area workers (exposure group) and 76 logistics management personnel (control group) as the research ob-ject, determination of 1-hydroxypyrene concentrations in the urine as polycyclic aromatic hydrocarbons expo-sure dose, using the alkaline comet assay evaluation a peripheral blood lymphocyte DNA damage degree, using TaqMan MGB real time PCR method to detect XRCC1 gene 3 loci (XRCC1-194, XRCC1-280 and XRCC1-399) single nucleotide polymorphism. Results: No significant differences was observed in age, sex, smoking and alco-hol consumption between the two groups (P>0.05). The level of 1-OHP in the exposed group was significantly higher than that in the control group (1.27±0.93 µg/g creatinine) (P<0.05). The comet Olive tail moment level (3.21±0.93) in the peripheral blood lymphocytes of the exposed group was significantly higher than that in the control group (0.94 ± 0.39) (P<0.05). There was no significant difference in genotype distribution of XRCC1-194, XRCC1-280 and XRCC1-399 between the two groups (P>0.05). There was a significant correlation be-tween the XRCC1-280 locus gene polymorphism and comet Olive tail moment in the exposure group (P<0.05) af-ter adjustment for sex, age, smoking rate, drinking rate, length of service and urinary 1-OHP concentration. The comet Olive tail moment level of GG individuals carrying wild homozygous genotype was significantly lower than that of individuals carrying heterozygous genotype GA and carrying mutant homozygous genotype AA (P< 0.05) , and the difference was statistically significant (P<0.05) The comet Olive tail moment level of heterozy-gous genotype GA was significantly lower than that of genotype AA with mutational homozygous genotype AA (P<0.05) , and the difference was statistically significant (P<0.05). Conclusion: Arg280His locus polymor-phism of XRCC1 gene may influence the DNA damage level of peripheral blood lymphocytes induced by occupational exposure to coal tar pitch.

Andrographolide radiosensitizes human esophageal cancer cell line ECA109 to radiation in vitro.

To explore the radiosensitivity of andrographolide on esophageal cancer cell line ECA109. The inhibition effects of andrographolide were measured using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT) assay. Clonogenic survival assay was used to evaluate the effects of andrographolide on the radiosensitivity of esophageal cancer cells. Immunofluorescence was employed to examine Bax expression. The changes in cell cycle distribution and apoptosis were assayed using flow cytometry. The expression of NF-κb/Cleaved-Caspase3/Bax/Bcl-2 was measured using Western blot analysis. DNA damage was detected via γ-H2AX foci counting. With a clear dose and time effects, andrographolide was found to inhibit the proliferation of esophageal cell line ECA109. The results of the clonogenic survival assay show that andrographolide could markedly enhance radiosensitivity (P < 0.05) with a sensitizing enhancement ratio of 1.28. Andrographolide caused a dose-dependent increase in Cleaved-Caspase3/Bax protein expression and a decrease in Bcl-2/NF-κb expression. Apoptosis in andrographolide-treated ECA-109 increased significantly compared with the apoptosis in the simple drug and radiation combined with drug groups (P < 0.001; P < 0.05). Moreover, compared with the independent radiation group, the andrographolide combined with radiation group increased the number of DNA double chain breaks. Andrographolide can increase the radiosensitivity of esophageal cell line ECA109. This result may be associated with the decrease in the NF-κb level and the induced apoptosis of esophageal cancer cells.

Sunitinib modulates the radiosensitivity of esophageal squamous cell carcinoma cells in vitro.

This study aims to explore the radiosensitivity of sunitinib on esophageal cancer cell lines. For in vitro studies, human esophageal squamous cell carcinoma (ESCC) cell lines were treated with sunitinib 24 hours before irradiation. ESCC cell lines were treated with sunitinib with or without radiation. Cell proliferation was detected by Cell Counting Kit 8 assay. Radiosensitization was evaluated by clonogenic survival assay. Cell apoptosis and cell cycle analysis were detected by flow cytometry. Deoxyribonucleic acid (DNA) double-strand breaks were performed by immunocytofluorescence analysis. Western blot analysis was used to determine the effect of sunitinib on radiation induced signal transduction. Sunitinib potently sensitized ESCC cells to radiation with a sensitization enhancement ratio of 1.13-1.72. Furthermore, sunitinib increased radiation induced DNA double-strand breaks, promoted the apoptosis of ESCC cells and induced the G2/M arrest. Radiosensitization was accompanied with enhanced apoptosis and regulated by the intrinsic pathway of apoptosis. Sunitinib sensitized ESCC cells to the cytotoxic effects of radiation. This compound is promising for future clinical trials with chemoradiation in esophageal cancer.

miR-146a and miR-196a2 polymorphisms in ovarian cancer risk.

We investigated the relationship between miR-146a and miR-196a2 genetic polymorphisms and development of ovarian cancer in a Chinese population. A total of 134 patients and 227 control subjects were involved in our study between January 2012 and October 2014 from China-Japan Union Hospital of Jilin University. Genotyping of miR-146a and miR-196a2 was accomplished by polymerase chain reaction coupled with restriction fragment length polymorphism analysis. Unconditional multiple-logistic regression analysis indicated that the GG genotype of miR-146a was associated with an increased risk of ovarian cancer when compared to the CC genotype, and the adjusted OR (95%CI) was 3.73 (1.79-7.80). Moreover, the CG+GG genotype of miR-146a was associated with an increased risk of ovarian cancer compared with the CC genotype (OR = 1.68, 95%CI = 1.06-2.66), and the GG genotype had a higher risk of ovarian cancer than the CC+CG genotype (OR = 3.02, 95%CI = 1.55-5.98). In conclusion, our study suggests that the miR-146a polymorphism is associated with increased risk of ovarian cancer and could be used as a biomarker for ovarian cancer susceptibility.

[Effects of genetic polymorphisms of GSTT1 and GSTM1 on metabolism of Polycyclic aromatic hydrocarbon in coal tar pitch workers].

Objective: To investigate the influence of genetic polymorphisms of GSTT1 and GSTM1 on metabolism of polycyclic aromatic hydrocarbon (PAHs) in coal tar pitch workers and to explore the effective bio-marker of occupational exposure to coal tar pitch. Methods: 374 cases of workers exposed to coal tar pitch work at the enterprise which use and product coal tar pitch in Shan Dong province named as exposure group.The ad-ministrative and the support staff 135 cases were selected as control group.The concentration of the metabolic product in urine by HPLC/MC.The genetic polymorphisms of GSTT1 and GSTM1 were detected by multiple PCR method. Results: The content of metabolic product in smoke group were significantly higher than workers do not smoke (P<0.05) . The content of metabolic product in exposure group were significantly higher than control group (P<0.05) . The content of metabolic product in workers carry positive GSTT1 and GSTM1 were significantly high-er than workers carry negative one (P<0.05) . The content of metabolic product in different types of labor were significantly different (P<0.05) . The content of metabolic product were significantly higher in urine after work than before work (P<0.05) . The content of metabolic product and workers carry positive GSTT1 and GSTM1 had a positive correlation (P<0.05) . Conclusion: Carrying positive GSTT1 and GSTM1 promote polycyclic aromatic hydrocarbons in the body's metabolism.

[The effect of occupational exposure to coal tar pitch workers' health].

Objective: To investigate the effect of occupational exposure to coal tar pitch on workers' health and metabolism. Methods: 805 workers exposed to coal tar pitch were selected as exposure group from the produce and em-ploy factory. Other people handle administrative and logistical affairs who not exposed to coal tar pitch were selected as control group. Fix-point sample of air were collected to detect the concentration of coal tar pitch. Do physical examination and questionnaire to collect workers' basic and healthy information. To detect the metabolic product of urine samples in laboratory. Results: Anomaly detection rate of the skin in exposure group is 10.61. The lung function indices (FEV1.0%) in exposure group were significantly lower than control group (P<0.05) . The monocyte count and monocyte rate in expo-sure group were significantly higher than control group (P<0.05) . The metabolic product content of PAHS in urine sam-ples is significantly higher in exposed group than control group (P<0.05) . Conclusion: The metabolic product content of polycyclic aromatic hydrocarbon is higher in exposed workers. Coal tar pitch damage workers' skin and lung function. It can cause pruritus chromatodermatosis and so on.

[The principle and practice of vidian neurectomy].

The latest research findings on bidirectional regulation of neuro-immunity through traditional neural circuits shed new light on the theoretical basis of the role of vidian neurectomy (VN). This article aims to provide a comprehensive understanding of VN, including the history of VN, the principle of neuroimmuno-interaction, the applied anatomy of VN as well as the methods of transnasal endoscopic surgery. Additionally, we introduce the concept of the nose-brain axis, which was proposed based on the advancement in the area of neuro-immune interactions.