Evaluation of a

We report on an evaluation of an optical clock that uses the ^{2}S_{1/2}→^{2}D_{5/2} transition of a single ^{88}Sr^{+} ion as the reference. In contrast to previous work, we estimate the effective temperature of the blackbody radiation that shifts the reference transition directly during operation from the corresponding frequency shift and the well-characterized sensitivity to thermal radiation. We measure the clock output frequency against an independent ^{171}Yb^{+} ion clock, based on the ^{2}S_{1/2}(F=0)→^{2}F_{7/2}(F=3) electric octupole (E3) transition, and determine the frequency ratio with a total fractional uncertainty of 2.3×10^{-17}. Relying on a previous measurement of the ^{171}Yb^{+} (E3) clock frequency, we find the absolute frequency of the ^{88}Sr^{+} clock transition to be 444 779 044 095 485.277(59) Hz. Our result reduces the uncertainty by a factor of 3 compared with the previously most accurate measurement and may help to resolve so far inconsistent determinations of this value. We also show that for three simultaneously interrogated ^{88}Sr^{+} ions, the increased number causes the expected improvement of the short-term frequency instability of the optical clock without degrading its systematic uncertainty.

Individualized risk assessment of distant metastases in oral cavity carcinoma: a validated predictive-score model.

BACKGROUND: We aimed to develop and validate a risk-scoring system for distant metastases (DMs) in oral cavity carcinoma (OCC). METHODS: Patients with OCC who were treated at 4 tertiary cancer institutions with curative surgery with or without postoperative radiation/chemoradiation therapy were randomly assigned to discovery or validation cohorts (3:2 ratio). Cases were staged on the basis of tumor, node, and metastasis staging according to the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control guidelines. Predictors of DMs on multivariable analysis in the discovery cohort were used to develop a risk-score model and classify patients into risk groups. The utility of the risk classification was evaluated in the validation cohort. RESULTS: Overall, 2749 patients were analyzed. Predictors (risk score coefficient) of DMs in the discovery cohort were the following: pathological stage (p)T3-4 (0.4), pN+ (N1: 0.8; N2: 1.0; N3: 1.5), histologic grade (G) 3 (G3, 0.7), and lymphovascular invasion (0.4). The DM risk groups were defined by the sum of the following risk score coefficients: high (>1.7), intermediate (0.7-1.7), and standard risk (<0.7). The 5-year DM rates (high/intermediate/standard risk groups) were 30%/15%/4% in the discovery cohort (C-index = 0.79) and 35%/16%/5% in the validation cohort, respectively (C-index = 0.77; both P < .001). In the whole cohort, this predictive model showed excellent discriminative ability in predicting DMs without locoregional failure (29%/11%/1%), later (>2 year) DMs (11%/4%/2%), and DMs in patients treated with surgery (20%/12%/5%), postoperative radiation therapy (34%/17%/4%), and postoperative chemoradiation therapy (39%/18%/7%) (all P < .001). The 5-year overall survival rates in the overall cohort were 25%/51%/67% (P < .001). CONCLUSIONS: Patients at higher risk for DMs were identified by use of a predictive-score model for DMs that included pT3-4, pN1/2/3, G3, and lymphovascular invasion. Identified patients may be evaluated for individualized risk-adaptive treatment escalation and/or surveillance strategies.

Differentiation between atypical sinonasal non-Hodgkin's lymphoma and inverted papilloma.

AIM: To seek additional magnetic resonance imaging (MRI) features to improve the accuracy of differentiation between atypical sinonasal non-Hodgkin's lymphoma (NHL) and inverted papilloma (IP) using conventional MRI and apparent diffusion coefficient (ADC) maps. MATERIALS AND METHODS: MRI examinations from 44 atypical cases (21 NHLs and 23 IPs) in sinonasal regions were reviewed retrospectively. Imaging features included tumour laterality, extension, T1-weighted imaging (WI)/T2WI signal intensity homogeneity and ratios, enhancement homogeneity and ratios, and ADCmean. RESULTS: In cases of NHL, homogeneous signal intensity was often observed on T2WI, which was homogeneous and significantly less enhanced than the turbinate, with lower ADCmean. Whereas in IPs, heterogeneous signal intensity was seen on T2WI, which was heterogeneous and of comparable enhancement to the turbinate, and higher ADCmean values were commonly seen. An ADCmean cut-off point of 1.10 × 10-3 mm2/s achieved 100% sensitivity, 90% specificity, and 90% accuracy. In addition, special features were observed that support the distinction between the two tumours, including intestinal pattern enhancement in NHL and spot-like appearance on T2WI and enhancement in IP. CONCLUSIONS: ADCmean was the most valuable metric for differentiating between the atypical sinonasal NHLs and IPs.

[The impact of the dosage of intraoperative opioids on postoperative survival outcomes in patients with pancreatic cancer].

Objective: To investigate the impact of the dosage of intraoperative opioids on postoperative survival of pancreatic cancer patients who underwent pancreatectomy. Methods: The clinical data of 95 patients with pancreatic cancer who underwent pancreatectomy at Harbin Medical University Cancer Hospital from September 2013 to August 2018 were retrospectively collected. Dosage of intraoperative opioid medications was converted to fentanyl equivalent dose. Patients were divided into high-dose group (fentanyl consumption ≥2.21 mg, n=46) and low-dose group (fentanyl consumption<2.21 mg, n=49) according to the median intra-operative fentanyl equivalents. The relapse-free survival (RFS) and overall survival (OS) between the two groups were compared. Cox proportional hazards regression model was used to analyze the impact of important covariates on RFS and OS. Results: RFS of patients in low-dose group at 1, 3 and 5 years was 75.5%, 26.5% and 15.2% respectively. OS of patients in low-dose group at 1, 3 and 5 years was 77.6%, 32.5% and 24.4% respectively. RFS of patients in high-dose group at 1, 3 and 5 years was 76.1%, 23.9% and 12.0% respectively. OS of patients in high-dose group at 1, 3 and 5 years was 76.1%, 37.0% and 15.0%. There was no significant difference in RFS and OS between the two groups (all P>0.05). Multivariate Cox analysis showed that dosage of intraoperative fentanyl was not associated with RFS (HR=1.205, 95%CI: 0.737-1.970, P=0.456) or OS (HR=1.062, 95%CI: 0.634-1.778, P=0.818). Conclusion: Dosage of intraoperative opioid has no effect on RFS and OS in pancreatic cancer patients undergoing pancreatectomy.

The expression of cytokeratin and apoptosis-related molecules in echinococcosis related liver injury.

The study aimed to investigate the expression of cytokeratin and apoptosis-related molecules in the livers of two types of hepatic echinococcosis mice models and to preliminarily explore the relationship between the expression of cytokeratin and apoptosis in echinococcosis related liver injury. We established a mouse model infected by Echinococcus granulosus and Echinococcus multilocularis and observed the expression of cytokeratin and apoptosis related proteins in the two types of hepatic echinococcosis tissues during different stages by immunohistochemical staining. A co-culture model was established using normal hepatocytes and different concentrations of E. granulosus and E. multilocularis protoscoleces. Cell Counting Kit-8 was used to detect cell proliferation, flow cytometry was used to detect hepatocyte apoptosis, and western blot was used to quantify cytokeratin and apoptosis-related proteins, such as caspase3, caspase9, Bcl-2, and Bax. Surgical specimens were obtained from patients with hepatic echinococcosis to analyze the expressions of cytokeratin, caspase3, caspase9, Bcl-2, and Bax by western blot. The expressions of cytokeratin and caspase3 were analyzed by immunohistochemistry. The qRT-PCR method was used to determine the expression of CK8 and CK18 in the liver tissues. In vivo experiments showed that compared to that in the control group, the cytokeratin and caspase3 proteins in the liver tissues of the two types of hepatic echinococcosis were strongly expressed around the lesions of liver echinococcosis; there was a difference between cytokeratin expression of the two different echinococcosis parasites in the liver. Echinococcus granulosus and Echinococcus multilocularis in the co-culture model in vitro could promote the expression of CK, caspase3, caspase9, and Bax protein, decrease the expression of Bcl-2, promote hepatocyte apoptosis, and inhibit cell proliferation; in clinical samples, we found that compared with that in the normal tissues, the expression of cytokeratin, caspase3, caspase9, and Bax in echinococcus tissues was high, but that in Bcl-2 was low. Furthermore, the expression of CK8 and CK18 mRNA were higher in echinococcus tissues than that in the normal tissues and immunohistochemistry analysis also showed that cytokeratin and caspase3 levels were higher in echinococcus tissues than that in the normal tissues. The expression of cytokeratin and apoptosis-related molecules, reflecting liver damage, is high in the liver and is caused due to hepatic echinococcosis. This study provides the first evidence of cytokeratin could be useful for evaluating liver tissue damage caused by echinococcus infection.

[Interventional effect of metformin on pulmonary inflammation and pulmonary fibrosis in silicotic rats].

Objective: To investigate the interventional effect of metformin on pulmonary inflammation and pulmonary fibrosis in silicotic rats. Methods: In April 2019, 48 Wistar male rats of SPF grade were randomly divided into negative control group, metformin control group, silicon dioxide (SiO2) model group, low, medium and high dose metformin intervention group according to the random number table method, 8 rats in each group. The SiO2 model group and the low, medium and high dose metformin intervention groups were given 1 ml 50 mg/ml of SiO2 by intratracheal instillation, the negative control group and the metformin control group were given 1 ml normal saline by intratracheal instillation. 24 hours later, the low, medium and high dose metformin intervention groups and the metformin control group were treated with 100, 200, 400 and 400 mg/kg metformin daily, the control and SiO2 model groups received normal saline daily. Then the rats were sacrificed at the 28th day after SiO2 exposure. The changes of rat body weight and pathological examination of rat lung tissue were observed, and the lung organ coefficient, the content of hydroxyproline (HYP) , the expression levels of inflammatory factors transforming growth factor beta1 (TGF-ß1) , tumor necrosis factor-alpha (TNF-α) , interleukin-1beta (IL-1ß) and the protein expression of E-cadherin (E-Cad) , Vimentin, α-SMA were detected. Results: Compared with the negative control group, SiO2 model group had a significant decrease in the body weight of rats (P<0.05) , lung organ coefficient, alveolitis and fibrosis scores, HYP content and the levels of TGF-ß1, TNF-α, IL-1ß were all significantly increased (P<0.05) . Compared with the SiO2 model group, the weights of the rats in the medium and high dose intervention group of metformin increased significantly (P<0.05) . And after intervention with different doses of metformin, the lung organ coefficient, alveolitis and fibrosis scores, HYP content and the levels of TGF-ß1, TNF-α and IL-1ß were significantly decreased (P<0.05) . Immunohistochemistry and Western blotting results showed that compared with the negative control group, the expression of E-Cad of the SiO2 model group was decreased, and the expression levels of Vimentin and α-SMA were significantly increased (P<0.05) . After metformin intervention, the expression of E-Cad was significantly increased, the expression levels of Vimentin and α-SMA were significantly decreased (P<0.05) . Conclusion: Metformin can reduce lung tissue inflammation and fibrosis in rats exposed to SiO2 dust, which may be related to reducing the expression of inflammatory factors in lung tissue and inhibiting the EMT process.

[Diagnosis, treatment and outcome of adnexal torsion at different gestational weeks during pregnancy].

Objective: To investigate the clinical characteristics, diagnosis, treatment and outcome of adnexal torsion at different gestational weeks during pregnancy. Methods: A retrospective analysis was conducted of the clinical data of 24 pregnancy patients with adnexal torsion, aged 21-38 (30.6±4.4) years old, who were admitted and delivered in Peking University Third Hospital from 2015 to 2019. According to the gestational age, all patients were divided into two groups:<28 weeks group (11cases) and ≥28 weeks group (13 cases), to compare the intergroup differences in clinical characteristics, treatment and outcome, and the differences of clinical data and outcome between two groups were compared. Results: The proportion of patients with twin pregnancy and assisted reproductive technology in the<28 weeks group was significantly higher than that in the ≥28 weeks group (5/11 vs 1/13, 8/11 vs 1/13, P<0.05). No significant differences between the two groups were recorded in terms of the size of the adnexal mass, the cycles of torsion and the duration from onset to operation. Compared with the≥28 weeks group, the adnexal removal rate of the<28 weeks group was lower (3/11 vs 6/13), but the difference was not statistically significant. The proportion of blood flow signals of ultrasound before operation, cases undergoing laparoscopic surgery and cases whose pathological findings were physiological cysts in the<28 weeks group were significantly higher than that in the ≥28 weeks group (8/11 vs 4/13, 8/11 vs 0, 8/11vs 4/13; P<0.05). Concerning the pregnancy outcomes, there was no difference in the mode of delivery, the delivery gestational age and the body weight of newborns between the two groups. Conclusions: The patients with adnexal torsion prior to 28 weeks(<28 weeks)of pregnancy were more likely to be conceived by assisted reproductive technologies, and the etiology was more likely to be ovarian physiological cysts. Both laparoscopy and laparotomy were safe and effective in the treatment of adnexal torsion with good outcome for mother and infant in the study.

[Analysis of incidence characteristics of occupational chronic benzene poisoning under two diagnostic criteria].

Objective: To analyze the incidence characteristics of occupational chronic benzene poisoning under two diagnostic criteria. Methods: In March 2020, 126 patients who were divided into the old criteria group (74 cases) and the new criteria group (52 cases) were retrospectively analyzed. These patients were diagnosed with occupational chronic benzene poisoning, and were diagnosed in our hospital during the period of January 2009 to December 2019. The gender composition, age of onset, years of benzene exposure, industry distribution, work type, benzene concentration in working environment and diagnostic grade of the two groups of patients were analyzed and compared. The follow-up of 22 benzene poisoning observation subjects under the old criteria were retrospectively analyzed. Results: There were no statistically significant differences in gender composition, age of onset, years of benzene exposure, industry distribution and work type between the old criteria group and the new criteria group (P>0.05) . In the old criteria group and the new criteria group, 41.9% (31/74) and 17.3% (9/52) of the patients' workplace benzene concentration exceeded the maximum allowable concentration, respectively. The composition of different benzene concentration in the workplace between the two groups showed statistically significant (P<0.05) . In the old criteria group, the proportion of mild poisoning (79.7%, 59/74) was the majority, while in the new criteria group, the proportion of moderate and severe poisoning (51.9%, 27/52) were the majority, and there was statistically significance in the composition ratio of diagnostic grade between the two groups (P<0.05) . Under the old criteria, after folow-up of 22 cases of benzene poisoning observation subjects, we observed that 8 cases (36.4%) progressed to the level of chronic benzene poisoning. Conclusion: The revision of diagnostic criteria for benzene poisoning may affect the composition of diagnosis classification. Based on the rights and interests of workers, formulating more complete diagnostic criteria and system policies will be more conducive to the development of occupational benzene poisoning prevention and control.

[Changes of neuron specific enolase in serum of patients with silicosis].

Objective: To explore the changes of neuron specific enolase (NSE) concentration in serum samples of patients with silicosis. Methods: In January 2020, 455 cases of silicosis diagnosed in Yantaishan Hospital from January 2018 to December 2019 were collected, and 60 healthy cases and 120 cases of lung cancer were selected as the healthy group and the lung cancer group. The serum levels of NSE were detected by chemical immunofluorescence assay and compared. Results: The serum NSE level of silicosis patients was [(22.88±7.86) ng/ml], higher than that of healthy group [(17.96±4.42) ng/ml] (P<0.05) . Serum NSE levels in the first, second and third stage silicosis groups were higher than those in the healthy group (P<0.05) , but there was no statistically significant difference between the silicosis groups at different periods (P>0.05) . The serum NSE level of silicosis patients was lower than that of the small cell lung cancer group (P<0.05) , but there was no statistically significant difference between silicosis group and non-small cell lung cancer group (P>0.05) . The area under curve of silicosis NSE was 0.718 (P<0.01) when the cut-off was 17.49 ng/ml, the sensitivity and specificity of NSE was 78% and 57% respectively. Conclusion: The serum NSE level of patients with silicosis is significantly increased, which can be used as an important reference index for the diagnosis and the differential diagnosis of silicosis.

[The spectrum of pathogens in 187 cases of pulmonary fungal disease diagnosed by histopathology-a retrospective analysis].

Objective: To investigate the spectrum of pathogens causing lung fungal disease diagnosed by histopathology through histochemical special staining, compared to the fungal culture results, and to further evaluate the diagnostic value of histochemical special staining in pulmonary fungal disease. Methods: We performed a retrospective analysis of 187 cases of pulmonary fungal disease diagnosed by histopathology in Peking Union Medical College Hospital from 2001 to 2015 (including 92 cases with pulmonary resection or open lung biopsy, 33 with percutaneous lung biopsy and 62 ones with fiberoptic bronchoscopic lung biopsy). All cases were treated with hexamine silver, PAS, mucus carmine and acid-fast staining in addition to conventional HE staining. The clinical records and the fungal culture results were reviewed. Results: There were 103 male and 84 female patients, aged from 12 to 70 years [average (48±14) years]. There were 85 cases(45.5%) of pulmonary aspergillosis(including 60 cases of invasive infection and 25 cases of aspergilloma), 51 cases(27.3%) of pulmonary cryptococosis, 6 cases (3.2%)of pulmonary mucormycosis, 3 cases(1.6%) of pulmonary histoplasmosis, 3 cases (1.6%)of pulmonary candidiasis, and 2 cases (1.1%) of pneumocystosis, while in the remaining 37 cases (19.8%) the pathogens could not be clearly classified by microscopy due to limited tissue or degeneration. Among the 88 patients with pulmonary fungal disease diagnosed by histopathology from 2011 to 2015, 35 ones (39.9%) were detected by fungal culture (including lung biopsy, intraoperative swab, blood, bronchoalveolar lavage fluid and sputum, etc.). The diagnostic results of 18 cases were completely consistent between histopathological examination and fungal culture (18/35, 51.4%), while 13 cases (13/35, 37.1%) were diagnosed by histopathology but no fungi were cultured, and in 3 cases (3/35,8.6%) the culture was positive for fungi which could not be classified clearly by histopathology. In another case the pathogen was found to be Cryptococcus histopathologically but the lavage culture grew"candida", but the patient's blood cryptococcal antigen was positive. Conclusions: Among patients with histopathological diagnosis of pulmonary fungal disease, pulmonary aspergillosis was the most common, followed by pulmonary cryptococcosis, pulmonary mucormycosis, pulmonary histoplasmosis, pulmonary candidiasis and pneumocystosis. A small number of cases could not be classified by histopathology through histochemical special staining. There was a high consistency in discovering fungal pathogens between pathological histochemical special staining and culture method, but 37% pulmonary fungal disease diagnosed by histopathology were culture negative. In practice, the role of histochemical special staining in diagnosing pulmonary fungal disease should be paid more attention.

Estimation of effective dose of propofol mono-sedation for successful insertion of upper gastrointestinal endoscope in healthy, non-obese Chinese adults.

WHAT IS KNOWN AND OBJECTIVE: Propofol is effective in sedation for upper gastrointestinal (UGI) endoscopy. However, the optimum dose is ill-defined. This study aimed to estimate the effective dose of propofol mono-sedation for successful endoscope insertion in healthy, non-obese Chinese adults undergoing single UGI endoscopy. METHODS: Twenty-six adult patients undergoing elective single UGI endoscopy were enrolled in this study. A modified Dixon's up-and-down method was utilized to assess the effective dose of propofol for successful endoscope insertion. The initial dose of propofol administered, 1.6 mg/kg, was adjusted with 0.1 mg/kg as a step size. The patient's responses to endoscope insertion were classified as either 'movement' or 'no movement'. When patient's responses were changed from 'movement' to 'no movement' or from 'no movement' to 'movement', a crossover was defined. After eight crossovers had been obtained, patient recruitment was stopped. The mean of midpoints of all crossovers obtained by the modified Dixon's up-and-down method in all 26 patients was defined as calculated median effective dose (ED50 ) of propofol for successful endoscope insertion. Furthermore, probit regression analysis was used to determine the dose of propofol where 50% (ED50 ) and 95% (ED95 ) of endoscope insertion attempts were successful. RESULTS: The calculated ED50 of propofol for successful endoscope insertion was 1.89 ± 0.12 mg/kg. The probit regression analysis showed that ED50 and ED95 of propofol for successful endoscope insertion were 1.90 mg/kg (95% CI, 1.78-2.10 mg/kg) and 2.15 mg/kg (95% CI, 2.01-3.56 mg/kg), respectively. No any patient had hypoxaemia and gag reflex during the UGI endoscopy with propofol mono-sedation. WHAT IS NEW AND CONCLUSION: In healthy, non-obese Chinese adults, propofol mono-sedation can provide excellent conditions of UGI endoscopy and the estimated ED50 of propofol for successful endoscope insertion is 1.89 ± 0.12 mg/kg.

Pre- and Post-Radiotherapy Radiologic Nodal Features and Oropharyngeal Cancer Outcomes.

OBJECTIVES: To assess the prognostic value of pre-/post-radiotherapy (pre-/post-RT) radiologic lymph node (LN) features in human papillomavirus (HPV)-positive and HPV-negative oropharyngeal carcinoma (OPC) patients treated with definitive (chemo-)RT. METHODS: Clinical node-positive OPCs treated from 2011 to 2015 were reviewed. Nodal features were reviewed by a radiologist on pre-/post-RT computed tomography (CTs). Univariable analysis calculated hazard ratio (HR) for regional failure (RF), distant metastasis (DM), and deaths. Multivariable analysis estimated adjusted HR (aHR) of significant nodal features identified in univariable analysis adjusting for confounders. RESULTS: Pre-RT CT was undertaken in 344 HPV-positive and 94 HPV-negative OPC patients, of whom 242 (70%) HPV-positive and 67 (71%) HPV-negative also had a post-RT CT. Median follow-up was 4.9 years. Pre-RT LN calcification (pre-RT_LN-cal) increased the risk of RF in HPV-negative (aHR: 5.3, P = .007) but not HPV-positive patients (P = .110). Pre-RT radiologic extranodal extension (pre-RT_rENE+) increased the risk of DM and death in both HPV-negative (DM: aHR 6.6, P < .001; death: aHR 2.1, both P = .019) and HPV-positive patients (DM: aHR 4.9; death: aHR 3.0, both P < .001). Increased risk of RF occured with < 20% post-RT LN size reduction in both HPV-negative (HR 6.0, P = .002) and HPV-positive cases (HR 3.0, P = .049). Post-RT_LN-cal did not affect RF, DM, or death regardless of tumor HPV status (all P > .05). CONCLUSION: Pre-RT_LN-cal is associated with higher RF risk in HPV-negative but not in HPV-positive patients. Pre-RT_rENE increases risk of DM and death regardless of tumor HPV status. Minimal post-RT LN size reduction (< 20%) increases risk of RF in both diseases. Post-RT_LN-cal + has no apparent influence on outcomes in either disease. LEVEL OF EVIDENCE: 4 (a single institution case-control series) Laryngoscope, 131:E1162-E1171, 2021.

Correlation between growth differentiation factor-15 and the severity of chronic heart failure in patients with coronary atherosclerosis.

OBJECTIVE: To explore the correlation of the growth differentiation factor-15 (GDF-15) with the severity of chronic heart failure (CHF) in patients with coronary atherosclerosis. PATIENTS AND METHODS: 300 coronary atherosclerosis patients with CHF treated in our hospital from January 2019 to December 2019 and 300 healthy people (control group) were collected and retrospectively analyzed. The basic clinical information of the patients, such as age, gender, smoking/drinking history, waist-hip ratio, BMI and blood lipid were collected, and GDF-15, cystatin C and c-reactive protein (CRP) were determined. The severity of heart failure was classified. RESULTS: No significant differences in clinical information were found such as age, gender, smoking/drinking history, waist-to-hip ratio, BMI and blood lipid. However, there were significant differences in GDF-15, cystatin C and CRP among patients with different severities of heart failure. The GDF-15 level was 582.6 ± 104.4 pg/ml in patients with grade IV heart failure and 408.4 ± 94.8 pg/ml in patients with grade I heart failure. There was a significance after GDF-15, cystatin C and CRP were adjusted (p = 0.03) and also after the clinical information and GDF-15 were adjusted (p < 0.001). CONCLUSIONS: GDF-15 level is correlated with the CHF severity in patients with coronary atherosclerosis, indicating that it is a potential index to evaluate the CHF severity, providing clues to the biological mechanism and treatment of heart failure.

[Research progress of ferroptosis-related mechanism and diseases].

Ferroptosis is a new programmed cell death characterized by iron dependent and intracellular oxidative accumulation. Current studies have confirmed that ferroptosis is involved in the occurrence and development of neurotoxicity injury, tumors, cardiovascular diseases and other diseases. This paper reviews the mechanisms of ferroptosis and its role in related diseases based on recent studies.

[Analysis of the relationship between the changes of lung function and serum proinflammatory cytokines in workers occupationally exposed to toluene diisocyanate].

Objective: To analyze the correlation between the changes of lung function and serum proinflammatory cytokines in workers occupationally exposed to toluene diisocyanate (TDI), and to explore the evaluation index of respiratory toxicity of TDI. Methods: In October 2014, 61 male workers engaged in TDI synthesis process, purification process, packaging process and the above production process in a TDI factory in western China were selected as TDI exposure group; 62 male enterprise managers who were not exposed to TDI and other known allergenic chemicals were selected as control group, which were matched at the age of workers in exposure group. The questionnaire survey obtained information such as gender, length of service, age, occupational history, exposed length of service and so on. The lung function indexes [forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC] and serum levels of interleukin (IL)-1 ß, IL-6, IL-8, tumor necrosis factor (TNF)-α, macrophage inflammatory factor-1 ß, monocyte chemoattractant factor-1 and vascular endothelial growth factor were measured. The urine was collected after the weekend shift, and the concentration of (TDA), the metabolite of TDI, was determined as the index of internal exposure. Spearman rank correlation was used to analyze the correlation between cytokines and lung function indexes, and multivariate linear regression was used to analyze the changes of lung function indexes and cytokines with TDI exposure concentration and time. Results: The median age (P5-P95) of the exposed group and the control group was 36.5 (24.0-51.0) and 38.0 (24.0-50.0) years, respectively. In the exposed group, the median length of service (P5-P95) was 6.94 (0.97-26.33) years, and the median concentration of TDA in urine was 15.56 (2.28-112.16) ng/ml. The three indexes of lung function, FVC, FEV1, FEV1/FVC and the levels of serum IL-8 and TNF-α were significantly lower than those in the control group (P<0.01). With the increase of exposure concentration and exposure time, the level of serum TNF-α, FVC and FEV1 decreased, and showed a good dose-effect and time-effect relationship (all Ptrend values< 0.05). Serum IL-8 and TNF-α were positively correlated with FVC, FEV1 and FEV1/FVC (all P values<0.01). Conclusion: The levels of serum inflammatory factors IL-8 and TNF-α in worker exposed to TDI are related to lung function indexes, which can be used as early evaluation indexes of respiratory toxicity induced by TDI.

[Inhibition of NLRP3 inflammasome activation on the inflammatory response of macrophage induced by silica dust].

Objective: To investigate the effect of inhibiting the activation of NLRP3 inflammatory bodies on the inflammatory response of macrophages induced by silica (SiO(2)) dust. Methods: Rat alveolar macrophages (NR8383) cells were used to establish the cell model, which was divided into four groups: blank control group, dust exposure group (50 mg/L silica dust suspension) , NLRP3 inhibitor group (50 mg/L silica dust suspension and 20 µmol/L NLRP3 inhibitor) , luteolin group (50 mg/L silica dust suspension and 20 µmol/L luteolin) . Samples were collected at 12, 24 and 48 hours after culture. The secretion of inflammatory factors IL and TGF-ß(1) were detected by ELISA. The levels of NLRP3 and Caspase-1 were detected by Western Blot. Results: Compared with the blank control group, the survival rates of NR8383 cells in the dust exposure group, NLRP3 inhibitor group and luteolin group were all decreased after 12, 24 and 48 hours of dust exposure, and the expression levels of IL-1ß, IL-18, TGF-ß1, NLRP3 and Caspase-1 were significantly increased (P<0.05) . Compared with the dust exposure group, NR8383 cells in NLRP3 inhibitor group and luteolin group had higher cell survival rates and lower levels of IL-1ß, IL-18, TGF-ß1, NLRP3 and Caspase-1 after 12, 24 and 48 hours of dust exposure (P<0.05) . Compared with the NLRP3 inhibitor group, the IL-1ß level of NR8383 cells in luteolin group decreased significantly at 12, 24 and 48 h, the IL-18 and TGF-ß1 levels decreased significantly at 48 h, the NLRP3 and Caspase-1 levels decreased significantly at 24 h (P<0.05) . Conclusion: Inhibition of NLRP3 inflammaasome activation can reduce the inflammatory response of macrophages induced by SiO(2) dust.

[Laparoscopic gastroduodenostomy with manual suture for Billroth â anastomosis: a report of 36 cases].

Objective: To examine the clinical efficiency of laparoscopic gastroduodenostomy with BillrothⅠanastomosis with manual suture. Methods: The clinic data of 36 patients with gastric cancer who underwent laparoscopic gastroduodenostomy with Billroth Ⅰ anastomosis from November 2017 to September 2019 in Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital were analyzed retrospectively.There were 22 males and 14 females, aged (64.3±9.3) years(range: 43 to 80 years), underwent complete laparoscopic gastroduodenostomy. The laparoscopic manual suture was used for Billroth Ⅰ anastomosis. Results: All the laparoscopic radical gastrectomy and manual suturing gastroduodenostomy were successfully performed. The operation time was (226.7±40.4) minutes (range: 180 to 320 minutes), including (24.8±7.1) minutes (range: 15 to 48 minutes) for gastroduodenostomy.There was (3.8±0.9) days (range: 2 to 6 days) for anal exhaust, (5.7±2.0) days (range: 3 to 13 days) for extubation of gastric tube, and (10.3±3.1) days (range: 7 to 19 days) for hospitalization. There was no death in perioperative period. Postoperative pathological report showed 3 cases of highly differentiated adenocarcinoma, 5 cases of moderately differentiated adenocarcinoma, 22 cases of poorly differentiated adenocarcinoma and 6 cases of signet ring cell carcinoma, including 27 cases in T1 stage and 9 cases in T2 stage. The number of lymph nodes harvested was 36.4±8.9 (range: 23 to 60). Lymph node metastasis was positive in 7 cases and negative in 29 cases. TNM stage included 24 cases in ⅠA stage, 8 cases in ⅠB stage and 4 cases in Ⅱ stage. After the operation, the upper digestive tract radiography showed that the anastomosis opening was unobstructed without complications such as anastomotic stenosis. Conclusion: Laparoscopic gastroduodenostomy with Billroth Ⅰ anastomosis with manual suture is safe and feasible, has a good short-term effect.