ObjectiveTo understand the survival time and possible influencing factors of pneumoconiosis patients in Ninghai County， Zhejiang Province who were followed up from 2019 to 2023， and to provide references for prolonging the survival time of pneumoconiosis patients. MethodsInformation about pneumoconiosis patients was collected from the sub-module Occupational Disease Follow-Up Management and Follow-Up Excel database of the Occupational Disease and Health Hazards Monitoring Information System. Survival analysis was conducted through applying Kaplan-Meier survival curves and Cox regression models. ResultsOf the 366 pneumoconiosis patients， 99.73% were male， 71.04% had stage Ⅰ pneumoconiosis， and the disease type was mainly silicosis. The survival rates at 5， 10， and 20 years after diagnosis of pneumoconiosis were 97%， 88%， and 62%， respectively， with a cumulative survival rate of 42%. The median survival time of patients with pneumoconiosis was 32.11 years. Log-rank test found statistically significant differences in the survival curves among pneumoconiosis patients with different pneumoconiosis stages， age at first diagnosis， and pneumoconiosis complications. Cox regression analysis revealed that the risk of reduced survival time in patients with pneumoconiosis stage Ⅲ was 2.184 times higher than that of patients with stage Ⅰ （P=0.007）. In comparison with the age of first diagnosis at <50 years old group， the risk of reduced survival time was 3.457 and 7.097 times higher， respectively， in the groups of patients who received the diagnosis at 50‒ and ≥60 years （both P<0.001）. The risk of reduced survival time in pneumoconiosis patients with complications was 2.030 times higher than that of patients without complications （P=0.003）. ConclusionSurvival time of pneumoconiosis patients in Ninghai County is affected by the age at first diagnosis， pneumoconiosis stage and pneumoconiosis complications. The survival time can be significantly prolonged by timely detection and diagnosis， as well as active prevention and treatment of pneumoconiosis complications.

Background Pneumoconiosis is one of the most common and widespread prescribed occupational diseases in China, and there is no cure for it at present. The Healthy China 2030 underlines that the prevention and treatment of pneumoconiosis are the critical element of promoting occupational health. Objective To understand the basic characteristics, social security, and death causes of pneumoconiosis cases in Ninghai County, and to provide a basis for scientific prevention and treatment of pneumoconiosis. Methods Information on pneumoconiosis cases in Ninghai County from 1974 to 2019 was obtained by consulting occupational disease and occupational health information monitoring systems, occupational disease diagnosis institutions, and employers, which may retain original data on occupational pneumoconiosis diagnosis, as well as specialized epidemiological survey projects on pneumoconiosis. Telephone or face-to-face follow-up visits were conducted based on relevant information to complete or verify relevant information such as length of service with dust exposure, type, stage, and diagnosis date of pneumoconiosis. ANOVA, chi-square test, and rank-sum test were used to analyze age of diagnosis and age of death, entitlement to social security and mortality rate of cases/length of service. Results As of the end of 2019, a total of 420 cases of pneumoconiosis were diagnosed among workers exposed to dust in Ninghai County, with 409 cases (97.38%) followed up and 11 cases (2.62%) lost to follow-up. Since the first case of pneumoconiosis was reported in 1974, 39 cases, 278 cases, and 101 cases of pneumoconiosis were reported before 2000, from 2000 to 2009, and from 2010 to 2019, respectively. Two other cases of pneumoconiosis were diagnosed with an unknown year, one as a dead case and one as a lost case. There were 294 surviving pneumoconiosis cases, who mainly lived in Sangzhou Town. The mean age of diagnosis was (58.68±15.37) years old, and the median length of service with exposure to dust was 8.0 (4.0, 15.7) years. The age of diagnosing stage III pneumoconiosis was less than that of stage I and stage II, and the difference between the age of diagnosing stage III and stage II pneumoconiosis was significant (P <0.05). There were 231 cases (78.57%) aged ≥ 60 years, while there were 74 cases aged ≥ 80 years (25.17%). There were 160 cases (54.42%) whose length of service was < 10 years. There were 12.59% and 7.82% of the total cases compensated by work injury insurance and civil compensation by employers, respectively. From the perspective of diagnosis period, the proportion of patients who collected work-related injury insurance and civil compensation from employers in the 2010—2019 year group was higher than that in the <2000 year group or the 2000—2009 year group (P<0.01). There were 115 fatal pneumoconiosis cases, and the fatality rates of stage I, II , and III pneumoconiosis were 23.86%, 18.18%, and 50.75%, respectively. The fatality rate of stage III pneumoconiosis was higher than that of stage I or II (P <0.05). The age of diagnosis and age of death of stage III pneumoconiosis cases were lower than those of stage I and II (P <0.05). The cause of death was definite in 65 patients, including 25 cases (38.46%) of respiratory diseases (except lung cancer) and 28 cases (43.07%) of tumors, and lung cancer accounted for 1/2 of the pneumoconiosis cases that died due to tumors. Conclusion The surviving pneumoconiosis cases in Ninghai are mainly older than 60 years old and largely live in Sangzhou Town. Constructing local rehabilitation stations should be taken as an opportunity to actively prevent and treat pneumoconiosis complications, further improving the quality of life of pneumoconiosis patients.

Abstract To investigate the curative effects of modified submucosal tunnel endoscopic resection(STER) and endoscopic submucosal resection(ESE) in the treatment of paracardial submucosal tumors. Eighty-four patients with paracardial submucosal tumors diagnosed through digestive endoscopy and endoscopic ultrasonography signed informed consent forms, and they were randomly divided into observation group(n=42) and control group(n=42) with the help of the table of random numbers. Patients in the control group received ESE treatment. Patients in the observation group received modified STER surgery.The operation time, average hospitalization time and treatment cost of patients in STER group were(61.32±32.01) min,(8.11±2.42) d and(21.7±3.4) thousand Chinese Yuan respectively, which were better than those in ESE group(87.63±34.09) min,(10.05±2.84) d and(25.9±3.9) thousand Chinese Yuan. The difference was statistically significant(P<0.05). The average number of titanium clips used in the observation group was(5.00±1.37), and in the control group the average number was(4.68±1.25). The difference was not statistically significant. In the STER group, there were 2 cases of intraoperative perforation and 1 case of delayed bleeding. In the ESE group, there were 4 cases of intraoperative perforation and 3 cases of intraoperative uncontrollable bleeding. The incidence of postoperative complications in the STER group was lower than that in the ESE group. The postoperative pathological examination revealed that in both groups the tumors were mostly stromal tumor and leiomyoma. A few of the patients were suffering from lipomas and schwannomas. There was no significant difference in terms of the pathological composition of the patients between the two groups.

Objective:To observe the expressions of complement 3 (C3) and endothelial cell injury-associated proteins before and after cathepsin L (CTSL) blockade in renal injury of trichloroethylene (TCE) -sensitized mice.Methods:In June 2018, 41 SPF female BALB/c mice were divided respectively into blank control group ( n=5) , vehicle control group ( n=5) , TCE group ( n=15) and TCE+CTSLi group ( n=16) to establish trichloroethylene-sensitized mice model by pretreating the mice with intraperitoneal injection of CTSL inhibitor (CTSLi) and using TCE for the first and last challenge. According to the skin sensitization score, the mice were divided into positive group and negative group. 72 hours after the last challenge, the renal function indexes of the mice were detected, the pathological changes of mice kidneys were observed, and the glomerular C3 and endothelial cell damage-related proteins [vascular cell adhesion molecule 1 (VCAM-1) , tight junction protein 5 (Claudin-5) and Syndecan-1] expression levels were detected. Results:The sensitization rates of mice in TCE group and TCE+CTSLi group were 53.3% (8/15) and 50.0% (8/16) , respectively, and there was no significant difference between the two groups ( P>0.05) . Compared with vehicle control group and the corresponding TCE negative group, the serum creatinine (CRE) and blood urea nitrogen (BUN) levels of mice in the TCE positive group was increased, while the TCE positive group were higher than the TCE+CTSLi positive group ( P<0.05) . Pathological examination showed obvious vacuolar degeneration and cellular edema in the mice kidney of the TCE positive group. In the TCE+CTSLi positive group, the above pathological damage was significantly improved. Immunohistochemical results showed that the expression of glomerular C3 fragment and VCAM-1 in TCE positive group were significantly higher than that of the vehicle control and TCE negative group ( P<0.05) , while TCE+CTSLi positive group was significantly lower than that of TCE positive group ( P<0.05) . Western blot test results showed that the relative expression levels of Claudin-5 and Syndecan-1 protein in the mice glomeruli of TCE positive group were significantly lower than those in the vehicle control group and TCE negative group ( P<0.05) . Compared with the TCE positive group, the Claudin-5 protein was increased in the kidney of the TCE+CTSLi positive group, but the difference was not statistically significant ( P>0.05) , while the Syndecan-1 protein was significantly increased in the TCE+CTSLi positive group ( P<0.05) . Conclusion:CTSL may mediate the glomerular structural damage by cutting complement C3, activating the complement system, damaging endothelial cell structural protein Syndecan-1 and overexpressing adhesion molecule VCAM-1 in TCE-sensitized mice. Inhibiting the expression of CTSL may be an effective way to protect the glomerular integrity of structure and function in pharmacology.

Objective:To observe the expressions of complement 3 (C3) and endothelial cell injury-associated proteins before and after cathepsin L (CTSL) blockade in renal injury of trichloroethylene (TCE) -sensitized mice.Methods:In June 2018, 41 SPF female BALB/c mice were divided respectively into blank control group ( n=5) , vehicle control group ( n=5) , TCE group ( n=15) and TCE+CTSLi group ( n=16) to establish trichloroethylene-sensitized mice model by pretreating the mice with intraperitoneal injection of CTSL inhibitor (CTSLi) and using TCE for the first and last challenge. According to the skin sensitization score, the mice were divided into positive group and negative group. 72 hours after the last challenge, the renal function indexes of the mice were detected, the pathological changes of mice kidneys were observed, and the glomerular C3 and endothelial cell damage-related proteins [vascular cell adhesion molecule 1 (VCAM-1) , tight junction protein 5 (Claudin-5) and Syndecan-1] expression levels were detected. Results:The sensitization rates of mice in TCE group and TCE+CTSLi group were 53.3% (8/15) and 50.0% (8/16) , respectively, and there was no significant difference between the two groups ( P>0.05) . Compared with vehicle control group and the corresponding TCE negative group, the serum creatinine (CRE) and blood urea nitrogen (BUN) levels of mice in the TCE positive group was increased, while the TCE positive group were higher than the TCE+CTSLi positive group ( P<0.05) . Pathological examination showed obvious vacuolar degeneration and cellular edema in the mice kidney of the TCE positive group. In the TCE+CTSLi positive group, the above pathological damage was significantly improved. Immunohistochemical results showed that the expression of glomerular C3 fragment and VCAM-1 in TCE positive group were significantly higher than that of the vehicle control and TCE negative group ( P<0.05) , while TCE+CTSLi positive group was significantly lower than that of TCE positive group ( P<0.05) . Western blot test results showed that the relative expression levels of Claudin-5 and Syndecan-1 protein in the mice glomeruli of TCE positive group were significantly lower than those in the vehicle control group and TCE negative group ( P<0.05) . Compared with the TCE positive group, the Claudin-5 protein was increased in the kidney of the TCE+CTSLi positive group, but the difference was not statistically significant ( P>0.05) , while the Syndecan-1 protein was significantly increased in the TCE+CTSLi positive group ( P<0.05) . Conclusion:CTSL may mediate the glomerular structural damage by cutting complement C3, activating the complement system, damaging endothelial cell structural protein Syndecan-1 and overexpressing adhesion molecule VCAM-1 in TCE-sensitized mice. Inhibiting the expression of CTSL may be an effective way to protect the glomerular integrity of structure and function in pharmacology.

OBJECTIVE: To observe the expression of interleukin(IL)-23 and IL-17 in the liver of mice sensitized by trichloroethylene(TCE), and to explore the role of IL-23 and IL-17 in polyinosinic: polycytidylic acid(Poly I:C) exacerbated TCE-sensitized mice with immune injury of the liver. METHODS: Female specific pathogens free BALB/c mice were randomly divided into control group(n=5), solvent control group(n=5), TCE group(n=20), and TCE+Poly I:C group(n=20). A TCE-sensitized mouse model was established in TCE group and TCE+Poly I:C group. Three hours before the last challenge, mice in TCE+Poly I:C group was intraperitoneally injected with a mass concentration of 0.5 g/L poly I:C, 100 μL per mouse. The two groups of mice were divided into sensitized and non-sensitized subgroups according to the results of skin sensitization. After 48 hours of the final challenge, serum alanine aminotransferase(ALT) was detected by colorimetric method. The histopathological changes of mouse liver were observed, and the expression of IL-23 and IL-17 in liver tissues was detected by immunohistochemistry and Western blotting method. RESULTS: The sensitization rates of TCE and TCE+Poly I:C groups were 35.0%(7/20) and 40.0%(8/20) respectively, with no significantly statistical difference(P>0.05). Pathological examination showed that there was cell edema in some areas of the liver tissues of mice in the TCE-sensitized subgroup, while the TCE+Poly I:C sensitized subgroup showed cell vacuolar degeneration and loose cytoplasm. Serum ALT activity and the expression of IL-23 and IL-17 in liver tissues in the TCE-sensitized subgroup were higher than that in the blank control group, the solvent control group and the TCE non-sensitized subgroup(P<0.05). Serum ALT activity and IL-23 and IL-17 expression in the TCE+Poly I:C sensitized subgroup were higher than that in the TCE-sensitized subgroup(P<0.05). The relative expression of IL-23 and IL-17 protein in liver tissues in TCE-sensitized subgroup was higher than that of the blank control group and the solvent control group(P<0.05), while that in TCE+Poly I:C sensitized subgroup was higher than that of TCE-sensitized subgroup(P<0.05). CONCLUSION: IL-23/IL-17 axis may play an important role in the development of immune injury of liver in the TCE-sensitized mice and Poly I:C exacerbated TCE-sensitized mice.

Objective: To establish a triple-color pseudovirion-based neutralization assay (PBNA) and evaluate its capability of detecting immunogenicity of the sera generated by the immunization of HPV 9-valent vaccine. Methods: HPV pseudovirus (PsVs) 6/11/16/18/31/33/45/52/58 with the encapsidated fluorescence expressing red fluorescent plasmid N31-MCHREEY, green fluorescent N31-EGFP or blue fluorescent N31-mTagBFP were generated. The concentration of HPV PsVs and the infection titers of HPV PsVs were detected by double-antibody sandwich ELISA and TCID₅₀, respectively. The single- and triple color HPV 16/33/45 PsVs were used to detect the neutralization titers of mice sera immunized with HPV 9-valent vaccine and confirmed the accuracy and specificity of the triple-color PBNAs. Then, the single- and triple color HPV 6/11/18/31/33/45/52/58 PsVs were employed to detect the neutralization titers of cynomolgus macaques sera immunized with HPV 9-valent vaccine and determined whether the triple-color PBNAs could be applied to evaluate the immunogenicity of the sera generated by the immunization of HPV9-valent vaccine. Results: The concentration of HPV16 PsVs encapsulating green, red or blue fluorescent plasmid was 5.0 to 6.0 μg/ml and HPV6/11/18/31/33/45/52/59 triple-color HPV PsVs was about 1.0 to 3.0 μg/ml. 9 types HPV PsVs containing EGFP, Mcherry or mTagBFP reporter plasmid were obtained and the concentration can meet the need of neutralization detection. 9 types single-color fluorescent HPV PsVs had similar infectivity against 293FT cells with the infection titer values between 1×10⁴ and 1×10⁵. The results of PBNAs showed that there was no significant difference in the anti-HPV neutralization titers of mice sera induced by HPV 9-valent vaccine between single-color and triple-color HPV16/33/45 PsVs (P>0.05). Similarly, there was also no significant difference in the anti-HPV neutralization titers of cynomolgus macaques sera induced by HPV 9-valent vaccine between single-color and triple-color HPV6/11/18/31/33/45/52/58 PsVs (P>0.05). Conclusion We successfully established the triple-color PBNAs and verified the accuracy and specificity of triple-color PBNAs consistent with single-color PBNAs. The triple-color PBNAs can be applied to evaluate the immunogenicity of HPV 9-valent vaccine's immune serum.

Objective To analyze the prognostic factors of patients with adenocarcinoma of gastroesophageal junction (AGEJ) after radical resection. Methods In this retrospective study, 269 patients with AGEJ who underwent curative resection from March 2004 to June 2007 were enrolled.The survival curve was drawn by Kaplan-Meier method and the survival analysis was done by Log-rank test. Univariate and multivariate analyses of the prognostic factors of AGEJ were made by Cox model. Results The overall 5-year survival rate of 269 patients was 25.0 % with the median survival time of 22 months.The Siewert type and the number of positive lymph nodes could influence the survival rate (both P < 0.05). Among the 269 patients, 216 (80.3 %) were Siewert Ⅱ type, their median survival time was 30 and 12 months in the thoracic surgery group and the laparotomy group when the tumor diameter was 3-7 cm, the difference was statistically significant (χ2= 5.036, P= 0.025). Univariate analysis showed that tumor diameter, pT, pN, operation time, age and sex were significantly associated with survival rate (all P < 0.05). Cox multivariate analysis showed that patients with a more advanced tumor size suffered from a poorer prognosis (P< 0.05). The risk of postoperative death in patients with lymph node metastasis was 1.854 times that of patients without lymph node metastasis. Conclusions Patients with AGEJ are predominantly Siewert Ⅱ type, the transthoracic approach or thoracoabdominal approach are reasonable selections for these patients. Tumor diameter and pN are independent prognostic factors of AGEJ patients.

Objective To investigate the prognosis of sepesis patients whose timing of hemopurification therapy was classified according to kidney disease:improving global outcomes acute kidney injury (KDIGO AKI) classification.Methods The clinic data of sepsis patients,who were treated with hemopurification therapy in Xiangya Hospital intensive care unit (ICU) during January 1,2014 to June 1,2014,were retrospectively analyzed.According to KGIDO AKI classification as their timing of hemopurification therapy,103 patients were divided to 2 groups,AKI Ⅰ group (n =34),AKI Ⅱ,Ⅲ group (n =69).Acute physiology and chronic health evaluation Ⅱ (APACHE-Ⅱ),sequential organ failure assessment (SOFA),rate of multiple organ injury 7-,28-,90-days mortality rate of 2 groups were analyzed.For 90 days survivors,the length of ICU stay,hospital stay,the frequency and time of hemopurification were analyzed,respectively.Results APACHE-Ⅱ,SOFA of KDIGO AKI Ⅰ group was less than KDIGO AKI Ⅱ,Ⅲ group.KDIGO AKI I group was less on rate of 3 and ≥4 organ injury than KDIGO AKI Ⅱ,Ⅲ group.7-,28-,90-days mortality rate of KDIGO AKI I group were less than AKI Ⅱ,Ⅲ group.In 90 days survivors,length of ICU stay,hospital stay,frequency and time of hemopurification of KDIGO AKI Ⅰ group were less than AKI Ⅱ,Ⅲ group.Conclusions KDIGO AKI classification is an effective indicator to sepsis patients for hemopurification therapy.Compared to KDIGO AKI Ⅱ,Ⅲ,sepsis patients with KDIGO AKI Ⅰ were less severity and multiple organ injuries.To start hemopurification during AKI Ⅰ,it could decrease mortality rate,length of ICU stay,hospital stay,and frequency and time of hemopurification therapy.

Objective To investigate the diagnosis value of homocysteine (Hcy) combined with carcinoembryonic antigen (CEA) and squamous cell carcinoma (SCC) antigen for esophageal cancer.Methods The serum levels of Hcy,CEA,CA199,CA724,CA50 and SCC antigen in 163 patients with esophageal cancer and 49 healthy people were measured.The diagnosis efficacy between the combination of Hcy,CEA and SCC antigen and the combination of CEA,CA199,CA724,CA50 and SCC antigen was compared.Results The levels of Hcy,CEA and SCC antigen were significantly raised in patients group as compared with the levels in control group (all P ＜ 0.05).The area under the ROC curve of Hcy was 0.722 (95 ％ CI 0.633-0.811),CEA was 0.619 (95 ％ CI 0.533-0.704) and SCC antigen was 0.685 (95 ％ CI 0.608-0.762),respectively.There were no significant differences among the three area under the ROC curve.The sensitivity,specificity and accuracy of the combination of CEA,CA199,CA724,CA50,SCC antigen were 69.9 ％,59.2 ％ and 67.5 ％,respectively,but the sensitivity,specificity and accuracy of the combination of Hcy,CEA,SCC antigen were 96.3 ％,69.4 ％ and 90.1％,respectively.There was significant difference between the combination of Hcy,CEA,SCC antigen and the combination of CEA,CA199,CA724,CA50,SCC antigen (P ＜ 0.05).Conclusion The combination of Hcy,CEA,SCC antigen is helpful to determine the diagnosis and efficacy of esophageal cancer.