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.

Objective:To investigate the clinicopathological characteristics of breast squamous cell carcinoma and to analyze the relationship between its immune microenvironment tumor infiltrating lymphocytes (TILs) and prognosis.Methods:Forty-four cases of primary squamous cell carcinoma of the breast diagnosed and treated in the First Affiliated Hospital of Air Force Medical University, Xi′an, China from January 2006 to July 2022 were selected. Their clinicopathological characteristics were analyzed. The cell composition of TILs was evaluated using immunohistochemistry (Mainly markers of B lymphocytes, T lymphocytes and plasma cells). The relationship between TILs and prognosis was also analyzed.Results:The 44 patients of breast squamous cell carcinoma were all female and all were invasive carcinoma. Eight cases (8/44, 18.2%) were squamous cell carcinoma, while 36 cases (36/44, 81.8%) were mixed squamous cell carcinoma. The mixed components included non-specific carcinoma and spindle cell metaplastic carcinoma (17 cases each). One case contained ductal carcinoma in situ of the breast and 1 case contained tubular carcinoma. The proportion of squamous cell carcinoma was 10% to 90%. The cases with pure squamous cell carcinoma often had a large cystic cavity, which was lined by atypical squamous epithelium, while infiltrating squamous cell carcinoma nests were seen in the breast tissue around the cystic cavity. Immunohistochemical staining showed that p63 and CK5/6 were expressed in the squamous cell carcinoma component, but ER, PR and HER2 were not, except for one case of HER2 1+. The positive rates of TRPS1 and PDL-1 were 76% and less than 1%, respectively. Fifteen cases were in the high TILs group (TILs≥30%) and 29 cases were in the low TILs group (TILs<30%). Twenty-three patients were followed up for 5 to 118 months. Among them, 12 died within 3 years and 9 were alive at the end of the follow up. There was no significant difference in TNM stage, TILs and prognosis between simple squamous cell carcinoma and mixed squamous cell carcinoma.Conclusions:Breast squamous cell carcinoma can be divided into simple squamous cell carcinoma and mixed squamous cell carcinoma. There are differences in gross findings and histology between the simple and mixed squamous cell carcinoma of the breast. Sufficient samples should be taken to avoid missing the diagnosis of a minor squamous component. The prognosis of patients with high TILs is significantly better than that of patients with low TILs. The expression rate of TRPS1 in primary squamous cell carcinoma of breast is high and helpful to the differential diagnosis from metastatic squamous cell carcinoma.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Objective:To investigate the influencing of inferior mediastinum and esophageal hiatus lymph node metastasis by submucosal different venous divisions of esophagogastric junction (EGJ) invaded in Siewert type Ⅱ adenocarcinoma of esophagogastric junction (AEG).Methods:The retrospective case-control study was conducted. The clinicopathological data of 547 patients with Siewert type Ⅱ AEG who were admitted to Shanxi Cancer Hospital from January 2018 to December 2021 were collected. There were 461 males and 86 females, aged 61 (range, 33?75)years. Observa-tion indicators: (1) lymph node metastasis rate in different groups; (2) influencing factors of inferior mediastinum lymph node metastasis in Siewert type Ⅱ AEG; (3) influencing factors of esophageal hiatus lymph node metastasis in Siewert type Ⅱ AEG. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Mann-Whitney U test. Count data were described as percentages or absolute numbers, and comparison between groups was conducted using the chi-square test. The univariate analysis was conducted using the corresponding statistical methods based on data type. The Logistic regression model was used for multivariate analysis. Results:(1) Lymph node metastasis rate in different groups. The lymph node metastasis rate in No. 1, 2, 3, 4sa, 4sb, 7, 8a, 9, 11,20, 108, 110 of the 547 patients was 17.37%(95/547), 6.76%(37/547), 46.44%(254/547), 1.65%(9/547), 1.10%(6/547), 23.22%(127/547), 4.39%(24/547), 3.11%(17/547), 3.47%(19/547), 3.66%(20/547), 0.55%(3/547), 4.20%(23/547), respectively. Of the 547 patients, there were 456 cases with proximal of AEG invading submucosal palisade venous of EGJ including 4 cases with inferior mediastinum lymph node metastasis and no case with media mediastinum or up media-stinum lymph node metastasis. There were 91 cases with proximal of AEG invading submucosal perforator venous of EGJ including 18 cases with inferior mediastinum lymph node metastasis, 3 cases with media mediastinum lymph node metastasis and no case with up mediastinum lymph node metastasis. (2) Influencing factors of inferior mediastinum lymph node metastasis in Siewert type Ⅱ AEG. Results of multivariate analysis showed that age, tumor invading submucosal perforator venous of EGJ and histological classification were independent influencing factors for inferior media-stinum lymph node metastasis of Siewert type Ⅱ AEG ( odds ratio=0.93, 23.33, 0.31, 95% confidence interval as 0.87?0.99, 4.18?130.28, 0.12?0.78, P<0.05). (3) Influencing factors of esophageal hiatus lymph node metastasis in Siewert type Ⅱ AEG. Tumor invading submucosal perforator venous of EGJ was an independent influencing factor for esophageal hiatus lymph node metastasis of Siewert type Ⅱ AEG ( odds ratio=14.95, 95% confidence interval as 2.46?90.76, P<0.05). Conclusion:Age, tumor invading submucosal perforator venous of EGJ and histological classification are independent influencing factors for inferior mediastinum lymph node metastasis of Siewert type Ⅱ AEG, and tumor invading submucosal perforator venous of EGJ is an independent influencing factor for esophageal hiatus lymph node metastasis.

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.

Gliomas are commonly central nervous system tumors. The conventional treatment is surgical resection combined with chemoradiotherapy， but glioma patients often have a poor prognosis. Therefore， there is an urgent need to identify new potential targets in gliomas and develop more effective treatments. Valproic acid has the properties of histone deacetylase inhibitor， which has been proven to have inhibitory effects on various tumors. It is confirmed that valproic acid could promote apoptosis and cell arrest of glioma cells， inhibit cell invasion and glioma stem cells， increase the sensitivity of glioma cells to radiotherapy and chemotherapy by regulating ERK/Akt signaling pathway， Akt/mTOR signaling pathway， and regulating expression levels of RECK， MGMT， Nrf2， PON2， Smad4， GSK3β and other proteins. In addition， valproic acid can also enhance the effectiveness of anticancer drugs by inhibiting the growth of glioma stem cells and inducing their differentiation. In conclusion， valproic acid can inhibit glioma through multiple targeted actions， and may become a new targeted drug for the treatment of glioma.

Objective:To investigate the expression of monoubiquitination histone H2B (H2Bub) in esophageal cancer tissues and its correlation with the prognosis of patients.Methods:A total of 75 patients who underwent thoracic esophagectomy in Shanxi Province Cancer Hospital from May 2010 to December 2015 were selected. The expression of H2Bub protein in esophageal carcinoma and para-carcinoma tissues was detected by using immunohistochemical method. The relationship between H2Bub expression level and the clinicopathological characteristics was analyzed, Kaplan-Meier method was used to analyze the relationship H2Bub expression level and the survival.Results:H2Bub was positively expressed in esophageal carcinoma and para-carcinoma tissues, and weakly positive expressed H2Bub was found in para-carcinoma tissues, while not found in esophageal carcinoma tissues. The strongly positive expression rate of H2Bub in esophageal carcinoma tissues was higher than that in para-carcinoma tissues [84.0% (63/75) vs. 22.7% (17/75), χ2 = 34.68, P < 0.001]. Compared with para-carcinoma tissues, 64.0% (48/75) of H2Bub expression level in carcinoma tissues was up-regulated, and 2.7% (2/75) of H2Bub expression level was down-regulated. The up-regulated expression of H2Bub in esophageal carcinoma tissues compared with para-carcinoma tissues was not related with the gender, age, tumor diameter, lymph node metastasis and T staging (all P > 0.05). The proportion of patients with up-regulated expression of H2Bub in poorly differentiated carcinoma tissues was lower than that in moderately and highly differentiated carcinoma tissues [43.8% (7/16) vs. 66.7% (34/51), 87.5% (7/8), P = 0.037]. The median overall survival time was 70 months (95% CI 45-95 months) and 68 months (95% CI 54-82 months), respectively in 12 esophageal carcinoma patients with moderately positive expressed H2Bub and 63 esophageal carcinoma patients with strongly positive expressed H2Bub, and the difference was statistically significant ( P = 0.606). Among 48 patients with up-regulated expression of H2Bub in esophageal carcinoma tissues compared with para-carcinoma tissues, the median overall survival time of poorly differentiated esophageal carcinoma group (7 cases) was shorter than that of highly differentiated (7 cases) and moderately differentiated (34 cases) esophageal carcinoma group [36 months (95% CI 24-37 months) vs. 68 months (95% CI 38-98 months), 68 months (95% CI 44-91 months)], and the differences were statistically significant (all P < 0.05). Conclusions:The expression level of H2Bub in esophageal carcinoma tissues is up-regulated compared with that in para-carcinoma tissues. The up-regulated H2Bub expression level of patients with poorly differentiated esophageal carcinoma with poor prognosis is obvious.

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.