Objective To investigate the clinicopathological characteristics of colorectal cancer patients with different mismatch repair (MMR) statuses and their correlation with KRAS/NRAF/BRAF (KNB) gene mutations. Methods The clinicopathological data of 477 patients with colorectal cancer were collected, and MMR, microsatellite instability (MSI), and KNB status were detected via immunohistochemistry (IHC), PCR–capillary electrophoresis, and next-generation sequencing (NGS), respectively. The clinicopathological features of patients with different MMR statuses and correlations with KNB mutations were analyzed. Results Compared with the patients in the pMMR group, the patients in the classical dMMR group were younger, included more females, and exhibited more tumors in the right colon, mostly mucinous adenocarcinoma and poorly differentiated tumors (all P<0.05). The tumors in the nonclassical dMMR group were commonly found in the right colon and were prone to special histologic types (all P<0.05). MLH1-PMS2 codeletion, BRAF mutation, and KRAS G13 codon mutation were common in patients in both the classical and the nonclassical dMMR groups (both P<0.05). The results of MMR IHC (100%) were highly consistent with those of MSI PCR (99.1%). Patients in the classical dMMR group with KRAS mutations were younger, included more males, and were prone to specific histologic types, but distant metastasis was rare (all P<0.05). Conversely, lymph node metastasis was rare in patients in the nonclassical dMMR group with KRAS mutations (P=0.005). The mutation rate of the MSH6 gene was relatively high in the nonclassical dMMR group (P=0.002), and all patients presented complete deletion of MLH1-PMS2 combined with nonclassical expression of MSH6 (100%). Five patients with medullary carcinoma components had complete deletions of MLH1-PMS2. Among the five patients, three had combined nonclassical expression of MSH2/MSH6. Two of the three patients carried the MSH6 gene c.3261 locus mutation. Conclusion The clinicopathologic features of patients with classical/nonclassical dMMR colorectal cancer differ from those of patients with pMMR, and MMR IHC could be used to predict effectively the MSI status. The clinicopathologic features differ between classical and nonclassical dMMR colorectal cancer patients with KRAS mutations, but both groups present codeletion of MLH1-PMS2, BRAF mutation, and KRAS G13 codon mutation. In patients with nonclassical dMMR, complete deletion of MLH1-PMS2 combined with nonclassical expression of MSH6 is common. Mutations in the MSH6 gene may play a key role in the development of colorectal cancer with medullary carcinoma components.

Objective To explore the application value of heparin binding protein(HBP),neutrophil to lymphocyte ratio(NLR),lymphocyte to monocyte ratio(LMR),and platelet to lymphocyte ratio(PLR)in the evaluation of immune function reconstruction in human immunodeficiency virus(HIV)infected individuals/acquired immunodeficiency syndrome(AIDS)patients.Methods Collect 138 HIV/AIDS patients from the Outpatient Department of Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University from January 1,to June 30,2023.According to CD4+T lymphocyte counts after antiretroviral treatment,categorize patients into groups with good immune function reconstruction(n=108)and poor immune function reconstruction(n=30).Compare the levels of HBP,NLR,LMR,and PLR between two groups,receiver operating characteristic(ROC)curve was used to evaluate the application value of HBP,NLR,LMR,and PLR in the reconstruction of patient immune function.Results The NLR and PLR of group with good immune function reconstruction was significantly higher than that of group with poor immune function reconstruction(P＜0.05).The LMR of group with good immune function reconstruction were significantly lower than those of group with poor immune function reconstruction(P＜0.05).The HBP between two groups was no significant differences(P＞0.05).LMR had the best efficacy in evaluating whether immune function reconstruction was good in HIV/AIDS patients area under the curve(AUC)=0.803,PLR was the second(AUC)=0.796,NLR was poor(AUC)=0.728.Conclusion NLR,LMR,and PLR are closely related to the immune function of HIV/AIDS patients and can be used as detection indicators to evaluate whether the immune function reconstruction of HIV/AIDS patients is good.

Objective: To investigate whether CD137-CD137L signaling could affect the secretion of mouse vascular smooth muscle cells (VSMCs) -derived exosomes through autophagy mediated Rab7 pathway. Methods: Primary thoracic aorta VSMCs from C57BL/6J mouse were obtained by tissue block adherence method. VSMCs between the third to fifth passages were used and VSMCs were divided into 4 groups: control group, CD137 agonist group, lentivirus control group, Rab7 lentiviral interference group. VSMCs in CD137 agonist group were treated with recombinant protein of CD137L (10 μg/ml), VSMCs in lentivirus control group were treated with lentiviral followed by recombinant protein of CD137L (10 μg/ml), VSMCs in Rab7 lentiviral interference group were treated with Rab7 lentiviral intervention followed by recombinant protein of CD137L (10 μg/ml). Western blot was used to detect the protein expression of LC3Ⅱ, p62, Rab7, CD9, CD81 and Hsc70. Fluorescence microscopy was used to track the changes of autophagy in cells infected with mRFP-GFP-LC3. Transmission electron microscope was used to observe the morphology and size of VSMCs-derived exosomes. The nanoparticle tracking analysis(NTA) was used to detect the concentration and size of exosomes in each group. Results: (1) The expressions of Rab7, LC3Ⅱ and p62 protein in VSMCs of CD137 activation group were significantly higher than those in control group (all P<0.05). The expressions of Rab7, LC3Ⅱ and p62 protein in Rab7 lentivirus interference group was lower than in CD137 activation group (all P<0.05), while the expressions were similar between the lentivirus control group and the CD137 activation group (all P>0.05). (2) The total number of fluorescent spots and yellow fluorescent spots in the VSMCs of the CD137 activation group were higher than those in the control group (all P<0.05), and the number of yellow fluorescent spots was higher than that of the red fluorescent spots in the VSMCs of the CD137 activation group ((50.3±0.9) vs. (10.3±1.5)/cell). The total numbers of fluorescent spots and yellow fluorescent spots in VSMCs of Rab7 lentivirus interference group were lower than those of CD137 activation group (both P<0.05), and the number of red fluorescent spots in VSMCs was higher than that of yellow fluorescent spots ((40.7±4.0) and (10.7±1.2)/cell) in the Rab7 lentiviral interference group. The total numbers of fluorescent spots and yellow fluorescent spots in the VSMCs were similar between the lentivirus control group and the CD137 activation group (all P>0.05). (3) Under transmission electron microscopy, the size of the VSMCs-derived exosomes was about 30-150 nm. The exosome markers (CD9, CD81) could be detected in vesicles by Western blot. NTA results showed that the concentration of VSMCs-derived exosomes was significantly higher in the CD137-activated group than in the control group (P<0.05), which was significantly lower in the Rab7 lentiviral interference group than in the CD137-activation group (P<0.05) and was similar between the lentivirus control group and the CD137 activation group (P>0.05). The expression of Hsc70 protein in exosomes secreted by CD137 activation group was higher than that in the control group (P<0.05). The expression of Hsc70 protein in exosomes was lower in Rab7 lentivirus interference group than in the CD137 activation group (P<0.05), which was similar between the lentivirus control group and the CD137 activation group (P>0.05). The expression of LC3Ⅱ protein in exosome was higher in CD137 activation group than in control group (P<0.05), which was lower in Rab7 lentivirus interference group than in CD137 activation group (P<0.05), which was similar between the lentivirus control group and the CD137 activation group (P>0.05). Conclusion The CD137-CD137L signaling may affect the secretion of mouse VSMCs-derived exosomes through modulating the Rab7 pathway mediated autophagy.

Objective To investigate whether CD137?CD137L signaling could affect the secretion of mouse vascular smooth muscle cells (VSMCs)?derived exosomes through autophagy mediated Rab7 pathway. Methods Primary thoracic aorta VSMCs from C57BL/6J mouse were obtained by tissue block adherence method. VSMCs between the third to fifth passages were used and VSMCs were divided into 4 groups: control group, CD137 agonist group, lentivirus control group, Rab7 lentiviral interference group. VSMCs in CD137 agonist group were treated with recombinant protein of CD137L (10 μg/ml), VSMCs in lentivirus control group were treated with lentiviral followed by recombinant protein of CD137L (10 μg/ml), VSMCs in Rab7 lentiviral interference group were treated with Rab7 lentiviral intervention followed by recombinant protein of CD137L (10 μg/ml). Western blot was used to detect the protein expression of LC3Ⅱ, p62, Rab7, CD9, CD81 and Hsc70. Fluorescence microscopy was used to track the changes of autophagy in cells infected with mRFP?GFP?LC3. Transmission electron microscope was used to observe the morphology and size of VSMCs?derived exosomes. The nanoparticle tracking analysis(NTA) was used to detect the concentration and size of exosomes in each group. Results (1) The expressions of Rab7, LC3Ⅱand p62 protein in VSMCs of CD137 activation group were significantly higher than those in control group (all P<0.05). The expressions of Rab7, LC3Ⅱ and p62 protein in Rab7 lentivirus interference group was lower than in CD137 activation group (all P<0.05), while the expressions were similar between the lentivirus control group and the CD137 activation group (all P>0.05). (2) The total number of fluorescent spots and yellow fluorescent spots in the VSMCs of the CD137 activation group were higher than those in the control group (all P<0.05), and the number of yellow fluorescent spots was higher than that of the red fluorescent spots in the VSMCs of the CD137 activation group ((50.3 ± 0.9) vs. (10.3 ± 1.5)/cell). The total numbers of fluorescent spots and yellow fluorescent spots in VSMCs of Rab7 lentivirus interference group were lower than those of CD137 activation group (both P<0.05), and the number of red fluorescent spots in VSMCs was higher than that of yellow fluorescent spots ((40.7 ± 4.0) and (10.7 ± 1.2)/cell) in the Rab7 lentiviral interference group. The total numbers of fluorescent spots and yellow fluorescent spots in the VSMCs were similar between the lentivirus control group and the CD137 activation group (all P>0.05). (3) Under transmission electron microscopy, the size of the VSMCs?derived exosomes was about 30-150 nm. The exosome markers (CD9, CD81) could be detected in vesicles by Western blot. NTA results showed that the concentration of VSMCs?derived exosomes was significantly higher in the CD137?activated group than in the control group (P<0.05), which was significantly lower in the Rab7 lentiviral interference group than in the CD137?activation group (P<0.05) and was similar between the lentivirus control group and the CD137 activation group (P>0.05). The expression of Hsc70 protein in exosomes secreted by CD137 activation group was higher than that in the control group (P<0.05). The expression of Hsc70 protein in exosomes was lower in Rab7 lentivirus interference group than in the CD137 activation group (P<0.05), which was similar between the lentivirus control group and the CD137 activation group (P>0.05). The expression of LC3Ⅱprotein in exosome was higher in CD137 activation group than in control group (P<0.05), which was lower in Rab7 lentivirus interference group than in CD137 activation group (P<0.05), which was similar between the lentivirus control group and the CD137 activation group (P>0.05). Conclusion The CD137?CD137L signaling may affect the secretion of mouse VSMCs?derived exosomes through modulating the Rab7 pathway mediated autophagy.

Objective To observe the effect oftert-Butylhydroquinone (tBHQ) on the expression of nuclear factor erythroid 2-related factor 2 (Nrf2),heme oxygenase (HO)-1 and phosphatidylinositol 3-kinase (PI3K) in high glucose cultured retinal Müller cells;and to investigate the anti-oxidative stress and anti-apoptotic effects oftBHQ.Methods Retinal Müller cells were divided into normal glucose group (5.5 mmol/L,N group),high glucose group (45 mmol/L,HG group) and tBHQ intervention group (HG+tBHQ group).After retinal Müller cells were cultured with high glucose for 48 hours,the pretreatment with tBHQ (20 μmol/L) induced the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1.The Müller cells were identified by immunofluorescence staining.The expressions of Nrf2,HO-1,PI3K,B-cell lymphoma-2 (Bcl-2) and Bax were detected by Western blot and real-time fluorescence quantitative PCR.Flow cytometry was used to detect the apoptosis of retinal Müller cells in rats.Results Müller cytoplasm and nucleus GS showed strong positive,large cell body,abundant cytoplasm,uniform green fluorescence;nuclear DAPI staining round or oval,clear boundary.The expression of Nrf2 protein (t=4.114,P=0.006),HO-1 protein (t=9.275,P=0.000),Nrf2 mRNA (t=7.292,P=0.000) and HO-1 mRNA (t=15.014,P=0.000) in the HG group were higher than those in the N group.The expressions of Nrf2 protein (t=7.847,P=0.000),HO-1 protein (t=7.947,P=0.000),PI3K protein (t=5.397,P=0.002),Bcl-2 protein (t=6.825,P=0.000),Nrf2 mRNA (t=18.046,P=0.000),HO-1 mRNA (t=39.458,P=0.000),PI3K mRNA (t=4.979,P=0.003) and Bcl-2 mRNA (t=9.535,P=0.000) in the HG+tBHQ group were significantly higher than those in the HG group.The protein and mRNA expressions of Bax protein in the HG+tBHQ group were significantly lower than those in the HG group (t=14.998,16.520;P=0.000,0.000).Flow cytometry showed that the apoptosis rate of Müiller cells in the HG group was significantly higher than that in the N group (t=39.905,P=0.000).The apoptosis rate of Müller cells in the HG+tBHQ group was significantly lower than that in the HG group (t=21.083,P=0.000).Conclusion tBHQ can inhibit the apoptosis of retinal Müller cells by up-regulating the expression ofNrf2,HO-1 and PI3K.

OBJECTIVETo evaluate the disease burden of colorectal cancer in Jinchang cohort, and provide evidence for preventing colorectal cancer and reducing the disease burden of colorectal cancer in the cohort.

METHODSThe colorectal cancer mortality data from 2001 to 2013 and the medical records of colorectal cancer patients from 2001 to 2010 were collected for this retrospective cohort study. The colorectal cancer disease burden was described by using mortality rate, standardized mortality rate, medical expenditure, potential years of life lost (PYLL), average potential years of life lost (APYLL), working potential years of life lost (WPYLL), and average working potential years of life lost (AWPYLL). The development trend in disease burden of colorectal cancer was analyzed by using Spearman correlation and the average growth rate.

RESULTSThe crude mortality rate of colorectal cancer from 2001 to 2013 was 9.53/100,000 with the average annual growth rate of 12.89%. The PYLL, APYLL, WPYLL and AWPYLL of colorectal cancer were 485.00 person-years, 9.15 years, 253.00 person-years, and 4.77 years, respectively. The direct medical expenditure due to colorectal cancer was 7064.38 Yuan per case and 408.43 Yuan per day. There was no increasing trend in the direct medical expenditure due to colorectal cancer.

CONCLUSIONColorectal cancer mortolity rate was on the rise and it caused heavy disease burden in Jinchang cohort.

China ; epidemiology ; Colorectal Neoplasms ; economics ; mortality ; Cost of Illness ; Health Expenditures ; statistics & numerical data ; Humans ; Retrospective Studies

OBJECTIVETo understand the disease burden caused by cancers in Jinchang cohort, and develop effective strategies for cancer prevention and control in this population.

METHODSThe cancer mortality data from 2001 to 2013 and the medical records for cancer patients from 2001 to 2010 in Jinchang cohort were collected. The disease burden caused by cancer was analyzed by using mortality rate, potential years of life lost (PYLL), working PYLL (WPYLL), and direct economic burden.

RESULTSDuring 2001-2013, in Jinchang cohort, the five leading cancers ranked by mortality rate were lung cancer (78.06/100,000), gastric cancer (38.03/100,000), liver cancer (37.23/100,000), esophageal cancer (19.06/100,000), and colorectal cancer (9.53/100,000). The five leading cancers in terms of PYLL (person-years) and WPYLL (person-years) were lung cancer (3480.33, 1161.00), liver cancer (2809.03, 1475.00), gastric cancer (2120.54, 844.00), esophageal cancer (949.61, 315.00), and colorectal cancer (539.90, 246.00). From 2001 to 2010, the five leading cancers in term of average daily cost of hospitalization were gastric cancer (8,102.23 Yuan), esophageal cancer (7135.79 Yuan), colorectal cancer (7064.38 Yuan), breast cancer (6723.53 Yuan), and lung cancer (6309.39 Yuan).

CONCLUSIONSThe cancers common causing higher disease burden in Jinchang cohort were lung cancer, gastric cancer, liver cancer, esophageal cancer and colorectal cancer. The lung cancer disease burden was the highest.

Breast Neoplasms ; economics ; mortality ; China ; epidemiology ; Cohort Studies ; Colorectal Neoplasms ; economics ; mortality ; Cost of Illness ; Esophageal Neoplasms ; economics ; mortality ; Female ; Hospitalization ; economics ; Humans ; Liver Neoplasms ; economics ; mortality ; Lung Neoplasms ; economics ; mortality ; Male ; Neoplasms ; economics ; mortality ; Stomach Neoplasms ; economics ; mortality

Our study explored the dynamic changes in and the relationship between the DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the DNA repair marker 8-hydroxyguanine DNA glycosidase 1 (hOGG1) according to the length of occupational employment in nickel smelting workers. One hundred forty nickel-exposed smelting workers and 140 age-matched unexposed office workers were selected from the Jinchang cohort. The 8-OHdG levels in smelting workers was significantly higher than in office workers (Z=-8.688, P<0.05) and the 8-OHdG levels among nickel smelting workers in the 10-14 y employment length category was significantly higher than among all peers. The hOGG1 levels among smelting workers were significantly lower than those of non-exposed workers (Z=-8.948, P<0.05). There were significant differences between employment length and hOGG1 levels, with subjects employed in nickel smelting for 10-14 y showing the highest levels of hOGG1. Correlation analysis showed positive correlations between 8-OHdG and hOGG1 levels (r=0.413; P<0.01). DNA damage was increased with employment length among nickel smelting workers and was related to the inhibition of hOGG1 repair capacity.
Biomarkers ; Case-Control Studies ; Cohort Studies ; DNA Damage ; drug effects ; DNA Glycosylases ; blood ; DNA Repair ; Deoxyadenosines ; blood ; Humans ; Male ; Metallurgy ; Nickel ; toxicity ; urine ; Occupational Exposure ; adverse effects ; Time Factors

China ; epidemiology ; Cohort Studies ; Female ; Humans ; Lung Neoplasms ; epidemiology ; mortality ; Male ; Metallurgy ; Nickel ; toxicity ; Occupational Exposure ; adverse effects ; Pulmonary Heart Disease ; epidemiology ; mortality ; Retrospective Studies ; Silicosis ; epidemiology ; mortality

There are more than 50 000 workers in Jinchuan Group Co, Ltd (JNMC). Since all staff in JNMC are eligible for a medical examination every two years, only 23 484 nickel-exposed subjects who participated in medical examination were included in this study. Their data, collected from June 22, 2011 to September 28, 2012, in a comprehensive epidemiological survey and during medical examinations, permitted an extensive evaluation of the relation between metal exposure, gene, epigenetics and risk of human diseases. Their lifestyle investigation showed that the overall prevalence of current smokers, alcohol drinkers, and tea drinkers was 39.1%, 19.7%, and 55.2%, respectively. The prevalence of hypertension, allergic rhinitis and cholecystitis , the top 3 prevalent diseases, was 11.7%, 11.0%, and 8.9%, respectively.
Adult ; Aged ; Alcohol Drinking ; epidemiology ; Biomarkers, Tumor ; analysis ; China ; epidemiology ; Cholecystitis ; epidemiology ; Cohort Studies ; Female ; Humans ; Hypertension ; epidemiology ; etiology ; Life Style ; Male ; Middle Aged ; Neoplasms ; epidemiology ; etiology ; mortality ; Nickel ; toxicity ; Occupational Exposure ; statistics & numerical data ; Rhinitis, Allergic ; Rhinitis, Allergic, Perennial ; epidemiology ; Smoking ; epidemiology ; Young Adult