Objective:To investigate the inhibitory effect of curcumin on oxidative stress in BCG-infected macrophages based on the Nrf2 pathway.Methods:THP-1-derived macrophages were infected.The experiment was divided into control group,BCG group,BCG+curcumin group and BCG+curcumin+ML385 group.Cellular ROS fluorescence intensity were observed under a fluores-cence microscope;Glutathione(GSH)levels were measured by Colorimetry;Western blot was used to detect the protein expressions of Nrf2,HO-1 and NQO1;MTT was used to detect the proliferation rate of macrophages.Results:BCG infection significantly enhanced ROS fluorescence intensity,reduced cell GSH content(P<0.01),inhibited protein expressions of Nrf2,HO-1 and NQO1,at the same time inhibited cell proliferation(P<0.01);curcumin significantly weakened ROS fluorescence intensity,increased GSH level(P<0.05),promoted Nrf2,HO-1 and NQO1 protein expressions and cell proliferation(P<0.01);Nrf2 inhibitor ML385 reversed the effect of curcumin.Conclusion:Curcumin can alleviate BCG-induced oxidative stress in macrophages by increasing the expression of Nrf2 and inducing the transcription of downstream antioxidant molecules.

Rheumatic diseases, a typical kind of autoimmune disease, are often treated with glucocorticoids, immunosuppressants, biological agents, and small-molecule targeted drugs, which often leads to immune dysfunction in patients and increases the risk of activation of latent tuberculosis infection. To regulate the screening, diagnosis, and prophylactic treatment of latent tuberculosis infection in patients with rheumatic diseases, reduce the risk of developing active tuberculosis and improve the prognosis, Peking University Shenzhen Hospital, Shenzhen Third People′s Hospital and Peking Union Medical College Hospital jointly organized domestic experts in the field of rheumatology and tuberculosis to establish the expert consensus on the diagnosis and treatment of latent tuberculosis infection in patients with rheumatic diseases. This consensus focuses on epidemiology, the importance of screening, screening methods, and prophylactic anti-tuberculosis treatment strategies for latent tuberculosis infection combined with rheumatic diseases.

Objective:To study the effectiveness of a strategy for detecting early gastric cancer using high-definition gastroscopy.Methods:A total of 849 patients over 35 years old who underwent gastroscopy in the Seventh Medical Center of PLA General Hospital from December 2018 to January 2019 were enrolled to a prospective study. During gastroscopy, biopsies were taken at any suspicious lesions in patients who had never been infected with Helicobacter pylori. In ulcer-type lesions, biopsies were taken at the edge of the ulcer. Outside the atrophic area, biopsies were taken at lesions in the cardia which were reddish under white light, or lesions in the non-cardiac area which were white or showed clear borders under white light. Inside the atrophic area, biopsies were taken at elevated lesions with clear borders or irregular depressions on the top, or flat/depressed lesions with irregular borders or being ocherous under narrow band imaging. In addition, biopsies were performed on any lesion that did not meet the above standard but was considered necessary. The high-risk patients were followed up by gastroscopy to observe the detection and missed diagnosis of neoplasm that meet the above standard, and to determine the sensitivity and positive predictive value of the strategy. Results:A total of 548 patients were biopsied (781 lesions). Among the 327 lesions that met the above standard, 16 lesions (4.9%) were diagnosed as epithelial neoplasm, of which 10 (3.1%) were high-grade neoplasm. Among the 454 lesions that did not meet the standard, only 1 (0.2%) epithelial neoplasm was diagnosed, and there was no high-grade neoplasm. The positive predictive value of this screening strategy for gastric epithelial neoplasm and high-grade neoplasm was higher than those who did not meet the standard (4.9% VS 0.2%, χ2=19.49, P<0.01; 3.1% VS 0, P<0.001). There were 146 patients (17.2%, 146/849) followed up by gastroscopy. During the follow-up, 2 high-grade intramucosal neoplasms were found. 84.2% (16/19) of epithelial tumors and 83.3% (10/12) of high-grade neoplasm were detected during the initial gastroscopy. Conclusion:This screening strategy can efficiently detect early gastric cancer under high-definition gastroscopy.

Objective:To propose a strategy for detecting early gastric cancer (EGC) under high-definition gastroscopy.Methods:Data of 469 lesions of EGC or high grade intraepithelial neoplasia (HGIN) confirmed by pathology detected at The Seventh Medical Center of Chinese People′s Liberation Army General Hospital from January 2013 to January 2020 were collected and gastroscopic images were re-interpreted. The Helicobacter pylori ( HP) infection status, lesion location in the area of atrophy or at the cardia, morphological type of lesions, lesions with/without clear or regular boundary, and lesion color were analyzed for morphological characteristics of EGC and HGIN under high-definition gastroscopy. Results:Among the 469 lesions of EGC or HGIN, HP-negative lesions accounted for 2.1% (10/469) and ulcerative lesions for 7.7% (36/469). Among non-ulcerative lesions of suspected HP infection ( n=423), there were 28 lesions in the cardia outside the atrophic area and 82.1% (23/28) were reddish under white light imaging. There were 29 non-cardiac lesions outside the atrophic area and 82.8% (24/29) were white or showed clear border under white light imaging. Inside the atrophic area, there were 73 elevated lesions, 95.9% (70/73) of which had clear border or irregular depression on the top. There were 293 flat/depressed lesions in the atrophic area, and 90.8% (266/293) had irregular border or were brown under narrow band imaging. Conclusion:According to the status of HP infection, the location and morphological category of lesions, above endoscopic features can be used as clues to detect EGC and HGIN.

Objective:To analyze the endoscopic and histological characteristics of Helicobacter pylori ( HP)-negative early gastric cancer (EGC) and high grade intraepithelial neoplasia (HGIN). Methods:Data of patients diagnosed as having EGC or HGIN confirmed by pathology at the Seventh Medical Center of Chinese People′s Liberation Army General Hospital from January 2013 to January 2020 were collected. Patients were included according to the diagnostic criteria of HP-negative gastric cancer, and their endoscopic features and histopathological characteristics were retrospectively analyzed. Results:Among 469 lesions of EGC/HGIN, HP-negative lesions accounted for 2.1% (10/469), which included 3 signet ring cell carcinomas, 3 fundic gland type carcinomas, 1 foveolar adenocarcinoma, 1 HGIN of the cardia, 1 familial adenomatous polyposis with gastric HGIN, and 1 Lynch syndrome with gastric HGIN. The 3 cases of signet ring cell carcinoma were all whitish flat/depressed lesions and commonly seen in the lower part of the stomach (2/3). Most of the 7 cases of differentiated EGC/HGIN were elevated type (5/7) and commonly seen in the upper and middle stomach (6/7). Conclusion:HP-negative EGCs are usually solitary lesions under gastroscopy. Undifferentiated type mostly appears whitish flat/depressed in the lower part of the stomach, while differentiated type appears elevated in the upper and middle part.

Objective: To investigate the effects of insulin-like growth factor 1 receptor (IGF-1R) inhibitor on tubulopathy in diabetic kidney disease (DKD) mice. Methods: C57BL/6J male mice were randomly divided into normal control group (n=10) and DKD model group (n=30), by giving a single intraperitoneal injection of STZ 150 mg/kg to establish a DKD model. After established successfully, the mice in DKD model group were randomly divided into DKD group (n=10), benazepril group (n=10) and IGF-1R inhibitor group (n=10). IGF-1R inhibitor group was given intraperitoneal injection of IGF-1R inhibitor (30 mg·kg^-1·d^-1) and benazepril group was given intraperitoneal injection of benazepril (30 mg·kg^-1·d^-1). Normal control group and DKD group were given an equal amount of normal saline. After 8 weeks of feeding, mice were euthanatized. Body weight and kidney weight were recorded. Blood, urine and kidney samples were collected. Biochemical tests such as blood glucose and urine albumin were measured by automatic biochemical instruments and albumin excretion rate was calculated. Pathological changes of mice were observed by hematoxylin-eosin staining (HE) and periodic acid-schiff staining (PAS). Phosph (p) IGF-1R expression level was determined by immunohistochemistry and Western blotting. Results: Compared with the normal control group, blood glucose, kidney weight/body weight and urinary albumin excretion rate were significantly higher in DKD group (all P<0.01). In DKD mice, glomerular expansion, tubular stenosis, tubular swelling and tubular atrophy were significantly detected. Meanwhile, the number of proximal tubular epithelial (PTE) cells was decreased, and the renal tubular injury scores, the average glomerular volume, and pIGF-1R protein expression were increased (all P<0.05). Compared with the DKD group, albumin excretion rate was significantly reduced (P<0.01), the above pathological changes were alleviated and the effect of IGF-1R inhibitor was more significant. Compared with the DKD group, the pIGF-1R protein expression was reduced in IGF-1R inhibitor group (P<0.05). Compared with the benazepril group, the pIGF-1R protein expression was reduced in IGF-1R inhibitor group (P<0.05). Conclusion IGF-1R inhibitor has better effect than benazepril on alleviating the tubulopathy of DKD mice.

Objective To explore the clinical significance of colonoscopy follow-up in Chinese Lynch syndrome mismatch repair (MMR) gene mutation carriers.Methods The results of colonoscopy follow-up was analyzed in 194 MMR gene mutation carriers of 50 Lynch syndrome families.The follow-up period was from April 2001 to November 2016.The detection rates of advanced adenomas and colorectal cancers,five-year survival rate and ten year survival rate were compared between 123 patients of regular follow-up group (colonoscopy interval less than two years) and 71 patients of irregular follow-up group (time colonoscopy interval more than two years).T test,chi-square test and Kaplan-Meier method were performed for statistically analysis.Results The incidence of colorectal cancer of irregular follow up group was significantly higher than that of regular follow-up group (57.7％,41/71 vs 22.8％,28/123);and the difference was statistically significant (x2 =24.00,P＜0.01).The average age at diagnosis for colorectal cancer in irregular follow up group was younger than that of regular follow up group ((45.3 ± 1.9) years vs (48.7±1.8) years);and the difference was statistically significant (t=4.10,P＜0.01).In regular follow-up group,28.6％ (8/28) advanced-stage colorectal cancer (TNM Ⅲ or Ⅳ) was found,while in irregular follow up group,73.2 ％ (30/41) advanced-stage colorectal cancer was found,and there was statistically significant difference in pathological stage between two groups (x2 =4.90,P =0.032).The five year and ten-year survival rates of regular follow-up group were 96.2 ％ and 85.1 ％,respectively,which were both higher than those of irregular follow-up group (46.3 ％ and 28.7 ％);and the differences were statistically significant (x2 =13.20 and 14.80,both P＜0.05).The incidence of advanced adenomas of irregular follow up group was significantly higher than that of regular follow-up group (49.3％,35/71 vs 18.7％,23/123);and the difference was statistically significant (x2 =20.10,P＜0.05).The detection rate of advanced adenomas of MMR gene mutation carriers was higher than those without MMR mutation gene (85.4％,35/41 vs 14.6％,6/41);and the difference was statistically significant (x2 =5.20,P＜ 0.05).Conclusion Regular colonoscopy surveillance may decrease the incidence and mortality of colorectal cancer in MMR mutation carriers of Lynch syndrome families,and increase five-year and tenyear survival rates.

Objective To explore the role and mechanism of thymosin β4 (Tβ4) in the treatment of non-alcoholic fatty liver disease (NAFLD).Methods Forty male C57BL/J6 mice were divided into normal group,NAFLD group,low dose Tβ4 group and high dose Tβ4 group with 10 mice in each group.NAFLD mice model was established by feeding with high fat and high sugar diet for 16 weeks.The mice in low-dose Tβ4 group and high dose Tβ4 group were intraperitonealy injected with Tβ4 at 0.05 mg · kg-1 · d-1 and 0.20 mg · kg-1 · d-1,respectively,for eight weeks.The liver function indexes and serum tumor necrosis factor-α (TNF-α) level were detected;the pathological changes of liver tissue were observed under optical microscope and non-alcoholic fatty liver disease activity score (NAS) was evaluated.The protein expression levels of nuclear factor-κB p65 (NF-κB p65) and nuclear factor κB inhibit protein a (IκBa) at the protein level in liver tissue were measured by Western blotting method.The expression of TNF-α in liver tissue was detected by immunohistochemistry.Mean integral absorbance (MIA) was calculated.T test was performed for groups comparison.Results The levels of alanine aminotransferase (ALT),γ-glutamine transferase (GGT) and serum TNF-α levels of high dose Tβ4 group were all lower than those of NAFLD group ((28±17) U/L vs.(76±29) U/L,(61±39) U/L vs.(102±56) U/L,(144.1± 48.2) ng/L vs.(187.3±58.8) ng/L,respectively),and the differences were statistically significant (t=4.52,2.78 and 2.30,all P＜0.05).The NAS of low dose Tβ4 group and high dose Tβ4 group were both lower than that of NAFLD group (3.7±40.4,2.3±0.3 vs.4.6±0.3),and the differences were statistically significant (t=5.69 and 17.14,both P＜0.01).The relative expression level of Tβ4 protein of NAFLD group was lower than that of normal group (0.2±0.1 vs.1.4±0.6),and the difference was statistically significant (t=6.24,P＜0.01).The relative expression levels of Tβ4 and IκBa of high dose Tβ4 group were higher than those of NAFLD group (1.0±0.3,0.5±0.3 vs.0.2±0.1),and the differences were statistically significant (t=8.00 and 3.00,both P＜0.01).The relative expression level of NF-κB p65 in liver tissue of high dose Tβ4 group was lower than that of NAFLD group (0.6±0.3 vs.1.5±0.7),and the difference was statistically significant (t=3.74,P＜0.01).The MIA of high dose Tβ4 group was lower than that of NAFLD group (0.4±0.2 vs.0.7±0.3),and the difference was statistically significant (t=2.63,P＜ 0.01).Conclusion Tβ4 can effectively treat NAFLD probably through inhibiting the NF-κB pathway.

Objective: To study the correlation of lifestyle characteristics with thyroid nodules in a population-based sample of centenarians in Hainan. Methods: The study was based on China Hainan Centenarian Cohort Study (CHCCS) conducted in 18 cities and counties in Hainan province from 2014 to 2016. A group of multidisciplinary team interviewed and examined local centenarians with structured questionnaires and ultrasonography procedures. A total of 918 centenarians were analyzed after excluding those who refused ultrasonographic examinations or had relevant missing data. Thyroids of centenarians were examined by 3-year experienced sonographer, details on lifestyle characteristics and dietary habits were collected by standard procedure. Results: Of the 918 centenarians, 683 (74.4%) had thyroid nodules under the ultrasonography procedures. The prevalence of thyroid nodules in different group of areca nut consumption varied significantly (P<0.05). In multivariate logistic regression model, the results showed female and areca nut intake were independently associated with thyroid nodules in centenarians (P<0.05). Conclusions The modifiable variables including areca nut intake as well as non-modifiable such as gender are independent determinants of thyroid nodules in centenarians. Further studies are warranted to explore and verify these associations in populations with different ranges of age.

Objective To investigate the value and safety of colonoscopy in patients aged 80 years and over.Methods Clinical and endoscopic data of 1 249 patients aged 80 years and over collected from December 2005 to December 2015 at PLA army General Hospital were analyzed retrospectively.Results The average age was 83.03 years.Reasons for receiving colonoscopy included constipation with abdominal distension(19.38 ％)and hematochezia(10.57％).The completion rate of colonoscopy for the entire length was 94.50 ％.There were no abnormal findings in 492 cases (39.39 ％).Colonic polyps (31.62 ％) and colorectal cancer (14.25 ％) were among the major lesions detected with colonoscopy.Colorectal neoplasms were found in 58.33％ of the 132 patients with hematochezia.The total complication rate from colonoscopy and treatment was 0.72％,with the complication rate from treatment at 1.32％.Conclusions Constipation with abdominal distension and hematoehezia are the main reasons for undergoing colonoscopy for very elderly patients.Colon polyps and colorectal cancer are common disorders in elderly patients over 80 years of age and people with hematochezia in this age group are at high risk of having colorectal cancer.Colonoscopy is a safe and effective procedure and an important examination method for very elderly patients with hematochezia.