Rheumatoid arthritis(RA)is a common chronic autoimmune disease with synovitis as its pathological basis and erosive arthritis as its main symptom.Pathogenesis of RA is complex,combination of genetic factors,environmental factors,immune cells,cytokines and autoantibodies causes joint injury,bone destruction and multi-system disease of RA.However,the above mecha-nisms can not fully explain the poor prognosis,high disability rate and poor clinical treatment effect of RA.Therefore,exploring new pathogenesis and therapeutic targets of RA is the focus of RA research.In recent years,with the deepening of RA research,it has been found that there is a new form of cell death in pathological process of RA,namely ferroptosis.Ferroptosis is a type of cell death caused by inhibition of glutathione peroxidase activity and accumulation of lipid reactive oxygen species.Previous studies have con-firmed the close correlation between RA and ferroptosis,this paper mainly explores ferroptosis-related signal pathways that affect the change and development of RA disease from the perspective of regulating the main signal pathways of ferroptosis,so as to find new therapeutic targets for RA and new therapeutic ideas for research.

BACKGROUND: Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules. METHODS: 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed. RESULTS: Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples. CONCLUSIONS CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.
Humans ; Lung Neoplasms ; Exome Sequencing ; Multiple Pulmonary Nodules ; Carcinoma ; DNA Repair

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Objective    To explore the mechanism of volume-related mitral regurgitation (MR) from the anatomy of mitral valve. Methods    A total of 32 patients with ventricular septal defect (VSD) combined MR meeting inclusion criteria in West China Hospital from September 2018 to November 2019 were enrolled in this study. The direction relative to the cardiac axis: the deviation of the MR bundle along the left atrial wall was eccentric, otherwises it was central. There were 23 patients of VSD and eccentric MR (EMR, a VSD-EMR group), including 10 males and 13 females aged 21 (10, 56) months, and 9 patients of VSD and central MR (CMR, a VSD-CMR group), including 4 males and 5 females aged 26 (12, 87) months. Besides, 9 healthy children were enrolled in a control group, including 4 males and 5 females aged 49 (15, 72) months. All patients underwent transthoracic echocardiography (TTE) examination at 2 weeks before surgery and 6 months after surgery, respectively, The MR degree, end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), antero-posterior diameter (AP), annulus circumference (AC), commissural diameter (CD) were assessed. Results    Before operation, EDV, ESV, SV, AP, AC and CD in the VSD-EMR and VSD-CMR groups were significantly larger or longer than those in the control group (P<0.05); after operation, EDV, ESV, SV, AP and CD decreased compared with those before operation (P<0.05), but there was no significant difference compared with the control group (P>0.05). Compared with the control group, AC was slightly decreased (P<0.05). There was no significant difference in EF between and within groups before and after operation (P>0.05). The improvement rate of MR was 78.9%(15/19) in the VSD-EMR group and 100.0% (9/9) in the VSD-CMR group. Conclusion    After unloading of volume, the valve structure is back to normal except AC. The improvement rate of MR in the VSD-EMR group is lower than that in the VSD-CMR group, which may indicate that the mechanism of VSD-EMR is more complicated.

To investigate the effects of equal concentration of Helicobacter pylori suspension on gastric mucosal infection in mice by different gavage methods. 
 Methods: Six-week-old male C57BL/6 mice were infected by a suspension of Brucella broth containing the same amount of NCTC11637 Helicobacter pylori suspension by A, B, C, and D methods. For method A, the mice were intragastrically administered with Helicobacter pylori suspension (0.2 mL per mouse), once two day for 5 times; for method B, the mice were intragastrically administered with Helicobacter pylori (0.2 mL per mouse) once a day for 5 times; for method C, the mice were perfused with 0.4 mL per mouse of Helicobacter pylori suspension on the first day, then once a day and 0.2 mL per mouse for 3 times; for method D, the mice were administrated with 0.4 mL per mouse Helicobacter pylori suspension on the first day, 0.2 mL per mouse every other day for 3 times. For method E, the mice received equal amounts of normal saline. The mice were killed at 2, 4, and 6 weeks after gavage. The gastric mucosa was detected by rapid urease test for Helicobacter pylori infection, and gastric mucosa was taken for HE staining to observe the degree of infection.
 Results: After 2 weeks of gavage, the infection rates of the mice in A, B, C, and D group were 33.3%, 50.0%, 66.7%, and 33.3%, respectively. The degree of inflammation infection was as following order: C group>B group>D group>A group>E group. The infection rates of mice after 4 weeks of gavage in the A, B, C, and D groups were 50.0%, 83.3%, 83.3%, and 66.7%, respectively. The degree of inflammation infection was as following order: C group>B group>D group>A group>E group. After 6 weeks of gavage, the infection rate in A, B, C, and D groups was 100%, while the degree of inflammation infection was as following order: C group>D group>B group>A group>E group.
 Conclusion: At the acute stage of Helicobacter pylori infection, different gavage methods show different infection rates in mice, and the degree of inflammation is different. At the chronic stage, different gavage methods display the same infection rate in mice with different degree. The gavage method that 0.4 mL Helicobacter pylori suspension on the first day, then once a day and 0.2 mL for 3 times is most conducive to Helicobacter pylori colonization in the gastric mucosa of mice. This method can induce the the most seriou inflammatory infection and is beneficial to the successful establishment of the Helicobacter pylori infection model.
Animals ; Gastric Mucosa ; Helicobacter Infections ; Helicobacter pylori ; Male ; Mice ; Mice, Inbred C57BL

Objective: To establish real-time recombinase polymerase amplification（RPA）for the rapid detection of Vibrio parahaemolyticus（VP）. Methods: An exo probe and primers were designed according to the conserved sequence of thermolabile hemolysin（tlh）gene of VP and then RPA for detection of VP was established. The sensitivity of the assay was evaluated by detecting different concentration of VP;the specificity was evaluated by detecting different bacteria;the stability was evaluated by repeat trials;the application effect was evaluated by detecting food samples which were simultaneously tested with traditional culture method according to GB 4798.7-2013 Detection of VP. Results: A real-time RPA was established to complete VP amplification within 20 min at a constant temperature of 39 ℃. The analytical sensitivity of the assay was five pg per reaction and no cross-reactivity with other pathogenic bacteria observed. The RPA detection results with different concentration of VP and E. coli DNA templates at three time points were consistent. The detection results of 51 food samples by RPA were the same as those by traditional culture method. Conclusion The established real-time RPA can qualitatively detect VP,with simple operation and interpretation of results,which is suitable for rapid detection of VP in public health emergencies and food safety supervision.

Objective: Using data of health information system (HIS) of medical institutions to study the incidence and hospitalization of herpes zoster in three districts of Beijing. Methods: According to the different level of economic development and geographical features in Beijing, 3 districts of Xicheng, Changping and Miyun were chosen and all 110 medical institutions of the first level and above in the 3 districts are included in the survey. All the outpatient and inpatient herpes zoster cases in 2015 were retrospectively reviewed by HIS system. After distinguishing the reduplicated cases, Using the first outpatient case as a molecule and the resident population as denominator to estimate the annual incidence rate, as well as the annual hospitalization rate was estimated based on primary diagnostic hospitalized cases as molecule and the resident population as denominator. Results: A total of 32 313 primary visit outpatient cases were investigated, of which 18 360 cases (56.8%) were women and 20 923 cases (64.8%) were ≥50 years old. The overall estimated incidence of the 3 districts was 8.8‰ with an increase trends with age and reached to the highest in ≥80 years old (30.5/1 000). The incidence of Xicheng, Changping and Miyun districts are respectively 16.2‰, 4.0‰ and 5.7‰. A total of 701 primary visit inpatient cases were identified, of which 366 cases (52.2%) were women and 651 cases (92.9%) were ≥50 years old. The estimated annual hospitalization rate was 19.4/100 000, with the primary and secondary diagnostic hospitalization rate are respectively 5.9/100 000 (212 cases) and 13.5/100 000 (489 cases). The disease types of secondary diagnostic inpatient herpes zoster cases were as follows: cardiovascular disease (19.0%, 93 cases), stroke (14.5%, 71 cases), pneumonia/chronic obstructive pulmonary disease (14.1%, 69 cases), tumor (12.5%, 61 cases) and diabetes (5.7%, 28 cases). Conclusion Most of the herpes zoster cases in Beijing are over 50 years old, and the incidence of female is slightly higher than male. This disease should become a public health issue of great concern.

Objective To investigate the infection rate and risk factors of Helicobacter pylori in healthy people in Luzhou. Methods From May 2017 to May 2018, the number of physical examinations for Helicobacter pylori infection was 18, 684 in the Affiliated Hospital of Southwestern Medical University of Ganzhou, the Affiliated Hospital of Southwestern Medical University and Cangzhou People 's Hospital and Jixian People's Hospital.C14, C13 breath test or Hp antibody positive could be considered as Helicobacter pylori infection. Eight hundred people were randomly selected to conduct a telephone survey. The survey content included general information, living habits, blood type and personal and family gastrointestinal related past medical history. Results The HP infection rate of the medical examination population in Cangzhou City was 31.6％, the male HP infection rate was32.4％ (3788/11836) , the female HP infection rate was 30.4％ (2086/6848) , and the male HP infection rate was higher than that of the female (P = 0.025). Univariate analysis showed that gender, BMI, drinking, drinking water, frequent eating, family members and the previous digestive tract diseases, and previous history of oral disease were risk factors for Helicobacter pylori infection. Results of multivariate logistic analysis showed Male, BMI, drinking, drinking water, eating out often, family members and the digestive tract disease, and a history of oral disease were risk factors for Helicobacter pylori infection. Conclusion BMI, drinking water, and eating out in the medical examination population of Quzhou City, family members, the digestive tract diseases and previous history of oral disease are risk factors for Helicobacter pylori infection.

Objective To construct a prognostic nomogram for predicting the prognosis of patients with colorectal cancer ( CRC) , and verify its accuracy. Methods The clinical pathologic data from 438 CRC patients hospitalized in the Third Affiliated Hospital of Soo-chow University during January 2006 and May 2013 were retrospectively analyzed. The independent risk factors for predicting the prog-nosis of CRC were determined by the univariate and multivariate regression model. The prognostic nomogram was established by the R-language software. Then, the nomograms of postoperative 3-year and 5-year disease free survivals ( DFS) were drawn, and compared with the actual status. The internal validation and accuracy of the nomogram were determined by the Bootstrap method and the calculat-ed concordance index ( C-index) , respectively. The sensitivity and specificity of the nomogram for predicting the 3-year and 5-year DFS were compared with those of TNM system established by the American Joint Committee On Cancer (AJCC) (7th ed.) by using the time-dependent ROC curve. Results Among 438 CRC patients, the metastasis of CRC occurred in 233 patients, including 105 liver metas-tasis and 57 lung metastasis. Multivariate COX regression analysis showed that tumor differentiation degree, TNM stage, serum CEA level, serum CA19-9 level, neutrophil lymphocyte ratio ( NLR) and P53 level were the independent risk factors of CRC. The C-index of the constructed nomogram for predicting the survival rate of CRC patients was 0.678. The predicted 3-year and 5-year DFS by the no-mogram were highly coincident with the actual status. The analysis results of the time-dependent ROC curve showed that the sensitivity and specificity of the established nomogram for predicting the postoperative 3-year and 5-year DFS were higher than those of AJCC-TNM stage.Conclusion The established nomogram may accurately predict the prognosis of CRC patients, which may be helpful for clinicians to follow up or make beneficial treatment for CRC patients.