[Study on optimization of image processing parameters of pneumoconiosis by DR].

Objective: To explore the effect of different post-processing parameters of digital radiography (DR) on the quality of chest X-ray for pneumoconiosis diagnosis, and to provide suggestions on parameter setting suitable for this kind of DR machine. Methods: From January 1, 2022 to June 30, 2022, the chest films of 35 workers in the department of radiology of Hangzhou occupational disease prevention and treatment hospital were randomly selected and printed after setting different image post-processing parameters. The quality of chest film was evaluated by the measurement of optical densitometer and the combination of subjective and objective by professional physicians. Results: When the density is set to 2 and the contrast/detail contrast is 4.5, the optical density of each area of DR chest film meets the requirements of chest X-ray quality, and the qualified rate of physician quality evaluation is the highest. Conclusion: Reasonable setting of image post-processing parameters can improve the quality of chest radiograph.

[China guideline for the screening, early detection and early treatment of gastric cancer (2022, Beijing)].

Gastric cancer (GC) is a major digestive tract malignancy in China, which seriously threatens the health of Chinese population. A large number of researches have demons-trated that screening, early detection and early treatment are effective in reducing the incidence and mortality of GC. The development of the guideline for GC screening, early detection and early treatment in line with epidemic characteristics of GC in China will greatly promote the homogeneity and standardization, and improve the effect of GC screening. This guideline was commissioned by the Bureau of Disease Control and Prevention of the National Health Commission. The National Cancer Center of China initiated and convened a working group comprising multidisciplinary experts. Following the World Health Organization Handbook for Guideline Development, this guideline combined the most up-to-date evidence of GC screening, China's national conditions, and practical experience in cancer screening. This guideline provided evidence-based recommendations with respect to the screening population, technology and procedure management, aiming to improve the effect of GC screening and provide scientific evidence for the GC prevention and control in China.

[China guideline for the screening, early detection and early treatment of esophageal cancer (2022, Beijing)].

Esophageal cancer (EC) is a major digestive tract malignancy in China, which seriously threatens the health of Chinese population. A large number of researches have demonstrated that screening and early detection are effective in reducing the incidence and mortality of EC. The development of the guideline for EC screening and early detection in line with epidemic characteristics of EC in China will greatly promote the homogeneity and standardization, and improve the effect of EC screening. This guideline was commissioned by the Bureau of Disease Control and Prevention of the National Health Commission. The National Cancer Center of China initiated and convened a working group comprising multidisciplinary experts. Following the World Health Organization Handbook for Guideline Development, this guideline combined the most up-to-date evidence of EC screening, China's national conditions, and practical experience in cancer screening. This guideline provided evidence-based recommendations with respect to the screening population, technology and procedure management, aiming to improve the effect of EC screening and provide scientific evidence for the EC prevention and control in China.

[A cross-sectional study on the clinical phenotypes of rheumatoid arthritis].

OBJECTIVE: To explore the characteristics and clinical phenotypes of rheumatoid arthritis (RA) and provide the basis for further understanding, interventions and outcomes of this disease. METHODS: RA patients attended at Peking University People's Hospital from 2018 to 2021 were enrolled in the study. Data collection included demographic data, the sites and numbers of joints involved, extra-articular manifestations (EAM), comorbidities and laboratory variables. Statistical and bioinformatical analysis was performed to establish clinical subtypes by clustering analysis based on the type of joint involved, EAM involvement and other autoimmune diseases overlapped. The characteristics of each subtype were analyzed. RESULTS: A total of 411 patients with RA were enrolled. The mean age was (48.84±15.17) years, and 346 (84.2%) were females. The patients were classified into 4 subtypes: small joint subtype (74, 18.0%), total joint subtype (154, 37.5%), systemic subtype (100, 24.3%), and overlapping subtype (83, 20.2%). The small joint subtype had no medium or large joint involvement, and 35.1% had systemic involvement. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and platelet count (PLT) were lower than those in other subtypes, and the rates of positive rheumatoid factors (RF-IgA and RF-IgG) were significantly higher in the small joint subtype. The total joint subtype had both large and small joint involvement but no systemic involvement. The rate of morning stiffness and positive antinuclear antibodies (ANA) in this subtype were lower than those in other subtypes. In the systemic subtype, interstitial lung disease and secondary Sjögren syndrome were the most common systemic involvements, with prominent levels of disease activity score 28-joint count (DAS28-ESR and DAS28-CRP). The overlapping subtype was commonly combined with Hashimoto's thyroiditis or primary Sjögren syndrome. Female in the overlapping subtype was more common than in other subtypes. This subtype was characterized by hyperglobulinemia, hypocomplementemia and high rate of positive ANA, especially spotting type. CONCLUSION: Based on the clinical features, RA patients could be classified into 4 subtypes: small joint subtype, total joint subtype, systemic subtype, and overlapping subtype. Each subtype had its own clinical characteristics. They help for further understanding and a more individualized treatment strategy of RA.

[A multi-center, randomized controlled study on the effect of Saccharomyces boulardii combined with triple therapy for the initial eradication of Helicobacter pylori infection].

Objective: To assess the efficacy and safety of Saccharomyces boulardii (S. boulardii) in combination with triple therapy as a first-line regimen for the eradication of Helicobacter pylori (H. pylori) in non-ulcer dyspepsia (NUD) patients. Methods: A total of 497 Helicobacter pylori-positive patients who underwent gastroscopy and diagnosed with NUD were enrolled from June 2018 to January 2020 in 9 medical centers across China. Participants were segmentedly randomly divided into 3 groups. Patients in group A received S. boulardii for 14 days and triple therapy for 10 days, while patients in group B received bismuth quadruple group for 10 days, and patients in group C received triple therapy for 10 days. The H. pylori status was determined by the 13C-urea breath test on the 44th day of the treatment. Symptom improvement and adverse reactions were assessed on the 14th and 44th day. Results: There were 229 males and 268 females in all 497 patients enrolled. They were aged 18-69 (46.1±11.8) years and 472 of them (158 cases in group A, 159 cases in group B, and 155 cases in group C) completed the trial. The intention-to-treat (ITT) eradication rates in patients in patients A, B and C were 77.8% (126/162), 80.1% (137/171) and 65.2% (107/164) respectively, and per protocol-based (PP) eradication rates were 79.7% (126/158), 86.2% (137/159) and 69.0% (107/155) respectively. The differences were statistically significant in ITT and PP analysis among 3 groups (ITT: χ²=11.14, P<0.01; PP: χ²=13.86, P<0.01). There was no significant difference between eradication rates of two quadruple therapys(all P>0.05), but both of them were significantly higher than that of standard triple therapy (both P<0.05). Statistics revealed that both quadruple therapys led to significantly higher symptom improvement of belching compared with that of standard triple therapy in day 14 (P<0.05). The relief of abdominal distension and belching symptom scores of group A were significantly higher than those of group C in day 44(all P<0.05). There was no serious adverse event reported. The incidence of diarrhea in group A was significantly lower than those in the other two groups (both P<0.05). Conclusions: The combination of S. boulardii and triple therapy can achieve a better eradication effect on H. pylori infection with NUD, and has advantages in symptom relief and safety.

[A prospective cohort study on blood pressure control and risk of ischemic stroke in patients with hypertension].

Objective: To explore the association between blood pressure control and risk of ischemic stroke (IS) in patients with hypertension. Methods: A total of 5 488 patients with hypertension from 60 communities were randomly selected from 101 communities in 8 streets of Nanshan District in Shenzhen City by using two-stage sampling method. The social demographic characteristics, behavior and life style, coronary heart disease and diabetes were collected and the physical condition, blood pressure and blood biochemical indexes were measured. From April 1, 2010 to August 31, 2017 as the follow-up period, the incidence of IS was annually collected by using telephone survey. Cox proportional hazard regression model was used to analyze the relationship between blood pressure control, systolic blood pressure (SBP), diastolic blood pressure (DBP) and the risk of IS. Results: The age of all patients was (58.50±12.14) years old, including 2 712 males (49.42%) and 3 112 patients with well-controlled blood pressure (56.71%). During the follow-up period, 358 new cases of IS were confirmed, and the incidence density was 1 346.27/100 000 person-years. Cox proportional hazard regression model analysis showed after adjusting for confounding factors, unstable blood pressure control, SBP≥150 mmHg (1 mmHg=0.133 kPa; compared with SBP<120 mmHg), and DBP≥95 mmHg (compared with DBP<80 mmHg) were associated with risk of IS. The HR (95%CI) was 1.29 (1.04, 1.59), 2.00 (1.26, 3.17) and 1.52 (1.01, 2.64), respectively. Subgroup analyses showed these associations only existed in female patients with hypertension. The HR (95%CI) was 1.39 (1.05, 1.85), 2.53 (1.41, 4.56) and 1.73 (1.00, 3.36), respectively. Conclusion: Unstable blood pressure control increases the risk of IS in female patients with hypertension.

[Significance of anti-carbamylated fibrinogen antibodies in systemic lupus erythematosus].

OBJECTIVE: Antibodies against carbamylated protein (anti-CarP) were found to be a promising marker to evaluate joint damage and disease activity in patients with rheumatoid arthritis (RA). However, whether anti-CarP antibodies were present in systemic lupus erythematosus (SLE) remained ambiguity. We have therefore undertaken this study to assess the levels of serum anti-CarP antibodies and to evaluate their clinical value in SLE. METHODS: Serum levels of antibodies against carbamylatedfibrinogen (anti-CarP) were measured by enzyme-linked immunosorbent assay (ELISA) in 105 SLE patients and 73 healthy controls. Other clinical and laboratory measurements of the SLE patients were collected from medical records. Data analyses between anti-CarP antibodies and other laboratory measurements were performed using SPSS software for Windows 24.0. RESULTS: The levels of serum anti-CarP antibodies in the patients with SLE were significantly higher than those in the healthy controls (P<0.05). There were significant differences between the anti-CarP-positive group and anti-CarP-negative group in many clinical features. The disease duration, values of ESR, CRP, RF, anti-cardiolipin, anti-dsDNA, D-dipolymer, IgA and IgG were significantly higher in the anti-CarP-positive group compared with the negative group (P<0.05). Conversely, the values of complement 3, complement 4, peripheral blood RBC, and hemoglobin were significantly lower in anti-CarP-positive group than in the negative group(P<0.05). Moreover, the incidence of increase of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), D-dipolymer, decrease of peripheral blood RBC, hemoglobin, complement 3, complement 4, and positive rate of anti-dsDNA were significant different between the two groups(P<0.05). The positive rate of anti-CarP (21.9%) was higher than that of anti-Sm (15.24%), and close to anti-ribosomal P protein (22.86%) in our SLE patients. In addition, anti-CarP antibody was present in the SLE patients lacking the disease specific antibodies, including anti-Sm (anti-CarP positive rate 20.2%, 18/89), anti-dsDNA (anti-CarP positive rate 9.3%, 4/43), anti-nucleosome (anti-CarP positive rate 12.5%, 6/48), and anti-ribosomal P protein antibody (anti-CarP positive rate 20.9%, 17/81). Moreover, the high levels of anti-CarP antibodies were correlated with short disease duration, low C3, C4, RBC, and hemoglobin (P<0.05), high ESR, CRP, IgA, IgG, RF, anti-cardiolipin, anti-dsDNA, and D-dipolymer (P<0.05). CONCLUSION: The level of anti-CarP antibody was increased in the serum of patients with SLE. There were correlations between anti-CarP antibodies and clinical and laboratory indicators of SLE patients.

[Role of erythroblast-like Ter cells in the pathogenesis of collagen-induced arthritis].

OBJECTIVE: To explore the role of Ter cells in the development of the collagen-induced arthritis (CIA), we detected their quantity changes in the spleen of different stages of CIA mice and analyzed the correlation between Ter cells and the joint scores, and we also analyzed the correlation between Ter cells and the frequencies of T and B cell subsets, so as to further understand the pathogenesis of rheumatoid arthritis. METHODS: The six to eight weeks DBA/1 mice were used to prepare CIA model. After the second immunization, we began to evaluate the joint score. According to the time of CIA onset and the joint score, the CIA mice were divided into three stages: early, peak and late stages. According to the final joint score, the CIA mice at the peak stage were subdivided into the high score group (score>8) and the low score group (score≤8). The frequencies of Ter cells in the spleen of the naïve mice and the CIA mice at various stages and the frequencies of T and B cell subsets in the spleen of the CIA mice at the peak stage were detected by flow cytometry, then we carried on the correlation analysis. RESULTS: The frequencies of Ter cells in the spleen of the CIA mice was significantly higher than those of the naïve mice (8.522%±2.645% vs. 1.937%±0.725%, P<0.01), the frequencies of Ter cells in the spleen of the high score group mice was significantly lower than those of the low score group (6.217%±0.841% vs. 10.827%±0.917%, P<0.01). The frequencies of Th1 cells in the spleen of the high score group mice was significantly higher than those of the low score group mice (1.337%±0.110% vs. 0.727%±0.223%, P<0.05). The frequencies of Th17 cells in the spleen of the high score group mice was higher than those of the low score group mice (0.750%±0.171% vs. 0.477%±0.051%, P=0.099). The frequencies of germinal center B cells in the spleen of the high score group mice was significantly higher than those of the low score group mice (1.243%±0.057% vs. 1.097%±0.015%, P<0.05). Correlation analysis results showed that the frequencies of Ter cells in the spleen of the CIA mice at the peak stage was strongly negatively correlated with the frequencies of CD4+ T, Th1, Th17, and germinal center B cells, and was strongly positively correlated with the frequencies of B10 cells, indicating that these cells might have a protective effect in CIA. Studies on dynamic changes showed that the frequencies of Ter cells in the spleen of the CIA mice at the late stage was significantly lower than those at the peak stage (0.917%±0.588% vs. 8.522%±2.645%, P<0.001), suggesting the protective effect of these cells in arthritis. CONCLUSION: Ter cells were significantly increased in the spleen of the CIA mice at peak stage, and were negatively correlated with joint scores and pathogenic immune cells, and positively correlated with protective immune cells. Ter cells were significantly decreased in the spleen of the CIA mice at the late stage. What we mentioned above suggests that Ter cells might be involved in the progression of rheumatoid arthritis as an immunomodulatory cell,but further in vivo and in vitro experiments are needed to verify its specific effects and mechanism.

[Efficacy and synergistic evaluation of compound allantoin in the treatment of mice infected with Helicobacter pylori].

Objective: To investigate the therapeutic effect of compound allantoin in Kunming mice infected with Helicobacter pylori (H. pylori). Methods: Eighty four male Kunming mice were randomly divided into normal control group, H. pylori infection control group, compound allantoin group, allantoin group, aluminum hydroxide group, triple therapy group, and compound allantoin combined with triple therapy group(drug combination group). The normal control group was administered with normal saline, and other groups were infected with H. pylori for 5 times by intragastric(IG) administration. After 4 weeks, mice were given corresponding drug solutions for 6 times by IG administration. H. pylori infection status was detected by rapid urease test(RUT) and immunohistochemistry assay(IHC). Mucosa damages were assessed by microscopic examination and electron microscopy. Results: The positive rates of the compound allantoin group detected by RUT and IHC were 9.1% and 0, respectively, which were significantly lower than those in the H. pylori infection control group (81.8% and 72.7%).The positive rates of aluminum hydroxide group(54.5% and 54.5%) have no significant difference with those in the allantoin group (27.3% and 18.2%), but were higher than those of compound allantoin group (P<0.05).The positive rate of both methods in the drug combination group were 0, and they were significantly lower than those in the triple therapy group (36.4%,45.5%) (P<0.05). There was no difference between the triple group and the compound allantoin group(P>0.05). The pathological and ultrastructural damage of compound allantoin group was obviously relieved than that of H. pylori infection group. Conclusion: Compound allantoin has therapeutic effect on H. pylori infection in mice, which can be further enhanced by combination with triple therapy group. In addition, compound allantoin can repair gastric mucosal injury caused by H. pylori, and its repair effect may be related to mitochondrial pathway.

[Protective effects of sucralfate on gastric mucosal injury induced by Helicobacter pylori and its effects on gastrointestinal flora in mice].

Objective: To investigate the effects of sucralfate suspension gel (SC) on Helicobacter pylori (H.pylori) colonization, H.pylori-induced gastric mucosal injury and gastrointestinal microecology in mice. Methods: C57BL/6J mice were randomly divided into 3 groups, including normal control (NC) group, H.pylori model (HP) group, and SC prevention (HP+SC) group. H.pylori infection mouse model was established by gavage with H.pylori Sydney strain (SS1). And HP+SC group was also administered with SC for 14 days. After mice were sacrificed, the gastric mucosa was taken for HE staining, immunohistochemical (IHC) staining [H.pylori, zonula occludens-1 (ZO-1), Occludin, interleukin (IL)-8, IL-10 and tumor necrosis factor-α (TNF-α)], qPCR (IL-8, IL-10, TNF-α) . And cell ultrastructure was observed by electron microscopy. Microbiota communities in the gastric mucosa or fecal were investigated using 16S ribosomal RNA (rRNA) gene sequencing. The detection of H.pylori in IHC staining or Giemsa staining was defined as H.pylori infection. Results: The H.pylori positive rate of HP group was 91.67%, and that of HP+SC group was 50.00%. The EDS of HP group were significantly higher than those of the NC group [(3.42±0.19) vs (1.17±0.17), P<0.05], while EDS of HP+SC group (2.42±0.29) were significantly lower than that of HP group (P<0.05). The mRNA levels and immunostaining scores of IL-8, IL-10 and TNF-α in HP group was higher than NC group (all P<0.05). Compared with HP group, mRNA levels and IHC scores of IL-8 significantly decreased (all P<0.05) in HP+SC group, while those of IL-10 and TNF-α was similar between two groups (all P>0.05). The IHC scores of ZO-1 and Occludin in HP group was significantly lower than NC group (all P<0.05), and that of ZO-1 and Occludin in the HP+SC group increased compared with HP group [(2.00±0.26) vs (1.17±0.48), P>0.05; (3.50±0.43) vs (2.33±0.21), P<0.05]. Compared with NC group, the diversity of gastric microbiota in HP group was significantly lower, and diversity of gut microbiota decreased insignificantly. There was no significant difference between HP+SC group and HP group in gastric or gut microbiota. Conclusion: SC reduces H.pylori colonization, protects H.pylori-induced gastric mucosal injury, decreases H.pylori-induced IL-8 expression, enhances Occludin. However, its effects on H.pylori-induced gastrointestinal microbiota disorders are limited.

[Tetracycline and metronidazole based quadruple regimen as first line treatment for penicillin allergic patients with Helicobacter pylori infection].

Objective: To evaluate the efficacy and safety of tetracycline and metronidazole based quadruple regimen as first line treatment for penicillin allergic patients with Helicobacter pylori (H.pylori) infection. Methods: The clinical data of 120 patients who had infected with H. pylori and were allergic to penicillin in out-patient clinic of Peking University First Hospital was retrospectively collected from January 2014 to June 2016. The regimen included: lansoprazole 30 mg twice a day+ Bismuth 150 mg three times a day+ tetracycline 500 mg three times a day+ metronidazole 400 mg three times a day, for 14 days. All patients were followed up 7 days, 14 days, at least 4 weeks after the treatment. Symptoms and side effects were recorded. The H.pylori status was evaluated by (13)C urease breath test at least 4 weeks after the end of the treatment. Results: All patients included 86 female and 34 male, and the average age is 59 years. There are 104 of the 120 cases who got success in eradication treatment. Mild to moderate adverse effects occurred in 56 cases (46.7%). 10 female patients dropped out because of headache, rash, vomiting and fatigue. The eradication rates were 86.7% (104/120, ITT) and 94.5% (104/110, PP). Conclusions: Tetracycline and metronidazole based 14-day quadruple regimen is effective as first line treatment for penicillin allergic patients with H. pylori infection because of its relatively high eradication rate. Patients should be watched closely during the treatment since the adverse effects of this regimen happen frequently,especially for female patients.

[Value of serum matrix metalloproteinase 3 in the assessment of early rheumatoid arthritis].

OBJECTIVE: To investigate the expression level of serum matrix metalloproteinase 3 (MMP3) in early rheumatoid arthritis (ERA) patients with normal C-reaction protein (CRP) or erythrocyte sedimentation rate (ESR), and the significance in disease assessment. METHODS: In the study, 133 cases of early RA patients, 25 osteoarthritis (OA) patients and 60 healthy controls in Peking University People's Hospital from 2011 to 2015 were included. The RA patients were further divided into 4 groups according to levels of CRP and ESR: 88 patients with increased CRP and increased ESR, 15 patients with normal CRP and normal ESR, 17 patients with normal CRP but increased ESR, and 13 patients with increased CRP but normal ESR. All the clinical information of the patients was collected, and the serum MMP3 levels of both patients and healthy controls were detected by enzyme-linked immune sorbent assay (ELISA). RESULTS: The serum MMP3 level of RA patients with normal CRP and/or normal ESR [(72.89±6.34) µg/L] was obviously higher than that of OA patients [(42.87±4.14) µg/L] (P=0.002) and healthy controls [(31.62±2.88) µg/L] (P<0.001). The serum MMP3 levels of the patients with normal CRP and normal ESR [(47.04±9.64) µg/L] were higher than those of the healthy controls, and there was statistical significance between the two groups (P<0.05). The serum MMP3 levels of the patients with increased CRP but normal ESR [(94.18±9.11) µg/L] and the patients with normal CRP but increased ESR [(79.42±10.60) µg/L] were both higher than those of the OA patients and healthy controls, and there was obvious statistical difference (P<0.05). In the early RA patients with normal CRP and/or normal ESR, the serum MMP3 level was positively correlated with the CRP level (r=0.336, P=0.024). The positive rate of MMP3 in the patients with normal CRP and/or normal ESR was 44.44%, higher than the positive rate of CRP (28.89%) and the positive rate of ESR (37.78%). In these early RA patients, the positive rate was 52.94% in the patients with normal CRP but increased ESR and 53.85% in the patients with increased CRP but normal ESR. CONCLUSION: The detection of the serum MMP3 level was significant in the assessment of early RA patients within 2-year duration who had normal CRP or ESR value.

[Increased receptor activator of nuclear factor kappa B ligand expressed on B10 cells in rheumatoid arthritis].

OBJECTIVE: To detect receptor activator of nuclear factor kappa B ligand (RANKL) expressed on B10 cells in rheumatoid arthritis (RA) and to evaluate the correlation between RANKL-producing B10 cells in RA and clinical features and laboratory parameters, trying to reveal the possible role of B10 cells in the pathogenesis of RA and the potential mechanism of impaired immunosuppressive capacities. METHODS: 25 RA patients and 20 healthy volunteers were enrolled. These RA patients did not received treatment with glucocorticoids, disease-modifying anti-rheumatic drug and biologics during the recent half of a year. The levels of RANKL-producing B10 cells were measured by flow cytometry (FCM) and polymerase chain reaction (PCR). The correlation between the frequencies of RANKL-producing B10 cells in RA and clinical data, laboratory parameters were analyzed. The role of tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) in inducing RANKL expression in B10 cells was evaluated by in vitro stimulation assay. Independent samples t test, Pearson and Spearman correlation were used for statistical analysis. RESULTS: B10 cells were capable of producing RANKL at a low level in health controls. The frequencies of RANKL-producing B10 cells were markedly higher in RA patients than in health controls (3.65%±1.59% vs. 2.25%±0.68%, P<0.01). The frequencies of these cells correlated positively with RA tender joint counts, swollen joint counts and disease activity score in 28 joints (DAS28) (r=0.479, P=0.035; r=0.519, P=0.008; r=0.526, P=0.019). However, no correlation was found between these cells and RA patient age, disease duration, or the levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA). After in vitro stimulation by TNF-α, but not IL-1ß, B10 cells isolated from healthy donors demonstrated fundamentally upregulated expression of RANKL. CONCLUSION: Our studies showed the frequencies of RANKL-producing B10 cells were markedly higher in RA patients, and their frequencies were positively correlated with RA tender joint counts, swollen joint counts and DAS28. These findings suggested that B10 cells might be involved in RA bone destruction.

[Myeloid-derived suppressor cells promoted autologous B cell proliferation in rheumatoid arthritis].

OBJECTIVE: To investigate the effect of myeloid-derived suppressor cells (MDSC) on pro-liferation of B lymphocytes in rheumatoid arthritis (RA) patients. METHODS: The peripheral blood specimens were collected from 15 healthy adults and 38 RA patients who were divided into high disease activity group, medium activity group and low activity group according to their 28-joint disease activity score (DAS28). And the frequencies of MDSC were determined by flow cytometry. Then, B cells and MDSC were isolated by flow cytometry, respectively. B cells were labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE) and then were co-cultured with MDSC in the presence of 3 mg/L anti-CD40 antibody and 10 mg/L CpG, for 3 days. Flow cytometry was performed to investigate the proliferation of B cells. RESULTS: MDSC expanded markedly in high disease activity patients (7.13% ±2.17%) compared with medium (5.35%±1.36%) and low disease activity patients (4.72%±1.08%) or healthy controls (4.79%±1.02%) (P<0.05), and there were no statistical differences between healthy controls, medium and low disease activity RA (P>0.05). Moreover, the frequencies of MDSC were positively correlated with the DAS28 (P<0.05). After co-culture, MDSC significantly promoted B cell proliferation (P<0.01). CONCLUSION: Our studies showed that MDSC expanded obviously in high disease activity RA patients, and their frequencies were positively correlated with the disease activities. Furthermore, MDSC could promote autologous B cell proliferation remarkably in vitro. These findings suggest that MDSC might be involved in RA pathogenesis through regulating B cell functions.

[Increased serum C-C chemokine ligand 19 levels correlated with B cell abnormalities in systemic lupus erythematosus].

OBJECTIVE: To detect the levels of serum C-C chemokine ligand 19 (CCL19) in patients with systemic lupus erythematosus (SLE) and to evaluate the correlation between CCL19 expression and clinical features and laboratory parameters, trying to reveal the possible role of CCL19 in the pathogenesis of systemic lupus erythematosus. METHODS: The levels of serum CCL19 were measured by enzyme linked immunosorbent assay (ELISA) in 90 patients with SLE and 30 healthy controls. These SLE patients included 75 patients who received treatment with glucocorticoids and disease-modifying anti-rheumatic drug (DMARD) and 15 patients without therapy. The frequencies of peripheral blood B cells and the B cell subsets were assessed in the patients with SLE by flow cytometry. The correlation between the clinical data, laboratory parameters, B cell subset frequencies and serum CCL19 levels were analyzed. Indepen-dent samples t test, paired t test, Pearson and Spearman correlation were used for statistical analyses. RESULTS: The levels of CCL19 were markedly higher in the SLE patients without therapy and the patients with therapy than in the health controls[(596.25±409.19) ng/L and (422.90±395.84) ng/L vs. (157.79±125.23) ng/L, all P<0.001]. Serum CCL19 levels in the SLE patients without therapy were higher than the SLE patients who accepted glucocorticoids and DMARD treatment (P<0.05). The levels of serum CCL19 were positively correlated with anti-double stranded deoxyribonucleic acid (dsDNA), anti-nucleosome antibody (AnuA), IgA, IgG and IgM (r=0.38, P=0.007; r=0.332, P=0.029; r=0.519, P=0.007; r=0.461, P=0.018, respectively). Serum CCL19 levels in the SLE patients with photosensitivity, arthritis and secondary Sjögren's syndrome were higher than the SLE patients without photosensitivity, arthritis and secondary Sjögren's syndrome, respectively [(562.25±399.12) ng/L, (565.6±435.24) ng/L and (694.9±531.02) ng/L vs. (394.7±281.42) ng/L, (385.90±325.33) ng/L and (424.8±305.46) ng/L, all P<0.05]. The levels of serum CCL19 were positively correlated with the percentage of CD27-B cells and CD27-IgD-double-negative memory B cells (r=0.519, P=0.007; r=0.461, P=0.018, respectively). However, the levels of serum CCL19 were negatively correlated with the percentage of CD27+ memory B cells and CD27+IgD- switched memory B cells (r=-0.433, P=0.027; r=-0.616, P=0.001, respectively). CONCLUSION: The increased serum CCL19 levels in SLE patients were associated with the production of autoantibodies, and CCL19 might be involved in the pathogenesis of SLE by disturbing the homeostasis of B cell subsets.

[Clinical significance of serum C-C chemokine ligand 19 levels in patients with rheumatoid arthritis].

OBJECTIVE: To investigate the serum level of C-C chemokine ligand 19 (CCL19) and its clinical significance in rheumatoid arthritis. METHODS: The serum CCL19 levels in both rheumatoid arthritis (RA) patients and health controls were detected by ELISA. The proportion of peripheral blood B cells and memory B cell subsets were also detected in some patients. Then the clinical and laboratory data of the patients were collected. The CCL19 levels in patients with different clinical features were analyzed. And the correlation between the clinical data, laboratory parameters, B cell subsets proportion and serum CCL19 levels were also analyzed. Independent samples t test, paired t test, Pearson and Spearman correlation were used for statistical analysis. RESULTS: The levels of CCL19 was higher in the RA patients than the health controls (P<0.05). The serum CCL19 levels were decreased in the RA patients who accepted disease-modifying anti-rheumatic drugs (DMARDs) treatment for 6 months (P<0.001). Serum CCL19 levels were correlated with the titers of both rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody (r=0.42, P=0.002; r=0.33, P=0.013), but not with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and disease activity score in 28 joints (DAS28) (P>0.05). The levels of CCL19 were higher in the serum positive (RF and anti-CCP antibody) patients, but there were no differences between low and high disease activity RA, as well as early and non-early RA. There was no correlation between the serum CCL19 levels and the proportion of B cells as well as memory B subsets. All the proportion of peripheral blood CD27+ memory B cell subsets in RA was lower than the healthy controls, including CD27+IgD+, CD27+IgD- and CD27+ B cells. CONCLUSION: The increased serum CCL19 levels in RA patients are associated with the activity of B cells, so CCL19 might predict whether the RA type is a B cell mediated RA, and specify the treatment directions for the rheumatologist.

[Clinical significance of serum C-C chemokine ligand 19 levels in patients with rheumatoid arthritis].

OBJECTIVE: To investigate the serum level of C-C chemokine ligand 19 (CCL19) and its clinical significance in rheumatoid arthritis. METHODS: The serum CCL19 levels in both rheumatoid arthritis (RA) patients and health controls were detected by ELISA. The proportion of peripheral blood B cells and memory B cell subsets were also detected in some patients. Then the clinical and laboratory data of the patients were collected. The CCL19 levels in patients with different clinical features were analyzed. And the correlation between the clinical data, laboratory parameters, B cell subsets proportion and serum CCL19 levels were also analyzed. Independent samples t test, paired t test, Pearson and Spearman correlation were used for statistical analysis. RESULTS: The levels of CCL19 was higher in the RA patients than the health controls (P<0.05). The serum CCL19 levels were decreased in the RA patients who accepted disease-modifying anti-rheumatic drugs (DMARDs) treatment for 6 months (P<0.001). Serum CCL19 levels were correlated with the titers of both rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody (r=0.42, P=0.002; r=0.33, P=0.013), but not with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and disease activity score in 28 joints (DAS28) (P>0.05). The levels of CCL19 were higher in the serum positive (RF and anti-CCP antibody) patients, but there were no differences between low and high disease activity RA, as well as early and non-early RA. There was no correlation between the serum CCL19 levels and the proportion of B cells as well as memory B subsets. All the proportion of peripheral blood CD27+ memory B cell subsets in RA was lower than the healthy controls, including CD27+IgD+, CD27+IgD- and CD27+ B cells. CONCLUSION: The increased serum CCL19 levels in RA patients are associated with the activity of B cells, so CCL19 might predict whether the RA type is a B cell mediated RA, and specify the treatment directions for the rheumatologist.

[Protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats].

OBJECTIVE: To investigate the protective effect of compound bismuth and magnesium granules on aspirin-induced gastric mucosal injury in rats and its possible mechanism. METHODS: Acute gastric mucosal injury model was developed with intraperitoneal injection of aspirin in Wistar rats. The rats were divided into normal control group, injury group, sucralfate protection group, compound bismuth and magnesium granules protection group and its herbal components protection group(each group 12 rats). In the protection groups, drugs as mentioned above were administered by gavage before treated with intraperitoneal injection of aspirin. To evaluate the extent of gastric mucosal injury and the protective effect of drugs, gastric mucosal lesion index, gastric mucosal blood flow, content of gastric mucosal hexosamine, prostaglandins (PG), nitric oxide(NO), tumor necrosis factor (TNF), and interleukin (IL) -1, 2, 8 were measured in each group, and histological changes were observed by gross as well as under microscope and electron microscope. RESULTS: Contents of hexosamine, NO, and PG in all the protection groups were significantly higher than those in the injury group (all P<0.01), and content of NO in the compound bismuth and magnesium granules group was significantly higher than that in the sucralfate group ((11.29±0.51) vs(10.80±0.36)nmol/ml, P<0.05). The gastric mucosal lesion index, contents of TNF, and IL-1, 2, 8 were significantly lower in all the protection groups than in the injury group (all P<0.01), and contents of IL-2 and IL-8 in the compound bismuth and magnesium granules group were significantly lower than those in the sucralfate group ((328.17±6.56) vs(340.23±8.05)pg/ml, P<0.01; (170.82±7.31) vs(179.31±7.80)pg/ml, P<0.05). Tissue injury and inflammatory reaction in all the protection groups were obviously mitigated compared with the injury group. CONCLUSION: Compound bismuth and magnesium granules and its herbal components may have significant protective effect on aspirin-induced gastric mucosal injury.

[Jinghuaweikang capsules combined with furazolidone-based triple or quadruple therapy as the rescue treatment for Helicobacter pylori infection: a multicenter randomized controlled clinical trial].

Objective: To explore the efficacy of Jinhuaweikang capsules plus furazolidone-based triple or quadruple therapy as the rescue treatment for Helicobacter pylori (H.pylori) infection. Methods: This is a prospective randomized controlled multicenter clinical trial. Patients with chronic gastritis from H. pylori infection in whom eradication treatment failed were recruited from 6 hospitals. All patients were divided into 4 groups using stratified randomization: group A1 (PAFJ), receiving pantoprazole 40 mg+ amoxicillin 1 000 mg+ furazolidone 100 mg+ Jinghuaweikang 3 capsules, twice a day for 10 d (d1-10); group A2, PAFJ therapy as in group A1, followed by Jinghuaweikang 3 capsules twice a day for 18 d (d11-28); group B1 (PAFB), receiving pantoprazole 40 mg+ amoxicillin 1 000 mg+ furazolidone 100 mg+ bismuth potassium citrate 220 mg, twice a day for 10 d (d1-10); group B2, PAFB therapy as in group B1, followed by Jinghuaweikang 3 capsules twice a day for 18 d (d11-28). At least 28 days after the end of treatment, all patients underwent 13C urea breath test for assessment of H. pylori eradication. Results: A total of 357 patients, 145 males and 212 females, were recruited, including 90 in group A1, 88 in group A2, 89 in group B1, and 90 in group B2. The eradication rates of H. pylori in groups A1 and A2 were 76.1%(67/88)and 79.6%(70/88) in per-protocol (PP) analysis, 74.4%(67/90) and 79.6%(70/88)in intention-to-treat (ITT) analysis; the rates in groups B1 and B2 were as 85.9%(73/85) and 92.1%(81/88) in PP analysis, 82.0%(73/89) and 90.0%(81/90)in ITT analysis. There were statistically significant differences in PP eradication rates among the 4 groups (P=0.020); there was statistically significant difference between groups A1 and B2, and also between groups A2 and B2 (P=0.003, 0.020), but not between groups A1/A2 and B1 (P>0.05), nor between groups B1 and B2 (P>0.05). No statistically significant differences in ITT eradication rates were found among the 4 groups (P>0.05). The improvement of belching and poor appetite for patients in groups A2 and B2 was better than those in groups A1 and B1. Conclusions: The efficacy of Jinghuaweikang capsules plus furazolidone-based quadruple therapy is superior to combination with furazolidone-based triple therapy as the rescue treatment of H. pylori, and superior to bismuth-containing quadruple therapy. Extending administration of Jinghuaweikang capsules to 28 days may better improve symptoms of indigestion.