[Clinical features and follow-up results of boys and girls with systemic lupus erythematosus: a comparative analysis].

OBJECTIVE: To compare the clinical features and follow-up results of systemic lupus erythematosus (SLE) between boys and girls. METHODS: A retrospective analysis was performed for the clinical data of 79 children (18 boys and 61 girls), aged ≤14 years, who were diagnosed with SLE from 2008 to 2018. The boys and the girls were compared in terms of initial and major clinical symptoms, injury of organs/systems, related laboratory markers, and follow-up results. RESULTS: As for the initial and non-initial symptoms, fever had the highest incidence rate in the boys, while facial erythema had the highest incidence rate in the girls. The boys tended to develop renal injury and hematological damage (P<0.05), with a significantly higher incidence rate of proteinuria than the girls (P<0.05), while the girls tended to develop joint pain (P<0.05). There were high abnormal rates (>80%) of anti-nuclear antibody, dsDNA, complement C3, and erythrocyte sedimentation rate in both boys and girls (P>0.05). The boys had a significantly higher disease activity than the girls at the first visit and in year 9 of follow-up (P<0.05). A one-month to ten-year follow-up showed that among the boys, 3 were lost to follow-up, 1 died, 7 were well controlled but required oral administration of large doses of hormones or immunosuppression, 2 progressed to chronic renal failure, and 1 developed lupus encephalopathy. Among the girls, 3 were lost to follow-up; 5 died; 34 were well controlled, among whom 5 were maintained on oral prednisone acetate with a dose of <10 mg, 1 was withdrawn from the drug for 1 year, and 2 were withdrawn from the drug for 2 years; 4 developed lupus encephalopathy; 1 developed depression and anxiety and had suicidal tendency in the 7th year after disease onset; 2 experienced impaired vision, blurred vision, and chloropsia; 1 developed a vascular necrosis of both femoral heads in the 3rd year of hormone administration. CONCLUSIONS: There are differences in clinical features, several laboratory markers, and prognosis between boys and girls with SLE. Boys tend to have a high severity at disease onset, develop renal injury and hematological damage, and have poor long-term prognosis, while girls tend to have joint involvement.

Acetazolamide protects rat articular chondrocytes from IL-1ß-induced apoptosis by inhibiting the activation of NF-κB signal pathway.

Because the excessive apoptosis of articular chondrocytes contributes to extracellular matrix (ECM) loss and cartilage damage in rheumatoid arthritis (RA), inhibiting chondrocyte apoptosis might be a promising strategy for RA. Aquaporin1 (AQP1) is overexpressed in RA cartilage and synovial tissues, and play a vital pathogenic role in RA development. Particularly, we previously reported that acetazolamide (AZ) as an AQP1 inhibitor suppressed secondary inflammation and promoted ECM production in cartilage of adjuvant-induced arthritis rats. Here, we investigated the antiapoptotic effect of AZ on interleukin-1ß (IL-1ß)-induced apoptosis, a classic in vitro model of chondrocyte apoptosis. AZ treatment could inhibit IL-1ß-induced apoptosis, evidenced by increasing cell viability, relieving apoptotic nuclear morphology, decreasing apoptosis rates, and restoring mitochondrial membrane potential. Additionally, AZ reversed IL-1ß-induced decrease of Bcl-2 protein and reduced IL-1ß-induced increases of Bax and caspase 3 protein, accompanied by inhibiting IκBα degradation and phosphorylation in cytoplasm, reducing NF-κB p65 protein level in nucleus and preventing NF-κB p65 translocation from cytoplasm to nucleus. In conclusion, our findings indicated that AZ could effectively attenuate IL-1ß-induced chondrocyte apoptosis mediated by regulating the protein levels of apoptosis-related genes and inhibiting the activation of NF-κB signal pathway, suggesting that AZ might be of potential clinical interest in RA treatment.

Therapeutic effect of acetazolamide, an aquaporin 1 inhibitor, on adjuvant-induced arthritis in rats by inhibiting NF-κB signal pathway.

OBJECTIVES: Previous studies have shown that aquaporin 1 (AQP1) is up-regulated in synovium and cartilage of rheumatoid arthritis (RA) patients and that AQP1 may be involved in joint swelling and synovial inflammation. This study was aimed to investigate the potential therapeutic effect of acetazolamide (AZ, an AQP1 inhibitor) on rat adjuvant-induced arthritis (AIA) and explore its related mechanisms. MATERIALS AND METHODS: Rat AIA was induced by complete Freund's adjuvant. The effect of AZ on rat AIA was evaluated by secondary hind paw swelling, arthritis index, TNF-α and IL-1ß serum levels and histological examination of ankle joint. Proteoglycans expression and mRNA levels of type-II collagen (COII) and aggrecan in cartilage were measured by alcian blue staining and real-time PCR, respectively. The protein levels of AQP1, IκBα, phospho-IκBα (p-IκBα), NF-κB p65 and phospho-NF-κB p65 (p-NF-κB p65) in synovial tissues were detected by western blot. RESULTS: AZ treatment could inhibit secondary hind paw swelling and arthritis index, reduce serum levels of TNF-α and IL-1ß, and ameliorate pathological changes of ankle joint in AIA rats. AZ increased proteoglycans production and mRNA levels of COII and aggrecan in cartilage tissues. Moreover, AZ decreased AQP1 protein level and suppressed the activation of NF-κB pathway in synovium, indicated by inhibiting the degradation and phosphorylation of IκBα and reducing p-NF-κB p65 protein level. CONCLUSIONS: AZ as an AQP1 inhibitor has a powerful therapeutic effect on rat AIA via inhibiting NF-κB activation, suggesting AQP1 inhibition might be of potential clinical interest in RA treatment.

Aberrant expression of MICO1 and MICO1OS in deceased somatic cell nuclear transfer calves.

Incomplete reprogramming of a donor nucleus following somatic cell nuclear transfer (SCNT) results in aberrant expression of developmentally important genes, and is the primary source of the phenotypic abnormalities observed in cloned animals. Expression of non-coding RNAs in the murine Dlk1-Dio3 imprinted domain was previously shown to correlate with the pluripotency of mouse induced pluripotent stem cells. In this study, we examined the transcription of the bovine orthologs from this locus, MICO1 (Maternal intergenic circadian oscillating 1) and MICO1OS (MICO1 opposite strand), in tissues from artificially inseminated and SCNT calves that died during the perinatal period. A single-nucleotide polymorphism (SNP), a T-to-C transition, was used to analyze the allelic transcription of MICO1. Our results indicate monoallelic expression of the MICO1C allele among the six analyzed tissues (heart, liver, spleen, lung, kidney, and brain) of artificially inseminated calves, indicating that this gene locus may be imprinted in bovine. Conversely, we observed variable allelic transcription of MICO1 in SCNT calves. We asked if DNA methylation regulated the monoallelic expression of MICO1 and MICO1OS by evaluating the methylation levels of six regions within or around this locus in tissues with normal or aberrant MICO1 transcription; all of the samples from either artificially inseminated or SCNT calves exhibited hypermethylation, implying that DNA methylation may not be involved in regulating its monoallelic expression. Furthermore, three imprinted genes (GTL2, MEG9, and DIO3) nearby MICO1 showed monoallelic expression in SCNT calves with aberrant MICO1 transcription, indicating that not all of the genes in the bovine DLK1-DIO3 domain are mis-regulated.

High iNOS and IL-1ß immunoreactivity are features of colitis-associated colorectal cancer tumors, but fail to predict 5-year survival.

Background: Inflammatory bowel disease (IBD; mainly ulcerative colitis and Crohn's disease) is associated with the development of colorectal cancer (CRC) referred to as colitis-associated colorectal cancer (CAC). In inflammatory flares of IBD, the production of luminal nitric oxide (NO) increases due to the increased inducible nitric oxide synthase (iNOS) activity in inflamed tissue. It is believed that iNOS parallels pro-inflammatory interleukin-1ß (IL-1ß). How these biomarkers relate to CAC pathogenesis or survival is unknown. Aim: The primary aim of this study was to investigate iNOS and IL-1ß immunoreactivity in CAC tumors in comparison with CRC and normal colonic mucosa, and the secondary aim was to determine if immunoreactivity correlates with 5-year survival of CAC. Methods: Immunohistochemistry was performed on tissue sections as follows: CAC (n = 59); sporadic CRC (sCRC) (n = 12); colonic mucosa >2 cm outside sCRC margin (normal mucosa) (n = 22); paracancerous IBD (pIBD) (n = 12). The expression of iNOS and IL-1ß was quantified separately for epithelium and stroma. Data were evaluated using the Mann-Whitney U-test and the log-rank test for 5-year Kaplan-Meier survival curves. Results were compared with online mRNA databases. Results: Immunoreactivity occurred predominantly in epithelial cells and to lesser extent in stroma. Compared with normal mucosa, immunoreactivity for iNOS (P < 0.01) and IL-1ß (P < 0.005) was higher in CAC epithelium. In CAC stroma, iNOS immunoreactivity was lower than normal mucosa (P < 0.001), whereas IL-1ß was higher (P < 0.05). Immunoreactivity differences of iNOS or IL-1ß among CAC patients failed to correlate with 5-year survival. These findings were supported by online mRNA databases. Conclusion: Consistent with high NO production in IBD, there is more iNOS in CAC epithelium, albeit not in stroma. This immunoreactivity difference exists for IL-1ß in both epithelium and stroma. The intervention of arginine or iNOS activity for CAC chemotherapy is not straightforward.

Mental health and psychosocial problems among laboratory technicians in response to the COVID-19 pandemic in Hebei, China.

Objective: During the coronavirus disease 2019 (COVID-19) pandemic, an increased mental burden has been widely reported among medical health workers such as physicians and nurses. However, data on laboratory technicians exposed to COVID-19 have rarely been published. The aim of this study was to assess the magnitude of psychological symptoms among laboratory technicians and analyze potential risk factors associated with these symptoms. Methods: A cross-sectional online survey was performed via the Wenjuanxing platform (a professional online questionnaire platform) (https://www.wjx.cn/mobile/statnew.aspx) to investigate the mental health of laboratory technicians during the COVID-19 pandemic in Hebei, China from October 4, 2021, to November 3, 2021. The online questionnaire included demographic and occupational characteristics data of responders, and the Symptom Check List-90-Revised (SCL90-R)was used to quantify the magnitude of psychological symptoms among laboratory technicians. Participants' demographic and occupational characteristics were analyzed using descriptive statistical analyses. Chi-square tests were applied to compare the severity of each symptom between two or more groups. A binary logistic regression model was developed to identify the predictors of laboratory technicians' mental health in response to the COVID-19 pandemic, and outcomes are presented as odds ratios and 95% confidence interval. Statistical analysis was performed using SPSS version 21 (SPSS, New Orchard Road, Armonk, New York, USA). Results: A total of 3081 valid questionnaires were collected. Of these 3081 participants, 338 (11.0%) reported a total SCL90-R score >160, which indicated positive psychological symptoms. Among the 338 participants who reported psychological problems, most of them were mild symptoms. Several factors associated with mental health problems in laboratory technicians during COVID-19 were found, which include a history of physical and/or psychological problems (all 10 symptoms p < 0.001), more than 10 years of work experience (depression symptoms: OR = 2.350, p = 0.024; anxiety symptoms: OR = 2.642, p = 0.038), frontline work (depression symptoms: OR = 1.761, p = 0.001; anxiety symptoms: OR = 2.619, p < 0.001; hostility symptoms: OR = 1.913, p = 0.001), participant in more than 3 times large-scale SARS-CoV-2 screenings and more than 36 h per week in SARS-CoV-2 nucleic acid testing. Conclusion: A portion of laboratory technicians reported experiencing varying levels of psychological burden. During the COVID-19 pandemic, multiple interventions should be developed and implemented to address existing psychosocial challenges and promote the mental health of laboratory technicians.

[The impact of proton pump inhibitors on esophageal acid exposure in gastroesophageal reflux disease].

OBJECTIVE: To explore the effects of proton pump inhibitors (PPIs) therapy on esophageal acid exposure of patients with gastroesophageal reflux disease (GERD), and the correlation of anxiety and depression with recurrence of acid-related symptoms after discontinuation of PPIs. METHODS: From February 2010 to June 2011, 28 patients with GERD diagnosed by ambulatory 24 h esophageal pH monitoring admitted to Beijing Jishuitan Hospital were treated with esomeprazole 20 mg 2 times/d for 8 weeks (male 16, female 12). Symptoms after drug discontinuation were monitored. Ambulatory 24 h esophageal pH monitoring was performed on patients, whose symptom recurred within 8 weeks after treatment. BMI, Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) were detected. RESULTS: Among the 28 patients with GERD, 15 (53.6%) recurred symptoms after withdraw of PPIs. Compared with the asymptomatic group after withdraw of PPIs, the pretreatment duration of pH 4 (supine), 24 h total acid reflux time, number of time periods with acid reflux > 5 minutes, the maximal acid reflux time and 24 h total number of acid reflux in the symptomatic recurrence group were statistically significantly increased (11.7% vs 4.5%, 138.8 minutes vs 62.1 minutes, 6.0 vs 2.0, 27.0 minutes vs 12.4 minutes, 74.0 times vs 43.0 times, respectively, all P values < 0.05). There were no significant differences in BMI, SAS and SDS between the two groups. CONCLUSIONS: The basic level of esophageal acid exposure of patients with GERD before PPIs therapy may influence the esophageal acid exposure after PPIs therapy and then may affect the recurrence of symptoms. Although anxiety and depression is common in patients with GERD, it is not found that the recurrence of acid-related symptoms after the discontinuation of PPIs therapy is related to the anxiety and depression.

Efficacy and safety of vibrating capsule for functional constipation (VICONS): A randomised, double-blind, placebo-controlled, multicenter trial.

Background: Functional constipation (FC) is an intractable disease that carries large financial burden as well as emotional and physical stress. We aimed to assess the efficacy and safety of the newly developed smartphone-controlled vibrating capsule (VC) in patients with FC. Methods: From December 2018 to February 2020, we did a multicenter, blinded, placebo-controlled randomised trial in six top general hospitals in China focusing on patients aged 18 to 80 with FC. Patients were randomly assigned in a 1:1 ratio to receive VCs or placebo treatment for six weeks (two capsules per week) after a two-week baseline period. The primary outcome was the responder rate, defined as the proportion of patients with an increase of at least one complete spontaneous bowel movement (CSBM) per week during treatment compared to baseline in the full analysis set. This trial is registered with ClinicalTrials.gov, number NCT04671264, and is completed. Findings: 107 patients aged from 18 to 74 were randomly assigned to receive VC (n = 53) or placebo treatment (n = 54). The responder rate in the VC group was significantly higher than that in the placebo group (64·2% vs. 35·8%; difference, 27·7% [95% CI, 10·4-45·1]; P = 0·005). More patients in the VC group reported weekly CSBMs ≥ 1 for at least four weeks during treatment (difference, 22·7% [95% CI, 8-46]; P = 0·022) and follow-up period (difference, 17.3% [95% CI, 0-35]; P = 0·048). The mean Patient Assessment of Constipation-Symptoms score and Patient Assessment of Constipation-Quality of Life score differed significantly from the baseline in both groups (all P < 0·0001). The most common adverse event associated with VC was abdominal discomfort (3·7%). Interpretation: VCs can promote defecation, as well as ameliorating symptoms and improving the quality of life in patients with FC with sustained efficacy. VC appears to be a potential alternative physical treatment for FC with the exact mechanism and parameters warranting further investigation. Funding: The study was supported by "One hundred leading scientists for 21st century" of Health Department of Shanghai Municipal Government (to ZL, No.2017BR005).

Activation of NMDA receptor is associated with up-regulation of COX-2 expression in the spinal dorsal horn during nociceptive inputs in rats.

Cyclooxygenases-2 (COX-2) in the spinal dorsal horn is up-regulated and plays an important role in pain and hyperalgesia induced by nociceptive stimulation. The mechanisms involved in the up-regulation of spinal COX-2 during nociceptive stimulation are yet not well understood. Because the important role of NMDA and its receptor in transmission of nociceptive information in the spinal cord, activation of the spinal NMDA receptor might contribute to the up-regulation of spinal COX-2 expression. The present study was undertaken to demonstrate the above hypothesis by observing changes of COX-2 expression in the spinal dorsal horn in rats subjected to formalin test and intrathecal administration of NMDA, a selective NMDA receptor agonist, in conditions with or without presence of MK-801, an antagonist of NMDA receptor, using methods of Western blotting, reverse transcription polymerase chain reaction and immunohistochemistry. The results showed that intrathecal injection of MK-801, a noncompetitive antagonist of NMDA receptor, significantly suppressed the up-regulation of the COX-2 expression and characteristic pain behavior responses evoked in formalin test. Whereas, intrathecal injection of NMDA significantly up-regulated the expression of COX-2 in the spinal dorsal horn in a time course corresponding to that of nociceptive behavioral responses elicited by the intrathecal NMDA administration. In addition, the up-regulation of the COX-2 expression induced by the intrathecal NMDA was dose-dependent and blocked by prior administration of MK-801. These findings proved that activation of NMDA receptor is associated with the up-regulation of COX-2 expression in the spinal dorsal horn during nociceptive stimulation in rats.

Fluorocitrate, an inhibitor of glial metabolism, inhibits the up-regulation of NOS expression, activity and NO production in the spinal cord induced by formalin test in rats.

Previous experiments have suggested that nitric oxide plays an important role in nociceptive transmission in the spinal cord. In order to explore the involvement of glia in the NO-mediated nociceptive transmission, the present study was undertaken to investigate the effect of fluorocitrate (FC), an inhibitor of glial metabolism, on NOS expression and activity and NO production in the spinal cord during the process of peripheral inflammatory pain and hyperalgesia induced by formalin test in rats. Sixty adult male Sprague-Dawley rats were randomly assigned into sham, formalin, formalin + normal saline (NS), and formalin + FC groups. The NOS expression, NOS activity and NO production was detected by NADPH-d histochemistry staining, NOS and NO assay kit, respectively. It was found that formalin test significantly up-regulated NOS expression and activity and NO production in the laminae I-II of the dorsal horn and the grey matter around the central canal in the lumbar spinal cord at 1 h after the formalin test. Selective inhibition of glia metabolism with intrathecal administration of FC (1 nmol) significantly inhibited the up-regulation in NOS expression and activity and NO production normally induced by the formalin test, which was represented with decreases in the number and density of the NADPH-d positive cells in the dorsal horn and grey matter around the central canal, and decrease in density of NADPH-d positive neuropil in the dorsal horn in formalin + FC group compared with formalin group. The results suggested that glia may be involved in the NO-mediated nociceptive transmission in the spinal cord.

[Analysis on disease distribution at Beijing 2008 Olympic venues].

OBJECTIVE: To analyze the incidence and the variety of diseases at Olympic competition venues, non-competition venues and special control zones through the statistical analysis of medical data of Beijing 2008 Olympic Games. METHODS: The proportions of people contracting diseases among different groups, i.e. non-registered people, athletes, staff, media, VIPs and others were analyzed. At different venues the incidence proportions of diseases in cardiovascular system, stomatology, gastroenterology, ENT, respiratory system, surgery, neuropsychiatry, physical injury, genitourinary system and burns were calculated. And the disease spectrum and incidence proportions at specified venues were analyzed. RESULTS: 1. Among all groups of people involved in Beijing 2008 Olympic Games, the proportion of disease-contracting staff was the highest (44.83%) while that of VIPs the lowest (4.76%) so that the incidence proportions were different among different groups of people. 2. Chi2 = 2427.803, (P < 0.01) The statistical analysis of disease distribution indicates that people at different venues might contract different diseases. 3. The proportions of disease-contracting people at competition venues, non-competition venues, training venues and special control zones were 36.08%, 50.66%, 2.31% and 10.96% respectively, which was related to the number of people at a particular venue. 4. The incidence proportion of surgical diseases was quite high, especially maxillofacial and orthopedic diseases (orthopedic trauma) ranking as top 2 at all venues. Thus there should be surgeons at every venue, especially maxillofacial (for hockey) and orthopedic surgeons. At training venues, the number of people contracting E.N.T. diseases ranked No. 1, chi2 = 74.859 (P < 0.01), compared with that of non-competition venues at No. 2. So the incidence proportion of ENT diseases was higher at training venues than at non-competition venues. The number of people contracting respiratory diseases was the largest in special control zones and the figure of competition venues ranked at No. 2, chi2 = 123.708 (P < 0.01). Therefore the incidence proportion of respiratory diseases at special control zones was higher than that of competition venues. CONCLUSION: The proportions of people contracting diseases were different among different groups of people and the staff ranked the first in this regard. People contracted different diseases at different venues so that the distribution of medical resources should cater to this situation. In case of such a large-scale international competition as the Olympic Games, the patients are mainly from competition venues and non-competition venues so these two places have the largest demand for medical staff. The incidence proportion of surgical diseases is quite high and it is important to have maxillofacial and orthopedic surgeons stationed at all the venues. The ophthalmological and ENT specialists are recommended at training venues and respiratory specialists at special control zones. Meanwhile, the gastroenterologic and stomatological specialists should be present at all venues.

Penta-acetyl geniposide induces apoptosis of fibroblast-like synoviocytes from adjuvant-induced arthritis rats in vitro, associated with inhibition of NF-κB activation.

BACKGROUND: Approaches promoting fibroblast-like synoviocytes (FLS) apoptosis are considered as a meaningful strategy for rheumatoid arthritis (RA) treatment. We have previously reported the anti-arthritic effect of penta-acetyl geniposide ((Ac)5GP, an active derivative of geniposide) on adjuvant-induced arthritis (AIA) rats in vivo. The present study aimed to investigate the pro-apoptotic effect of (Ac)5GP on AIA FLS in vitro and the underlying molecular mechanisms. METHODS: Rat AIA was induced by complete Freund's adjuvant, and FLS were primary-cultured from synovial tissues. AIA FLS were treated with (Ac)5GP (50, 100 and 200 µM) for 48 h and cell proliferation and apoptosis were respectively examined. The involvement of apoptosis-related proteins (Bax, Bcl-2 and caspase 3) and nuclear factor kappa B (NF-κB) signaling pathway was checked. RESULTS: (Ac)5GP inhibited the viability of AIA FLS and reduced the percentage of Ki67-positive cells in AIA FLS. Particularly, (Ac)5GP promoted AIA FLS apoptosis in vitro by inducing apoptotic nuclear morphology, facilitating DNA ladder formation and increasing percentages of both early and late apoptotic cells. (Ac)5GP treatment on AIA FLS decreased Bcl-2 protein level whereas increased the levels of Bax and caspase 3 proteins. Moreover, (Ac)5GP reduced the degradation and phosphorylation of IκBα, down-regulated NF-κB p65 protein level in nucleus and inhibited NF-κB p65 nuclear translocation. CONCLUSIONS: (Ac)5GP had a potent pro-apoptotic effect on AIA FLS in vitro, which is associated with regulating apoptosis-related proteins and inhibiting NF-κB activation.

[Progress in the research of stanniocalcin].

Stanniocalcin (STC) is a glycoprotein hormone first identified in bony fish in which it regulates calcium and phosphate homeostasis. Stanniocalcin is also identified in human and mammals and is named STC1 and STC2 by the sequence of finding. There are two forms of STC produced by the STC1 gene; a 50 kD polypeptide known as STC50 and a group of higher molecular weight variants that are collectively referred to as big STC. Both STC1 and STC2 are widely expressed in various tissues. STC is identified as a novel marker for human cancer and plays an important role in heart disease, transendothelial migration of inflammatory cells, embryo implantation and decidualization.

Therapeutic Effect of Penta-acetyl Geniposide on Adjuvant-Induced Arthritis in Rats: Involvement of Inducing Synovial Apoptosis and Inhibiting NF-κB Signal Pathway.

Previous studies demonstrated that penta-acetyl geniposide ((Ac)5GP, an acetylated derivative of geniposide) exhibited better pharmacological functions than geniposide. This study was aimed to observe the potential effect of (Ac)5GP on adjuvant-induced arthritis (AIA) in rat and explore the involved mechanisms. Rat AIA was induced by complete Freund's adjuvant. (Ac)5GP (30, 60, 120 mg/kg) was given to AIA rats by intragastric administration. Paw swelling, polyarthritis index, serum pro-inflammatory cytokines levels, histological assessments of ankle joint, and proteoglycan expression were respectively measured to evaluate the therapeutic effect of (Ac)5GP on rat AIA. Immunohistochemistry for Ki67 and TUNEL assay were performed to reveal the anti-proliferative and pro-apoptotic effects of (Ac)5GP on AIA synoviocytes in vivo. Protein levels of Bcl-2, Bax, caspase 3, IκBα, p-IκBα, and NF-κB p65 in synovial tissues were detected by Western blot. We found that (Ac)5GP treatment could suppress secondary hind paw swelling, reduce polyarthritis index, decrease TNF-α and IL-1ß serum levels, attenuate pathological damage of ankle joint, and promote proteoglycans expression. (Ac)5GP treatment also could reduce Ki67 positive expression rate and raise the synovial apoptosis index in synovial tissues. Additionally, (Ac)5GP (120 mg/kg) could significantly decrease Bcl-2 protein level, increase Bax and cleaved caspase 3 protein levels, and normalize the ratio of Bcl-2 to Bax. Moreover, (Ac)5GP (120 mg/kg) could inhibit the degradation and phosphorylation of IκBα and reduce NF-κB p65 protein level in nuclear extracts. In conclusion, (Ac)5GP showed a potent anti-arthritic effect on AIA rats via inducing synovial apoptosis and inhibiting NF-κB activation in synovial tissues.

Aquaporin-4 Blockage by siRNA Protects Rat Articular Chondrocytes from IL-1ß-induced Apoptosis by Inhibiting p38 MAPK Signal Pathway.

Accumulating evidence reveals that articular chondrocytes undergo increased apoptosis in rheumatoid arthritis (RA) and inhibiting chondrocyte apoptosis might be a promising therapeutic strategy. We recently found that aquaporin-4 (AQP4) protein level in the cartilage of rats with adjuvant-induced arthritis was higher than normal rats. Herein, cultured rat articular chondrocyte impaired by interleukin-1 beta (IL-1ß) was used as an in vitro model of chondrocyte apoptosis. We observed the protective effect of AQP4 blockage by siRNA on IL-1ß-induced chondrocyte apoptosis and explored the underlying mechanisms. Our findings revealed that AQP4 siRNA protected articular chondrocytes from IL-1ß-induced apoptosis, evidenced by increased cell proliferation (MTT assay), few observations of apoptotic morphologic changes (Hoechst 33258 staining assay) and decreased cell apoptosis rates (Annexin V-FITC/PI staining assay). Additionally, AQP4 siRNA remarkably decreased Bax and caspase 3 mRNA levels and increased Bcl-2 mRNA level, accompanied by reducing phosphorylated-p38 (P-p38) protein level, without affecting p38 protein. The above effects of AQP4 siRNA were similar to SB203580, a specific p38 inhibitor. Together, AQP4 siRNA attenuated IL-1ß-induced chondrocyte apoptosis by regulating apoptosis-related gene expressions and inhibiting p38 MAPK. Our results provide experimental evidence that AQP4 inhibition contributes to preventing chondrocyte apoptosis in joint diseases such as RA and provide a novel therapeutic target for RA.

Overexpression of aquaporin 4 in articular chondrocytes exacerbates the severity of adjuvant-induced arthritis in rats: an in vivo and in vitro study.

BACKGROUND: The dysfunction of articular chondrocytes is a crucial step in rheumatoid arthritis (RA) pathogenesis while its molecular mechanisms are not fully known. This study was aimed to investigate the expression of aquaporin 4 (AQP4) in articular chondrocytes of adjuvant-induced arthritis (AIA) rats and its involvement in AIA development. METHODS: Thirty rats were divided into normal and AIA group (n = 15). Rat AIA was induced by intradermal injection of complete Freund's adjuvant and evaluated by secondary paw swelling and histological assessments on knee joint damage. Localization and protein expression of AQP4 in articular cartilage were examined by immunohistochemistry and western blot. In vitro study, AIA articular chondrocytes were cultured and treated with acetazolamide, an AQPs inhibitor. AQP4 protein level, cell proliferation and mRNA levels of type-II collagen (COII) and aggrecan were measured by western blot, MTT assay and real-time PCR, respectively. RESULTS: The results of immunohistochemistry and western blot indicated that AQP4 showed higher protein levels in cartilage tissues of AIA rats than that of normal rats. Correlation analysis revealed that AQP4 protein level in cartilage tissues of AIA rats remarkably correlated positively with secondary paw swelling on day 26 after AIA induction as well as pathological scores on joint damage. Additionally, acetazolamide treatment effectively decreased AQP4 protein level, increased cell proliferation and mRNA levels of COII and aggrecan, suggesting AQP4 inhibition by acetazolamide could normalize the dysfunction of AIA articular chondrocytes in vitro. CONCLUSIONS: Our data provide certain experimental evidence that AQP4 over-expression in articular chondrocytes aggravated AIA severity and might be a novel target for RA treatment.

[Development of a gold-immunochromatography test for rapid detecting E. coli O157].

OBJECTIVE: To develop a method for rapid detecting Escherichia coli (E. coli) O157 on site. METHODS: A colloidal gold immunochromatography test based on double-antibody sandwich assay for detecting E. coli O157 was developed. Its sensitivity and specificity were then evaluated, and its feasibility of screening food samples were evaluated by analyzing various samples added with E. coli O157. RESULTS: Typical detecting time is less than 15 minutes per sample. The sensitivity of the test is 1 x 10(5) cfu/ml. No any cross-reaction with 30 strains of 24 species in Enterobacteriaceae (including non-O157 E. coli, Salmonella, Shigella, Proteus, Citrobacter, Enterobacter, Serratia and Yersinia), Staphylococus, Listeria, Aeromonas and Vibrios was found. The test could be used to detect E. coli O157 in various samples such as milk powder, flour, starch, coffee, biscuit, cake, jelly and juice. CONCLUSION: The gold-immunochromatography test appears to be a rapid, convenient, specific and sensitive test for detecting E. coli O157: H7 on site.

Increased oxidative DNA damage, inducible nitric oxide synthase, nuclear factor kappaB expression and enhanced antiapoptosis-related proteins in Helicobacter pylori-infected non-cardiac gastric adenocarcinoma.

AIM: Several epidemiological studies have demonstrated a close association between Helicobacter pylori (H pylori) infection and non-cardiac carcinoma of the stomach. H pylori infection induces active inflammation with neutrophilic infiltrations as well as production of oxygen free radicals that can cause DNA damage. The DNA damage induced by oxygen free radicals could have very harmful consequences, leading to gene modifications that are potentially mutagenic and/or carcinogenic. The aims of the present study were to assess the effect of H pylori infection on the expression of inducible nitric oxidative synthase (iNOS) and the production of 8-hydroxy-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA injury in human gastric mucosa with and without tumor lesions, and to assess the possible factors affecting cell death signaling due to oxidative DNA damage. METHODS: In this study, 40 gastric carcinoma specimens and adjacent specimens were obtained from surgical resection. We determined the level of 8-OHdG formation by HPLC-ECD, and the expression of iNOS and mechanism of cell death signaling (including nuclear factor-kappaB(NFkappaB), MEKK-1, Caspase 3, B Cell lymphomal leukemia-2 (Bcl-2), inhibitor of apoptosis protein (IAP) and myeloid cell leukemia-1 (Mcl-1)) by Western-blot assay. RESULTS: The concentrations of 8-OHdG, iNOS, NFkappaB, Mcl-1 and IAP were significantly higher in cancer tissues than in adjacent non-cancer tissues. In addition, significantly higher concentrations of 8-OHdG, iNOS, NFkappaB, Mcl-1 and IAP were detected in patients infected with H pylori compared with patients who were not infected with H pylori. Furthermore, 8-OHdG, iNOS, NFkappaB, Mcl-1 and IAP concentrations were significantly higher in stage 3 and 4 patients than in stage 1 and 2 patients. CONCLUSION: Chronic H pylori infection induces iNOS expression and subsequent DNA damage as well as enhances anti-apoptosis signal transduction. This sequence of events supports the hypothesis that oxygen-free radical-mediated damage due to H pylori plays a pivotal role in the development of gastric carcinoma in patients with chronic gastritis.

Disease distribution and medical resources during the Beijing 2008 Olympic and Paralympic Games.

BACKGROUND: Appropriate planning and staffing for medical services at large-scale athletic events is essential to provide for a safe and successful competition. There are few well-documented accounts describing the demand for such services. The present study provided the data from the Beijing 2008 Olympics and Paralympics, with a view to provide the guidance for planning future events. METHODS: A total of 22 029 and 8046 patients, who received medical care from a physician at an Olympic or Paralympic medical station, were included. The patient proportion among different personnel, various disease proportions at different kinds of venues, and the disease spectrum at specified venues at the Olympics and Paralympics were analyzed. RESULTS: At both games, the patient proportion varied by accreditation status. The staff accounted for the largest number of visits at the Olympics (44.83%) and Paralympics (36.95%), with respiratory diseases the most common. Various disease spectrums were discovered at the different kinds of venues. Surgical diseases were the most frequently listed reason for visits, both at competition and non-competition venues, especially during the Paralympics. The sport-related injuries accounted for a majority of the surgical cases during both games. At training venues, ear nose and throat diseases accounted for the greatest number of visits during both games. CONCLUSIONS: During both games, people contracted different diseases at different venues. Adequate surgeons should be designated to offer assistance mostly in trauma situations. Appropriate numbers of physicians in respiratory diseases and otorhinolaryngology is of great importance.