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Objective:To prepare rabbit polyclonal antibodies against respiratory syncytial virus (RSV) N protein and use them as the detection antibodies to establish a N-ELISA-based method for rapid detection of neutralizing antibodies.Methods:A plasmid of pET30a-N for the expression of RSV N protein was constructed. After purification, the protein was immunized into New Zealand rabbits to prepare polyclonal antibodies, which were used as the detection antibodies. Positive serum samples were diluted and used to neutralize RSV (100 TCID 50/well). Hep-2 cells were inoculated and cultured, and then the cells were fixed with 80% acetone. ELISA was performed to detect RSV N protein in infected cells. When the absorbance value of a well was below the cut-off value, it was regarded as the positive well in the neutralization test. The highest dilution of a positive well serum was the neutralizing antibody titer. After optimizting the antibody dilution, detection time, cell density and the duration of neutralization, the method for neutralizing antibody detection was established based on N-ELISA. The established method was verified by analyzing the influences of different cell generations and edge effects, and calculating the accuracy, repeatability and precision. The correlation between the established method and microneutralization method was analyzed by detecting human RSV IgG-positive serum. Results:The plasmid pET30a-N was successfully constructed, and the expressed N protein showed high purity and good specificity. After the third immunization, the antibody titer in rabbit serum was 1∶51 200, and the antibodies could specifically bind to RSV. The prepared rabbit anti-RSV N polyclonal antibodies had a titer of 1∶51 200, and showed good specificity. The neutralizing antibodies could be detected on day 4 with the established method, and the duration of neutralization was shortened to 30 min. Cell generations and the position of wells in the 96-well plate (edge well and non-edge well) had no significant effect on the method, and the repeatability, precision and accuracy of the method were good. In the detection of 64 RSV IgG-positive human serum samples by the established method and microneutralization method, the correlation coefficient was 0.929 6, indicating a good positive correlation between the two methods.Conclusions:A N-ELISA-based method for rapid neutralizing antibody detection is successfully established, which can be used to evaluate the serum antibody level after RSV vaccination.
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Respiratory syncytial virus (RSV) is one of the major pathogens of acute respiratory infections, becoming a huge global burden. Virus-receptor interactions play a key role in the pathogenesis of RSV infection. The distribution of receptors influences the cellular and the tissue tropism of RSV as well as the viral replication and proliferation in the host. However, the RSV receptors are currently unknown, which is one of the reasons that hinders the development of RSV vaccines and therapeutic drugs. In this study, the existing RSV receptors are reviewed with the hope to provide ideas for the research of RSV vaccines and therapeutic drugs.
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Objective:To investigate the clinical characteristics and risk factors of multiple tophi among gout patients.Methods:Gout patients treated at Affiliated Hospital of Qingdao University from September 2017 to September 2021 were included retrospectively. According to the number of tophi, the patients were divided into the multiple tophi group, the single tophi group and the non-tophi group. Clinical data were collected, biochemical indices and urine pH value were determined. One- way ANOVA or Chi-square test was used to compare groups, and multivariate logistic regression was used to analyze the risk factors. Results:The age, disease course, blood pressure, serum uric acid, urea nitrogen, and the rate of family history, smoking, drinking, gout attacks≥2 twice per year, hypertension, cardio-cerebrovascular diseases, kidney stones in the multiple tophi group were significantly higher than those in the single tophi group and the non-tophi group. The glomerular filtration rate, urine pH value and the rate of regular exercise were significantly lower than those of single tophi group and non-tophi group. In the multiple tophi group, 245 cases(44.46%) were involved in the interphalangeal joint or metacarpophalangeal joint, 212 cases(38.47%) were involved in other joints of the upper limb, which was second only to the first metatarsophalangeal joint(349 cases, 63.33%). Logistic regression analysis showed that the course of disease, urea nitrogen, serum uric acid, positive family history, drinking, gout attacks ≥twice per year and hypertension were the risk factors for multiple tophi in gout patients. Conclusion:Patients with a long disease course, elevated uric acid, high urea nitrogen, positive family history, alcohol consumption, frequent gout flare and hypertension are more likely to develop multiple tophi.
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The occurrence of obesity has increased across the whole world. Many epidemiological studies have indicated that obesity strongly contributes to the development of cancer, cardiovascular diseases, type 2 diabetes, liver diseases and other disorders, accounting for a heavy burden on the public and on health-care systems every year. Excess energy uptake induces adipocyte hypertrophy, hyperplasia and formation of visceral fat in other non-adipose tissues to evoke cardiovascular disease, liver diseases. Adipose tissue can also secrete adipokines and inflammatory cytokines to affect the local microenvironment, induce insulin resistance, hyperglycemia, and activate associated inflammatory signaling pathways. This further exacerbates the development and progression of obesity-associated diseases. Although some progress in the treatment of obesity has been achieved in preclinical and clinical studies, the progression and pathogenesis of obesity-induced diseases are complex and unclear. We still need to understand their links to better guide the treatment of obesity and associated diseases. In this review, we review the links between obesity and other diseases, with a view to improve the future management and treatment of obesity and its co-morbidities.
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Objective:To explore the application and effect of multidisciplinary collaboration in patients with tophi during perioperative period.Methods:Forty-five patients undergoing tophaceous gout surgery in our hospital from May to October 2020 were selected as the control group and treated with routine treatment.From November 2020 to April 2021, 41 patients undergoing tophaceous gout surgery in our hospital who were treated with multidisciplinary collaboration management mode were included as the intervention group. Postoperative pain, blood uric acid level, hospitalization expenses, hospitalization days and patient satisfaction were compared between the two groups.Results:After implementing the multidisciplinary integration man-agement mode, the pain score of the patients at 4 hours, 1 day and 3 days after operation was lower than that of the control group [(3.6±1.0) vs (4.1±1.0), t=2.33, P=0.022; (2.5±0.8) vs (3.0±0.6), t=3.85, P<0.001; (1.8±0.5) vs (2.2±0.7), t=3.52, P<0.001], the serum uric acid level was significantly lower than that of the control group at 1 month and 3 months after operation [(355±58) vs (3928±39), t=3.50, P=0.001; (316±48) vs (366±47), t=4.84, P<0.001], the hospitalization days and hospitalization expenses were significantly decreased [(8.90±2.48) d vs (10.62±3.96) d, t=2.44, P=0.017; (1.00±0.13) ten thousand yuan vs (1.11±0.17) ten thousand yuan, t=3.34, P=0.001], and the patient satisfaction was markedly improved (97.6% vs 82.2%, χ2=3.87, P=0.049). Conclusion:The multi-disciplinary collaboration mode in patients with tophi during perioperative period can effectively reduce the postoperative pain, improve the quality of care, promote reha-bilitation, improve the outcome, and reduce the economic burden of patients, which is worthy of popularization and being applied in clinic.
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Objective:To explore early-onset gout and related risk factors in Shandong Province, and provide decision-making information on prevention.Methods:Data from electronic medical records and face-to face interview were collected from 8 393 patients with gout who first visited the gout clinic of the Affiliated Hospital of Qingdao University from September 2016 to December 2021. Data included demographics, comorbidity and biochemical examinations. The dynamic changes of onset age from 2002 to 2021 were statistically analyzed. The clinical characteristics and related risk factors of patients with early-onset and late-onset gout were statistically analyzed.Results:The age of onset of gout decreased significantly from 2002 to 2021. Compared with 2002, the average age of onset in 2021 decreased by 2.3 years [(41.9±10.6 vs 39.6±14.0) years]. The median age of onset decreased by 3 years in 2012-2021 compared with 2002-2011(37 vs 40 years, P<0.001). The proportion of gout patients with onset age<40 years old increased significantly, from 45.1% in 2002 to 57.8%, and increased by 12.7% in 20 years( P<0.001). The constituent ratios of 20-29 years old group( Ptrend<0.001) and≤19 years old group( Ptrend=0.011) increased by 9.3%( P<0.001) and 4.2%( P=0.002) over 20 years, which was the highest increase among all age groups with onset age<40 years old. Multivariate stepwise linear regression analysis showed that positive family history, blood uric acid level, metabolic syndrome and smoking were independent risk factors for early onset of gout. Conclusion:The age of gout onset in tends to be younger. The increase of the proportion of patients younger than 30 years old is probably the key factor leading to the early-onset gout in Shandong Province. Early and effective intervention on the risk factors related to early-onset gout is essential to prevent the early-onset gout as well as to reduce the prevalence of gout and complications.
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Traditional Chinese Medicine (TCM) can inhibit the proliferation of leukemia cells and induce apoptosis. The signaling pathways involved mainly include PI3K/Akt pathway, MAPK signaling pathway, JAK-STAT pathway, Wnt pathway and mitochondrial pathway. Among them, the mitochondrial apoptotic pathway is affected by many key apoptotic pathways, which plays a terminal role in promoting apoptosis. At present, there is a great need for the systematic and comprehensive research on various signaling pathways and intermolecular interactions.
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Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 day and 7 days after single-dose vaccination or 6 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight, caused by either the prototype-like strain or beta variant of SARS-CoV-2. Lasted data showed that the animals could be well protected against beta variant challenge 9 months after vaccination. Notably, the weight loss and lung pathological changes of hamsters could still be significantly reduced when the hamster was vaccinated 24 h after challenge. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to fight against the ongoing COVID-19 pandemic, compensating limitations of current intramuscular vaccines, particularly at the start of an outbreak.
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Objective:To explore the impact of pain, functional disability, self-efficacy and social support on health-related quality of life (HRQOL) in gout patients.Methods:From November 2019 to January 2020, a total of 218 patients with gout were investigated using the general information questionnaire, Visual Analogue Scale, Health Assessment Questionnaire Disability Index, General Self-Efficacy Scale, Perceived Social Support Scale, and Gout Impact Scale. The structural equation model was established by AMOS 24.0 for parth analysis, and the mechanism of pain dysfuction, self-efficacy and social support affecting the quality of life in gout patients was tested.Results:The total score of Gout Impact Scale, pain, functional disability, self-efficacy and social support respectively was 59.94±18.39, 6.00±2.76, 0.25 0, 0.88, 23.39±6.40 and 62.92±8.24. Pain directly influenced HRQOL ( β=-0.293, P<0.01), and indirectly influenced HRQOL ( β=-0.039, P<0.05). Functional disability directly influenced HRQOL ( β=-0.244, P<0.01). Self-efficacy directly influenced HRQOL ( β=0.182, P<0.01), and indirectly influenced HRQOL ( β=0.202, P<0.01) through pain and functional disability. Social support indirectly influenced HRQOL ( β=0.278, P<0.01) through pain, functional disability and self-efficacy. Conclusions:HRQOL of patients among gout is affected by several factors, mainly affected by pain, functional disability and self-efficacy; and there are interactions among them. Targeted interventions should be strengthened to relieve pain, prevent or slow down the progress of physical disability, enhance self-efficacy and social support to improve HRQOL.
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Objective:To investigate the associations between serum uric acid levels during the third trimester of pregnancy and risks of adverse pregnancy outcomes.Methods:In this retrospective study, a cohort of 7 995 pregnant women who were hospitalized for childbirth from January 2014 to January 2019 were collected to compare pregnancy outcomes between subjects with or without hyperuricemia (HUA). A smooth curve analysis was used to evaluate the relationship between uric acid levels and preterm delivery, low birth weight and smaller than gestational age. Logistic regression analyses were performed to identify risk factors for adverse pregnancy outcomes, and the interaction of the factors.Results:During the third trimester of pregnancy, the uric acid levels of about 10% pregnant women were over 420 μmol/L. In those with HUA, the median neonatal birth weight was 2 590 (1 790, 3 410) g, the probability of premature birth was 49.81%, and the incidence of small than gestational age was 20.41%. These were significantly different from the women without HUA (the median neonatal birth weight: 3300 (2850, 3640) g; the probability of premature birth 23.09%; the incidence of small than gestational age 6.55%, respectively) (All P<0.001). Maternal uric acid levels were negatively correlated with neonatal birth weight, and positively correlated with the risk of smaller than gestational age. It has a U-shaped association with the probability of premature birth, and the lowest probability of premature birth was at 200-400 μmol/L of the uric acid. Risks of low birth weight (adjusted β=-5.22, 95% CI-6.46—-3.99) and smaller than gestational age (adjusted OR=1.03, 95% CI 1.02-1.04) were increased in the function of uric acid levels. High uric acid, hypertension, oligoamnios and preeclampsia were important risk factors for the adverse pregnancy outcomes. The risk of preterm delivery and low birth weight enhanced when hyperuricemia combined with hypertension and preeclampsia. Conclusions:Serum uric acid level can be used as one of reliable markers for predicting adverse pregnancy outcomes, which might provide theoretical basis for clinical intervention in practice.
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Objective:To analyze the clinical characteristics and risk factors associated with the formation of subcutaneous tophi among young gout patients.Methods:Gout patients treated at the Affiliated Hospital of Qingdao University from September 2016 to June 2020 were included. The clinical information was collected and relevant biochemical indices were detected. Fasting urine was collected to test urine pH value, urine uric acid and urine creatinine. Patients were divided into young tophi group and non-tophi group according to age. The measurement data of normal distribution was expressed as Mean±Standard deviation, and independent sample t test and one-way analysis of variance were used. The counting data was tested by Chi-square test. The risk factors were analyzed by logistic regression. Results:A total of 4 798 primary gout patients were collected. There were 915 patients with subcutaneous tophi, 2 308 young gout patients, 252 young gouty tophi patients among them. The average BMI, waist circumference, hip circumference, triglyceride level, serum uric acid level, glomerular filtration rate, alanineamino -transferase (ALT) and aspartate amino -transferase (AST) in the young tophi group were significantly higher than those in the middle-age tophi group ( F=46.074, 2.551, 9.203, 10.370, 15.118, 68.741, 35.023, 5.175, all P<0.05). Average age of disease onset, systolic blood pressure, fasting blood glucose, urine FEUA, Uua/Ucr and urea nitrogen level in young tophi group were significantly lower than those in middle-age tophi group ( F=474.876, 7.629, 6.441, 34.877, 3.633, 50.867, all P<0.05]. The age [(35±7) years old vs (33±7) years old], disease course [(7±4) years vs (4±3) years], blood pressure [(139±17) mmHg vs (135±16) mmHg], [(90±13) mmHg vs (86±12) mmHg], serum triglyceride [(2.6±2.1) mmol/L vs (2.4±2.0) mmol/L], total cholesterol [(4.9±1.4) mmol/L vs (4.6±1.4) mmol/L], serum uric acid [(547±171) μmol/L vs (490±160) μmol/L], urea nitrogen [(5.0±2.0) mmol/L vs (4.4±1.7) mmol/L], family history (27.0% vs 19.6%) and smoking rate(56.0% vs 48.9%) of tophi patients were significantly higher than those of non-tophi patients in young patients ( t=4.717, P<0.05; t=12.838, P<0.05; t=3.414, P<0.05; t=4.676, P<0.05; t=2.085, P<0.05; t=2.451, P<0.05; t=5.308, P<0.05; t=4.090, P<0.05; χ2=7.423, P<0.05; χ2=4.235, P<0.05) . The age of disease onset [(28±6) years vs (29±7) years] and glomerular filtration rate [(96±21) ml·min -1·1.73 m -2vs (103±21) ml·min -1·1.73 m -2] were statistically significantly lower than those of non-tophi patients ( t=-2.711, P<0.01; t=-4.907, P<0.01). Logistics regression analysis showed that age, course of disease, blood pressure, blood lipids level, serum uric acid level, family history of gout and smoking were risk factors for the formation of tophi in young people. After further adjusted for age, course of disease and family history of gout, it was found that serum uric acid, systolic blood pressure, diastolic blood pressure and urea nitrogen remined risk factors for tophi, while glomerular filtration rate remained a protective factor in young patients. Conclusion:Young tophi patients are always obese and have lipid metabolism disorder. Young patients with high level of serum uric acid and blood pressure, decreased renal function are prone to complicate with subcutaneous tophi. More attention should be paid in clinical practice to prevent or delay the formation of tophi.
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BackgroundA safe and effective coronavirus disease 2019 (COVID-19) vaccine is urgently needed to control the ongoing pandemic. Although progress has been made recently with several candidates reporting positive efficacy results, COVID-19 vaccines developed so far cannot meet the global vaccine demand. We developed a protein subunit vaccine against COVID-19, using dimeric form of receptor-binding domain (RBD) as the antigen. We aimed to assess the safety and immunogenicity of this vaccine in humans and determine the appropriate dose and schedule for an efficacy study. MethodsWe did two randomized, double-blind, placebo-controlled, phase 1 and 2 trials for an RBD-based protein subunit vaccine, ZF2001. In phase 1 study, 50 healthy adults aged 18-59 years were enrolled and randomly allocated to three groups to receive three doses of vaccine (25 g or 50 g RBD-dimer, with adjuvant) or placebo (adjuvant-only) intramuscularly, 30 days apart. In phase 2 study, 900 healthy adults aged 18-59 years were enrolled and randomly allocated to six groups to receive vaccine (25 g or 50 g RBD-dimer, with adjuvant) or placebo (adjuvant-only) intramuscularly, with the former 3 groups given two doses and the latter 3 groups given three doses, 30 days apart. For phase 1 trial, the primary outcome was safety, as measured by the occurrence of adverse events and serious adverse events. The secondary outcome was immunogenicity as measured by the seroconversion rate and magnitude of antigen-binding antibodies, neutralizing antibodies and T-cell cytokine production. For phase 2 trial, the primary outcome included both safety and immunogenicity. These trials are registered with ClinicaTrials.gov, NCT04445194 and NCT04466085. FindingsBetween June 22 and September 15, 2020, 50 participants were enrolled to the phase 1 study (mean age 32.6 years) and 900 participants were enrolled to phase 2 study (mean age 43.5 years), to receive vaccine or placebo with a two-dose or three-dose schedule. For both trials, local and systemic adverse reactions were absent or mild in most participants. There were no serious adverse events related to vaccine in either trial. After three doses, neutralizing antibodies were detected in all participants receiving either 25 g or 50 g dose of vaccine in phase 1 study, and in 97% (the 25 g group) and 93% (the 50 g group) of participants, respectively, in phase 2 study. The SARS-CoV-2-neutralizing geometric mean titres (GMTs) were 94.5 for the 25 g group and 117.8 for the 50 g group in phase 1, and 102.5 for the 25 g group and 69.1 for the 50 g group in phase 2, exceeding the level of a panel of COVID-19 convalescent samples (GMT, 51). Vaccine induced balanced TH1 and TH2 responses. The 50 g group did not show enhanced immunogenicity compared with the 25 g group. InterpretationThe protein subunit vaccine ZF2001 is well-tolerated and immunogenic. The safety and immunogenicity data from phase 1 and 2 trials for ZF2001 support the use of 25 g vaccine dose with three-dose schedule to an ongoing phase 3 large-scale evaluation for safety and efficacy. FundingNational Program on Key Research Project of China, National Science and Technology Major Projects of Drug Discovery, Strategic Priority Research Program of the Chinese Academy of Sciences, and Anhui Zhifei Longcom Biopharmaceutical.
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BACKGROUNDIn-depth investigations of the safety and immunogenicity of inactivated SARS-CoV-2 vaccines are needed. METHODIn a phase I randomized, double-blinded, and placebo-controlled trial involving 192 healthy adults 18-59 years of age, two injections of three different doses (50 EU, 100 EU and 150 EU) of an inactivated SARS-CoV-2 vaccine or the placebo were administered intramuscularly with a 2- or 4-week interval between the injections. The safety and immunogenicity of the vaccine were evaluated within 28 days. FINDINGIn this study, 191 subjects assigned to three doses groups or the placebo group completed the 28-day trial. There were 44 adverse reactions within the 28 days, most commonly mild pain and redness at the injection site or slight fatigue, and no abnormal variations were observed in 48 cytokines in the serum samples of immunized subjects. The serum samples diluted from 1:32 to 1:4096 and incubated with the virus did not show antibody-dependent enhancement effects (ADEs) with regard to human natural killer cells, macrophages or dendritic cells. At day 14, the seroconversion rates had reached 92%, 100% and 96% with geometric mean titers (GMTs) of 18.0, 54.5 and 37.1, and at day 28, the seroconversion rates had reached 80%, 96% and 92% with GMTs of 10.6, 15.4 and 19.6in 0, 14 and 0, 28 procedures, respectively. Seroconversion was associated with the synchronous upregulation of ELISA antibodies against the S protein, N protein and virion and a cytotoxic T lymphocyte (CTL) response. Transcriptome analysis shaped the genetic diversity of immune response induced by the vaccine. INTERPRETATIONIn a population aged 18-59 years, this inactivated SARS-CoV-2 vaccine was safe and immunogenic. Trial registrationNCT04412538 FUNDINGThe National Key R&D Program of China (2020YFC0849700), the Program of Chinese Academy of Medicine Science and the Major Science and Technology Special Projects of Yunnan Province.
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With the relatively serious global epidemic outbreak of SARS-CoV-2 infection, public concerns focus on not only clinical therapeutic measures and public quarantine for this disease but also the development of vaccines. The technical design of our SARS-CoV-2 inactivated vaccine provides a viral antigen that enables the exposure of more than one structural protein based upon the antibody composition of COVID-19 patients convalescent serum. This design led to valid immunity with increasing neutralizing antibody titers and a CTL response detected post-immunization of this vaccine by two injections in rhesus macaques. Further, this elicited immunoprotection in macaques enables not only to restrain completely viral replication in tissues of immunized animals, compared to the adjuvant control and those immunized by an RBD peptide vaccine, but also to significantly alleviate inflammatory lesion in lung tissues in histo-pathologic detection, compared to the adjuvant control with developed interstitial pneumonia. The data obtained from these macaques immunized with the inactivated vaccine or RBD peptide vaccine suggest that immunity with a clinically protective effect against SARS-CoV-2 infection should include not only specific neutralizing antibodies but also specific CTL responses against at least the S and N antigens.
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The COVID-19 pandemic caused by SARS-CoV-2 has brought about an unprecedented crisis, taking a heavy toll on human health, lives as well as the global economy. There are no SARS-CoV-2-specific treatments or vaccines available due to the novelty of this virus. Hence, rapid development of effective vaccines against SARS-CoV-2 is urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies potently neutralized 10 representative SARS-CoV-2 strains, indicative of a possible broader neutralizing ability against SARS-CoV-2 strains circulating worldwide. Immunization with two different doses (3g or 6 g per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without any antibody-dependent enhancement of infection. Systematic evaluation of PiCoVacc via monitoring clinical signs, hematological and biochemical index, and histophathological analysis in macaques suggests that it is safe. These data support the rapid clinical development of SARS-CoV-2 vaccines for humans. One Sentence SummaryA purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc) confers complete protection in non-human primates against SARS-CoV-2 strains circulating worldwide by eliciting potent humoral responses devoid of immunopathology
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Objective@#To analyze the risk factors of frequent gout flare, and to evaluate its susceptibility to identify patients with≥2 acute attacks per year.@*Methods@#A total of 579 of cases gout patients with no history of taking urate lowering treatment (ULT) in recent 12 months were enrolled. The patients were divided into frequent group (gout episodes≥twice per year) and non-frequent group(gout attacks<twice per year). The clinical information was collected and relevant biochemical indices were detected.@*Results@#There were significant differences in involvement of upper limb joints, tophi, combining hypertension and renal stone between two groups. The two groups had no statistical differences in family history, gender, history of smoking and drinking, ratios of regular exercise, and combining diabetes, hepatic insufficiency, hypertriglyceridemia, hypercholesterolemia, and overweight/obesity. There was significant differences in the number of joints involved, the history of disease duration, the level of SUA and TG[(4.66±2.54) vs (2.77±1.64), (6.68±5.11) vs (5.14±3.89) years, (525.82±132.11) vs (489.33±139.81) μmol/L, (2.51±1.94) vs (2.05±1.22) mmol/L, P<0.05 or P<0.01]; There were no statistical differences in age of onset, SBP, DBP, age of initial diagnosis, fasting blood glucose, TC, creatinine, glomerular filtration rate, AST, ALT, body mass index, waist circumference, and waist-to-hip ratio. Logistic regression analysis indicated that a large number of joints involved and higher serum uric acid level were risk factors of frequent gout attacks. The ROC curve showed that the number of joints involved had qualified performance in identifying patients with frequent gout attacks. When the number of joints involved was >2, and the sensitivity, specificity, positive predictive value and negative predictive value were 77.8%, 43.3%, 85.6%, and 56.6%, respectively, and the difference was significant.@*Conclusion@#Higher SUA and a larger number of joints involved associate independently with frequent gout attacks. The number of joints involved at initial diagnosis>2, which can predict the frequent flare, and start ULT as earlier as possible. Patients with joints involved at initial diagnosis>2 are at greater risk of frequent gout flare.
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Objective@#To investigate the risk factors for susceptibility of abnormal liver function in patients with gout.@*Methods@#A total of 5 044 cases of male gout patients in remission were selected and divided into normal liver function group with 3 693 patients and abnormal liver function group with 1 351 patients. The clinical information was collected and relevant biochemical indices were detected. Serum uric acid(SUA) was divided into quartiles, and its associations with elevated ALT were evaluated.@*Results@#There were significant differences in the history of drinking, family history, combining with hyperlipidemia, fatty liver, and coronary heart disease between the abnormal liver function group and normal function group(P<0.05 or P<0.01). There were significant statistical differences in age, disease duration, body mass index, waist circumference, diastolic blood pressure, serum cholesterol and triglyceride, uric acid, and creatinine clearance rate between 2 groups(P<0.01), while without significant difference in history of smoking, regular exercise, combining hypertension and diabetes, the means of systolic blood pressure, and fasting blood glucose(all P>0.05). Further logistic regression analysis indicated that body mass, waist circumference, combining fatty liver, higher SUA level, higher cholesterol and triglyceride were risk factors of the early onset of abnormal liver function. ALT and the proportion of abnormal liver function were increased with the increase of UA. After adjustment for BMI, TG, TC and fatty liver, the ALT level and the proportion of abnormal liver function decreased significantly while still showed an upward trend.@*Conclusion@#Patients with obesity, high level of uric acid, high blood lipids and fatty liver were more likely to develop abnormal liver function, SUA was independently associated with elevated ALT.
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Objective@#To screen gene mutation information of gout pedigree through whole genome sequencing and to carry out preliminary analysis.@*Methods@#One typical gout pedigree was selected as the study subjects. The clinical data and the peripheral blood samples were collected and constructed charts of the pedigree. DNAs were extracted from peripheral blood and analyzed by the whole genome sequencing, and by the software analysis and comparison, screening out the pathogenic genes and related mutations. Then the verifications were conducted in the family members and the controls. Bioinformatics software was applied to predict the effect of mutation on gene expression.@*Results@#Based on the sequencing results, advanced informational analysis was performed to screen out the mutations 1040-8 A> G near the 5 ′end near the exon 8 of the PLAA gene. The results showed that all the gout patients in the family had 1040 -8 A> G sites, and none of the mutants were found in the non-gout group and 200 controls; bioinformatics analysis suggested that the mutation could affect PLAA gene expression, but not affecting PLAA mRNA structure.@*Conclusion@#PLAA gene 1040-8 A> G mutation is separated from patients in the gout pedigree, and the newly discovered PLAA gene may act as a gout pathogenic gene.
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Objective:To screen gene mutation information of gout pedigree through whole genome sequencing and to carry out preliminary analysis.Methods:One typical gout pedigree was selected as the study subjects. The clinical data and the peripheral blood samples were collected and constructed charts of the pedigree. DNAs were extracted from peripheral blood and analyzed by the whole genome sequencing, and by the software analysis and comparison, screening out the pathogenic genes and related mutations. Then the verifications were conducted in the family members and the controls. Bioinformatics software was applied to predict the effect of mutation on gene expression.Results:Based on the sequencing results, advanced informational analysis was performed to screen out the mutations 1040-8 A> G near the 5 ′end near the exon 8 of the PLAA gene. The results showed that all the gout patients in the family had 1040 -8 A> G sites, and none of the mutants were found in the non-gout group and 200 controls; bioinformatics analysis suggested that the mutation could affect PLAA gene expression, but not affecting PLAA mRNA structure.Conclusion:PLAA gene 1040-8 A> G mutation is separated from patients in the gout pedigree, and the newly discovered PLAA gene may act as a gout pathogenic gene.
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Objective:To analyze the risk factors of frequent gout flare, and to evaluate its susceptibility to identify patients with≥2 acute attacks per year.Methods:A total of 579 of cases gout patients with no history of taking urate lowering treatment (ULT) in recent 12 months were enrolled. The patients were divided into frequent group (gout episodes≥twice per year) and non-frequent group(gout attacks<twice per year). The clinical information was collected and relevant biochemical indices were detected.Results:There were significant differences in involvement of upper limb joints, tophi, combining hypertension and renal stone between two groups. The two groups had no statistical differences in family history, gender, history of smoking and drinking, ratios of regular exercise, and combining diabetes, hepatic insufficiency, hypertriglyceridemia, hypercholesterolemia, and overweight/obesity. There was significant differences in the number of joints involved, the history of disease duration, the level of SUA and TG[(4.66±2.54) vs (2.77±1.64), (6.68±5.11) vs (5.14±3.89) years, (525.82±132.11) vs (489.33±139.81) μmol/L, (2.51±1.94) vs (2.05±1.22) mmol/L, P<0.05 or P<0.01]; There were no statistical differences in age of onset, SBP, DBP, age of initial diagnosis, fasting blood glucose, TC, creatinine, glomerular filtration rate, AST, ALT, body mass index, waist circumference, and waist-to-hip ratio. Logistic regression analysis indicated that a large number of joints involved and higher serum uric acid level were risk factors of frequent gout attacks. The ROC curve showed that the number of joints involved had qualified performance in identifying patients with frequent gout attacks. When the number of joints involved was >2, and the sensitivity, specificity, positive predictive value and negative predictive value were 77.8%, 43.3%, 85.6%, and 56.6%, respectively, and the difference was significant. Conclusion:Higher SUA and a larger number of joints involved associate independently with frequent gout attacks. The number of joints involved at initial diagnosis>2, which can predict the frequent flare, and start ULT as earlier as possible. Patients with joints involved at initial diagnosis>2 are at greater risk of frequent gout flare.