Objective To evaluate the values of diagnosis in anomalies of aortic valve with transesophogeal echocardiography (TEE) before operation. Methods Thirty-seven cases of anomalies of aortic valve which were diagnosed by TEE and treated by operation were analyzed retrospectively, the features of anomalies of aortic valve, pattern of cardiac structure changing and the reference values of diagnosis with TEE in choosing correct operation method were summarized. Results There were different characteristics in the number of valve and juncture, location of juncture, opening and closing shape of aortic valve, aortic valvular stenosis, aortic valvular regurgitation or both of them.Pattern of changes of cardiac structure included ascending aorta dilatation, left ventricle enlarge and left ventricle hypertrophy. Features of aortic valve anomalies and pattern of changes of cardiac structure were the important consulting information for the selection of operation method. Conclusion TEE is an important diagnosis method for anomalies of aortic valve, and it can provide abundant and valuable information for choosing an appropriate operational method.

Objective To discuss the risk factors for susceptibility of subcutaneous tophi with an aim to provide clinical evidence for the prevention and treatment of tophi.Methods A total of 5 321 cases of gout patients whose course of disease was less than 10 years were selected and divided into two groups according to whether a subcutaneous tophus was present. The clinical information was collected and relevant biochemical indices were detected.Results There were significant differences in the ratios of regular exercise, involvement of upper limb joints, combining renal insufficiency, kidney stone and coronary heart disease between the tophus group and the non-tophus group(P<0.05 or P<0.01). There were significant statistical differences in age, disease duration, body mass index, systolic blood pressure, diastolic blood pressure, serum uric acid, serum creatinine, creatinine clearance rate, the number of joints involved between the two groups[(51.80±14.58 vs 48.45±14.45)year,(5.61±3.20 vs 3.28±3.06)year,(26.50±3.39 vs 27.05±3.45)kg/m2,(138±20 vs 133±18)mmHg, 1 mmHg=0.133 kPa,(89±13 vs 87±12)mmHg,(486.66±121.96 vs 460.02±119.10) μmol/L,(112.11±62.97 vs 104.43±46.28) μmol/L, (86.46±37.99 vs 93.00±40.11 )ml/min,(2.89±1.86 vs 1.76±1.22) joints, all P<0.01]. There were no statistical differences in family history, gender, history of smoking and drinking, the means of waistline, fasting blood glucose, triglyceride, and total cholesterol between the two groups(all P>0.05). Further logistic regression analysis indicated that disease duration, a large number of joints involved, the involvement of upper limb joints, combining kidney stones, higher serum uric acid level, and higher diastolic pressure were risk factors of the early onset of subcutaneous tophi, while regular exercise and body mass index were protective factors.Conclusion Patients with long duration, high serum level of uric acid, a large number of joints involved, upper limb joint involved, kidney stones, and hypertension were more likely to develop subcutaneous tophi. These risk factors should be intervened actively in clinic.

Objective Obesity is one of the risk factors for gout.The aim of the present study was to evaluate clinical characteristics of gout patients with different BMI.Methods A total of 5 104 patients with gout were enrolled and divided into three groups according to the BMI.The clinical information was collected and relevant biochemical indices were detected.SPSS software was applied for the statistical analyses.Results There were significant differences in the ratios of gender,regular exercise,hypertension,tophus,renal insufficiency,hyperlipidemia,impaired glucose metabolism,liver dysfunction among the three groups (all P＜0.01).The onset age in overweight [45(36,55) years] and obese subjects [40(31,50)years] were earlier than that of the normal weight subjects [50 (38,61) years].Moreover,waist circumstances [103(99,108) cm and 94 (90,98) cm vs 87 (82,91) cm],systolic pressure [130 (120,145) mmHg (1 mmHg =0.133 kPa) and 130 (120,140) mmHg vs 128 (115,140) mmHg],diastolic pressure [90 (80,100) mmHg and 85 (80,92) mmHg vs 80 (79,90) mmHg],fasting blood glucose [5.77 (5.30,6.44) mmol/L and 5.65 (5.19,6.26) mmol/L vs 5.55 (5.10,6.15) mmol/L],TG [2.10 (1.46,3.04) mmol/L and1.88 (1.35,2.78) mmol/L vs 1.52 (1.07,2.39) mmol/L],TC [5.20 (4.55,5.93) mmol/L and 5.07 (4.46,5.75) mmol/L vs 4.95 (4.27,5.65) mmol/L],serum uric acid [483(418,552) μmol/L and461(395,524) μmol/L vs440 (368,517) μmol/L],ALT [30 (21,46) U/L and25 (18,36) U/L vs 21 (14,29) U/L],AST [21(17,28) U/L and 20 (17,26) U/L vs 20 (6,25) U/L],the number of joints involved [2 (1,3) joints and 2 (1,2) joints vs 1 (1,2) joints] in the overweight and obese groups were higher than those in the normal weight group (all P ＜ 0.01).There were no statistical differences in family history,involvement of upper limb joints,kidney stones and coronary heart disease among the three groups (all P ＞ 0.05).Conclusions Obesity is associated with an earlier age of gout onset.With the increase of BMI,the blood pressures,glucose,lipid,serum uric acid,liver transaminase levels and the number of involved joints increased gradually.Cautions should be taken in treating patients with different BMI.

Tophus is the sign of chronic gout, which can lead to bone destruction, joint dysfunction, and significantly increase the risk of cardiovascular disease and death. Tophus has a structure of chronic foreign body granuloma,and extracellular reticular trap of neutrophils may be the main mechanism for the formation of tophi. Several factors can lead to the tophus formation. This article reviews the recent advances in the study of biology,risk factors and therapy of tophus.

Objective:To investigate the efficacy of salbutamol combined with budesonide aerosol inhalation in the treatment of patients with acute attack of bronchial asthma and its influence on serum inflammatory factors.Methods:From January 2017 to December 2018, 78 patients with acute attack of bronchial asthma in Zhejiang Xin'an International Hospital were selected, and they were divided into combined group and control group according to the random number table method, with 39 cases in each group.The control group was treated with routine western medicine, and the combined group was treated with salbutamol and budesonide aerosol inhalation on the basis of the control group.The two groups were treated for 2 weeks.The changes of vital capacity(VC), forced expiratory volume in one second(FEV 1) and peak expiratory flow(PEF) were compared before and after treatment.The changes of serum high mobility group protein 1(HMGB1), C-reactive protein(CRP) and tumor necrosis factor-alpha(TNF-α) were measured before and after treatment. Results:The total effective rate of the combined group was 87.18%(34/39), which was higher than 68.57%(24/39) of the control group, the difference was statistically significant(χ 2=5.791, P<0.05). The values of VC, FEV 1 and PEF between the two groups before treatment had no statistically significant differences( t=0.588, 0.892, 0.371, all P>0.05), which in the two groups after treatment were all increased(the combined group: t=16.045, 7.193, 6.667; the control group: t=7.834, 8.354, 4.262, all P<0.05). The values of VC, FEV 1 and PEF in the combined group after treatment were higher than those in the control group ( t=6.591, 9.615, 11.383, all P<0.05). The levels of HMGB1, CRP and TNF-α in the two groups before treatment had no statistically significant differences( t=0.306, 0.669, 0.371, all P>0.05), which in the two groups after treatment were all decreased (the combined group: t=10.235, 16.992, 12.371; the control group: t=4.763, 15.663, 13.115, all P<0.05). The levels of HMGB1, CRP and TNF-α in the combined group were lower than those in the control group after treatment( t=6.591, 3.559, 8.307, all P<0.05). Conclusion:Salbutamol combined with budesonide aerosol inhalation in the treatment of acute attack of bronchial asthma has better effect, which can effectively improve the lung function of patients, inhibit the release of inflammatory factors, and with high safety.

Objective:To investigate the therapeutic effect and influencing factors of alkalized urine in patients with gout, thus providing the basis for the clinical treatmeat.Methods:A total of 90 cases of gout patients in remission without alkalization of urine and lowering uric acid treatment were selected from January 2019 to June 2019. All patients were given a low purine diet (purine intake<200 mg/d). 90 patients were randomly divided into different drugs of alkalized urine groups according to rardom number table: sodium bicarbonate group, taking potassium sodium hydrogen citrate 1.0 g tid; the citrate granule group, taking potassium sodium hydrogen citrate 2.5 g tid; and control group, taking low purine diet only. On the 5th day of treatment, fasting urine in the morning was retained, breakfast was prescribed, and alkalized urine drugs were taken after the meal. Their urine pH was determined at 1 h, 2 h, 3 h, and 4 h after the medicine taken, and copmare the changes of urine pH in different groups. Taking urine pH 6.2 as cut-off point, patients receiving alkalized urine drugs were divided into the standard group (urine pH≥6.2) and the non-standard group (urine pH<6.2) according to their mean urine pH at 2 h, 3 h, and 4 h after taking medicine. Finally, the influencing factors of urine pH were compared between the groups.Results:There were no significant differences in fasting urine pH between the sodium bicarbonate group and the control group, but the urine pH of 2 h and 3 h after sodium bicarbonate taken were significantly higher than the control group ( P<0.05). The urine pH of the citrate granule group was higher than the control group and the sodium bicarbonate group on fasting and at any time after taking drugs ( P<0.05 or P<0.01). The peak pH value of urine in the sodium bicarbonate and citrate granule groups was 4 h after taking drugs, followed by 2 h and 3 h. There were statistically significant differences in body mass index, waist circumference, and blood pressure between the standard and non-standard groups ( P<0.05 or P<0.01). Conclusion:Fasting urine pH alone can not be used as an index for the efficacy of alkalized urine, it is recommended to refer to the pH value of 2-4 h after taking drugs. The efficacy of potassium sodium hydrogen citrate was better than that of sodium bicarbonate. Obesity or overweight seems to be an adverse factor affecting the alkalized urine.

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.

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.

Objective:To explore the mediating effects of self-control and rumination between neuroticism and insomnia in college students.Methods:A cross-sectional survey was conducted among 767 college students from a university in Sichuan province with Chinese big five personality inventory-15, insomnia severity index, ruminative responses scale, and self-control scale.Results:The prevalence of insomnia was 36.6% among college students.The scores of neuroticism (9.63±3.41), rumination (22.27±5.44) and ISI (6.61±4.28) were positively correlated with each other ( r=0.281-0.389, P<0.01), while each of them was negatively correlated ( r=-0.453--0.194, all P<0.01) with self-control (60.71±9.41). Analysis of mediating effects revealed that neuroticism not only directly affected insomnia, but also indirectly affected insomnia through the mediating effects of rumination and self-control respectively. Conclusion:Self-control and rumination have mediating effects between neuroticism and insomnia in college students.

Objective:To investigate the effect of digoxin on bleomycin-induced pulmonary fibrosis in mice, and investigate its possible mechanism through in vitro and in vivo experiments. Methods:① In vivo experiment: 60 C57/BL6J mice were randomly divided into control group, pulmonary fibrosis model group (model group), pirfenidone (300 mg/kg) group, digoxin 1.0 mg/kg and 0.2 mg/kg groups, with 12 mice in each group. The pulmonary fibrosis model of mice was reproduced by single intratracheal infusion of bleomycin (5 mg/kg). The control group was given the same amount of sterile normal saline. From the next day after modeling, each group was received corresponding drugs by intragastric administration once a day for 28 days. Control group and model group were given the same amount of normal saline. The mice were sacrificed and the lung tissue was collected to detect the lung coefficient. After hematoxylin-eosin (HE) and Masson staining, the lung tissue morphology and collagen changes were observed under light microscope. Immunohistochemistry was used to detect the positive expressions of α-smooth muscle actin (α-SMA) and extracellular matrix (ECM) collagen (COL-Ⅰ and COL-Ⅲ) in lung tissue. The protein expressions of ECM fibronectin (FN), transforming growth factor-β (TGF-β) and phosphorylation of Smad3 (p-Smad3) in lung tissue were detected by Western blotting. ② In vitro experiment: human embryonic lung fibroblast-1 (HFL-1) cells were cultured and divided into blank control group, fibroblast activation model group (model group), pirfenidone (2.5 mmol/L) group and digoxin 100 nmol/L and 50 nmol/L groups when cell density reached 70%-90%. After 3-hour treatment with corresponding drugs, except blank control group, the other groups were treated with TGF-β for 48 hours to establish fibroblast activation model. The expressions of α-SMA, FN and p-Smad3 proteins and the phosphorylations of phosphatidylinositol-3-kinase (PI3K)/Akt pathway proteins PI3K and Akt (p-PI3K, p-Akt) were detected by Western blotting. Results:① In vivo, compared with the control group, the alveolar structure of mice in the model group was significantly damaged, a large number of inflammatory cells infiltrated, collagen deposition in the lung interstitium was increased, the deposition of ECM in the lung tissue was also increased, and the expressions of α-SMA, FN, TGF-β and p-Smad3 protein were increased, indicating that the model of bleomycin-induced pulmonary fibrosis in mice was successfully prepared. Compared with the model group, digoxin significantly inhibited airway inflammation and collagen fiber deposition, reduced ECM deposition, and decreased the protein expressions of α-SMA, FN, TGF-β and p-Smad3, while the effect was better than that of the pirfenidone group, and the digoxin 1.0 mg/kg group had a better effect except FN [α-SMA ( A value): 5.37±1.10 vs. 9.51±1.66, TGF-β protein (TGF-β/GAPDH): 0.09±0.04 vs. 0.33±0.23, p-Smad3 protein (p-Smad3/GAPDH): 0.05±0.01 vs. 0.20±0.07, all P < 0.01]. ② In vitro, compared with the blank control group, the expressions of FN, α-SMA, p-Smad3 and PI3K/Akt signaling proteins in the model group were increased, indicating that the fibroblast activation model induced by TGF-β was successfully reproduced. Compared with the model group, digoxin significantly inhibited fibroblast activation, and decreased the expressions of FN, α-SMA, p-Smad3, and PI3K/Akt pathway proteins, moreover, the effect was better than that of the pirfenidone group, and decreased FN, SMA and p-Akt protein expressions were more obvious in digoxin 100 nmol/L group [FN protein (FN/GAPDH): 0.21±0.15 vs. 0.88±0.22, α-SMA protein (α-SMA/GAPDH): 0.20±0.01 vs. 0.50±0.08, p-Akt protein (p-Akt/GAPDH): 0.30±0.01 vs. 0.65±0.10, all P < 0.01]. Conclusion:Digoxin could suppress the pulmonary fibrosis in mice induced by bleomycin, which might be associated with the regulation of fibroblast activation via suppressing PI3K/Akt signaling pathway in a dose-dependent manner.