This study was performed to explore the effects of berberine(BBR)and berbamine(BA)on the apoptosis and activity of eosinophils,and to provide new ideas for the treatment of eosinophil-related diseases.Anticoagulated whole blood was taken from hospitalized patients,and eosinophils were purified by magnetic bead sorting technology,and the cell purification rate was compared by using flow cytometry.The purified eosinophils were cultured and stimulated with different concentrations of BBR and BA,and the apoptosis of eosinophils was observed using immunofluorescence microscopy.Flow cytometry was used to detect the apoptosis rate,reactive oxygen species(ROS)release,mitochondrial membrane potential,and CD11b,CD62L and CD63 molecular expression of eosinophils.Data showed that 10 μmol/L BBR displayed significant anti-apoptosis effect on eosinophils at 18 h,24 h,48 h,however,100 μmol/L and 150 μmol/L BBR displayed significant apoptosis-promoting effects on eosinophils at 24 h,48 h,especially in the early stage.BA at 5 μmol/L,15 μmol/L and 25 μmol/L showed significant apoptosis-promoting effects on eosinophils at 24 h,48 h,especially in the late stage.In eosinophils,BA stimulated the production of ROS and the decrease of mitochondrial membrane potential in a concentration-dependent manner,reaching the maximum effect at 25 μmol/L,while BBR stimulation did not change mitochondria and ROS.Pretreatment with 25 μmol/L BA significantly inhibited the increase of CD11b expression and the decrease of CD62L expression in eosinophils after eotaxin-2 stimulation.In conclusion,berberine has a bidirectional regulatory effect on the quantity of eosinophils,while berbamine promotes eosinophil apoptosis and inhibits eosinophil activation.Both compounds hold significant potential for regulating the progression of eosinophil-associated diseases,and their regulatory mechanisms need further investigation.

OBJECTIVE To observe the efficacy of vericiguat in the treatment of acute decompensated heart failure （HF） and its effect on left ventricular ejection fraction （LVEF） in patients with different left ventricular end-diastolic internal diameters （LVDd）. METHODS A total of 52 patients with acute decompensated HF who were hospitalized in Anqing Municipal Hospital from September 2022 to May 2023 and were stabilized by intravenous injection of diuretics or vasodilators and then given vericiguat orally were selected. Clinical baseline data were collected， and blood creatinine （Scr）， estimated glomerular filtration rate （eGFR）， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， echocardiographic indexes（LVEF， LVDd）， and Kansas City cardiomyopathy questionnaire （KCCQ） scores and so on were recorded and analyzed at 1 and 6 months after treatment. The patients were divided into two subgroups according to whether they had dilated cardiomyopathy or not， the baseline data were compared between the two subgroups， and the changes in the above follow-up indexes for the entire population and two subgroups of patients were analyzed by using mixed effect model. RESULTS Patients in the dilated cardiomyopathy group were significantly younger than those in the nondilated cardiomyopathy group， while the former had a lower proportion of patients with combined coronary artery disease， longer LVDd， lower LVEF levels， and more HF patients with reduced ejection fraction （P＜0.05）. Compared with baseline values， KCCQ scores were significantly higher in patients in the whole population， non-dilated cardiomyopathy group and dilated cardiomyopathy group at 1 month after treatment （P＜0.001）. The difference between the whole population in terms of elevated KCCQ scores and decreased lg（NT-proBNP） levels was statistically significant at 6 months after treatment （P＜0.05）； the levels of lg（NT-proBNP）of two subgroups were significantly decreased and KCCQ scores were significantly increased （P＜0.05）， but the difference was not statistically significant （P＞0.05）； LVEF levels of the patients E-mail：guangf4-508@163.com in both subgroups were significantly elevated （P＜0.05） and the difference between the subgroups amounted to 7.52% （P＝0.030）. Mixed effect model result showed that whether patients had coronary artery disease and different baseline levels of LVDd were likely to affect follow-up LVEF levels， with coronary artery disease contributing to follow-up LVEF elevation （P＝0.043）， but the coronary artery disease subgroup × time interaction was not significant （P＞0.05）；compared with patients with baseline LVDd ≥62 mm， patients with baseline LVDd≤61 mm had a faster LVEF improvement （P＜0.05）. CONCLUSIONS Vericiguat is able to improve cardiac function and quality of life in patients with acute decompensated HF without negatively affecting their renal function. The drug is able to significantly improve LVEF levels in patients with baseline LVDd ≤61 mm.

OBJECTIVE To observe the efficacy of vericiguat in the treatment of acute decompensated heart failure （HF） and its effect on left ventricular ejection fraction （LVEF） in patients with different left ventricular end-diastolic internal diameters （LVDd）. METHODS A total of 52 patients with acute decompensated HF who were hospitalized in Anqing Municipal Hospital from September 2022 to May 2023 and were stabilized by intravenous injection of diuretics or vasodilators and then given vericiguat orally were selected. Clinical baseline data were collected， and blood creatinine （Scr）， estimated glomerular filtration rate （eGFR）， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， echocardiographic indexes（LVEF， LVDd）， and Kansas City cardiomyopathy questionnaire （KCCQ） scores and so on were recorded and analyzed at 1 and 6 months after treatment. The patients were divided into two subgroups according to whether they had dilated cardiomyopathy or not， the baseline data were compared between the two subgroups， and the changes in the above follow-up indexes for the entire population and two subgroups of patients were analyzed by using mixed effect model. RESULTS Patients in the dilated cardiomyopathy group were significantly younger than those in the nondilated cardiomyopathy group， while the former had a lower proportion of patients with combined coronary artery disease， longer LVDd， lower LVEF levels， and more HF patients with reduced ejection fraction （P＜0.05）. Compared with baseline values， KCCQ scores were significantly higher in patients in the whole population， non-dilated cardiomyopathy group and dilated cardiomyopathy group at 1 month after treatment （P＜0.001）. The difference between the whole population in terms of elevated KCCQ scores and decreased lg（NT-proBNP） levels was statistically significant at 6 months after treatment （P＜0.05）； the levels of lg（NT-proBNP）of two subgroups were significantly decreased and KCCQ scores were significantly increased （P＜0.05）， but the difference was not statistically significant （P＞0.05）； LVEF levels of the patients E-mail：guangf4-508@163.com in both subgroups were significantly elevated （P＜0.05） and the difference between the subgroups amounted to 7.52% （P＝0.030）. Mixed effect model result showed that whether patients had coronary artery disease and different baseline levels of LVDd were likely to affect follow-up LVEF levels， with coronary artery disease contributing to follow-up LVEF elevation （P＝0.043）， but the coronary artery disease subgroup × time interaction was not significant （P＞0.05）；compared with patients with baseline LVDd ≥62 mm， patients with baseline LVDd≤61 mm had a faster LVEF improvement （P＜0.05）. CONCLUSIONS Vericiguat is able to improve cardiac function and quality of life in patients with acute decompensated HF without negatively affecting their renal function. The drug is able to significantly improve LVEF levels in patients with baseline LVDd ≤61 mm.

Objective:To study the macrolides resistance of Mycoplasma pneumoniae(MP) in Suzhou area, and try to explore the relationship between drug resistance and refractory Mycoplasma pneumoniae pneumonia (RMPP). Methods:From a series of hospitalized children who were diagnosed as Mycoplasma pneumoniae pneumonia (MPP) from October 2013 to September 2014 in Suzhou area, 48 children were treated with Azithromycin (10 mg/kg, once a day, intravenous drip for 5-7 days), and the clinical symptoms and chest imaging were still progressing so they were clinically diagnosed as RMPP, and 34 children who were successfully treated with macrolides antibiotics (MA) were clinically diagnosed as general MPP (GMPP). MP DNA was extracted from the airway secretion of children in the two groups, and the point mutations of 2063 and 2064 of 23S rRNA were sequenced, and according to the MP 23S rRNA sequencing results, the children were divided into macrolides antibiotic resistant MP group (MRMP) and macrolides antibiotic sensitive MP group (MSMP). The clinical characteristics of the two groups were compared. Results:In the MRMP group, the incidence of RMPP was 62.2% (46/74 cases), while in MSMP group, the incidence of RMPP was 25.0% (2/8 cases). The point mutation of MP 23S rRNA had no significant effect on the occurrence of RMPP ( χ2=2.719, P=0.099). Compared with MRMP group, MSMP group presented shorter fever time and less glucocorticoid use.No significant differences between the two groups were found in chest imaging examination, as well as some laboratory results, including the total number and classification of white blood cell (WBC), C-reactive protein (CRP), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB). Conclusions:The fever duration of MPP lasted more than 1 week, suggesting the possibility of macrolides resistance of MP, but macrolides resistance did not aggravate the occurrence of RMPP.It is unreliable to judge the MRMP by chest imaging features and laboratory results.

Gout is a crystal associated arthritis caused by monosodium urate (MSU) accumulating in joint, and it belongs to metabolic rheumatic disease. In China, gout is common but it is insufficient for education of standardized diagnosis and treatment for gout. Based on the evidence and guidelines from China and other countries, Chinese gout Collaborative Research Group developed standardization of diagnosis and treatment of gout in China. The purpose is to standardize the methods for diagnosis of gout, treatment opportunity and strategies in order to reduce misdiagnosis, missed diagnosis and irreversible damage.

Objective To compare the efficacy and safety of the long-term intermittent maintenance treatment with tacrolimus 0.03％ ointment versus traditional treatment in reducing relapses and prolonging the recurrence interval in children with moderate to severe atopic dermatitis (AD).Methods A two-phase randomized,open-labelled,controlled clinical trial was conducted from September 2012 to November 2013.In the first phase,a total of 171 children aged 2-15 years with moderate to severe AD were enrolled from 7 hospitals in China,and received conventional treatment with tacrolimus 0.03％ ointment twice a day for 2-6 weeks.At the end of the treatment,the patients who achieved an investigator's global assessment (IGA) score ≤ 2 (n =125) were randomly classified into 2 groups to receive the second-phase treatment:test group (n =62) receiving intermittent maintenance treatment with tacrolimus 0.03％ ointment twice a week (Monday and Thursday),and control group (n =63) receiving no treatment.If the patients in the 2 groups experienced relapse,they received conventional treatment with tacrolimus 0.03％ ointment twice a day.The overall observation period was 6 months.The primary endpoint was the time to the first relapse,which was defined as the number of days from the end of the first-phase treatment to the first relapse.The secondary endpoints included the number of relapses at the second-phase trial,the disease severity at the time of relapse,the duration of relapse,the pruritus score at the time of relapse,the total amount of tacrolimus ointment used,the total response rate at the second-phase trial,and the incidence of adverse events.Results A total of 125 children with AD were enrolled into the second-phase trial,and 121 of them completed the follow-up.Among the 121 patients,the recurrence rate was significantly lower in the test group (25/60,41.7％) than in the control group (46/61,75.4％;x2 =14.20,P ＜ 0.001).The time to the first relapse was significantly longer in the test group (46.9 ± 37.7 d) than in the control group (28.8 ± 32.3 d;Z =1 093.50,P =0.020).The total number of recurrence was 31 and 86 in the test group and control group respectively,and the mean number of recurrence in each patient was significantly lower in the test group (0.52 ± 0.68) than in the control group (1.41 ± 1.23,t =4.96,P ＜ 0.001).There were no significant differences between the two groups regarding disease severity during relapse (eczema area and severity index:Z =971.50,P =0.39),duration of relapse (Z =747.00,P =0.07),and pruritus score during relapse (Z =894.00,P =0.95).The therapeutic drug was tolerated well in all the children,and no tacrolimus-related serious adverse events occurred.Conclusion The intermittent maintenance treatment with tacrolimus 0.03％ ointment twice a week for 6 months can effectively and safely prevent and reduce relapses,and prolong the recurrence interval in children with moderate to severe AD.

Objective To analyze the epidemiological characteristics of Streptococcus pneumonia (SP) in children with respiratory tract infection in Suzhou area,and the correlation between the air pollutants and the epidemiological characteristics of SP.Methods The real-time air quality test data of Suzhou in Jiangsu province was recorded from January 2012 to December 2014,and sputum specimens of 6 653 cases of hospitalized children with respiratory tract diseases in the same period were collected.The SP detection content and the correlation between SP and the concentration level of PM2.5,PM 10,nitrogen dioxide (NO2),sulfur dioxide (SO2),carbon monoxide (CO),ozone (O3) in Suzhou were analyzed.Results The SP detection rate was 9.94％ in 6 653 children.The SP detection rates were respoctively 7.69％ (183/2 381 cases),10.87％ (235/2 161 cases),11.51％ (243/2 111 cases) between 2012 and 2014.The SP detection rates of children at the age of ≤ 1 year old,＞ 1-3 years old,＞ 3-＜ 7 years old and ≥ 7 years old more respectively were 7.11％ (227/3 192 cases),13.48％ (244/1 810 cases),13.76％ (168/1 221 cases),5.12％ (22/430 cases).The SP detection rate of children at the age of ＞ 1-3 years old and ＞3-＜7 years old was higher than that of ≤ 1 years old and ≥7 years old,and the difference was significant (x2 =84.980,P ＜ 0.001).The SP detection rates in spring,summer,antumn and winter respectively were 9.79％ (173/1 768 cases),7.66％ (130/ 1 697 cases),11.76％ (187/1 590 cases),10.70％ (171/1 598 cases).The SP detection rate of children in summer was the lowest (x2 =4.897,15.839,9.165,all P ＜ 0.05).The concentrations of PM2.5,PM 10,SO2,NO2,CO and O3 were in a state of fluctuation during the survey period.The SP detection rate had positive correlation with the concentration of PM2.5,PM10,SO2,NO2,CO and O3 (r =0.650,0.586,0.680,0.467,all P ＜ 0.005),and there was no obvious correlation between the SP detection rate and the concentration of CO,O3 (all P ＞ 0.05).Conclusions SP is one of the important pathogens of respiratory tract infection in children in Suzhou area,and the detection rate in infants and preschoolers is higher but the detection rate in summer is lower.The SP detection rate is closely correlated with the concentration of PM2.5,PM10,SO2,NO2.

Objective To evaluate the applicability of small molecular markers of nephrotoxicity that in prediction of drug toxicity.Method Extracts of five kinds of traditional Chinese medicines (Tripterygium wilfordii,Strychni semen,Aristolochiafangchi,Rhei Radix et Rhizoma,and Xanthium sibiricum) that had known as nephrotoxicity were ig given to rats to establish renal injury models,and the blood samples were collected after administration for 1 and 7 d.Then blood samples were analyzed by UPLC/Q-TOF-MS for five kinds of small molecule biomarkers-thymidine,lyso-phosphatidylcholine (LPC 16:1),LPC (18:4),LPC (20:5),and LPC (22:5).The support vector machine (SVM) prediction model was established to determine the toxicity.The levels of Cr and BUN in serum were determined by automatic biochemical analyzer.The rats in each group were sacrificed after blood collection,and the kidneys were taken for HE staining.Result No toxicity was observed in the control group,and the biochemical test results showed no renal injury after mentioned five kinds Chinese herbs were given for 1 d,while SVM model of nephrotoxicity had been found abnormal.After administration for 7 d,the results of SVM model show renal toxicity,which were consistent with biochemical and pathological examination.Conclusion Metabonomics combined with the earlier established SVM model enabled prediction of drug nephrotoxicity more sensitively,quickly and \ccurately,and it is of great significance for the discovery of drug toxicity as well as the prevention and treatment of drug-induced renal injuries in clinic.

Objective To analyze the correlation between response to hepatitis B virus (HBV) vaccine and cellular immunity and clinical characteristics in children with respiratory infection.Methods Nine hundred and sixty children in Department of Respiratory in Children's Hospital of of Soochow University,who were over 7 months old and had full course of HBV vaccination between January and December 2015 were enrolled in this study.Peripheral blood (1-2 mL) was collected,and antigen-antibody of HBV was detected by using enzyme-linked immunosorbent assay and PCR included HBV surface antigen,hepatitis B antibody,HBV e antigen,HBV e antibody,HBV core antibody,and HBV nucleic acid.According to the results,these children were divided into 4 groups:non response group,low response group,normal response group and high response group according to their responses to HBV vaccine.Cellular immunity was detected by using flow cytometry and patients' clinical data was collected.Results There was no statistical differences of CD3 + CD4 +,which were (3.43 ± 0.28) ％,(3.42 ± 0.30) ％,(3.43 ± 0.36) ％ and (3.52 ± 0.29) ％,among the four groups (F =0.520,P =0.669).CD3 + CD8 + in non response group was (3.18 ±0.28)％,which was significantly higher than that in low response group,normal response group and high response group [(3.08 ± 0.36)％,(3.05 ±0.34)％,(2.93 ±0.30)％],the differences were significant (all P＜0.05);CD4/CD8 in non response group (0.26 ± 0.43) were significantly lower than that in normal response group (0.40 ± 0.50),the differences were significant (P =0.001).There was no significant difference of CD3 +,CD3 + CD8 + and CD4/CD8 among low response group,normal response group and high response group (all P ＞ 0.05).CD3-CD19 + and CD19 + CD23 + level were lowest in non response group [(3.00 ± 0.57) ％,(2.25 ± 0.67) ％] and highest in high response group [(3.33 ± 0.45) ％,(2.57 ± 0.38) ％],the differences were significant (all P ＜ 0.05).Among the 4 groups,children in normal response group had the shortest average hospitalization days [(1.88 ±-0.31) d],which was significantly shorter than that in non response group,low response group and high response group [(1.96 ± 0.39) d,(1.95 ± 0.38) d,(1.96 ±0.15) d],the differences were significant (all P ＜0.05),there was no significantly difference of average hospitalization days among other 3 groups (all P ＞ 0.05).Proportion of severe pneumonia was significantly higher in non response group [6.1％ (22/363cases)] and high response group [13.3％ (2/15 cases)] compared to those in normal response group [2.6％ (7/274cases)],the differences were statistically significant (x2 =4.417,P =0.036;x2 =5.476,P =0.019).The total white blood cell number was lowest in non response group (F =4.695,P =0.003).Platelet number was increased with higher degree of response to HBV (F =6.598,P ＜ 0.001).Conclusions Cellular immunity is lower in respiratory infection children with non response or low response to HBV vaccine.After they have respiratory infection,children with non response to HBV vaccine may have a longer course of disease and worse condition.

Objective To study the characteristics of etiology of lobar pneumonia in hospitalized children.Methods Medical history and sputum specimens were collected from 1 179 hospitalized children with lobar pneumonia from January 2006 to December 2015.Multiple pathogenic joint detection combined with the history data were used for analysis.Seven kinds of common respiratory virus were detected by direct immunofluorescence.Mycoplasma pneumoniae (MP), Chlamydia pneumoniae (CP) and human Bocavirus (hBoV) were detected by fluorescence quantitative polymerase chain reaction (PCR).Human Rhinovirus (HRV) and human Metapneumovirus (hMPV) were detected by reverse transcription PCR.Aspirates were cultured for bacteria.MP specific antibody IgG and IgM were tested by enzyme-linked immunosorbent assay (ELISA).Positive rates of each group were compared by χ2 test or Fisher exact test.Results Total etiology detection rate of lobar pneumonia in hospitalized children was 83.9% (989/1 179).The etiology detection rate of MP, virus, bacteria and streptococcus pneumoniae (SP) were 74.0%, 14.2%, 18.3% and 12.2%, respectively.The virus detection rate in 1-3 years old group was the highest, and that in ≥6 years old group was lower than other group (χ2=70.095, P<0.01).The MP detection rate increased with age (χ2=119.777, P<0.01).The bacteria detection rate in ≥6 years old group was significantly lower than those of <1 years old group, 1-3 years old group and 3-6 years old group (χ2=8.939, 14.319, 45.738, all P<0.01).The detection rates of total virus, MP, bacteria and mixed infection had no statistical difference in the four seasons (all P>0.05).The MP detection rate was above 70% in every season.The detection rates of SP and hBoV were basically the same in every season.The detection rate of HI was higher in spring, Pinf 3 and SA were higher in summer, HRV was higher in autumn, and respiratory syncytial virus (RSV) and moraxella catarrhalis (MC) were higher in winter.Conclusions Lobar pneumonia occurs more common in elder children.MP is the major pathogen of lobar pneumonia, and SP is the second.The MP detection rate increases with age.The pathogen detection rate varies with age, but the effect of seasonal factor is not obvious on pathogen detection in lobar pneumonia.