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.

Background and aims:Antiviral therapy is essential for hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF).No data are available on the long-term prognosis or safety of tenofovir alafenamide(TAF),tenofovir disoproxil fumarate(TDF),or entecavir(ETV)in treating HBV-ACLF globally.This study was conducted to investigate the long-term efficacy and safety of the three nucleos(t)ide analogs in the treatment of HBV-ACLF.Methods:In this prospective,real-world cohort study,patients with HBV-ACLF were assigned to the TAF,TDF,and ETV groups.A total of 199 patients completed the 144-week follow-up.After propensity score matching(PSM),44 patients remained in each group for further analysis of survival status,incidence of hepatocellular carcinoma(HCC),virological response,and liver and renal function indicators.Results:In the original cohort,HCC developed in one patient in each group.No serious drug-related adverse events were observed.In the PSM cohort,the 144-week survival rates were 56.82％,75.00％,and 59.09％in the TAF,TDF,and ETV groups,respectively(P=0.118).When stratified into noncirrhosis and cirrhosis subgroups at baseline,the survival rate of the ETV group was slightly lower than that of the TAF and TDF group in noncirrhosis patients(P=0.338),and the survival rate of the TAF group was slightly lower than that of the TDF and ETV group in cirrhosis patients(P=0.052),but the differences were not statistically significant.The long-term overall survival rates in the TAF,TDF,and ETV groups were comparable.After 144 weeks,no significant difference in the virological response rate or liver or renal function indicators was found among the three groups,except for the level of aspartate amino-transferase,which was significantly higher in the TDF group than in the ETV group at week 144(P=0.001).Conclusions:There were no significant differences in the survival rate,incidence of HCC,efficacy or safety associated with the use of these three nucleos(t)ide analogs in treating HBV-ACLF.Trial registration:ClinicalTrials.gov NCT03920618.

OBJECTIVE：To investigate the efficacy of hormone combined with cyclophosphamide in the treatment of connective tissue disease-associated interstitial lung disease （CTD-ILD）and to analyze its influential factors. METHODS ：100 patients diagnosed as CTD-ILD in our hospital from Jan. 2018 to Jan. 2019 were randomly divided into observation group and control group ，with 50 cases in each group. Control group was treated with Compound cyclophosphamide tablets ，50 mg each time，3-4 times each day. Observation group was additionally treated with Prednisone acetate tablets ，10 mg each time ，3-4 times each day ，on the basis of control group. Treatment courses of 2 groups lasted for 6 months. The clinical efficacy ，the occurrence of ADR，lung function before and after treatment ，the levels of peripheral IL- 6，CRP and PCT and quality of life （SGRQ score ）were compared between 2 groups. According to the therapeutic efficacy ，all patients were divided into effective group and ineffective group. The related factors influencing the clinical efficacy of CTD-ILD were analyzed by univariate and multivariate Logistic regression analysis. RESULTS ：After treatment ，total response rate ，FVC，FEV1 and DLCO of observation group were significantly higher than those of control group ，while SGRQ score ，levels of IL- 6，CRP and PCT in peripheral blood were significantly lower than control group （P＜0.05）. There was no significant difference in the total incidence of ADR between 2 groups（P＞0.05）. Univariate analysis showed that there were no significant differences in gender ，age，past medical history and CTD type between effective group and ineffective group （P＞0.05）. However ，there were statistical significancant differences in the distribution of different levels of IL- 6，CRP and PCT in peripheral blood between 2 groups（P＜0.05）. Multivariate Logistic regression analysis showed that IL- 6 was an independent risk factor for therapeutic efficacy of combined therapy [OR （95％CI）＝ 4.537（3.668，10.352），P＝0.002]. CONCLUSIONS ：Hormone combined with cyclophosphamide can significantly improve the therapeutic efficacy of CTD-ILD patients ，improve their lung function and quality of life ，and reduce the expression level of inflammatory factors. The level of IL- 6 is an independent risk factor affecting the efficacy of the treatment ，and its changes should be paid close attention to during the treatment.

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 investigate the regulatory effects of CD24 on Ly6Chi macrophages in liv-er and its influences on bile duct ligation ( BDL)-induced hepatic fibrosis in mice. Methods Liver fibrosis was induced in wild-type ( WT) and CD24-/- mice by surgical ligation of the biliary duct. Levels of alanine amino transferase ( ALT) in serum were detected and liver sections were stained with haematoxylin and eosin ( H&E) staining to assess the severity of liver injury. Sirius Red staining was used to observe the degree of liver fibrosis. Real-time PCR was performed for detecting the expression of hepatic fibrosis-related markers and TGF-β1 at mRNA level. The percentage of macrophages and the number of TGF-β1-producing macro-phages were measured by flow cytometry. Results BDL-induced liver fibrosis was exacerbated in CD24-/-mice than in WT mice as demonstrated by more serious hyperplasia in bile duct, more inflammatory infiltra-tion at the portal area and higher levels of ALT in serum. Results of Sirius red staining also showed that the liver fibrosis was more severe in CD24-/- mice than in WT mice. Moreover, α-SMA and collagen typeⅠalpha 1 (Col1a1) were significantly upregulated in CD24-/- mice. Flow cytometry analysis revealed that CD24 was highly expressed by hepatic macrophages in BDL-induced WT mice, and the percentages of hepat-ic macrophages were significantly elevated in CD24-/-mice compared with those in WT mice. Further analy-sis revealed that the percentages of Ly6Chi hepatic macrophages in CD24-/- mice were higher than those in WT mice, but there was no significant difference in the percentages of Ly6Clo macrophages. The expression of TGF-β1 at mRNA level was increased in CD24-/-mice as compared with that in WT mice after BDL. Mo-reover, intracellular staining showed that Ly6Chi hepatic macrophages in CD24-/- mice secreted more TGF-β1 than the macrophages in WT mice. Conclusions CD24 might attenuate the BDL-induced liver fibrosis in mice via regulating the percentage of hepatic Ly6Chi macrophages and the secretion of TGF-β1.

Objective: To establish a real-time fluorescence recombinase acid amplification (RAA) method for the detection of adenovirus type 3(HAdV-3)without extraction nucleic acid. Methods: According to the conserved sequence of adenovirus type 3 gene, a pair of primers and a probe were designed, and a real-time fluorescence RAA without extracting nucleic acid was established and optimizing the condition of DNA-free extraction. The sensitivity of the method was analyzed by a series of dilution and the specificity of the method was evaluated by detecting the original samples of other respiratory viruses. The clinical samples of HAdV-3 were detected and compared with the traditional real-time fluorescence quantitative PCR method for nucleic acid extraction. Results: The sensitivity of the real-time fluorescence RAA method was as high as that of qPCR in the detection of 10 series diluted HAdV-3 strains. The highest corresponding CT value of qPCR was 36.87. The sensitivity of the real-time fluorescence RAA method was similar to that of the real-time fluorescence quantitative PCR method . There was no cross-reaction to other common types of respiratory viruses. The two method were used to detect 56 clinical samples at the same time, and the result were completely consistent. Conclusions We provide the first report of the real-time fluorescent RAA assays for the detection of HAdV-3 without extracting nucleic acid and it has high sensitivity and specificity. Is suitable for rapid detection of HAdV-3 in clinical laboratories and on-site unite.

Objective To investigate the effects of CD24 on CCl4-induced murine liver fibrosis and to analyze the possible molecular mechanism.Methods Wild type (WT) and CD24 knockout (CD24-/-) C57BL/6 mice were treated with CCl4 through intraperitoneal injection.Levels of ALT in serum samples were detected and liver tissues were stained with hematoxylin and eosin (HE) to assess liver tissue injury.Sirius Red staining was used to observe liver fibrosis.Real-time PCR was performed to detect the expression of α-SMA (α-smooth muscle actin), Col1a1 (Collagen, typeⅠ, alpha 1), TGF-β1 (transforming growth factor-β1) and CD24 at mRNA level in liver tissues.Western blot was performed to analyze the expression of α-SMA and Col1a1 at protein level.Flow cytometry analysis was used to detect the macrophages in liver tissues.ELISA was used to detect the expression of TGF-β1 in the culture supernatants of M1 and M2 macrophages.Results The expression of CD24 at both mRNA and protein levels were up-regulated in mice with CCl4-induced liver fibrosis.HE staining showed that liver inflammation in CD24-/-mice was more severe than that in WT mice after treated with CCl4.Sirius Red staining of paraffin-embadded liver sections revealed that compared with WT mice, CD24-/-mice presented with more severe liver fibrosis.Moreover, α-SMA and Col1a1, indicators of liver fibrosis, in CD24-/-mice were significantly higher than those in WT mice.Flow cytometry analysis showed that murine hepatic macrophages significantly increased in CD24-/-mice than in WT mice following CCl4 treatment.Real-time PCR analysis also confirmed that significantly enhanced expression of TGF-β1 at mRNA level in liver tissues was observed in CD24-/-mice than in WT mice.TGF-β1 secreted in the culture supernatant of M2 macrophages derived from CD24-/-mice group was more than that of the WT mice group.No significant difference in TGF-β1 secretion in culture supernatant of M1 macrophages was observed between the two groups.Conclusion Taken together, these data suggest that CD24 plays an important role in attenuating CCl4-induced chronic inflammation and hepatic fibrosis in mice.The mechanism of CD24 in alleviating liver fibrosis might be through regulating intrahepatic macrophages, inhibiting the secretion of TGF-β1 by M2 macrophages and suppressing the activation of hepatic stellate cells.

OBJECTIVE To compare the effect of intranasal corticosteroids-gelatin sponge and saline-gelatin sponge in the treatment of nasal adhesion.METHODS A total of 208 noses(170 patients) with nasal adhesions after receiving the endoscopic sinus surgeries from July,2012 to December,2015 were selected.All the cases were divided randomly into two groups:the treatment group and the control group.Both groups received separation treatments of the nasal adhesions.The intranasal corticosteroidsgelatin sponges were used as the separation material for the treatment group,while saline-gelatin sponges for the control group.The severity score and the time of treatment were evaluated as the indicators for curative efficacy of the treatment in each case.The differences of efficacy between two groups were analysed statistically.RESULTS The severity scores of the two groups after the treatment were both substantially lower than those before the treatment;The after-treatment severity scores of the treatment group were significantly lower than those of the control group;the times of treatment in the treatment group were substantially lower than those of the control group.The differences stayed for 3 months,and they became insignificant after 3 months.CONCLUSION The intranasal corticosteroids-gelatin sponge can be a quicker and more effective treatment of nasal adhesion in comparison with saline-gelatin sponge.

OBJECTIVE: This study was designed to explore the risk factors associated with severity of juvenile onset recurrent respiratory papillomatosis. METHOD: A retrospective study was conducted to study determinants of severe forms of juvenile recurrent onset respiratory papillomatosis. The patients were separated into different groups based on the onset age, the first recurrence of age, the first recurrence of period, gender and incision of tracheal respectively. The relationship among the lesion severity score,the involvement of the subregion, operation period and the next operation period were also explored. RESULT: It was observed that some children who recurred before 4 years old required more surgery, shorter operation period(the average, longest or shortest operation period) than those elder children, the differences were statistically (P=0. 029, 0. 003, 0. 010, 0. 039, respectively). The severity score of lesion was correlated positively with the involvement of the subregion and negatively with operation period (r=0. 914, -0. 451, respectively). Some children who diagnosed before 4 years old had to endure more severity score and shorter operation period than those older children, the differences were statistically (P= 0. 036, 0. 000, respectively). 8 cases accepted incision of tracheal, they accepted more surgery too. But the differences in the onset age, the first recurrence of age, and the operation period were not statistically. CONCLUSION The results showed that the clinical course of juvenile onset recurrent respiratory papillomatosis was closely related to the first recurrence age and period, while the severity of disease was associated to the onset age and the involvement of the subregion.
Adolescent ; Age of Onset ; Child ; Child, Preschool ; Humans ; Papilloma ; Papillomavirus Infections ; classification ; epidemiology ; surgery ; Respiratory Tract Infections ; classification ; epidemiology ; surgery ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Trachea