OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of generic drugs and original drugs of voriconazole. METHODS The information of patients who used voriconazole generic drugs selected in National Centralized Drug Procurement （generic drug group） or non-selected original drugs （original drug group） in the treatment of fungal infection was collected from the our hospital. The propensity score matching was carried out to eliminate bias. The comprehensive efficacy was evaluated according to clinical efficacy， image findings and microbiological test， and stratified analysis of different populations was conducted based on fungal species， underlying diseases， etc.， the efficacy of different stratifications was evaluated. Evaluation of safety was performed by using the incidence of adverse reactions. The total cost， defined daily doses （DDDs） and defined daily dose cost （DDDc） were used to evaluate the cost-effectiveness. RESULTS A total of 436 patients were included， and there were 190 patients in each group after matching. In terms of efficacy， the effective rates of voriconazole generic drugs and original drugs were 62.63% and 59.47% （P＝0.528）； in terms of safety， the incidence of adverse reactions caused by generic drugs and original drugs of voriconazole was 13.68% and 7.89%， respectively（P＝0.069）. In terms of cost-effectiveness， the average total cost of generic drugs was 4 636.26 yuan， and that of original drugs was 8 613.20 yuan （P＜0.001）. After the implementation of National Centralized Drug Procurement， replacement rate of generic drugs increased to 87.30%， and DDDc decreased by 59.08%. CONCLUSIONS The efficacy and safety of voriconazole generic drugs are similar to those of original drugs in the treatment of fungal infection， and it is more cost-effective in terms of treatment cost.

Objective To investigate the expression of inflammatory factors and brain-derived neurotro-phic factor(BDNF)in the brain hippocampus of Alzheimer's disease(AD)-like mice caused by amyloid β-protein 25-35(Aβ25-35).Methods A total of 40 six-week-old male Kunming mice were taken to construct an AD-like mouse model using bilateral ventricular injection of Aβ25-35,and were divided into the 0 d,7 d,14 d,and 28 d groups for observation,with 10 mice in each group.The Y-maze and new object recognition assay were used to test the learning and memory functions of the mice.The hematoxylin-eosin(HE)staining was used to observe the neuronal damage in the hippocampal region.Immunohistochemical staining was used to detect the expression levels of phosphorylated-tau(p-tau),CD11b and BDNF in hippocampus.ELISA was used to detect the expression levels of inflammatory factors in hippocampus,including interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF)-α,and real-time quantitative reverse transcription PCR(RT-qPCR)and Western blot were used to detect the mRNA and protein expression levels of BDNF.Results Aβ25-35 could impair memory and cognitive function in the mice.Compared with the 0 d group,the neuron number in the hippocampal tissue of mice in the 14 d and 28 d groups was significantly reduced(P<0.05),and the optical density values of p-Tau and CD11b,and expression levels of IL-1β and TNF-α in the hippocampal region of mice in the 14 d and 28 d groups were significantly increased(P<0.05).In addition,compared with the 0 d group,the relative expression levels of BDNF mRNA and protein in the hippocampal tissue of mice were sig-nificantly increased in the 7 d group(P<0.05),while the relative expression levels of BDNF mRNA and pro-tein were significantly decreased in the 14 d and 28 d groups(P<0.05).Conclusion Aβ25-35 may increase the expression of TNF-α,IL-1β and p-tau in hippocampal tissue by activating microglia,which in turn impaired the memory and cognitive functions of mice,and the expression level of BDNF in hippocampal tissue showed a first increase and then a decrease in the injury period.

Recent studies show that graphene and its derivatives have good physical and chemical properties and biocompatibility,and can promote cell proliferation and stem cell differentiation.The process of pulp regeneration involves the proliferation and differen-tiation of seed cells,suggesting that graphene and its derivatives have the potential applications perspective in pulp regeneration.How-ever,it has not been reported whether the physical and chemical properties of graphene and its derivatives are suitable for pulp cavity or root canal environment and its effect on pulp regeneration seed cells.This article reviews the physical and chemical properties,cyto-logical effects and the application of graphene and its derivatives in tissue engineering,and provides a basis for its application in dental pulp regeneration.

Objective To observe the effect of non-invasive ventilator assisted vibration sputum evacuation on the level of cardiac function indicators in patients with acute heart failure in the intensive care unit(ICU).Methods A total of 120 patients with acute heart failure who received treatment in the ICU of Tongde Hospital of Zhejiang Province from September 2020 to March 2023 were selected as the study subjects.The patients were randomly divided into a control group and an experimental group using a random number table method,with 60 patients in each group.A total of 120 patients were treated with conventional symptom therapy and non-invasive ventilation.The control group received routine nursing intervention,while the experimental group received non-invasive ventilator assisted vibration sputum evacuation.Arterial partial pressure of oxygen(PaO2),arterial partial pressure of carbon dioxide(PaCO2),pulse oxygen saturation(SpO2),respiratory rate(RR),heart rate,blood pressure,central venous pressure,serum and ultrasound cardiac function indicators,and prognosis of two groups of patients were recorded after 2 weeks of intervention.Results After the intervention,PaO2,SpO2,and left ventricular ejection fraction(LVEF)were significantly increased in both groups,while PaCO2,RR,heart rate,blood pressure,central venous pressure,N-terminal pro-brain natriuretic peptide(NT-proBNP),cardiac troponin T(cTnT),left ventricular end-systolic diameter(LVESD),and left ventricular end-diastolic diameter(LVEDD)were significantly decreased compared to before the intervention(all P<0.05).Compared with the control group,the experimental group showed significant increases in PaO2,SpO2,blood pressure,central venous pressure,and LVEF after intervention[PaO2(mmHg,1 mmHg≈0.133 kPa):68.24±5.81 vs.59.63±6.86,SpO2:0.95±0.03 vs.0.87±0.04,systolic blood pressure(mmHg):116.05±4.11 vs.104.13±3.95,diastolic blood pressure(mmHg):68.19±4.13 vs.62.85±4.12,central venous pressure(mmHg):9.42±1.29 vs.8.12±4.12,LVEF:0.49±0.05 vs.0.43±0.04,all P<0.05],while PaCO2,RR,heart rate,NT-proBNP,cTnT,LVESD,and LVEDD were significantly reduced[PaCO2(mmHg):42.12±4.08 vs.52.13±4.61,RR(beats/min):18.85±1.75 vs.21.54±2.51,heart rate(bpm):89.53±8.14 vs.101.11±10.26,NT-proBNP(ng/L):1687.25±589.67 vs.2145.36±751.03,cTnT(ng/L):70.58±5.15 vs.81.45±6.89,LVESD(mm):34.51±3.11 vs.38.89±3.55,LVEDD(mm)46.11±3.22 vs.49.74±3.75,all P<0.05].The mechanical ventilation time,ICU hospitalization time,and pulmonary infection relief time of the experimental group were significantly shortened compared to the control group[mechanical ventilation time(hours):72.14±10.06 vs.78.96±12.97,ICU hospitalization time(days):10.74±2.15 vs.12.88±3.26,pulmonary infection relief time(days):3.58±0.79 vs.5.14±1.12,all P<0.05],and the incidence of pulmonary infection was significantly reduced[1.67%(1/60)vs.11.67%(7/60),P<0.05],However,there was no statistically significant difference in the mortality rate between the experimental group and the control group[10.00%(6/60)vs.21.67%(13/60),P>0.05].Conclusion The non-invasive ventilator assisted vibration sputum evacuation can improve symptoms of hypoxemia and cardiac function,stabilize hemodynamics,shorten the course of acute heart failure in ICU patients,and reduce the incidence of pulmonary infections.

Objective To study the role of microRNA(miR)-483-3p in reducing myocardial fibrosis in rats,and explore the relationship between its mechanism and autophagy.Methods A total of 24 male SD rats were randomly divided into sham operation group,model group,blank transfec-tion group and high expression group,with 6 rats in each group.The blank transfection group and the high-expression group were pretreated with a single injection of adeno-associated virus(AAV)-blank transfection and AAV-miR-483-3p(5×1011 vg)in the tail vein,respectively.In 14 d later,the sham group was injected with 2.5 ml/(kg·d)normal saline for 14 d,and rat model of myocardial fibrosis was established by 2 mg/ml isoproterenol[2.5 ml/(kg·d)]injection through tail vein for 14 consecutive days.Myocardial pathological damage,severity of myocardial fibrosis,and expression levels of collagen-Ⅰ,microtubule-associated protein light chain 3(LC3),autoph-agy-related protein 5(Atg5)and autophagy degradation substrate(P62)in cardiomyocytes were evaluated and measured.Results Compared with the sham operation group,the model group had obviously larger myocardial fibrosis area,higher positive expression of Collagen-Ⅰ,and increased protein levels of Atg5 and LC3-Ⅱ/LC3-Ⅰ,and decreased expression level of P62 protein(P＜0.05).The myocardial fibrosis area,positive expression of Collagen-Ⅰ,the expression levels of Atg5 and LC3-Ⅱ/LC3-Ⅰ protein[(13.64±1.51)％vs(27.47±1.55)％,(13.48±3.07)％vs(30.91±2.45)％,0.98±0.17 vs 1.24±0.28,0.66±0.05 vs 1.26±0.09,P＜0.05]were significant-ly decreased,and the expression level of P62 was notably increased(0.91±0.11 vs 0.74±0.06,P＜0.05)in the high expression group than the model group.Conclusion MiR-483-3p attenuates myocardial fibrosis in rats,and the mechanism may be related to the inhibition of cardiomyocyte autophagy.

Objective To explore the therapeutic effect of bicyclol(BIC)on rat model of myocardial fibrosis and its possible mechanism.Methods Twenty-four SPF male SD rats were randomly di-vided into sham group,model group,low-and high-dose groups,with 6 rats in each group.Except for the sham group,all other groups were injected with 5 mg/(kg·d)isoproterenol by tail vein to establish myocardial fibrosis model,and the low-and high-dose groups were administered by ga-vage with 100 and 200 mg/(kg·d)BIC,respectively for 14 consecutive days.HE staining and Masson staining were used respectively to observe the severity of myocardial injury and fibrosis.Western blot assay was employed to detect the protein expression of Collagen Ⅰ,Collagen Ⅲ,al-pha smooth muscle actin(α-SMA),methyltransferase-like protein 3(METTL3),α-ketoglutarate-dependent dioxygenase AlkB homolog 5(ALKBH5)and YTH domain family protein 1(YTHDF1)in rat myocardium.Results Compared with the sham group,myocardial cell necrosis and myocardial fibrosis were significantly more serious in the model group.Low-and high-dose BIC treatment reduced myocardial cell rupture and necrosis and myocardial fibrosis when com-pared with the model group.The expression levels of Collagen Ⅰ,Collagen Ⅲ,α-SMA,METTL3 and YTHDF1(P＜0.05)were significantly higher,and that of ALKBH5(0.58±0.02 vs 0.88±0.07,P＜0.05)was notably lower in the myocardial tissues of the model group than the sham group.While,both doses of BIC treatment significantly reversed above changes in protein levels(P＜0.05).Conclusion BIC can effectively alleviate myocardial structural damage and interstitial collagen deposition in rats with isoproterenol-induced myocardial fibrosis,and its mechanism may be related to m6A methylation modification.

Background and objective Metabolic change is one of the important characteristics of radiation pneu-monitis.Radiotherapy,as a conventional method for the treatment of thoracic tumors,can not only effectively kill tumor cells,but also cause adverse reactions such as local inflammation and fibrosis,which leads to limited therapeutic effect and profound impact on the quality of life of patients.Therefore,it is of great significance to explore the metabolic changes caused by radio-therapy.The aim of this study was to investigate the effects of X-ray irradiation on the metabolism of a mouse lung epithelial cell line(murine lung epithelial-12,MLE12).Methods MLE12 cells were cultured in vitro and randomly divided into radiation group(IR)and control group(NC).Cells in the IR group were irradiated at a dose of 10 Gy using a Hitachi X-ray irradiator.Cell supernatant samples were collected at 48 h after irradiation.Metabolomic analysis of the samples was performed by liq-uid chromatograph mass spectrometer(LC/MS).Results LC/MS metabolomics analysis revealed the metabolic changes of MLE12 cells at 48 h after irradiation.A total of 38 secretory metabolites were altered in the IR group compared with the NC group.According to the annotation of Kyoto Encyclopedia of Genes and Genomes(KEGG)database,the differential metabo-lites are mainly involved in nucleotide metabolism,amino acid metabolism and lipid metabolism,among which the difference in nucleotide metabolism is the most significant.Conclusion The metabolism ofMLE12 cells was significantly affected by X-ray irradiation,mainly affecting the nucleotide metabolic pathways,including purine and pyrimidine metabolites and related meta-bolic pathways.

Objective To explore the predictive value of systemic immune inflammatory index(SII),systemic inflammatory response index(SIRI),neutrophil to lymphocyte ratio(NLR),lymphocyte to monocyte ratio(LMR),platelet to lymphocyte radio(PLR),albumin to globulin(AGR)and heat shock protein 90α(HSP90α)in Fuhrman grade of clear cell renal cell carcinoma(ccRCC).Methods From October 2019 to August 2022,212 patients who underwent surgical treatment for ccRCC were divided into low-grade tumor group and high-grade tumor group according to Fuhrman grade.The independent influencing factors of Fuhrman grading were determined by univariate and multivariate Logistic regression analysis,and the predictive value of each inflammatory index to Fuhrman grading was evaluated by drawing Receiver operating characteristic curve(ROC).We constructed the line chart prediction model and evaluated the effectiveness of the model.Results The preoperative levels of SII,PLR,AGR,HSP90α and the maximum diameter of tumor were significantly different between high-grade group and low-grade group(P＜0.05).Logistic regression analysis showed that the maximum diameter of tumor,PLR,AGR and HSP90α were independent influencing factors of Furhman grade.By drawing the ROC curve,it was found that the area under the curve(AUC)of PLR,AGR and HSP90α to predict Furhman grade were 0.641,0.675 and 0.696.In addition,the Furhman grade line chart prediction model had good prediction ability,the AUC was 0.789(95％CI:0.717～0.862),the sensitivity was 61.80％,and the specificity was 85.40％.Conclusions There was a significant correlation between inflammation-related indexes in peripheral blood and Furhman grade of clear cell renal cell carcinoma.The Furhman grade line chart prediction model based on the maximum diameter of tumor and peripheral blood inflammation index has good predictive ability.

Objective:To explore the application effect of ultrasound evaluation of atelectasis in general anesthesia.Methods:Eighty patients who underwent general anesthesia surgery at the Second Affiliated Hospital of Wannan Medical College from January 2019 to December 2020 were selected as the study subjects. The gold standard was chest CT diagnosis of perioperative atelectasis, and they were divided into atelectasis group (39 cases) and control group (41 cases). Twelve regional images, including left upper anterior chest, left lower anterior chest, right upper anterior chest, right lower anterior chest, left upper chest, left lower chest, right upper chest, right upper chest, right lower chest, right upper chest, right lower chest, right upper chest, right lower chest, right lower chest, right lower chest, left upper chest, right lower chest, left upper chest, right lower chest, left upper posterior region, left lower chest, left lower posterior region, left lower posterior region, right upper posterior region, and right lower posterior region, were collected by pulmonary ultrasound (LUS) at time points T 1 after entering the room, 30 minutes after tracheal intubation (T 2), 30 minutes after extubation (T 3), 24 hours after surgery (T 4), and 48 hours after surgery (T 5), And an improved semi quantitative scoring method for evaluating lung ventilation was used to compare the LUS scores of the two groups at 5 time points. Results:There was no statistically significant difference in LUS scores between the two groups of patients in different lung zones at T 1 (all P>0.05); There are varying degrees of differences in LUS scores for the same lung partition at different times (all P<0.05). There was no statistically significant difference in LUS scores between T 2 and T 5 for left upper anterior chest, left lower anterior chest, right upper anterior chest, left upper chest, right upper chest, left upper posterior region, and right upper posterior region (all P>0.05); The LUS scores of the T 2-T 5 atelectasis group in the lower left chest, lower right chest, lower left posterior area, and lower right posterior area were higher than those of the control group (all P<0.05). Conclusions:LUS can be used to evaluate atelectasis during general anesthesia and has broad clinical application and promotion value.

Objective To establish sensitive indicators for the evaluation of emergency nursing quality in patients with acute aortic dissection. Methods Based on the three-dimensional quality theory model of "structure-process-outcome", evidence-based nursing methods were used to synthesize evidence and conduct two rounds of expert consultation to determine sensitive indicators for the quality of emergency nursing in patients with acute aortic dissection. Results The effective recovery rates of the two rounds of expert consultation questionnaires were 100.00% and 94.12%, respectively. The judgment basis coefficients (Ca) of the experts who participated in the two rounds of consultation were 0.893 and 0.914, respectively, and the familiarity coefficients (Cs) were 0.902 and 0.921, respectively, and the authority coefficients (Cr) were 0.898 and 0.918, respectively. The Kendall coefficients of the first round of consultation experts for the first, second, and third-level indicators were 0.212, 0.247, and 0.327, respectively, and were 0.225, 0.349, and 0.257, respectively in the second round of consultation experts. Finally, the sensitive indicators for the quality of emergency nursing of AAD patients were constructed, including 3 first-level indicators, 8 second-level indicators, and 29 third-level indicators. Conclusion The sensitive indicators for the quality of emergency nursing of AAD patients constructed in this study can be used as a basis for evaluating the quality of emergency nursing in patients with acute aortic dissection.