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.

Hepatic cystic echinococcosis (HCE) is a global public health problem. At present, the research of echinococcosis mainly focuses on etiology, epidemiology, immunology, imaging and treatment programs, while ignoring the systematic study of its natural decline and death course. The popularization of modern imaging examination methods enable researchers to obtain the clinical data of HCE in different stages, with different imaging features and pathological states. Based on CT imaging features and clinical practice, the authors discuss the natural decline and death course of HCE, in order to provide new ideas for its diagnosis and treatment.

Single-cell transcriptome sequencing (scRNA-seq) can resolve the expression characteristics of cells in tissues with single-cell precision, enabling researchers to quantify cellular heterogeneity within populations with higher resolution, revealing potentially heterogeneous cell populations and the dynamics of complex tissues. However, the presence of a large number of technical zeros in scRNA-seq data will have an impact on downstream analysis of cell clustering, differential genes, cell annotation, and pseudotime, hindering the discovery of meaningful biological signals. The main idea to solve this problem is to make use of the potential correlation between cells and genes, and to impute the technical zeros through the observed data. Based on this, this paper reviewed the basic methods of imputing technical zeros in the scRNA-seq data and discussed the advantages and disadvantages of the existing methods. Finally, recommendations and perspectives on the use and development of the method were provided.
Cluster Analysis ; Transcriptome

Objective:To compare the clinical outcomes between modified percutaneous kyphoplasty (PKP) and conventional PKP in the treatment of Kümmell disease.Methods:A retrospective cohort study was conducted of the 57 patients with single level kummell disease who had undergone PKP between January 2015 and December 2017 at Department of Spinal Surgery, Jiangmen Hospital Affiliated to Sun Yat-sen Uni-versity.Of them, 36 received modified PKP and 21 conventional PKP.In the modified PKP group, there were 24 males and 12 females with an age of 73.9 years±9.4 years and a course of disease of 2.2 months±1.5 months; the disease was located at a thorocic vertebra in 20 cases and at a lumbar vertebra in 16.In the conventional PKP group, there were 15 males and 6 females with an age of 72.6 years±11.9 years and a course of disease of 1.8 months±1.1 months; the disease was located at a thorocic vertebra in 10 cases and at a lumbar vertebra in 11.The 2 groups were compared in terms of operation time, bone cement volume, cement leakage, visual analogue scale (VAS), Oswestry disability index (ODI), anterior and middle heights and cobb angle of injured vertebra at postoperative 3 days, 1 and 3 months, and final follow-up.Results:There were no significant differences in the general clinical data between the 2 groups, showing compatibility between groups ( P>0.05).All the operations were accomplished uneventfully with no such serious complications as spinal cord nerve injury, wound infection, pulmonary embolism, bone cement poisoning reaction or death. There was no significant difference between the 2 groups in operation time or bone cement volume ( P>0.05).The rate of cement leakage in the modified PKP group [33.3%(9/27)] was significantly lower than that [52.4%(11/21)] in the conventional PKP group ( P<0.05).There were no significant differences be-tween the 2 groups in VAS, ODI, anterior or middle height of injured vertebra or cobb angle at postoperative 3 days or one month ( P>0.05), but the postoperative values were improved compared to the preoperative ones.At postoperative 3 months and final follow-up, the modified PKP group was significantly better in all the indexes than the conventional PKP group ( P<0.05). Conclusion:Compared with conventional PKP, the modified PKP may lead to better outcomes for Kümmell disease.

Objective To investigate the effects of simulated microgravity by rotary cell culture system (RCCS) on expression profiles of miRNA in mouse fibroblasts L929 cell line.Methods L929 cells were cultured in vitro and divided into simulated microgravity (SMG) group and normal gravity (NG) group according to the simple random method.Samples of two groups were collected on 7th day of culture and the total RNAs were extracted,labeled,and hybridized in sequence.Feature Extraction Software was used to collect the array images and get raw data,which were analyzed by Genespring Software.Differentially expressed miRNAs were identified and then validated by qRT-PCR.Target genes of differentially expressed miRNAs were predicted by the databases of Targetscan and microRNAorg,and the intersections of databases were identified as potential regulatory target genes.Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis were applied to determine the roles of these target genes.Relevant biological functions and/or signaling pathways of the regulated genes especially related with wound healing process were categorized based on their enrichments.Then integration predictions of the miRNA and mRNA expression profiles had been proposed to refine the functional miRNA-mRNA relationships.The miRNA-mRNA functional network and miRNA-mRNA control network were constructed.Results Four miRNA genes were up-regulated significantly including mmumiR-669j,-122-5p,-30a-3p,-6516-3p,among which mmu-miR-669j was up-regulated at 52.84 folds with the greatest significance (P ＜ 0.05).Seventeen miRNA genes were down-regulated significantly including mmu-miR-21a-3p,-miR-28a-5p,-218-5p,-210-3p,-miR-19a-3p,-miR-31-3p,and-miR-19b-3p,among which mmu-miR-28a-5p was down-regulated at 15.47 folds with the greatest significance (P ＜ 0.05).The qRT-PCR showed a high concordance with the microarray results (P ＜ 0.05).Target gene prediction and functional enrichment analysis suggested that a variety of biological processes and signaling pathways involved in wound repair were significantly enriched (P ＜ 0.05).Function network and regulation network of miRNA-mRNA covered all the differentially expressed miRNAs,which suggested that miR-21 a-3p and predicted target gene Smad3 might play an important role in wound healing under microgravity.Conclusions Simulated microgravity by RCCS can significantly affect the expression of stress-related miRNAs in mouse fibroblasts L929.The miRNA target gene prediction and functional enrichment analysis based on gene chip technology may provide theoretical basis for illustrating the mechanism and management of weightlessness stress injury.

We analyzed the cost effectiveness of four different surgical methods (A,B,C and D) in treatment of hepatic echinococcosis.Totally 757 cases of hepatic echinococcosis surgery clinical data and cost information of hospitalized cases were collected from nine hospitals in Xinjiang during 2005-2013.The clinical effects,cost effectiveness ratio and incremental costeffectiveness ratio were analyzed and compared.The total complication rates were 15.8％,9.2％,0％ and 2.9％;the recurrence rates were 7.3％,6.2％,0％ and 0％;the cure rates were 77.8％,84.6％,100.0％ and 97.1％;the cost (RMB) were 11 947.3,18 543.6,25 510.7 and 18 877.4,cost-effectiveness ratio were 153.6,219.1,255.1 and 194.3,incremental cost-effectiveness ratio /C//E were 964.4,610.4 and 358.0 respectively for group A,B,C and D.The results after adjusting of price factor were consistent with original cost effectiveness analysis.The complete resection of inner and outer capsule (D) is the most effective and economical way of clinical operation and may worthy be promoted in treatment of hepatic echinococcosis.

Objective:To observe the effect of protoscolex on Th subsets and correlative cytokine in mice spleen cells in vitro.Methods:Co-culture spleen cells from BALB/c mice with protoscolices,then IL-4,IFN-γand TGF-βproduction in cell culture supernatants were analyzed by ELISA.The percentage of Th subsets were detected by Flow Cytometry analysis.Results:Secretion levels of IL-4 and TGF-βwere significantly increased in spleen cells at different time point in co-culture system with protoscolices.Ratios of Th2 and Treg cells were also significantly increased in co-culture system at different time points than the control groups.However,there was no statistical significance for ratio of Th1 cells at different time points.Conclusion:The protoscolex can increase the ratios of Th2 cells and Treg cells from spleen cells.Secretion levels of IL-4 and TGF-βwere also increased in spleen cells co-cultured with protosco-lices.The results suggest that these Th cell subsets play a role in the immune escape of the hydatid disease.

Aim To study the effects of prenatal hy-poxia on the risk of fatty liver disease to search the drug targets .Methods Intrauterine hypoxia rats model was established .The bodies and livers of fetal rats of 21 days, and adult offspring rats of 5 months with and without anoxic treatment were all weighed .The liver index was calculated and the concentrations of renin-angiotensin system components in circulation system and livers of offspring rats were measured .Results The weight of the bodies , livers and index of liver weight to body weight ( liver index ) were significantly decreased in the PH group compared with the normal group.These differences disappeared in adulthood . However, the liver index of adult offsprings in the PH group after hypoxia stress for 7 days was significantly increased compared with that of adult offsprings in nor-mal group.There were no significant differences in the concentrations of AngⅠ, AngⅡ and ACE in plasma and livers between the two groups of fetal rats and the two groups of adult offspring rats separately .The con-centrations of AngⅡ in the livers of adult rats in PH group were significantly higher than those in normal group.The concentrations of AngⅠ in livers and the concentrations of AngⅡ in plasma and livers in the group treated with hypoxia stress for 7 days were signif-icantly higher than those without hypoxia stress .The concentrations of ACE in livers and the concentrations of AngⅡ in plasma and livers in PH adult offsprings were significantly higher than those of normal adult off-springs .Conclusion PH can induce the increase of RAS content in the livers of fetus and adult rats , RAS is more likely to be activated after hypoxia stimulation in the following adulthood .PH is a potential mecha-nism that mediates offspring susceptibility of fatty liver .

Aim Toexaminethecombinedeffectsof 5-ALA and metformin on diabetes mellitus induced by streptozotocin( STZ) in mice, and to discuss the mech-anisminitially.Methods Thediabeticmiceinduced by intraperitoneal injection of STZ were treated with 5-ALA and/or metformin for 30 days. Physical signs, fasting blood glucose ( FBG ) , fasting plasma insulin ( FIns) , plasma leptin ( Lep) , glucose tolerance, and histological changes of liver and pancreas were as-sessed. Insulin resistance was evaluated by the homeo-stasismodelassessment(HOMA).Results There were more significant effects when 5-ALA combined with metformin than only using metformin on lowering FBG, FIns and Lep. And 5-ALA combined with met-formin could improve glucose tolerance and the insulin sensitivity. Microscopic analysis demonstrated that sig-nificant changes in pancreatic islet and characteristic feature of the vacuolization phenotype in liver was ob-served on diabetic mice, and use of 5-ALA could in-hibit shrinking pancreatic islet number and hepatic morphological changes, especially in combination with metformin.Conclusions Asynergisticeffectof5-ALA and metformin is observed. Combined therapy of 5-ALA and metformin can decrease FBG and improve glucose tolerance, insulin sensitivity and islet ? cells function and morphology.

Objective:To understand the expression levels of Tim-3,a new proinflammatory factor in the early stages of Echinococcus granulosus infection in mice.Methods: BALB/c mice were infected with E.granulosus.Peritoneal macrophages and spleen cells were collected at 1,5,9 and 13 days post-infection.At different time points ,the levels of Tim-3 in peritoneal macrophages and spleen CD3+lymphocyte subsets were detected by FCM , and the relative expression of TLR 4 mRNA was detected by qRT-PCR.Results:There was no significant difference in the expression levels of Tim-3 of CD3+spleen lymphocyte subsets between E.granulosus group and control group (P>0.05).The expression levels of Tim-3 of spleen macrophages (9,13 days) and peritoneal macrophage (5,9,13 days) were much higher in E.granulosus infected group than those in control group with statistical significance (P<0.05).The numbers of macrophages were no change.Compared with control groups,the relative expression of TLR4 mRNA at 1 day post-infection was statistically higher in E.granulosus infected group ( P<0.05 ).Conclusion:During early stage of E.granulosus infection in mice,the levels of Tim-3 expression are upregulated,while the expression of TLR4 are downregulated,which may inhibit the function of macrophages resulting in host-immunity-defensive-system inhibition and immune tolerance of E.granulosus to host.