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Objective To investigate the mechanism of electroacupuncture in relieving the apoptosis of retinal cells in experimental myopia based on mitochondrial dynamics.Methods In the study,140 two-week-old tricolor guinea pigs were divided into the normal control(NC)group,lens-induced myopia(LIM)group,LIM+sham acupoint(LIM+SHAM)group,and LIM+electroacupuncture intervention(LIM+EA)group,with 35 guinea pigs in each group.Guinea pigs in the NC group were fed normally,and those in the LIM group,LIM+SHAM group and LIM+EA group wore a-6.0D lens on the right eye to induce myopia.Guinea pigs in the LIM+EA group were treated at Hegu and Taiyang acupoints,while those in the LIM+SHAM group were treated at sham acupoints.After 2-and 4-week myopia induction,the diopter and axial length of the guinea pigs were measured,and the messenger ribonucleic acid(mRNA)and protein levels of dynam in-related pro-tein 1(DRP1),optic atrophy 1(OPA1),Bcl-2 associated X protein(BAX)and B cell lymphoma-2(BCL-2)in the retinas of the guinea pigs in each group were detected by quantitative PCR and Western blot,respectively.Meanwhile,HE staining was taken to observe the morphological changes in the retina of the guinea pigs in each group,and TUNEL staining was used to detect apoptosis.Results After 2-and 4-week myopic induction,compared with the NC group,the differences in diopter and axial length between the right and left eyes of guinea pigs in the LIM and the LIM+SHAM groups significantly increased(all P<0.001).Compared with the LIM group,the differences in diopter and axial length between both eyes of guinea pigs in the LIM+EA group significantly decreased(all P<0.01).At 4 weeks after myopic induction,HE staining re-sults showed that the retinas of the guinea pigs in the NC group were evenly arranged,and the morphology of inner and out-er nuclear layer cells was normal.Compared with the NC group,the retinas of the guinea pigs in the LIM and the LIM+SHAM groups were significantly thinner and disorderly arranged.Compared with the LIM group,the retinal thickness of guinea pigs in the LIM+EA group slightly increased,and the arrangement was relatively regular.The TUNEL staining re-sults showed that compared with the NC group,the green fluorescence of the guinea pig retina in the LIM group and LIM+SHAM group was significantly enhanced;compared with the LIM group,the green fluorescence of the guinea pig retina in the LIM+EA group was significantly weaken.After 2-and 4-week myopic induction,the mRNA and protein expression lev-els of DRP1 and BAX in the LIM and the LIM+SHAM groups were significantly higher than those in the NC group(all P<0.05),while the mRNA and protein expression levels of OPA1 and BCL-2 were significantly lower(all P<0.05).The mR-NA and protein expression levels of DRP1 and BAX in the LIM+EA group were significantly lower than those in the LIM group(all P<0.05),while the mRNA and protein expression levels of OPA1 and BCL-2 were significantly higher(all P<0.05).Conclusion Experimental myopia can enhance retinal mitochondrial fission.Electroacupuncture intervention can alleviate retinal cell apoptosis and improve the morphological structure of the retina by inhibiting retinal mitochondrial fis-sion and increasing mitochondrial fusion,thereby delaying myopia development.
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OBJECTIVE@#To analyze the dynamic changes of chest CT images of patients with coronavirus disease 2019 (COVID-19).@*METHODS@#Fifty-two cases of COVID-19 were admitted in the First Affiliated Hospital of Zhejiang University School of Medicine. The consecutive chest CT scans were followed up for all patients with an average of 4 scans performed per patient during the hospitalization. The shortest interval between each scan was 2 days and the longest was 7 days. The shape, number and distribution of lung shadows, as well as the characteristics of the lesions on the CT images were reviewed.@*RESULTS@#The obvious shadows infiltrating the lungs were shown on CT images in 50 cases, for other 2 cases there was no abnormal changes in the lungs during the first CT examination. Ground-glass opacities (GGO) were found in 48 cases (92.3%), and 19 cases (36.5%) had patchy consolidation and sub-consolidation, which were accompanied with air bronchi sign in 17 cases (32.7%). Forty one cases (78.8%) showed a thickened leaflet interval, 4 cases (7.6%) had a small number of fibrous stripes. During hospitalization, GGO lesions in COVID-19 patients gradually became rare,the fibrous strip shadows increased and it became the most common imaging manifestation. The lesions rapidly progressed in 39 cases (75.0%) within 6-9 days after admission. On days 10-14 of admission, the lesions distinctly resolved in 40 cases (76.9%).@*CONCLUSIONS@#The chest CT images of patients with COVID-19 have certain characteristics with dynamic changes, which are of value for monitoring disease progress and clinical treatment.
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Humans , Betacoronavirus , China , Coronavirus Infections , Diagnostic Imaging , Pathology , Disease Progression , Pandemics , Pneumonia, Viral , Diagnostic Imaging , Pathology , Tomography, X-Ray ComputedABSTRACT
OBJECTIVE@#To analyze the dynamic changes of chest CT images of patients with corona virus disease-19 (COVID-19).@*METHODS@#Fifty-two cases of COVID-19 were admitted in the First Affiliated Hospital of Zhejiang University School of Medicine. The consecutive chest CT scans were followed up for all patients with an average of 4 scans performed per patient during the hospitalization. The shortest interval between each scan was 2 days and the longest was 7 days. The shape, number and distribution of lung shadows, as well as the characteristics of the lesions on the CT images were reviewed.@*RESULTS@#The obvious shadows infiltrating the lungs were shown on CT images in 50 cases, for other 2 cases there was no abnormal changes in the lungs during the first CT examination. Ground-glass opacities (GGO) were found in 48 cases (92.3%), and 19 cases (36.5%) had patchy consolidation and sub-consolidation, which were accompanied with air bronchi sign in 17 cases (32.7%). Forty one cases (78.8%) showed a thickened leaflet interval, 4 cases (7.6%) had a small number of fibrous stripes. During hospitalization, GGO lesions in COVID-19 patients gradually became rare, the fibrous strip shadows increased and it became the most common imaging manifestation. The lesions rapidly progressed in 39 cases (75.0%) within 6-9 days after admission. On days 10-14 of admission, the lesions distinctly resolved in 40 cases (76.9%).@*CONCLUSIONS@#The chest CT images of patients with COVID-19 have certain characteristics with dynamic changes, which are of value for monitoring disease progress and clinical treatment.
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Objective To investigate the safety and efficacy of conversion from calcineurin inhibitors (CNI) to mammalian target of rapamycin (mTORi) in liver transplant recipients.Methods Such databases as MEDLINE (PUBMED),EMBASE,Cochrane Library and clinical trial registries (ClinicalTrials.gov,WHO International Trial Registry Network,Australian & New Zealand Clinical Trials Registry) were searched from the inception of each resource up to April 2015 for collecting the randomized controlled trials (RCTs) about liver transplant recipients after conversion from CNIs to mTORi,and the references of those trials were also searched by hand.After study selection,assessment and data extraction conducted by two reviewers independently,meta-analyses were performed by using the RevMan5.3 software.The quality of those trials was assessed by using the Jadad Score.Then,the safety and efficacy of conversion from CNI to mTORi were systematically assessed as a strategy for eliminating CNI exposure in liver transplant recipients.Results Ten RCTs (1917 patients) were included in this meta-analysis.The follow-up duration post-randomization was 6 to 36 months.The mean mTORi conversion time after transplantation was ≤6 months in 4 trials,and >6 months in 6.The meta-analysis revealed that the estimated glomerular filtration rate was significantly increased,and the incidence of renal failure and hyperglycemia was significantly reduced in mTORi conversion group as compared with those in CNI treatment group (P<0.05 for all).The incidence of acute rejection in mRORi conversion group and CNI treatment group was 11.3% and 6.3% respectively (P<0.01),and that confirmed by biopsy was 14.0% and 8.4% respectively (P<0.01).The percentage of recipients discontinuing the medication in mRORi conversion group and CNI treatment group was 41.6% and 21.5% respectively (P<0.01).The main reasons for drug withdrawal were drug-related adverse events (Aes),including acute rejection,bone marrow depression,anemia,leucopenia,thrombocytopenia,mouth sores/stomatitis,hyperlipidemia,hypercholesterolemia,rash,edema,and pyrexia.There was no significant difference between the two groups with regard to death,graft loss,loss to follow-up,infection,gastrointestinal symptoms,malignancy,and hypertension.Conclusion Conversion from CNI to mTORi therapy results in a significant improvement in renal function.However,this conversion strategy may lead to the high discontinuation rate due to mTORi-associated Aes,indicating that conversion may only be a treatment option in selected patients.
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Objective To investigate the changes of short chain fatty acids (SCFA) induced by tacrolimus (FK506) in rats and evaluate its effect on blood glucose levels. Methods Ten SD rats were divided into the FK506 group and control group (n=5 in each group). In the FK506 group, the rats were received a subcutaneous injection of FK506 (3 mg/kg) +sunflower oil solution containing 10% ethanol daily for consecutive 4 weeks. In the control group, the rats were received a subcutaneous injection of an equivalent amount of sunflower oil solution containing 10% ethanol for consecutive 4 weeks. During the drug injection period, the body mass of rats was measured every week in two groups. After the drug injection period, blood glucose level, SCFA content in the blood and feces samples were measured in two groups. Results Compared with the control group, the relative body mass of rats in the FK506 group was significantly lower at the 2nd, 3rd and 4thweeks (all P<0.01). Compared with the control group, the blood glucose levels of rats in the FK506 group were significantly increased at 0, 30, and 60 min after giving glucose (P<0.01-0.05). Compared with the control group, the contents of acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid and valeric acid in the feces sample were significantly lower in the FK506 group (P<0.01-0.05). Conclusions FK506 can upregulate the blood glucose level in rats, which is probably induced by the decrease of SCFA content in rat feces.
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Myelodysplastic syndromes (MDS) are a diverse group of malignant clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, dysplastic cell morphology in one or more hematopoietic lineages, and a risk of progression to acute myeloid leukemia (AML). Approximately 50% of MDS patients respond to current FDA-approved drug therapies but a majority of responders relapse within 2-3 years. There is therefore a compelling need to identify potential new therapies for MDS treatment. We utilized the MDS-L cell line to investigate the anticancer potential and mechanisms of action of a plant-derived compound, Withaferin A (WFA), in MDS. WFA was potently cytotoxic to MDS-L cells but had no significant effect on the viability of normal human primary bone marrow cells. WFA also significantly reduced engraftment of MDS-L cells in a xenotransplantation model. Through transcriptome analysis, we identified reactive oxygen species (ROS)-activated JNK/AP-1 signaling as a major pathway mediating apoptosis of MDS-L cells by WFA. We conclude that the molecular mechanism mediating selective cytotoxicity of WFA on MDS-L cells is strongly associated with induction of ROS. Therefore, pharmacologic manipulation of redox biology could be exploited as a selective therapeutic target in MDS.
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Objective: To observe the correlation between hand-foot syndrome (HFS) and prognosis of patients with human epidermal growth factor receptor 2 (HER2)- negative locally recurrent/metastatic breast cancer (LR/mBC) receiving chemotherapy with capecitabine (CAP) plus bevacizumab (BEV). Methods: One hundred patients with HER2-negative LR/mBC receiving first-line CAP plus BEV were divided into HFS group and non-HFS group, then the relationship between HFS and clinicopathologic characteristics of patients with HER2-negative LR/mBC and the related factors influencing the progression-free survival (PFS) and overall survival (OS) were analyzed by COX proportional hazards model. Results: There were statistically significant differences in menopausal status and the number of metastatic organs between HFS group and non-HFS group (all P < 0.05). The median PFS of the HFS group was significantly longer than that of the non-HFS group (10.7 months vs 5.8 months, P = 0.007). The median survival time of the HFS group was also significantly longer than that of the non-HFS group (22.8 months vs 14.9 months, P < 0.001). There was an association of Eastern Cooperative Oncology Group (ECOG) performance status (PS) score, hormone receptor status, metastasis at first diagnosis, metastatic organ site, the number of metastases and HFS with PFS (all P < 0.05). ECOG PS score, hormone receptor status, metastasis at first diagnosis, metastatic organ site and HFS were independent risk factors for PFS (all P < 0.05). There was an association of menopausal status, ECOG PS score, hormone receptor status, metastasis at first diagnosis, the number of metastatic organ and HFS with OS (all P < 0.05). Menopausal status, hormone receptor status, metastasis at first diagnosis, and HFS were independent risk factors for OS (all P < 0.05). Conclusion: HFS can be used as a predictor of therapeutic effect of HER2-negative LR/mBC patients receiving CAP-BEV. The patients with HFS have a better prognosis than patients without HFS.
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Ensilage is a traditional way of preserving fresh biomass. However, in order to apply ensilage to the ethanol biorefinery, two parameters need to be evaluated: quantity and quality changes of the biomass; and its effects on bioconversion process. To study these two aspects, switchgrass harvested on three different time points (Early, mid and late fall) were used as feedstock. The early fall harvested biomass was ensiled at 5 moisture levels ranging from 30% to 70%. Silage of 40% moisture and 3 other raw switchgrass were pretreated with liquid hot water, followed by enzymatic hydrolysis as well as simultaneous saccharification and fermentation. After 21 days storage pH values of all silages decreased below 4.0 and the dry matter losses were less than 2.0%, and structural sugars contents did not change dramatically. Liquid hot water caused more hemicellulose dissolution in the silage than in unensiled switchgrass. However, ensilage also increased the risk of releasing more sugar degradation products; After enzymatic hydrolysis, silage obtained higher total glucose, xylose and galactose yields than raw materials; After simultaneous saccharification and fermentation, ethanol concentration in silage was 12.1 g/L, higher than the unensiled switchgrass (10.3 g/L, 9.7 g/L and 10.6 g/L for early, mid and late fall respectively). Our results suggest that ensilage helps increase pretreatment efficiency and sugar yield, which increases final ethanol production.
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Biomass , Ethanol , Chemistry , Fermentation , Galactose , Chemistry , Glucose , Chemistry , Hot Temperature , Hydrolysis , Panicum , Chemistry , Polysaccharides , Chemistry , Silage , Water , Xylose , ChemistryABSTRACT
Objective To observe the metabolic changes in the whole brain of chronic unpredictable mild stimulations ( CUMS)-induced depressive rats using PET imaging technology.Methods After 4 weeks’ of CUMS, rats of experimental group were divided into two groups:Group D( depression) and Group ND( no depression) , according to the degree of sugar addiction, distance of spontaneous activity and relative body mass.Then metabolic changes in the whole brain of these rats and those in control group ( CON) were observed using PET technology, and the differences were companred between the threegroups.Results (1)ComparedwithGroupCON,metabolismofGroupDwaselevatedinbilateralS1,thalamus, globus pallidus, insula, M2 and left claustrum, but descended in right inferior colliculus, splenium of corpus callosum and cerebellum.(2) Metabolism of Group D increased in the bilateral CA3 region of hippocampus, M1, M2, striatum, S1 and olfactory bulb, but decreased in the left cuneate nucleus and hippocampus compared to Group ND.( 3 ) Compared with Group CON, there was no region of the brain in Group ND where metabolism was enhanced, but metabolism in the lateral septal nucleus, bilateral striatum, hypothalamic paraventricular nucleus, bilateral S1 and right globus pallidus of Group ND was reduced.Conclusion The metabolic characteristic in the brain of depressive rats is that heightened regions are all in front of the coronal plane 4 mm post bregma, while lowered regions are behind.Moreover, both cerebral hemispheres are roughly symmetrical.It can be concluded that abnormal interactions between different regions of the brain contributes to the occurrence of depression.
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Morphea complicated by Hashimoto's thyroiditis is reported in two sisters.Case 1:a 64-year-old female presented with skin rashes on the anterior neck,trunk and bilateral anterior shins for 5 years,itching skin rashes on the perineum for 4 years,and Hashimoto's thyroiditis for 9 years.Physical examination revealed grade 1 enlargement of firm thyroid gland without exophthalmos or pretibial myxedema.Dermatological examination showed pink patches on the neck and breast,sclerosis and atrophy of skin over the back,porcelain-white patches on the perineum.Histopathological findings suggested the diagnosis of morphea on the breast and lichen sclerosus et atrophicus on the perineum.Case 2:a 55-year-old female,who was the younger sister of case 1,suffered from gradual sclerosis and atrophy of skin in the left inframammary region and abdominal region for 4 years,as well as Hashimoto's thyroiditis for 3 years.Similarly,physical examination revealed grade 1 enlargement of firm thyroid gland without exophthalmos or pretibial myxedema.Hypopigmentation,sclerosis and atrophy of skin were observed in the left inframammary region,abdominal region and central back region.Histopathological examination suggested a diagnosis of morphea.According to the clinical and histopathological manifestations,periodic acid-Schiff staining and thyroid gland function test results,the 2 cases were both diagnosed as morphea complicated by Hashimoto's thyroiditis.
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Objective To build a RNA interference vector for PQ-loop repeat protein (LRP) gene,and to evaluate the effect of the vector on the expression of PQ-LRP gene in Microsporum canis.Methods The PUC-PLULT and PCB309-PLULT vectors were constructed sequentially by using Agrobacterium tumefaciens-mediated T-DNA insertional mutagenesis,adding multiple cloning sites,and introducing the hygromycin-resistance gene.Microsporum canis was transformed with the PCB309-PLULT vector followed by a series of passages and hygromycin selection.Real-time quantitative PCR was performed to measure the expression of PQ-LRP gene in Microsporum canis before and after transformation.Results The intermediate vectors PUC-PLUT and PUC-PLULT were constructed and identified by PCR and gene sequencing.The 8 825-bp interference vector PCB309-PLULT was successfully built and confirmed by enzyme digestion.The optimum concentration of hygromycin for screening for Microsporum canis transformants was determined as 300 mg/L.The mRNA expression level of PQ-LRP was decreased by 61% in the transformants as compared with untransformed Microsporum canis (0.39 vs.1.00).Conclusion The constructed PCB309-PLULT interference vector can effectively inhibit the expression of PQ-LRP gene in Microsporum canis.
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ObjectiveTo observe the clinical efficacy of combined irbesartan and alprostadil treatment of early diabetic nephropathy (DN).Methods A total of 120 patients with early type 2 diabetes of hospitalization were randomly divided into 3 groups: irbesartan group of 40 patients (150 mg, once per day)(group irbesartan),40 patients treated with alprostadil (physiological saline and alprostadi 10 μg))(group alprostadi) ,40 patients treated with alprostadil combined irbesartan (dose same as the other two groups)(combined group).All cases were observed for 4 weeks.Comparison of serum creatinine (Cr), blood urea nitrogen(BUN) ,24 hour urinary albumin(24hUAE) changes after treatment.ResultsAfter treatment 4 weeks 24hUAE of the three groups were significantly decreased (t = 2.07, t = 2.01 and t = 3.15, Ps < 0.05) .The decrease of 24hUAE in the combined treatment group ([252.69 ± 33.56]mg/24h) was better than that in the irbesartan group([268.75 ± 34.42)](t = 2.11, P < 0.05)and in the alprostadil group ([267.95 ± 30.75])mg/24h (t = 1.998, P < 0.05) .No significant difference were observed between the Irbesartan and alprostadil group.During treatment, several patients affected by swell, uncomfortable in the alprostadil group, but improved after treatment.No other adverse effect was observed.Conclusion Alprostadil combined with irbesartan treatment of early diabetic nephropathy is an effective way.
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Objective To evaluate the effects of Alprostadil combined with Enalapril on high sensitivity C-reactive protein and Cystatin in patients with early diabetic nephropathy.Methods One hundred and fifteen cases of outpatients were randomized into 3 groups.Thirty-seven cases were assigned to Alprostadil group and treated with Alprostadil 10 μg + NS 100 ml,iv,qid;Thirty-eight cases were assigned to the Analapril group and treated with Enalapril 5 mg bid;Forty cases were assigned to the combined treatment group and treated with Alprostadil 10 μg + NS 100 ml,iv qid and Enalapril 5mg bid.All patients were observed for twelve weeks.Changes before and after treatment in the blood pressure,plasma glucose,glycolated hemoglobin (HbA1 c),24 hours urinary albumin (24 hUAE),high-sensitive C-reactive protein(hs-CRP) and Cystain C( Cys C) were observed and compared between the three groups.Results After treatment,hs-CRP,CysC and 24 h UAE were significantly improved in the three groups compared with baseline levels( P < 0.05).In the combined treatment group,hs-CRP,CysC and 24 h UAER had a more significant improvement than the other two groups (P <0,05 ).Conclusion Alprostadil combined with Enalapril is a clinically effective strategy in the treatment of early diabetic nephropathv and can reduce the levels of CysC and hs-CRP.
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Objective:To investigate the role of dendritic cells (DCs) in the anti-CD45RB antibody-induced immune tolerance,and the mechanism of immune tolerance induced by anti-CD45RB antibodies.Methods:DCs were induced by conventional methods(rmGM-CSF,IL-4 and LPS),different doses of anti-CD45RB antibodies were added in the induction process.Then,mature cells were harvested,and flow cytometry(FCM) was used to determine cell phenotypes,cycle and phagocytosis,ELISA method was performed to examine the concentration of IL-12 and the ability of T cell proliferation was observed by mixed lymphocyte culture.Results:The DCs preparation was shown a high expression of CD11C and CD83,a low expression of CD86,with strong proliferative and phagocytic capacity after treated with anti-CD45RB antibody.Its secretion of IL-12 was decreased,and it could less effectively stimulate T cell proliferation after treated with anti-CD45RB antibody.Conclusion:One of the mechanisms of anti-CD45RB monoclonal antibody-induced tolerance is to generate tolerogenic dendritic cells(tDCs),significantly inhibiting the proliferation of T cells.
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The influence of Cibotium barometz (L.) J. Sm. and its processed samples on thrombin-induced platelet aggregation in rabbits was studied. The results showed that all differently processed sam-ples tested could inhibit platelet aggregation, with activities in the decreasing order of Rhizoma Cibotiiroasted in stirring sand>steamed after being salted>steamed after steeped in wine>simply steamed>theunprocessed crude Rhizoma Cibotii.