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Four unreported monoterpene indole alkaloids, tabernaecorymines B-E (1-4), together with twenty-one known indole alkaloids (5-25) were obtained from the stem bark of Tabernaemontana corymbosa. Their structures and absolute configurations were elucidated by extensive spectroscopy, quantum chemical calculations, DP4+ probability analyses and Mo2(OAc)4-induced electronic circular dichroism experiment. The antibacterial and antifungal activities of these compounds were evaluated and some of them showed significant activity against Staphylococcus aureus,Bacillus subtilis, Streptococcus dysgalactiae and Candida albicans.
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Tabernaemontana , Anti-Infective Agents , Antifungal Agents , Anti-Bacterial Agents , Indole AlkaloidsABSTRACT
Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.
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Animals , Humans , Squamous Cell Carcinoma of Head and Neck/therapy , Heterografts , Photothermal Therapy , Biomimetics , Disease Models, Animal , Head and Neck Neoplasms/therapy , Cell Line, Tumor , Tumor MicroenvironmentABSTRACT
Objective:To explore the feasibility of statistical parametric mapping (SPM) aided semi-quantitative analysis in 11C-Pittsburgh compound B (PIB) β-amyloid (Aβ) PET imaging acquired by hybrid PET/MR, and evaluate its possibility in assisting the diagnosis or differential diagnosis for cognitive impairment. Methods:From January 2018 to September 2019, 13 Alzheimer′s disease (AD) patients (4 males, 9 females; age (59.2±5.8) years) and 10 vascular cognitive disorders (VCD) patients (9 males, 1 female; age (59.5±11.5) years) who underwent 11C-PIB PET/MR in PET center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed. The standardized uptake value ratio (SUVR) of eight key brain regions (cerebral white matter, striatum, thalamus, posterior cingulate gyrus, frontal cortex, posterior parietal cortex, lateral temporal cortex and occipital cortex) to cerebellum cortex were obtained by manual delineation and SPM-aided semi-automatic segmentation with the help of synchronous three-dimensional T 1 weighted imaging (3D T 1WI). Pearson correlation analysis was carried out on the SUVR obtained by the two methods. Independent-sample t test and paired t test were used to analyze the data. Results:There was no significant difference between AD group and VCD group in age and Mini-Mental State Examination (MMSE) score (19.7±4.7 vs 21.7±3.8; t values: 0.095 and 1.098, both P>0.05). Except thalamus( r=0.179, P=0.413), there were good correlations between SUVR obtained by segmentation and delineation in the other 7 key regions ( r values: 0.678-0.893, all P<0.05). The SUVR of 8 key regions obtained by the two methods in AD group was significantly higher than that in VCD group (1.519-2.055 vs 1.105-1.618; t values: 2.799-11.582, all P<0.01). The SUVR of striatum (1.942±0.205), posterior cingulate gyrus (1.915±0.249), frontal lobe (1.983±0.264), parietal lobe (2.008±0.296) and temporal cortex (1.931±0.254) in AD group was significantly higher than that of cerebral white matter (1.746±0.192; t values: 3.793-6.992, all P<0.01). But in VCD group, there was no region with the SUVR higher than that of cerebral white matter. Conclusions:Hybrid PET/MR can acquire the PET and MRI images synchronously, which can realize the accurate brain segmentation and obtain the semi-quantitative data of key brain regions aided by SPM. The method can analyze the characteristics and differences of amyloid imaging in AD and VCD, which is expected to provide an accurate imaging analysis method for the diagnosis and differential diagnosis of cognitive disorders.
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Objective@#To discuss the correlation between 18F-fluorodeoxyglucose (FDG) imaging and arterial spin labeling perfusion weighted imaging (ASL-PWI) using synchronous PET/MR, and explore the feasibility of 18F-FDG PET and ASL for differential diagnosis in Parkinsonism (PS).@*Methods@#A retrospective analysis was performed in 24 patients with Parkinson′s disease (PD), 10 patients with multiple system atrophy (MSA) and 6 patients with progressive supranuclear palsy (PSP) who all underwent 18F-FDG PET/MR imaging from October 2017 to December 2018 (15 males, 25 females, age: 34-77 years). Synchronously acquired data, including MRI T1, 18F-FDG PET and three dimensional (3D) ASL-PWI were extracted. T1 structure image was used to register with standard brain template, and the personalized brain template of each patient was obtained. Then, the templates were matched to the corresponding PET and ASL-PWI images, and the mean standardized uptake value (SUVmean) and mean cerebral blood flow (CBFmean) of each brain region could be extracted. Pearson correlation analysis was used to evaluate the correlation between SUVmean and CBFmean of the whole brain and the regions of interest (ROI; caudate nucleus, putamen, midbrain, pons and cerebellum). One-way analysis of variance and least significant difference t test were used to evaluate the characteristics of SUVmean and CBFmean in different diagnostic groups. The diagnostic values of SUVmean and CBFmean in different ROI were evaluated with receiver operating characteristic (ROC) curve analysis.@*Results@#A total of 2 800 pairs of SUVmean and CBFmean were obtained from 40 cases in 3 groups. The overall correlation between them was good (r=0.468, P<0.01). There were also significant correlations between SUVmean and CBFmean in caudate nucleus, putamen, pons and cerebellum (r values: 0.346-0.492, all P<0.05). The CBFmean of cerebellum in MSA group was significantly lower than that in PD group ((36.92±11.35) vs (47.92±10.75) ml·100 g-1·min-1; F=4.817, t=2.675, P<0.05). Compared to the PSP group, CBFmean in caudate nucleus was higher in PD group ((30.02±3.51) vs (40.21±8.13) ml·100 g-1·min-1; F=5.393, t=2.969, P<0.05). The similar results were obtained for SUVmean. To differentiate PD with MSA, CBFmean of cerebellum possessed the highest diagnostic efficiency, with the area under ROC curve (AUC), sensitivity and specificity reaching 0.792, 83.3% and 70.0% respectively. To differentiate PSP with PD or MSA, CBFmean in caudate nucleus had the highest diagnostic efficiency, and the AUC were 0.903 and 0.933 respectively.@*Conclusions@#In patients with PD, MSA and PSP, the level of 18F-FDG glucose metabolism is in good agreement with the ASL cerebral blood flow perfusion obtained by synchronous PET/MR. The distribution characteristics of specific ROI in both PET and MR imaging can be helpful to the differential diagnosis of PS.
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Objective To discuss the correlation between 18 F-fluorodeoxyglucose (FDG) imaging and arterial spin labeling perfusion weighted imaging (ASL-PWI) using synchronous PET/MR,and explore the feasibility of 18F-FDG PET and ASL for differential diagnosis in Parkinsonism (PS).Methods A retrospective analysis was performed in 24 patients with Parkinson's disease (PD),10 patients with multiple system atrophy (MSA) and 6 patients with progressive supranuclear palsy (PSP) who all underwent 18 F-FDG PET/MR imaging from October 2017 to December 2018 (15 males,25 females,age:34-77 years).Synchronously acquired data,including MRI T1,18F-FDG PET and three dimensional (3D) ASL-PWI were extracted.T1 structure image was used to register with standard brain template,and the personalized brain template of each patient was obtained.Then,the templates were matched to the corresponding PET and ASL-PWI images,and the mean standardized uptake value (SUVmean) and mean cerebral blood flow (CBFmean) of each brain region could be extracted.Pearson correlation analysis was used to evaluate the correlation between SUVmean and CBF of the whole brain and the regions of interest (ROI;caudate nucleus,putamen,midbrain,pons and cerebellum).One-way analysis of variance and least significant difference t test were used to evaluate the characteristics of SUVmean and CBFmean in different diagnostic groups.The diagnostic values of SUVmean and CBF in different ROI were evaluated with receiver operating characteristic (ROC) curve analysis.Results A total of 2 800 pairs of SUVmean and CBFmean were obtained from 40 cases in 3 groups.The overall correlation between them was good (r=0.468,P＜0.01).There were also significantcorrelations between SUVmean and CBFmean in caudate nucleus,putamen,pons and cerebellum (r values:0.346-0.492,all P＜0.05).The CBFmean of cerebellum in MSA group was significantly lower than that in PD group ((36.92±11.35) vs (47.92±10.75) ml · 100 g-1 · min-1;F=4.817,t=2.675,P＜0.05).Compared to the PSP group,CBF in caudate nucleus was higher in P D group ((30.02± 3.51) vs (40.21±8.13) ml · 100 g-1 · min-1;F=5.393,t=2.969,P＜0.05).The similar results were obtained for SUVmean.To differentiate PD with MSA,CBFmean of cerebellum possessed the highest diagnostic efficiency,with the area under ROC curve (AUC),sensitivity and specificity reaching 0.792,83.3％ and 70.0％ respectively.To differentiate PSP with PD or MSA,CBF in caudate nucleus had the highest diagnostic efficiency,and the AUC were 0.903 and 0.933 respectively.Conclusions In patients with PD,MSA and PSP,the level of 18F-FDG glucose metabolism is in good agreement with the ASL cerebral blood flow perfusion obtained by synchronous PET/MR.The distribution characteristics of specific ROI in both PET and MR imaging can be helpful to the differential diagnosis of PS.
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Objective To investigate the role of estrogen and progesterone in the tumorigenesis of triple-negative breast cancer and its molecular mechanism. Methods To construct of MDA-MB-231/miR-145 and MDA-MB-231/ miR-SCR(scramble control) stable cell lines. The cells were cultured in five groups that were respectively miR-SCR group, miR-145 group, miR-145 + E2 group, miR-145 + P4 group, miR-145 +E2 +P4 group, grouped adminis-tradion. Cell proliferation was detected by CCK-8 kit, the expression level of miR-145 target gene insulin-like growth factor receptor-1 (IGF-IR), N-RAS was detected by Western blot, expression of IGF-1R, N-RAS downstream signaling molecule vascular endothelial growth factor(VEGF) and expression of miR-145 after transfection was detected by real-time quantitative PCR(qRT-PCR). Results The results of CCK-8 assay showed that estrogen and progesterone combined administration could reverse the inhibitory effect of miR-145 on the proliferation of triple-negative breast cancer cells (P ＜ 0. 05 ). The results of Western blot showed that estrogen and progesterone combined administration could increase the expression level of IGF-1 R and N-RAS in the target gene of miR-145. The results of qRT-PCR showed that the expression level of miR-145 was significantly higher than that of control group (P ＜ 0. 05) and the expression of VEGF was significantly increased by estrogen and progesterone combined administration (P ＜0. 01). Conclusion Estrogen and progesterone combined administration can promote the expression of VEGF and cell proliferation, and then reverse the anti-tumor effect of miR-145 in the triple-negative breast cancer.
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[Objective]The article summarizes the experience of Professor SUN Wei in treating nephritic hematuria.[Methods]The article discusses the clinical experience of Professor SUN Wei in the treatment on nephritic hematuria from the methods of learning from his daily treatment in inpatient and outpatient department,reading relative books and articles,recognition from the study of ancient classics,from etiology and pathogenesis,treatment,illustrating Professor's medication experience in the treatment of nephritic hematuria and with a case for evidence.[Results]Professor SUN Wei believes that the basic pathogenesis of nephritic hematuria is deficiency of the kidney with dampness heat and blood stasis,he creates the therapeutic modality of tonifying the kidney and promoting blood circulation and clearing away the damp-heat,he emphasizes reinforcing kidney and spleen, clearing heat and dampness,promoting blood circulation,conditioning the blood,he considers that the kidney Qi and Yin deficiency come first among kidney deficiency,long-term hematuria should not to be over-astringed.Professor SUN Wei is apt at the use of the herbs,all of these usually lead to good curative effect.[Conclusion]Professor SUN Wei's clinical experience in treating nephritic hematuria from tonifying the kidney and promoting blood circulation and clearing away the damp-heat is well worth extending in clinic for it always has significant effect.
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The main intention of this paper is to propose suggestions for optimizing China 's high-value medical consumables centralized procurement .In this paper , we have analyzed the developed countries 'best practices in high-value medical consumables procurement from the perspectives of procurement principle ( s), key procurement bodies, procurement patterns, supervision, and management.The results of our analysis show that “Value for mon-ey” is the core principle in procurement and hospital route , national/regional centralized route ( s) , and group pur-chase organization ( GPO) route are four primary procurement patterns in foreign countries .Procurement management is optimized through improving product coding system and encouraging health technology assessment ( HTA) and clin-ical practitioners'involvement in procurement decision-making.In that perspective, it's been suggested that China's high-value medical consumables centralized procurement could be improved from three aspects:referring partial HTA indicators so as to enhance tender evaluation and realize value-based purchasing;establishing a standard and unified coding system for medical devices;introducing GPO route and make market surveillance mechanism into full play .
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Objective To acknowledge the spouse comorbid conditions of diabetes patients by comparing the average blood sugar level of the spouse of the diabetes patients with normal Guangzhou residents.Methods To sift and analyze the spouse test results of 152 hospitalized diabetes patients from January 2012 to January 2013,by testing the blood sugar level of the experimental subjects,comparing the different blood sugar level results between when they were with empty stomach and 2 hours after oral glucose tolerance test (OGTT).Results There were 32 cases with diabetes,9 cases with impaired glucose tolerance (IGT) and 11 cases with impaired fasting glucose (IFG) in the above 152 experimental subjects.The morbidity rates were 21.05％,5.92％ and 7.24％.All the above results were higher than the Guangzhou residents survey level,there were statistical differences between them.Conclusions The high morbidity rates of diabetes and impaired glucose regulation in diabetes patients spouse are obvious.The works for diabetes sifting and analyzing together with the health education instruction need to be strengthened.
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Objective: To explore the clinical research on the treatment of osteoporosis with calcitonin and Low frequency pulse electromagnetic field. Methods:Selected 84 cases of primary osteoporosis were randomly divided into control group and treatment group, 42 cases in each group, two groups were given calcium, vitamin D and other drugs conventional treatment, on the basis of the control group, intramuscular injections salmon calcitonin in the treatment group and intramuscular injection of salmon calcitonin with PEMF therapy, before treatment and after 3 and 6 months, respectively. Results: Two groups of patients after treatment, the pain was significantly reduced compared with before treatment, the longer the treatment, the more obvious decline;Treatment of three months, six months later, the treatment group compared with the control group bone mineral density were significant differences(t=3.129, t=6.457;P<0.05);The two groups no serious adverse reactions. Conclusion:Osteoporosis patients in the conventional therapy treatment based on intramuscular injection of salmon calcitonin and with PEMF treatment can significantly reduce the patient's pain, increase bone density, efficacy, adverse reactions, with some clinical reference significance.
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OBJECTIVE:To observe the clinical efficacy of Chinese medicine inunction wet dressing therapy and helium neon laser in the treatment of rheumatoid arthritis.METHODS:Both groups received Methotrexate tablets,Salazosulfapyridine tablets,Loxoprofen tablets.Observation group were additionally treated with Chinese medicine inunction wet dressing therapy and helium neon laser with a treatment course of 30 days.RESULTS:The effective rate was 70.00% for control group and 93.55% for observation group,there was significant difference between two groups(P
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OBJECTIVE:To observe the clinical effect of Shenmai injection for primary sjogren syndrome.METHODS:61 patients were randomized to receive anethole trithione (control group,n=29) or anethole trithione and Shenmai injection (treatment group,n=32) respectively with 15 days as a course of treatment.RESULTS:The total effective rate was 68.96% for control group and 90.63% for treatment group.There were 3 cases of abdominal discomfort ordiarrhea in control group,and no serious ADR was detected in treatment group.Significant difference was noted between two groups (P