To separate and identify the chemical constituents from the leaves of Broussonetia papyrifera (Linn.) Vent, various columns including Diaion HP-20, Toyopearl HW-40C, Sephadex LH-20, silica gel were employed for the isolation and purification of compounds from the leaves of B.papyrifera. The structures of the compounds were elucidated by their physiochemical characteristics and spectral data. Nineteen compounds were isolated from the leaves of B.papyrifera and their structures were identified as apigenin (1), apigenin-7-O-β-D-glucopyranoside (2), chrysoerid-7-O-β-D-glucopyranoside (3), apigenin-7-O-β-D-glucopyranuronide (4), vitexin-7-O-β-D-glucopyranoside (5), luteolin (6), 5,7,4′-trihydroxyl-6-C-[a-L-rhamnopyranosyl(1→2)]-β-D-glucopyranosyl flavone (7), 5,7,4′-trihydroxyl-8-C-[a-L-rhamnopyranosyl(1→2)]-β-D-glucopyranosyl flavone (8), saponaretin (9), vitexin (10), benzyl benzoate-2,6-di-O-β-D-glucopyranoside (11), (2R,3R,5R,6S,9R)-3-hydroxy-5,6-epoxy-β-ionol-2-O-β-D-glucopyranoside (12), (2R,3R,5R,6S,9R)-3-hydroxyl-5,6-epoxy-acetyl-β-ionol-2-O-β-D-glucopyranoside (13), ficustriol (14), (6S,9S)-roseoside (15), 3β-hydroxy-5α,6α-epoxy-β-ionone-2α-O-β-D-glucopyranoside (16), icariside B1 (17), sammangaoside A (18), 3-hydroxy-5α,6α-epoxy-β-ionone (19). Compounds 11, 12 and 13 are new compounds, the others are isolated from this genus Broussonetia for the first time.

Objective To optimize the exposure parameters and reduce the irradiation dose level in infants and young children during digital radiography (DR) chest radiography under the premise of satisfied image quality.Methods The thoracic thickness of 100 patients were measured.Determined the aluminum equivalent of the thoraxes of the infants and young children by comparing the grayscale value and the aluminum step wedge.Another 100 infants and young children of experimental exposure were performed with the aluminum step wedge as a phantom,under AEC control,kV was the only variant to explore the optimal exposure parameters with dose monitor simultaneously.At last,clinical validation was performed.Images quality was compared with x2 test.The radiation dose of two groups was compared with t test.Results The maximum,minimum,average thoracic thickness and their correspondent aluminum equivalent were 13.5 and 2.3 cm,8.0 and 1.4 cm,(10.6 ± 1.3) and 2.0 cm,respectively.The average thoracic thickness of experimental group was (10.1 ± 2.2) cm.The range of entrance surface dose was 0.068-0.056 mGy while the tube voltage range was 55-65 kV.The exposure index range was 0.60-0.74.The visual inspection of aluminum step wedge was from grades 8 to 11 with satisfying image quality at lower radiation.The infant chest X-ray photography exposure parameters formula have been optimized,that was kV =thoracic thickness (cm) × 2 + 38 (constant),mAs (0.8-1.0) with SID =100 cm,without filter grid.Compare to the conventional parameters,the image quality of new method had no significant differences (P ＞ 0.05).The actual average entrance surface dose was (0.048 ± 0.007) mGy,lower than AEC group (0.066 ± 0.008) mGy.The difference was statistically significant (t =16.781,P ＜ 0.001).Conclusions The optimized formula kV =thoracic thickness (cm) ×2 + 38(constant),mAs (0.8-1.0) with SID =100 cm was credible for lowering the radiation exposure with good image quality for clinical diagnosis.

Many species of the genus Ephedra plants are used as Chinese traditional medicines, in Chinese which are known as "Mahuang" (Ephedrae Herba). In order to get a clear picture of resources distribution and varieties on Chinese markets of the crude drug Mahuang and provide scientific basis for their resource conservation and sustainable use, during recent years we conducted field investigations and market researches many times. The results showed that the most common species on the Chinese markets was E. sinica (33/38 commercial samples), followed by E. intermedia (5/38 commercial samples), which was also used in local clinics in Qing-hai, Gansu and Xinjiang province, no E. equisetina was found in the market. We noticed that the resources of both official and non-official plants of Mahuang, especially Zhong-Mahuang and Muzei-Mahuang, were seriously damaged in the past decade because of the ecological environment damage and over-digging. Zhong-Mahuang was distinguished in Ningxia and north Gansu, which was once one of the most distribution areas and contains more than 10,000 t Zhong-Mahuang. Muzei-Mahuang was distinguished in most places and distributed sparsely around Altay Mountains in northeast in Xinjiang. Thus, Cultivation of Mahuang, especially Zhong-Mahuang and Muzei-Mahuang should be greatly developed. At the same time, wild resources of Mahuang must be preserved strictly, i.e., proper method of cutting Ephedra plant could prevent the damage of the resource.
China ; Conservation of Natural Resources ; Drugs, Chinese Herbal ; classification ; supply & distribution ; Ephedra sinica ; classification ; growth & development

Objective:To investigate the role of speckle-type POZ(pox virus and zinc finger protein) protein (SPOP) in enterovirus 71 (EV71) infection.Methods:Immunoprecipitation analysis was employed to examine the impact of SPOP on the ubiquitin level of EV71 non-structural protein 2A protease (2A pro), while the phosphorylation level of IFR3 protein was assessed through Western blot. Cells were either overexpressed or knockdown of SPOP, followed by infection with EV71. RT-qPCR was utilized to analyze the transcription level of IFN-β, and the transcription level and protein level of EV71 structural protein VP1 were determined using RT-qPCR and Western blot, respectively. Results:The inhibition of EV71 infection in RD cells was observed following transfection with HA-SPOP. Additionally, it was found that the ubiquitin level of EV71-2A pro increased in a gradient-dependent manner. Subsequent transfection with shSPOP plasmid for endogenous SPOP knockdown resulted in a dose-dependent decrease in the levels of melanoma differentiation-associated gene 5 (MDA5), mitochondrial antiviral signaling (MAVS), and p-IRF3. Conversely, transfection with HA-SPOP plasmid led to a dose-dependent increase in the levels of MDA5, MAVS, and p-IRF3. The expression of SPOP, whether high or low, had an impact on the expression of IFN-β in cells. Additionally, the levels of VP1 mRNA or protein were found to be inhibited or increased. Conclusions:SPOP plays a role in increasing the ubiquitination level of EV71-2A pro, which in turn promotes the phosphorylation level of IRF3 and secretion of IFN-β. This effect is achieved by inhibiting the cleavage of 2A pro against key molecules MAVS and MDA5 in the RLR signaling pathway, ultimately leading to the inhibition of EV71 replication.

Objective To investigate the safety and efficacy of 177Lu-prostate specific membrane antigen (PSMA)-617 in the treatment of metastatic castration-resistant prostate cancer (mCRPC).Methods From August 2017 to September 2018,11 patients(average age 70.6 years) with mCRPC who underwent 177Lu-PSMA-617 therapy in Nanjing First Hospital were studied.All patients underwent 68Ga-PSMA-11 PET/CT before therapy to assess the tumor radioactive uptake.Blood routine examination and renal function test results were documented before and after therapy to assess the safety.The efficacy was reflected by the changes of prostate specific antigen (PSA) levels and maximum standardized uptake value (SUVmax) on 68Ga-PSMA-11 PET/CT imaging.Paired t test and Wilcoxon's sign rank test were used to analyze the data.Results No acute side effects were observed after therapy of 177Lu-PSMA-617.There were no statistically significant differences after therapy in WBC counts,RBC counts,and PLT,as well as Hb levels (t values:-0.28-1.11,all P＞ 0.05).No kidney toxicity was found.The PSA level after 177Lu-PSMA-617 therapy was significantly lower than that before therapy (80.70 (14.29,1 538.00) μg/L vs 604.60 (88.41,3 980.00) μg/L;u =59,P =0.023).Of the 11 patients,only 2 had elevated PSA levels and disease progression,while the other 9 patients had varying decreases,of which 2/11 decreased by ＞30％ and 7/11 decreased by ＞50％.After therapy,SUVmax of metastatic lesions and metastatic lymph nodes were decreased in 9 and 2 patients respectively.Conclusions 177Lu-PSMA-617 has a good therapeutic value for mCRPC.It is safe and has no obvious side effects.

Nanoparticulate drug delivery systems (Nano-DDSs) have emerged as possible solution to the obstacles of anticancer drug delivery. However, the clinical outcomes and translation are restricted by several drawbacks, such as low drug loading, premature drug leakage and carrier-related toxicity. Recently, pure drug nano-assemblies (PDNAs), fabricated by the self-assembly or co-assembly of pure drug molecules, have attracted considerable attention. Their facile and reproducible preparation technique helps to remove the bottleneck of nanomedicines including quality control, scale-up production and clinical translation. Acting as both carriers and cargos, the carrier-free PDNAs have an ultra-high or even 100% drug loading. In addition, combination therapies based on PDNAs could possibly address the most intractable problems in cancer treatment, such as tumor metastasis and drug resistance. In the present review, the latest development of PDNAs for cancer treatment is overviewed. First, PDNAs are classified according to the composition of drug molecules, and the assembly mechanisms are discussed. Furthermore, the co-delivery of PDNAs for combination therapies is summarized, with special focus on the improvement of therapeutic outcomes. Finally, future prospects and challenges of PDNAs for efficient cancer therapy are spotlighted.

Objectives Objectives To investigate how the imbalance of innate lymphoid cells (ILCs)in the peripheral blood of patients with lung adenocarcinoma affects the balance of downstream mononuclear macrophages and T helper (Th) cells, and to identify the impact of the imbalance of ILCs on the immune status and prognosis of lung adenocarcinoma. Methods The peripheral blood of 20 patients with lung adenocarcinoma and normal controls were collected. The percentage of ILCs, mononuclear macrophages and T lymphocyte in peripheral blood were analyzed by flow cytometry. The characteristic cytokine secretion levels of various types of immune cells in peripheral blood were detected by real-time fluorescence quantitative PCR. Results Compared with the normal controls, the proportion of M2 mononuclear macrophages, ILC1 and ILC2 in patients with lung adenocarcinoma was up-regulated, while the proportion of M1 mononuclear macrophages, CD4⁺ T and CD8⁺ T was down-regulated. The mRNA expression of related cytokines of M1 mononuclear macrophages and ILC1 were decreased; while the mRNA expression of related cytokines of M2 mononuclear macrophages and ILC2 were increased. Along with the decreased CD4⁺T cells-associated cytokine T-bet mRNA expression, and the increased GATA3 mRNA expression. Moreover, the expression of PD-1 in CD8⁺ T cells was also up-regulated. Conclusion The imbalance of ILCs in peripheral blood of patients with lung adenocarcinoma promotes the imbalance of mononuclear macrophages and Th cells, which altogether maintains the immunosuppression in patients with lung adenocarcinoma, and promotes the development of lung adenocarcinoma.
Humans ; Lymphocytes ; Immunity, Innate ; CD8-Positive T-Lymphocytes ; Cytokines/metabolism* ; Adenocarcinoma of Lung ; Immunosuppression Therapy ; RNA, Messenger

Objective To investigate the protective effect of NDUFA13 protein against acute liver injury and liver fibrosis in mice and explore the possible mechanisms.Methods BALB/C mice(7 to 8 weeks old)were divided into normal group,CCl4 group,CCl4+AAV-NC group and CCl4+AAV-NDU13 group(n=18).Mouse models of liver fibrosis were established by intraperitoneal injection of CCl4 twice a week for 3,5 or 7 weeks,and the recombinant virus AAV8-TBG-NC or AAV8-TBG-NDUFA13 was injected via the tail vein 7-10 days prior to CCl4 injection.After the treatments,pathological changes in the liver of the mice were observed using HE and Masson staining.Hepatic expression levels of NDUFA13 and α-SMA were detected with Western blotting,and the coexpression of NDUFA13 and NLRP3,TNF-α and IL-1β,and α-SMA and collagen Ⅲ was analyzed with immunofluorescence assay.Results HE and Masson staining showed deranged liver architecture,necrotic hepatocytes and obvious inflammatory infiltration and collagen fiber deposition in mice with CCl4 injection(P<0.001).NDUFA13 expression markedly decreased in CCl4-treated mice(P<0.001),while a significant reduction in inflammatory aggregation and fibrosis was observed in mice with AAV-mediated NDUFA13 overexpression(P<0.001).In CCl4+AAV-NDU13 group,immunofluorescence assay revealed markedly weakened activation of NLRP3 inflammasomes(P<0.001),significantly decreased TNF-α and IL-1β secretion(P<0.001),and inhibited hepatic stellate cell activation(P<0.05)and collagen formation in the liver(P<0.001).Conclusion Mitochondrial NDUFA13 overexpression in hepatocytes protects against CCl4-induced liver fibrosis in mice by inhibiting activation of NLRP3 signaling.

Objective To investigate the protective effect of NDUFA13 protein against acute liver injury and liver fibrosis in mice and explore the possible mechanisms.Methods BALB/C mice(7 to 8 weeks old)were divided into normal group,CCl4 group,CCl4+AAV-NC group and CCl4+AAV-NDU13 group(n=18).Mouse models of liver fibrosis were established by intraperitoneal injection of CCl4 twice a week for 3,5 or 7 weeks,and the recombinant virus AAV8-TBG-NC or AAV8-TBG-NDUFA13 was injected via the tail vein 7-10 days prior to CCl4 injection.After the treatments,pathological changes in the liver of the mice were observed using HE and Masson staining.Hepatic expression levels of NDUFA13 and α-SMA were detected with Western blotting,and the coexpression of NDUFA13 and NLRP3,TNF-α and IL-1β,and α-SMA and collagen Ⅲ was analyzed with immunofluorescence assay.Results HE and Masson staining showed deranged liver architecture,necrotic hepatocytes and obvious inflammatory infiltration and collagen fiber deposition in mice with CCl4 injection(P<0.001).NDUFA13 expression markedly decreased in CCl4-treated mice(P<0.001),while a significant reduction in inflammatory aggregation and fibrosis was observed in mice with AAV-mediated NDUFA13 overexpression(P<0.001).In CCl4+AAV-NDU13 group,immunofluorescence assay revealed markedly weakened activation of NLRP3 inflammasomes(P<0.001),significantly decreased TNF-α and IL-1β secretion(P<0.001),and inhibited hepatic stellate cell activation(P<0.05)and collagen formation in the liver(P<0.001).Conclusion Mitochondrial NDUFA13 overexpression in hepatocytes protects against CCl4-induced liver fibrosis in mice by inhibiting activation of NLRP3 signaling.