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Steroid-refractory (SR) acute graft-versus-host disease (aGVHD) is one of the leading causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the efficacy, safety, prognostic factors, and optimal therapeutic protocol for SR-aGVHD patients treated with basiliximab in a real-world setting. Nine hundred and forty SR-aGVHD patients were recruited from 36 hospitals in China, and 3683 doses of basiliximab were administered. Basiliximab was used as monotherapy (n = 642) or in combination with other second-line treatments (n = 298). The cumulative incidence of overall response rate (ORR) at day 28 after basiliximab treatment was 79.4% (95% confidence interval [CI] 76.5%-82.3%). The probabilities of nonrelapse mortality and overall survival at 3 years after basiliximab treatment were 26.8% (95% CI 24.0%-29.6%) and 64.3% (95% CI 61.2%-67.4%), respectively. A 1:1 propensity score matching was performed to compare the efficacy and safety between the monotherapy and combined therapy groups. Combined therapy did not increase the ORR; conversely, it increased the infection rates compared with monotherapy. The multivariate analysis showed that combined therapy, grade III-IV aGVHD, and high-risk refined Minnesota aGVHD risk score before basiliximab treatment were independently associated with the therapeutic response. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real-world data suggest that basiliximab is safe and effective for treating SR-aGVHD.

To investigate the morphological, histological and ultrastructural changes of acute closed rupture of Achilles tendon, in order to clarify the pathological basis of the injury and to explore the significance.From January 2015 to January 2019, 35 patients with acute Achilles tendon rupture who underwent the minimally invasive Achilles tendon suture technique were retrospectively analyzed. Among these patients, 12 cases in acute open Achilles tendon rupture group included 10 males and 2 females, with an average age of (35.1±9.7) years old ranging from 19 to 50, and the time from injury to operation was 2 to 8 hours with an average of(5.6±1.8);23 cases in acute closed Achilles tendon rupture group included 21 males and 2 females, with an average age of (35.5±6.6) years old ranging from 18 to 50, and the time from injury to operation was 3 to 15 hours with an average of (7.5±3.1). The gross appearance and imaging findings of the broken end of Achilles tendon tissue in the two groups were compared by naked eye observation and foot and ankle MRI at 4 to 6 hours before operation. HE staining, scanning and fluoroscopic electron microscopy, immunohistochemistry(Sirius red staining) were performed on the intraoperative Achilles tendon tissue specimens at 1 to 2 days after operation, the collagen fiber degeneration and local fat infiltration, collagen fiber shape, cell morphology and function, and the distribution of typeⅠand type Ⅲ collagen fibers in Achilles tendon were compared between the two groups.Compared with the acute open Achilles tendon rupture group, the acute closed Achilles tendon rupture group had poor elasticity, hard texture, moderate edema, irregular shape of Achilles tendon broken end, horsetail shape, and more calcification around the broken end. HE staining results:the collagen fibers in the Achilles tendon of the acute open Achilles tendon rupture group were arranged irregularly, with hyaline degeneration and fat infiltration;The results of electron microscopy showed that collagen arranged disorderly and fibroblasts atrophied in the acute closed Achilles tendon rupture group. Immunohistochemical(Sirius staining) results:the proportion of collagenⅠin the acute open Achilles tendon rupture group and the acute closed Achilles tendon rupture group was(91.12±4.34)% and(54.71±17.78)% respectively, and the proportion of collagen Ⅲ was (8.88±4.34)% and (45.29±17.78)% respectively. The content of collagenⅠin the acute closed Achilles tendon rupture group was lower than that in the acute open Achilles tendon rupture group, and the content of collagen Ⅲ in the acute closed Achilles tendon rupture group was higher than that in the acute open Achilles tendon rupture group(The morphology, histology and ultrastructure of the acute closed ruptured Achilles tendon are significantly altered compared with the normal Achilles tendon. The original fine and orderly spatial structure cannot be maintained, part of collagen Ⅰ is replaced by collagen Ⅲ, and the toughness and strength of the tendon tissue decreased, which may be the feature of degeneration of the Achilles tendon and an important pathological basis for closed Achilles tendon rupture.

The rhizome of Ligusticum chuanxiong Hort. has been widely used for the therapy of diabetic nephropathy (DN) in traditional Chinese medicine (TCM). The nuclear transcription factor erythroid 2-related factor (Nrf2) is a potential target for treating DN. The purpose of this research was to study the chemical constituents from the rhizome of L. chuanxiong, evaluate their Nrf2 inducing activity, and find the molecules with potential therapeutic effect against DN. In this study, two new phthalides (1-2) along with twenty-seven known constituents were obtained from the rhizome of L. chuanxiong. Their structures were elucidated through various spectroscopic methods. Twelve constituents, including eight phthalides (2, 5, 6, 10-13, 14) and four other compounds (17, 18, 20, 28), stimulated NAD(P)H: quinone reductase (QR) activity, suggesting that these bioactive constituents were potential Nrf2 activators. Among the isolated compounds, phthalide levistolide A (LA, 14) upregulated the protein levels of Nrf2, NQO1, and γ-GCS in a dose-dependent manner. Our results implied that the clinical application of the rhizome of L. chuanxiong as an anti-DN drug in TCM might be attributed to the Nrf2 inducing effect of phthalides. Thus, phthalides is a group of promising leading molecules for discovering anti-DN agents.

Oxidative stress is one of the main pathogenesis for many human diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway plays a key role in regulating intracellular antioxidant responses, and thus activation of Nrf2/ARE signaling pathway is a potential chemopreventive or therapeutic strategy to treat diseases caused by oxidative damage. In the present study, we have found that treatment of Beas-2B cells with botrysphins D (BD) attenuated sodium arsenite [As (III)]-induced cell death and apoptosis. Meanwhile, BD was able to upregulate protein levels of Nrf2 and its downstream genes NQO1 and γ-GCS through inducing Nrf2 nuclear translocation, enhancing protein stability, and inhibiting ubiquitination. It was also found that BD-induced activation of the Nrf2/ARE pathway was regulated by PI3K, MEK1/2, PKC, and PERK kinases. Collectively, BD is a novel activator of Nrf2/ARE pathway, and is verified to be a potential preventive agent against oxidative stress-induced damage in human lung tissues.

Three new C21 pregnane steroids, chonemorphols A–C (1, 3, and 4), 11 new C21 steroidal glycosides, chonemorphosides A–K (2 and 5–14), and 11 known compounds (15–25) were obtained from the vines and leaves of Chonemorpha megacalyx Pierre. Their structures were established using extensive spectroscopic data. The X-ray crystallographic data of 1 and 3 permitted definition of their absolute configurations. Notably, 1 and 2 possessed an uncommon 6/5/6/5/5-fused steroidal ring system. Compound 7 displayed significant cytotoxicity against several cancer cell lines with IC50 values of 2.0–3.6 μM.

Background Oxidative stress contributes to the pathogenesis of many human diseases. Cinnamon is a worldwide used spice, dietary supplement and traditional medicine, and is used for the therapy of oxidative stress related diseases. A well-established concept is that the functions of cinnamon preventing oxidative stress-induced diseases are attributed to the occurrence of cinnamaldehyde and its analogues. Hypothesis In our continuous searching of natural molecules with antioxidant capacity, we have found that cinnamaldehyde and its analogues in cinnamon are weak inhibitors of oxidative stress, and thus we speculate that there are novel and/or potent molecules inhibiting oxidative stress in cinnamon. Study design and methods A systemic phytochemical investigation of cinnamon using column chromatography was performed to identify the chemical constituents of cinnamon, and then their capacity of inhibiting oxidative stress and action of mechanism targeting Nrf2 pathway were investigated using diverse bioassay, including NAD(P)H: quinone reductase (QR) assay, immunoblot analysis, luciferase reporter gene assay, immunofluorescence and flow cytometry. Results Cinnamon improved the intracellular antioxidant capacity. A systemic phytochemical investigation of cinnamon gave the isolation of twenty-two chemical ingredients. The purified constituents were tested for their potential inhibitory effects against oxidative stress. Besides cinnamaldehyde analogues, a lignan pinoresinol (PRO) and a flavonol (-)-(2R,3R)-5,7-dimethoxy-3′, 4′-methylenedioxy-flavan-3-ol (MFO) were firstly identified to be inhibitors of oxidative stress. Further study indicated that PRO and MFO activated Nrf2-mediated antioxidant response, and protected human lung epithelial cells against sodium arsenite [As(III)]-induced oxidative insults. Conclusion The lignan PRO and the flavonoid MFO are two novel Nrf2 activators protecting tissues against oxidative insults, and these two constituents support the application of cinnamon as an agent against oxidative stress related diseases.

To observe the clinical efficacy of allogeneic peripheral blood stem cell transplantation（allo-HSCT） on the treatment of adult acute leukemia patients, moreover, to establish and evaluate a Logistic model to predict the risk of relapse in adult acute leukemia patients after allo-HSCT.The clinical data of 145 adult acute leukemia patients treated by peripheral blood stem cell transplantation in the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2019 was enrolled and analyzed retrospectively. Complications and survival of patients were observed. The relationship between patients' age, diagnosis, leukocyte count at onset, risk stratification, time of diagnosis to transplantation, HCT-CI, minimal residual disease pre-transplantation, donor-recipient sex relationship, HLA match degree, prophylaxis of graft versus host disease(GVHD), donor age, number of transfused mononuclear cells, CD34 positive cells, engraftment time, acute and chronic GVHD, CMV, EBV infection, and hemorrhagic cystitis and recurrence after transplantation were analyzed by logistic regression. Relapse prediction model was established and evaluated according to the results.Among 145 acute leukemia patients, 81 with acute myeloid leukemia, 64 with acute lymphocytic leukemia, 18 with EBV infection, 2 with post-transplant lymphoproliferative disorder(PTLD), 85 with CMV, 26 with hemorrhagic cystitis, 65 patients developed acute GVHD, 51 patients developed chronic GVHD and 45 patients relapsed. The overall survival （OS） rates in one and three years were 86.4% and 61.8%, and the progress-free survival （PFS） rates in one and three years were 67.5% and 62.4%, respectively. There were significant differences in OS and PFS between relapsed and non-relapsed patients, as well as AML and ALL patients. Univariate analysis revealed that patient's age, risk stratification, time to transplantation, HCT-CI index, ATG based GVHD prophylaxis, minimal residual disease pre-transplantation, GVHD prophylaxis, and acute and chronic GVHD were associated with the relapse of disease, multivariate logistic regression analysis showed that pre-transplantation minimal residual disease showed positively correlation with relapse of the disease, while chronic GVHD showed negatively correlation.The relapse rate of adult acute leukemia patients treated with allo-HSCT in our hospital is 31.0%, and OS of AML patients is better than ALL patients'. OS of relapsed patients is significantly lower than non-relapsed patients'. Pre-transplantation minimal residual disease is a risk factor of relapse. The risk of relapse is reduced in patients with chronic GVHD.异基因外周血造血干细胞移植治疗成人急性白血病疗效及移植后复发风险预测模型的建立.观察成人急性白血病异基因外周血造血干细胞移植的临床疗效，并建立预测急性白血病移植后复发风险的Logistics模型.选取西安交通大学第一附属医院2010年1月至2019年12月收治的行异基因外周血造血干细胞移植的成人急性白血病患者145例及其供者的临床资料，观察移植后并发症及生存情况；通过多因素Logistics回归分析患者年龄、诊断、起病时白细胞数、危险度分层、移植前微小残留病灶、诊断到移植的时间、HCT-CI、供受者性别关系、HLA配型相合程度、移植物抗宿主病（GVHD）预防方案、供者年龄、输注单个核细胞及CD34+细胞数、造血重建时间、有无急慢性GVHD、CMV及EBV感染、出血性膀胱炎与移植后复发的关系；依据多因素分析的结果建立预测成人急性白血病移植后复发风险的模型，并进行评价.145例急性白血病患者中，急性髓系白血病（AML）81例,急性淋巴细胞白血病（ALL）64例，18例合并有EBV感染，其中2例合并移植后淋巴细胞增殖性疾病，85例合并CMV血症，26例合并出血性膀胱炎症，65例并发急性GVHD，51例并发慢性GVHD，共计45例复发。移植后1、3年OS率分别为86.4%和61.8%，移植后1、3年PFS率分别为67.5%和62.4%。急性髓系白血病与急性淋巴细胞白血病患者移植后OS及PFS存在统计学差异。未复发患者与复发患者OS及PFS存在统计学差异。单因素分析结果显示，患者年龄、危险度分层、诊断到移植的时间、HCT-CI指数、移植前微小残留病灶、GVHD预防方案中是否含有抗人胸腺细胞免疫球蛋白、移植后急慢性GVHD与移植后复发相关，纳入多因素Logistics回归分析，结果显示，移植前残留病灶与复发呈正相关，移植后慢性GVHD与复发呈负相关.成人急性白血病异基因外周血造血干细胞移植后复发率为31.0%，AML患者移植后长期生存率优于ALL患者,移植后复发患者长期生存率显著低于未复发患者。移植前微小残留病灶阳性是移植后复发的高危因素，移植后合并慢性GVHD的患者复发风险降低.

Ethnopharmacological relevance The flower buds of Tussilago farfara L. (Abbreviated as FTF) were widely used in traditional Chinese medicine (TCM) to treat respiratory diseases, including asthma, dry throat, great thirst, turbid saliva, stinky pus, and coughs caused by various causes. Aim of study The aim of study is to explore the efficiency of FTF in vitro and in vivo for the treatment of lung inflammation, and to illustrate the possible mechanisms of FTF in treating inflammation-related respiratory diseases targeting NOD-like receptor 3 (NLRP3) inflammasome, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear transcription factor-κB (NF-κB). Methods Lung inflammation model in vivo was induced by exposure of mice to cigarette smoke (CS) for two weeks. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), inflammatory factors, and histology in lung tissues were investigated in presence or absence of ethanol extract of the flower buds of T. farfara L. (FTF-EtOH). In the cell-based models, nitric oxide (NO) assay, flow cytometry assay, enzyme-linked immunosorbent assay (Elisa), and glutathione (GSH) assay were used to explore the anti-inflammatory and anti-oxidant effects of FTF-EtOH. Possible anti-inflammatory mechanisms of FTF targeting NLRP3 inflammasome, Nrf2, and NF-κB have been determined using western blot, quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), immunofluorescence assay, nuclear and cytoplasmic extraction, and ubiqutination assay. Results FTF-EtOH suppressed CS-induced overproduction of inflammatory factors [e.g., tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)], and upregulation of the content of intracellular MDA in the lung homogenate of mice. In cell-based models, FTF-EtOH reduced the lipopolysaccharide (LPS)-induced overproduction of inflammatory factors, and attenuated the CS extract-induced overgeneration of reactive oxygen species (ROS). Furthermore, FTF-EtOH up-regulated Nrf2 and its downstream genes through enhancing the stability of Nrf2 protein, and inhibited the activation of NF-κB and NLRP3 inflammasome, which have been confirmed by detecting the protein levels in the mouse model. Conclusions FTF-EtOH effectively attenuated lung inflammation in vitro and in vivo. The protection of FTF-EtOH against inflammation was produced by activation of Nrf2 and inhibitions of NF-κB and NLRP3 inflammasome. These datas definitely support the ethnopharmacological use of FTF as an anti-inflammatory drug for treating respiratory diseases in TCM.

To analyze the risk factors affecting hemorrhagic cystitis(HC) after allogeneic hematopoietic stem cell transplantation(allo-HSCT).The clinical data of 153 patients underwent allogeneic hematopoietic stem cell transplantation in the First Affiliated Hospital of Xi'an Jiaotong University from January 2010 to December 2018 were selected and retrospectively analyzed. The incidence, median time and treatment outcome of HC should be observed. Multivariate analysis was used to observe the risk factors of HC in patients, including sex, age, diagnosis, disease status before transplantation, transplantation type, ATG and CTX in the pretreatment scheme, stem cell source, neutrophil and platelet implantation time; CMV, EBV and BKV infection, and acute graft-versus-host disease(aGVHD).Among 153 patients underwent allogeneic hematopoietic stem cell transplantation, 25 (16.34%) patients had HC, the median occurance time was 31 days, all patients achieved complete remission after treatment, no bladder irritation and bladder contracture were left. The results of univariate and multivariate Logistic regression analysis showed that the type of transplantation, ATG, CMV viremia before treatment, aGVHD (r=1.036, 3.234, 3.298 and 2.817, respectively) were the independent risk factors of HC.The urinary BKV detections in the patients with HC are positive, mainly occured during the period from day +13 to days +56. HLA haplotype, pretreatment including ATG, and CMV viremia, and aGVHD are the independent risk factors for HC after allo-HSCT.异基因造血干细胞移植后并发出血性膀胱炎的危险因素分析.分析异基因造血干细胞移植（allo-HSCT）后并发出血性膀胱炎（HC）的危险因素.回顾性分析2010年1月-2018年12月于西安交通大学第一附属医院行allo-HSCT的153例患者的临床资料。观察HC的发生率、发生中位时间及治疗转归。利用多因素分析观察患者性别、年龄、诊断、移植前疾病状态、移植类型、预处理方案中是否含有ATG、预处理方案中是否含有CTX、干细胞来源、中性粒细胞植入时间、血小板植入时间、CMV感染、EBV感染、BKV感染、急性移植物抗宿主病（aGVHD）是否为发生HC的高危因素.153例allo-HSCT患者中，25例发生HC，发生率为16.34%，发生的中位时间为31 d，治疗后全部好转，无1例遗留膀胱刺激症状及膀胱挛缩 。经单因素和多因素Logistic回归分析，结果显示，移植类型、预处理中含ATG、CMV血症以及aGVHD 4项因素（R值分别为1.036、3.234、3.298、2.817）是HC的独立危险因素.HC患者尿BKV检测均为阳性,主要发生在移植后13-56 d。 HLA配型半相合、含ATG的预处理方案、CMV血症及aGVHD是allo-HSCT后发生HC的独立危险因素.

Eight new lignans, dracomolphin A-E (1-8), together with eight known lignans (9-16) were isolated from the aerial part of Dracocephalum moldavica. The structures of the isolated compounds were established based on NMR and HRESIMS data. Dracomolphin A (1-4) was elucidated as a lignan possessed a 5-membered ketal ring formed between C-8' and C-3, C-4. The two stereogenic centers rendered dracomolphin A as a mixture of two diastereomeric pairs of enantiomers (1-4). All of the four isomers were separated successfully by using chiral HPLC and their stereochemical features were determined by CD spectra. Bioactivity screening revealed that compounds 1-4, 6, 7, 12, 15 and 16 were potential Nrf2 transcriptional activators. Dracomolphin E (8) reduced cell viability of lung cancer NCI-H292 cells associated with apoptosis.

Ethnopharmacological relevance Thesium chinense Turcz. has been used to treat mastitis, pulmonitis, tonsillitis, iaryngopharyngitis and upper respiratory tract infections in the indigenous medicine of China for a long history. Presently, several pharmaceutics prepared by this medical herb have been clinically used for the therapy of infectious diseases. Aim of the review This review aims to comprehensively summarize the current researches on the ethnomedical, phytochemical and pharmacological aspects of T. chinense, and discuss their possible opportunities for the future research. Materials and methods Extensive database searches, including Web of Science, SciFinder, Google Scholar and China Knowledge Resource Integrated, were performed using keywords such as ‘Thesium chinense’, ‘Bai Rui Cao’, and their chemical constituents. In addition, local classic herbal literature on ethnopharmacology and relevant textbooks were consulted to provide a comprehensive survey of this ethnomedicine. Results Thirty four chemical constituents, including flavonoids, alkaloids, and terpenoids, have been identified from T. chinense. Of which, flavonoids are the predominant and characteristic constituents. The crude extracts, the purified constituents, and commercial available pharmaceutics have displayed diverse in vitro and in vivo pharmacological functions (e.g. anti-inflammation, antimicrobial activity, analgesic effect, hepaprotection), and are particularly useful as a potential therapeutic agent against inflammation-related diseases. Conclusions T. chinense is an important ethnomedical medicine and possesses a satisfying effect for treating inflammation, microbial infection, and upper respiratory diseases. It has received plenty of researches on its phytochemical and pharmacological aspects since 1970s. These findings definitely establish the link between chemical composition and pharmacological application, and support the ethnomedical use of T. chinense in the indigenous medicine of China. However, chemical composition of this plant and the molecular mechanisms of purified constituents have not been comprehensively investigated, and thus the trace constituents and the therapeutic targets of bioactive constituents deserve a further exploration. Collectively, the researchers should pay more attention to a better understanding and application of this ethnomedical plant.

Environmental toxicant- and oxidant-induced [e.g., cigarette smoke (CS)] respiratory oxidative stress and inflammatory response play a vital role in the onset and progression of COPD. The nuclear factor erythroid 2-related factor 2 (Nrf2) represents an important mechanism for regulating intracellular oxidative stress and inflammatory response and is a promising target for developing agents against COPD. Herein, a bioactivity-guided purification of goldenberry (whole fruits of

Osteogenesis induced by mechanical stretch is the main factor affecting the orthodontic treatment. Due to the masticatory force transmitted by tooth, human periodontal ligament fibroblasts (hPDLFs) could enhance osteogenic differentiation, and remolding of periodontal. Therefore, in-depth study of hPDLFs osteogenic differentiation and its regulatory mechanism is helpful in the understanding of periodontal remolding promoted by orthodontic force. In the present study, 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide showed that miR-140 inhibited the viability of hPDLFs cells. Moreover, we provided evidence that miR-140 inhibited alkaline phosphatase (ALP) activity, Alizarin Red S (ARS) activity and the mRNA expression of osteogenesis associated genes, including ALP, runt-related transcription factor 2, collagen 1, and osteocalcin. Besides, double-luciferase reporter result demonstrated that Ras homolog gene family, member A (RhoA) was a downstream target gene of miR-140, and by inhibiting RhoA-transcriptional co-activator with PDZ-binding motif (TAZ) signaling pathway, miR-140 suppressed the osteogenesis differentiation of hPDLFs. Furthermore, overexpression of RhoA or TAZ promoted ALP activity, ARS activity and osteogenesis associated genes expression, which was inhibited by miR-140 mimics. Our findings not only provided a possible mechanism of hPDLFs osteogenic differentiation but also proposed the clinical application of miR-140 inhibitor to target RhoA-TAZ for orthodontic treatment.

Ethnopharmacology relevance Rhizome of Ligusticum chuanxiong Hort. (Abbreviated as LC) is a frequently prescribed component in plenty of traditional Chinese medicine (TCM) formulas which are used to treat diabetic nephropathy (DN). The aims of the present study are to investigate the protective effect of the ethanol extract of LC rhizome (EEL) against DN in vivo, evaluate its potential mechanism, and find the evidence supporting its enthopharmacological use as an anti-DN agent. Materials and methods Hepa 1c1c7 murine hepatoma cells, human breast carcinoma MDA-MB-231 cells, human renal glomerular endothelial cells (HRGEC), and RAW 264.7 murine macrophages were adopted to test the effects of EEL and its active constituents on inhibitions of oxidative stress and inflammation in vitro. A streptozotocin (STZ) -induced DN C57BL/6 mice model was established and used to investigate the preventive effect of EEL against DN in vivo. Results EEL demonstrated potential inhibitory effects against oxidative stress and inflammation in vitro. Using a STZ-induced DN mice model, it has been found that EEL treatment significantly prevented STZ-induced increases of urine production, urinary albumin excretion (UAE) and urine albumin-to-creatinine ratio (UACR), and markedly attenuated STZ-induced renal damages (e.g. glomerulosclerosis and fibrosis). The predominant bioactive constituents, Z-ligustilide (LGT), ferulic acid (FA), and tetramethylpyrazine (TMP), were inhibitors of oxidative stress and inflammation through acting with Nrf2 and NF-κB pathways. Conclusions EEL attenuates structural and functional damages of kidney in STZ-induced DN model in vivo, which might be related to the functions of EEL on inhibitions of oxidative stress and inflammation. These finding definitely supports the ethnopharmacological use of LC as an anti-DN agent.

Alisol B-23-acetate (AB23A), a tetracyclic triterpenoid isolated from the rhizome of Alisma orientale, has been reported to exert anti-proliferative activities in human colon, ovarian and gastric cancer cells. However, the anti-cancer effect of this compound on human lung cancer cells has not yet been thoroughly elucidated. In the present study, we investigated the effects of AB23A on the cell viability and apoptosis in human lung cancer A549 and NCI-H292 cells. The results indicated that AB23A inhibited the growth of A549 and NCI-H292 cells in dose- and time-dependent manner, however, there was only weak cytotoxicity on normal bronchial epithelial cells. The induction of apoptosis by AB23A was demonstrated by DAPI and annexin-V-FITC/PI staining. Further investigation revealed that AB23A decreased mitochondrial membrane potential (MMP) and up regulated reactive oxygen species (ROS) level. Meanwhile, the increased Bax/Bcl-2 ratio, activated caspase-3, caspase-9 and PARP were observed. In addition, AB23A increased the release of cytochrome c from mitochondria and the translocation of apoptotic inducing factor (AIF) into nuclei. Taken together, these results indicated that AB23A induced apoptosis by activating the intrinsic pathway, and suggested that AB23A can be used as a potential modulating agent in lung cancer.

Continuous overproduction of reactive oxygen species (ROS), termed as oxidative stress, plays a crucial role in the onset and progression of many human diseases. Activation of nuclear transcription factor erythroid 2-related factor (Nrf2) by small molecules could eliminate ROS, and thus block the pathogenesis of oxidative stress-induced diseases. In this study, a natural flavonoid library was established and tested for their potential Nrf2 inducing effects. Based on QR inducing effect of flavonoids, their structure-activity relationship (SAR) on Nrf2 induction was summarized, and twenty flavonoids were firstly identified to be potential activators of Nrf2-mediated defensive response. Then, 7-O-methylbiochanin A (7-MBA) was further investigated for its capability on the Nrf2 activation and prevention against oxidative insults in human lung epithelial cells. Further studies indicated that 7-MBA activated Nrf2 signaling pathway and protected human lung epithelial Beas-2B cells against sodium arsenite [As(III)]-induced cytotoxicity in an Nrf2-dependent manner. Activation of Nrf2 by 7-MBA upregulated intracellular antioxidant capacity, which was produced by enhancement of Nrf2 stabilization, blockage of Nrf2 ubiquitination, as well as Nrf2 phosphorylation by mitogen-activated protein kinase (MAPK), protein kinase C (PKC), protein kinase R-like endoplasmic reticulum kinase (PERK), and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). Taken together, 7-MBA is a novel isoflavone-type Nrf2 activator displaying potential preventive effect against oxidative damages in human lung epithelial cells.

Excess intracellular reactive oxygen species (ROS) production is a significant causative factor of many diseases, exemplified by vascular diseases. Mitochondria are a major source of endogenous ROS, which simultaneously induce mitochondrial dysfunction. Nuclear factor-erythroid 2-related factor 2 (Nrf2) represents an important intracellular defense system that protects cells against oxidative insults caused by ROS. Therefore, molecules with the capacities of inducing Nrf2, and preventing mitochondrial dysfunction can inhibit cell apoptosis, and thus are potential drug candidates for the therapy of ROS-mediated vascular diseases. Homoeriodictyol (HE), previously isolated from Viscum articulatum Burm, has been found to be an Nrf2 inducer. In the present study, we investigated its protection on ROS-induced endothelial cell injury using a H2O2-induced human umbilical vein EA.hy926 cell oxidative insult model. Our results indicated that HE activated Nrf2 signaling pathway and protected cells against H2O2-induced cell damage. HE alleviated H2O2-induced loss of mitochondrial membrane potential (MMP), blocked the releases of cytochrome C and apoptosis inducing factor (AIF) from mitochondria, and thus inhibited mitochondria-mediated cell apoptosis. Furthermore, HE inhibited H2O2-induced changes of apoptosis-related proteins, such as Bcl-2, Bcl-xL, caspases -3, -9 and PARP. Further study demonstrated that the protection of HE against H2O2-induced endothelial cell damage was Nrf2-dependent. Collectively, our observations suggest that HE is capable of counteracting oxidative insults in endothelial cells, and has a potential to be a therapeutic agent against ROS-mediated vascular diseases.

Caged-polyprenylated xanthonoids represent a rare class of natural products. This type of compounds is mainly isolated from Genus Garcinia. Phytochemical studies on the leaves and twigs of Garcinia oligantha led to the isolation of four new caged-polyprenylated xanthonoids, oliganthone CF (1-4), and two new simple xanthones (5-6), oliganthaxanthone D and oliganthaxanthone E. Eight known other polyprenylated xanthones (7-14) including five caged-polyprenylated xanthonoids (7-11) were also isolated. Their structures were elucidated based on the analyses of extensive spectroscopic data. All the isolated compounds except for 5, 6 and 14 showed cell viability reducing effect against human lung cancer A549 cells. Compounds 1-3 were proved to be potential apoptosis inducing agents.

OBJECTIVE. The purpose of this study was to investigate whether diffusion kurtosis imaging (DKI) is useful for predicting upgrades in Gleason score (GS) in biopsy-proven prostate cancer with a GS of 6. MATERIALS AND METHODS. A total of 46 patients with biopsy-proven GS 6 prostate cancer, 3-T DWI results, and surgical pathologic results were retrospectively included in the study. DWI data were postprocessed with monoexponential and DK models to quantify the apparent diffusion coefficient (ADC), apparent diffusion for gaussian distribution (Dapp), and apparent kurtosis coefficient (Kapp). The volume of the lesions, prostate-specific antigen (PSA) level, and diffusion variables (ADCmin, Dappmin, Kappmax, ADCmean, Dappmean, and Kappmean) were evaluated. PSA and DKI were combined as a parameter in a logistic regression model. The utility of these parameters in predicting an upgrade in GS was analyzed with ROC regression. RESULTS. The rate of GS upgrade was 50.0% (23/46). The GS upgrade group had significantly ...

To investigate whether machine learning-based analysis of MR radiomics can help improve the performance PI-RADS v2 in clinically relevant prostate cancer (PCa). This IRB-approved study included 54 patients with PCa undergoing multi-parametric (mp) MRI before prostatectomy. Imaging analysis was performed on 54 tumours, 47 normal peripheral (PZ) and 48 normal transitional (TZ) zone based on histological-radiological correlation. Mp-MRI was scored via PI-RADS, and quantified by measuring radiomic features. Predictive model was developed using a novel support vector machine trained with: (i) radiomics, (ii) PI-RADS scores, (iii) radiomics and PI-RADS scores. Paired comparison was made via ROC analysis. For PCa versus normal TZ, the model trained with radiomics had a significantly higher area under the ROC curve (Az) (0.955 [95% CI 0.923–0.976]) than PI-RADS (Az: 0.878 [0.834–0.914], p

Oxidative stress is closely associated to the onset and progression of many human diseases. Activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway using naturally-derived molecules is an efficient strategy for alleviating the intracellular oxidative insults, and thus blocking the pathogenesis of oxidative stress-induced diseases. In the present study, a naturally-derived isopimarane-type diterpenoid sphaeropsidin C (SC) was identified to be an activator of Nrf2/ARE signaling pathway. Our data indicated that SC was able to stimulate Nrf2-mediated defensive system through promoting Nrf2 translocation, inhibiting Nrf2 ubiquitination, and enhancing Nrf2 stability in normal human lung epithelial Beas-2B cells. Furthermore, SC-induced Nrf2 activation required the involvement of protein kinases, exemplified by protein kinase C (PKC), protein kinase R-like endoplasmic reticulum kinase (PERK), and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). It alleviated sodium arsenite [As(III)]-induced intracellular oxidative stress in an Nrf2-dependent manner. These results suggested that SC displayed potential application for the prevention and therapy against oxidative stress-induced diseases. Moreover, isopimarane-type diterpenoid represents a promising skeleton for developing Nrf2 activators.

To investigate the effect of decitabine on proliferation and apoptosis of multiple myeloma KMS-18 cells and its possible mechanism.CCK-8 was used to detect cell proliferation, flow cytometry was used to detect the changes of apoptosis, real-time quantitative PCR was used to detect the expression of P53 gene mRNA in myeloma KMS-18 cells, and MSP assay was used to detect the methylation status of P53 gene promoter.The proliferation inhibition and apoptosis of KMS-18 cells significantly increased after treatment by decitabine (P＜0.05). The expression of P53 mRNA increased in KMS-18 cells after treatment of decitabine (P＜0.05). The methylation status of the P53 gene promoter in KMS-18 cells could be partially reversed by decitabine.Decitabine can inhibit the proliferation of KMS-18 cells and induce their apoptosis, its mechanism ralates with partially reversing the methylation of P53 gene promoter in KMS-18 cells.地西他滨诱导多发性骨髓瘤KMS-18细胞凋亡及其机制研究.研究地西他滨对多发性骨髓瘤KMS-18细胞的抑制增殖及诱导凋亡的作用及其可能机制.采用CCK-8法检测不同浓度地西他滨干预后KMS-18细胞增殖抑制率；流式细胞术检测地西他滨干预的细胞凋亡变化；实时荧光定量PCR检测地西他滨干预前、后P53基因mRNA表达水平；MSP法检测地西他滨干预前后P53基因启动子甲基化的状态.地西他滨干预后KMS-18细胞增殖抑制率呈时间及浓度依赖性增加（r =0.9790，P＜0.05）；干预后细胞凋亡率显著增加，差异有统计学意义（P＜0.05）；地西他滨干预后KMS-18细胞P53基因mRNA表达增加（P＜0.05）；地西他滨可以部分逆转KMS-18细胞P53基因启动子甲基化状态.地西他滨可抑制细胞增殖，并诱导其凋亡，与其部分逆转KMS-18细胞P53基因启动子甲基化有关.

One new pentanortriterpenoid, 23,24,25,26,27-pentanorlanost-7,9(11)-dien-3β,22-diol (

The nuclear factor erythroid 2-related factor 2 (Nrf2) plays a crucial role in regulating the intracellular oxidative stress, and thus activation of Nrf2 by nature-derived molecules effectively alleviates the pathological process of oxidative stress-induced chronic diseases. The isopentenyl-substituted flavonoid norartocarpin (NOR) induced the activity of NAD(P)H: quinone reductase (QR), implying that it might be a potential Nrf2 activator. Further studies indicated that NOR upregulated the protein levels of Nrf2 and its downstream genes, NAD(P)H quinone oxidoreductase 1 (NQO1), and γ-glutamyl cysteine synthetase (GCLM) through facilitating the nuclear translocation of Nrf2 and enhancing Nrf2 protein stability. NOR-induced activation of Nrf2 pathway was associated with multiple upstream kinases, including mitogen-activated protein kinase (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), protein kinase C (PKC), and protein kinase R-like endoplasmic reticulum kinase (PERK). Moreover, NOR protected human lung epithelial Beas-2B cells against sodium arsenite [As(III)]-induced cytotoxicity in an Nrf2-dependent manner. Collectively, NOR was firstly identified to be an Nrf2 activator, which demonstrated the capability of preventing oxidative insults in human lung epithelial cells.

Cinnamaldehyde analogues are a class of chemical substances originated from derivatization of cinnamaldehyde, and are structurally characterized by the presence of cinnamoyl moiety. Due to the presence of highly reactive α,α-unsaturated carbonyl pharmacophore (Michael acceptor) in their structures, these molecules are apt to react with some enzymes and/or receptors as electrophiles, and consequently produce diverse therapeutically relevant pharmacological functions. Naturally occurring molecules, trans-cinnamaldehyde (CA), 2-benzoyloxycinnam-aldehyde (2-BCA), and 2- hydroxycinnamaldehyde (2-HCA) are representatives of this group, and have attracted lots of interest for their bioactivities, especially the anti-cancer and anti-inflammatory properties. Owing to the potential of CA, 2-BCA, and 2-HCA as therapeutic agents, researches on chemical syntheses and modifications have been carried out to gain chemical entities with potent bioactivity and favorable druggability. This review summarizes the progress on phytochemical and pharmacological aspects of natural cinnamaldehyde analogues, illustrate the representative of synthetic molecules with potent bioactivity, and discuss their potential as therapeutic agents.

Due to drug resistance and side effects, the development of novel therapeutics for the treatment of lung cancer is still in an urgent need. Morusin, a naturally occurring prenylated flavonoid isolated from the root bark of Morus alba, has been reported to be a promising candidate for cancer treatment including lung cancer. This study aimed to validate the anti-cancer effects of morusin in human non-small cell lung cancer (NSCLC) cell lines A549 and NCI–H292. The results indicated that morusin had growth inhibitory, pro-apoptotic and pro-autophagic effects on A549 and NCI–H292 cells. The induction of apoptosis was characterized by chromatin condensation and PARP cleavage. Mitochondrial membrane potential (MMP) loss, cytochrome c release, Bax/Bcl-2 dysregulation, and caspase-3 cleavage were also observed, indicating a mitochondria-dependent apoptosis was induced by morusin. A pro-autophagic effect was demonstrated by the increased level of LC3-Ⅱ and decreased level of SQSTM1/p62. Furthermore, morusin inhibited PI3K/Akt signaling and activated JNK, ERK pathways as indicated by the alteration in the ratio of phosphorylation level over total protein expression level. A PI3K/Akt inhibitor (LY294002), a JNK inhibitor (SP600125) and a MEK/ERK inhibitor (U0126) contributed to the determination that these pathways were involved in both apoptosis and autophagy induced by morusin. Moreover, morusin treatment strikingly enhanced intracellular ROS level, an ROS scavenger NAC blocked cell death and changes of Akt, JNK and ERK induced by morusin.

To explore the characteristics and diagnostic values of bone marrow cell morphology and immunophenotyping in lymphoma cell leukemia patients.Data of the bone marrow cell morphology and immunophenotyping of 35 patients with lymphoma cell leukemia admitted from January 2012 to January 2017 were analyzed retrospectively, and the value of bone marrow cell morphology and immunophenotype in the diagnosis of lymphoma cell leukemia was evaluated.Bone marrow cell morphological examination showed the typical lymphoma cells in all the patients. The expression of differentiation antigens in lymphoma cell leukemia was consistent with that of original pathological diagnosis. In T-cell lymphoma cell leukemia, the expression of CD7, CD3, CD2, CD5, CD11b, CD34, and HLA-DR were present predominantly, among them the CD7 was the most sensitive antigen and its positive expression rate was 69.2%. In B-cell lymphoma cell leukemia, the expression of CD19, CD20, CD22, CD79a, Skappa, and early antigen HLA-DR were observed predominantly, among them the positive expression rate of CD19 was the highest (89.5%). Out of 35 cases, 28 cases showed that the percentage of lymphoma cells on bone marrow smears was consistent with that of bone marrow immunophenotyping, and 7 cases showed that the percentage of lymphoma cells between bone marrow smears and immunophenotyping differed by more than 1.5-fold.Bone marrow slides combined with immunophenotyping may be helpful for judging lymphoma cell marrow invasion and making early diagnosis of lymphoma cell leukemia.

One new 9,10-seco-abietane derivative, crotontomentosin A (1), four new abietane-type diterpenoids, crotontomentosins B-E (2-5), one new ent-halimane-type diterpenoid, crotontomentosin F (6), along with five known diterpenoids (7-11) and one known sesquiterpenoid (12) were obtained from the twigs and leaves of Croton caudatus Geisel. var. tomentosus Hook. The structures of the compounds were established on the basis of extensive spectroscopic data. Compounds 1-4 and 11 exhibited moderate to weak inhibitory activity against the proliferation of the Hela, Hep G2, MDA-MB-231, or A549 cell lines selectively.

Three new tetramic acid derivatives, tolypocladenols A1, A2, and B (1-3), a new pyridone alkaloid, tolypyridone A (4), and a new coumarin derivative, 3,8-dihydroxy-4-(4-hydroxyphenyl)-6-methylcoumarin (5), together with four known compounds (6-9) were isolated from the endolichenic fungus Tolypocladium cylindrosporum, which inhabits the lichen Lethariella zahlbruckneri. Structures of these compounds were determined by comprehensive analysis of spectroscopic data and single-crystal X-ray diffraction determination. Bioassay of the isolated compounds found that pyridoxatin (7) was cytotoxic to human cancer cells by induction of G0/G1 cell cycle arrest and apoptosis.

Three new metabolites, asperfumigatin (1), isochaetominine (10), and 8'-O-methylasterric acid (21), together with nineteen known compounds, were obtained from the culture of Aspergillus fumigatus, an endophytic fungus from the Chinese liverwort Heteroscyphus tener (Steph.) Schiffn. Their structures were established by extensive analysis of the spectroscopic data. The absolute configurations of 1 and 10 were determined by analysis of their respective CD spectra. Cytotoxicity of these isolates against four human cancer cell lines was also determined.

The purpose of this study was to compare histogram analysis of apparent diffusion coefficient (ADC) and R2* for differentiating low-grade from high-grade clear cell renal cell carcinoma (RCC).Forty-six patients with pathologically confirmed clear cell RCC underwent preoperative BOLD and DWI MRI of the kidneys. ADCs based on the entire tumor volume were calculated with b value combinations of 0 and 800 s/mm(2). ROI-based R2* was calculated with eight TE combinations of 6.7-22.8 milliseconds. Histogram analysis of tumor ADCs and R2* values was performed to obtain mean; median; width; and fifth, 10th, 90th, and 95th percentiles and histogram inhomogeneity, kurtosis, and skewness for all lesions.Thirty-three low-grade and 13 high-grade clear cell RCCs were found at pathologic examination. The TNM classification and tumor volume of clear cell RCC significantly correlated with histogram ADC and R2* (ρ = -0.317 to 0.506; p0.05). High-grade clear cell RCC had significantly lower mean, median, and 10th percentile ADCs but higher inhomogeneity and median R2* than low-grade clear cell RCC (all p0.05). Compared with other histogram ADC and R2* indexes, 10th percentile ADC had the highest accuracy (91.3%) in discriminating low- from high-grade clear cell RCC. R2* in discriminating hemorrhage was achieved with a threshold of 68.95 Hz. At this threshold, high-grade clear cell RCC had a significantly higher prevalence of intratumor hemorrhage (high-grade, 76.9%; low-grade, 45.4%; p0.05) and larger hemorrhagic area than low-grade clear cell RCC (high-grade, 34.9% ± 31.6%; low-grade, 8.9 ± 16.8%; p0.05).A close relation was found between MRI indexes and pathologic findings. Histogram analysis of ADC and R2* allows differentiation of low- from high-grade clear cell RCC with high accuracy.

To investigate diagnostic efficiency of DWI using entire-tumor histogram analysis in differentiating the low-grade (LG) prostate cancer (PCa) from intermediate–high-grade (HG) PCa in comparison with conventional ROI-based measurement. DW images (b of 0–1400 s/mm2) from 126 pathology-confirmed PCa (diameter >0.5 cm) in 110 patients were retrospectively collected and processed by mono-exponential model. The measurement of tumor apparent diffusion coefficients (ADCs) was performed with using histogram-based and ROI-based approach, respectively. The diagnostic ability of ADCs from two methods for differentiating LG-PCa (Gleason score, GS ≤6) from HG-PCa (GS > 6) was determined by ROC regression, and compared by McNemar’s test. There were 49 LG-tumor and 77 HG-tumor at pathologic findings. Histogram-based ADCs (mean, median, 10th and 90th) and ROI-based ADCs (mean) showed dominant relationships with ordinal GS of Pca (ρ = −0.225 to −0.406, p

Two new 2-arylbenzofuran derivatives, moracinfurol A and B (1–2), and ten known compounds (3–12) were isolated from the leaves of Morus alba. Their structures were determined on the basis of spectroscopic analysis including 1D, 2D NMR and HR-ESI-MS. All of the 2-arylbenzofuran derivatives were evaluated for cytotoxicity against A549 cells. Some cytotoxic 2-arylbenzofuran derivatives might induce autophagy characterized by the accumulation of LC-3 Ⅱ.

To study the expression of DNMT3b gene in myeloma RPMI8226 cells and its biological significance.The activity of DNA methyltransferase was detected by ELISA, and the expression of DNMT3b in RPMI8226 cells was analyzed by semi-quantitative RT-PCR and real-time fluorescent quantitative PCR. The proliferation and expression of DNMT3b gene in RPMI8226 cells intervened with capecitabine for 24 hours were detected.The activity of DNMT and expression of DNMT3b in RPMI 8226 cells increased. The proliferation of RPMI8226 cells was inhibited, and the apoptosis occurred in RPMI 8226 cells intervened with capecitabine for 24 hours. The expression level of DNMT3b gene was decreased after being intervened with capecitabine for 24 hours.The expression level of DNMT3b in myeloma RPMI 8226 cells increase, and capecitabine can inhibit the proliferation of RPMI 8226 and induce apoptosis by inhibiting the expression of DNMT3b gene. Therefore, DNMT3b is expected to be a new target for myeloma therapy.

Oxidative stress and inflammation undoubtedly contribute to the pathogenesis of many human diseases. The nuclear transcription factor erythroid 2-related factor (Nrf2) and the nuclear factor κB (NF-κB) play central roles in regulation of oxidative stress and inflammation and thus are targets for developing agents against oxidative stress- and inflammation-related diseases. Our previous study indicated that the EtOH extract of Litsea garrettii protected human bronchial epithelial cells against oxidative insult via the activation of Nrf2. In the present study, a systemic phytochemical investigation of L. garrettii led to the isolation of twenty-one chemical ingredients, which were further evaluated for their inhibitions on oxidative stress and inflammation using NAD(P)H:quinone reductase (QR) assay and nitric oxide (NO) production assay. Of these ingredients, 3-methoxy-5-pentyl-phenol (MPP, 5) was identified as an Nrf2 activator and an NF-κB inhibitor. Further studies demonstrated the following: (i) MPP upregulated the protein levels of Nrf2, NAD(P)H:quinone oxidoreductase 1 (NQO1), and glutamate-cysteine ligase regulatory subunit (GCLM); enhanced the nuclear translocation and stabilization of Nrf2; and inhibited arsenic [As(III)]-induced oxidative insult in normal human lung epithelial Beas-2B cells. And (ii) MPP suppressed the nuclear translocation of NF-κB p65 subunit; inhibited the lipopolysaccharide- (LPS-) stimulated increases of NF-κB p65 subunit, COX-2, iNOS, TNF-α, and IL-1β; and blocked the LPS-induced biodegrade of IκB-α in RAW 264.7 murine macrophages. Taken together, MPP displayed potential preventive effects against inflammation- and oxidative stress-related diseases.

Human lung tissue, directly exposed to the environmental oxidants and toxicants, is apt to be harmed to bring about acute or chronic oxidative insults. The nuclear factor erythroid 2-related factor 2 (Nrf2) represents a central cellular defense mechanism, and is a target for developing agents against oxidative insult-induced human lung diseases. Our previous study found that the EtOH extract of Cinnamomum chartophyllum protected human bronchial epithelial cells against oxidative insults via Nrf2 activation. In this study, a systemic phytochemical investigation of the aerial parts of C. chartophyllum led to the isolation of thirty chemical constituents, which were further evaluated for their Nrf2 inducing potential using NAD(P)H: quinone reductase (QR) assay. Among these purified constituents, a sesquiterpenoid bearing α, β-unsaturated ketone group, 3S-(+)-9-oxonerolidol (NLD), and a diphenyl sharing phenolic groups, 3, 3′, 4, 4′-tetrahydroxydiphenyl (THD) significantly activated Nrf2 and its downstream genes, NAD(P)H quinone oxidoreductase 1 (NQO-1), and γ-glutamyl cysteine synthetase (γ-GCS), and enhanced the nuclear translocation and stabilization of Nrf2 in human lung epithelial cells. Importantly, NLD and THD had no toxicities under the Nrf2 inducing doses. THD also demonstrated a potential of interrupting Nrf2-Keap1 protein–protein interaction (PPI). Furthermore, NLD and THD protected human lung epithelial cells against sodium arsenite [As(III)]-induced cytotoxicity. Taken together, we conclude that NLD and THD are two novel Nrf2 activators with potential application of preventing acute and chronic oxidative insults in human lung tissue., Graphical abstract fx1, Highlights • The chemical compositions of Cinnamomum chartophyllum are firstly identified. • The active ingredients supporting the biological functions of C. chartophyllum are verified. • NLD and THD are identified to be Nrf2 activators for the first time. • NLD and THD protect human lung epithelial cells against As(III)-induced cytotoxicity.

To investigate the risk factors and therapeutic outcome of acute graft versus host disease (aGVHD) in patients with acute leukemia after haploidentical peripheral hematopoietic stem cell transplantation.The clinical data of 19 cases of acute leukemia underwent haploidentical hematopoietic stem cell transplanttion during January 2010 and December 2010 were retrospectively analyzed. The effects of patients sex, donor-recipient sex difference, donor age, conditioning regimen, dosage of anti-thymocyte globulin(ATG), mononuclear cell and CD34Intestinal aGVHD occurred in 5 cases with 1 case at stage II 3 cases at stage III and 1 case at stage IV on the 7th, 22th, 27th, 70th and 154th day after transplantation, respectively. Single factor analysis showed that the patient's sex, donor-recipient sex difference, donor age, dosage of ATG, mononuclear cell and CD34Conditioning regimen of haploidentical peipheral hematopoieitc stem cell transplantaion has effects on the intestinal aGVHD, which needs to be confirmed by further research.

Chemical investigation of the root bark of Morus alba led to the isolation of a new flavone, dioxycudraflavone A (1) and a new 2-arylbenzofuran, 5-hydroxyethyl moracin M (2), together with seven known compounds namely sanggenon V (3), morusin (4), morusignin L (5), licoflavone C (6), moracin C (7), alfafuran (8) and mulberrofuran G (9). The structure elucidation of these compounds was based on analyses of spectroscopic data including 1D, 2D NMR and HR-ESI-MS. All compounds were evaluated for the α-glucosidase inhibitory and cytotoxic activities. Compounds 2–4, 8 and 9 exhibited strong α-glucosidase inhibitory activities with IC50 less than 10 μM, while only 4 and 9 showed moderate cytotoxic effects against lung cancer cells.

Background China is one of 22 countries with a high tuberculosis (TB) burden in the world. Healthcare workers (HCWs) have a high risk of contracting Mycobacterium tuberculosis infection due to insufficient infection control practices. We conducted a cross-sectional study to explore the prevalence of TB and its associated risk factors among HCWs in Chinese TB facilities. Methods Two hundred and forty-one TB facilities employing a total of 9663 HCWs were selected from 12 provinces in China to represent healthcare settings at the provincial, prefectural, and county levels. Structured questionnaires were used to collect information on TB infection control practices and HCWs in those facilities. Data was double entered into EpiData 3.1; TB prevalence and associated risk factors were analyzed using SPSS 21.0 with bivariate and multivariate regression models. Results The results showed that 71 HCWs had been diagnosed with TB, accounting for a prevalence of 760/100 000. The multivariate analysis showed that associated risk factors included belonging to the age group of 51 years and above (aOR: 6.17, 95% CI: 1.35–28.28), being a nurse (aOR = 3.09, 95% CI: 1.15–8.32), implementation of 0–9 items of management measures (aOR = 2.57, 95% CI: 1.37–4.80), and implementation of 0–1 items of ventilation measures (aOR = 2.42, 95% CI: 1.31–4.47). Conclusion This was the first national large sampling survey on TB prevalence among HCWs in China. It was found that the implementation of TB infection control practices in some facilities was poor. The TB prevalence in HCWs was higher than that in the general population. Therefore, TB infection control practices in Chinese medical facilities should be strengthened. Electronic supplementary material The online version of this article (10.1186/s40249-018-0407-6) contains supplementary material, which is available to authorized users.

Ethnopharmacological relevance The calyxes and fruits of Physalis alkekengi L. var. franchetii (Mast.) Makino (Physalis Calyx seu Fructus), have been widely used in traditional and indigenous Chinese medicines for the therapy of cough, excessive phlegm, pharyngitis, sore throat, dysuria, pemphigus, eczema, and jaundice with a long history. Aim of the review The present review aims to achieve a comprehensive and up-to-date investigation in ethnomedical uses, phytochemistry, pharmacology, and toxicity of P. alkekengi var. franchetii, particularly its calyxes and fruits. Through analysis of these findings, evidences supporting their applications in ethnomedicines are illustrated. Possible perspectives and opportunities for the future research are analyzed to highlight the gaps in our knowledge that deserves further investigation. Material and Methods Information on P. alkekengi var. franchetii was collected via electronic search of major scientific databases (e.g. Web of Science, SciFinder, Google Scholar, Pubmed, Elsevier, SpringerLink, Wiley online and China Knowledge Resource Integrated) for publications on this medicinal plant. Information was also obtained from local classic herbal literature on ethnopharmacology. Results About 124 chemical ingredients have been characterized from different parts of this plant. Steroids (particularly physalins) and flavonoids are the major characteristic and bioactive constituents. The crude extracts and the isolated compounds have demonstrated various in vitro and in vivo pharmacological functions, such as anti-inflammation, inhibition of tumor cell proliferation, antimicrobial activity, diuretic effect, anti-diabetes, anti-asthma, immunomodulation, and anti-oxidation. Conclusions P. alkekengi var. franchetii is an important medicinal plant for the ethnomedical therapy of microbial infection, inflammation, and respiratory diseases (e.g. cough, excessive phlegm, pharyngitis). Phytochemical and pharmacological investigations of this plant definitely increased in the past half century. The chemical profiles, including ingredients and structures, have been adequately verified. Modern pharmacological studies supported its uses in the traditional and folk medicines, however, the molecular mechanisms of purified compounds remained unclear and were worth of further exploration. Therefore, the researchers should be paid more attention to a better utilization of this plant.

One new diketopiperazine heterodimer, asperazine A (1), and eight known compounds, asperazine (2), cyclo(d-Phe-l-Trp) (3), cyclo(l-Trp-l-Trp) (4), 4-(hydroxymethyl)-5,6-dihydro-pyran-2-one (5), walterolactone A (6), and campyrones A-C (7-9), were isolated from an endophytic fungus Aspergillus niger. Their structures were determined unequivocally on the basis of extensive spectroscopic data analysis. This is the first report of the presence of compound 3 as a natural product. Cytotoxicity test against human cancer cell lines PC3, A2780, K562, MBA-MD-231, and NCI-H1688 revealed that compounds 1 and 2 had weak activities.

Cells and tissues counteract insults from exogenous or endogenous carcinogens through the expression of genes encoding antioxidants and phase II detoxifying enzymes regulated by antioxidant response element promoter regions. Nuclear factor-erythroid 2-related factor 2 plays a key role in regulating the antioxidant response elements-target gene expression. Hence, the Nrf2/ARE pathway represents a vital cellular defense mechanism against damage caused by oxidative stress and xenobiotics, and is recognized as a potential molecular target for discovering chemopreventive agents. Using a stable antioxidant response element luciferase reporter cell line derived from human breast cancer MDA-MB-231 cells combined with a 96-well high-throughput screening system, we have identified a series of plant extracts from the family Lauraceae that harbor Nrf2-inducing effects. These extracts, including Litsea garrettii (ZK-08), Cinnamomum chartophyllum (ZK-02), C. mollifolium (ZK-04), C. camphora var. linaloolifera (ZK-05), and C. burmannii (ZK-10), promoted nuclear translocation of Nrf2, enhanced protein expression of Nrf2 and its target genes, and augmented intracellular glutathione levels. Cytoprotective activity of these extracts against two electrophilic toxicants, sodium arsenite and H2O2, was investigated. Treatment of human bronchial epithelial cells with extracts of ZK-02, ZK-05, and ZK-10 significantly improved cell survival in response to sodium arsenite and H2O2, while ZK-08 showed a protective effect against only H2O2. Importantly, their protective effects against insults from both sodium arsenite and H2O2 were Nrf2-dependent. Therefore, our data provide evidence that the selected plants from the family Lauraceae are potential sources for chemopreventive agents targeting the Nrf2/ARE pathway.

Aims: To explore efficacy and side effects of intrapleural or intraperitoneal lobaplatin for treating patients with malignant pleural or peritoneal effusions. Methods: Patients in Jiangsu Cancer Hospital and Research Institute with cytologically confirmed solid tumors complicated with malignant pleural effusion or ascites were enrolled into this study. Lobaplatin (20-30 mg/m 2 ) was intrapleurally or intraperitoneally infused for patients with malignant pleural effusion or ascites. Results: From 2012 to 2013, intrapleural or intraperitonea lobaplatin was administered for patients with colorectal or uterus cancer who were previous treated for malignant pleural effusion or ascites. Partial response was achieved for them. Main side effects were nausea/vomiting, and bone marrow suppression. No treatment related deaths occurred. Conclusion: Intrapleural or intraperitoneal infusion of lobaplatin is a safe treatment for patients with malignant pleural effusion or ascites, and the treatment efficacy is encouraging. most commonly associated to ascites are ovarian (37%), pancreatic biliary (21%), gastric (18%), oesophageal (4%), colorectal (4%), and breast (3%) (Ayantunde, 2007). Intracavitary administration of anticancer drugs is a common method for treating malignant pleural effusion or ascites. Platinums are the common used drugs, cisplatin and carboplatin have been reported (Bogholo et al., 1991; Esposito et al., 1994). We hypothesize that intrapleural lobaplatin is also an effective option for patients with malignant pleural effusion or ascites.

Dehydrobruceine B (DHB) is a quassinoid isolated from Brucea javanica. We have shown previously that DHB induced apoptosis on two kinds of lung cancer cell lines, A549 and NCI-H292. In the present study, we investigated the interactions of DHB and cisplatin (CDDP) on apoptotic-related cancer cell death. Synergistic effects on cell proliferation and apoptosis were observed when A549 cells were treated with DHB plus CDDP. DHB combined CDDP exposure increased depolarization of mitochondrial membrane potential (MMP) and release of cytochrome c from mitochondria into the cytoplasm. The combination treatment also enhanced protein expression of Bax, reduced the protein levels of Bcl-xL and Bcl-2, and increased the cleavage of caspase-3, caspase-9 and poly (ADP-ribose) polymerase (PARP). These results indicated that DHB sensitized A549 cells to cisplatin by regulating the mitochondrial apoptotic pathway. High constitutive expression of Nrf2 was found in A549 cells, which enhance the resistance of cancer cells to chemotherapeutic agents including cisplatin. DHB reduced the protein levels of Nrf2 and its target genes, which may contribute to the increase of intracellular ROS level, consequently, induced mitochondria apoptosis. These results generated a rationale for further investigation of DHB combined with CDDP as a potential therapeutic strategy in lung cancer.

To investigate the effects of different hemapheresis procedures on the components of hematopoietic stem cells(HSCs) collected from helathy donors.twelve donors were underwent stem cell collection from January 2015 to August 2016, and the stem cells were randomly colleted by AutoPBSC procedure of COBE spectra and MNC procedure of the Spectra Optia blood cell separator, the mononuclear cells, CD34The circulating blood volume, the acquisition time and dosage of anticoagulants were not significantly different between two procedures. The volume and the mononuclear cell count collected by AutoPBSC procedure were lower than those by the MNC procedure, while the CD34Compared with MNC procedure of the Spectra Optia blood cell separator, the number of collected stem cells, lymphocytes and platelets are higher by using AutoPBSC procedure of the COBE spectra blood cell separator.

Filopodia are dynamic membrane extensions generated by F-actin bundling and are involved in cancer cell migration, invasion and metastasis. Fascin is the crucial actin-bundling protein in filopodia, with phosphorylation at fascin serine 39 being well characterized to regulate fascin-mediated actin bundling in filopodia. However, increasing evidence indicates that fascin is phosphorylated at a number of sites. Whether phosphorylation at other sites also regulates fascin function is unknown. In this study, we show that four potential phosphorylation sites in fascin, specifically tyrosine 23, serine 38, serine 39 and serine 274, regulate cell behavior and filopodia formation in esophageal squamous cancer cells. Expression of non-phosphorylatable mutations at each of the four sites promoted anchorage-independent growth, cell motility and filopodia formation, whereas phosphomimetic mutations at each of these sites inhibited these cell behaviors, implying that fascin function in esophageal squamous cancer is regulated by fascin phosphorylation at multiple sites. Furthermore, phosphorylation at S38 and S39 cooperatively regulated cell behavior and filopodia formation, with dual dephosphorylation at both S38 and S39 residues maximally enhancing cell proliferation, migration and filopodia formation, and phosphorylation at any of the two phosphorylatable sites resulting in reduced enhancement. Taken together, our results reveal that phosphorylation at fascin amino acids Y23, S38, S39 and S274, in combination, downregulates the extent of anchorage-independent growth, cell migration and filopodia formation in esophageal squamous cancer cells.

To investigate the effect of hepatovirus B(HBV) infection on the hematopoietic stem cell collection and implantment in lymphoma patients received autologous peripheral hematopoietic blood stem cells transplantation.Clinical data of 40 lymphoma patients who received autologous peripheral hematopoietic blood stem cell transplantation between January 2006 and October 2014 was analyzed retrospectively. Among 40 patients with lymphoma 8 patients combined with HBV infection were prophylacticly given nucleoside analogues and 32 patients without HBV infection. The counts of mononuclear cells(MNC) and CD34 positive cells were collected and the hematopoietic reconstitution as well as overall survival rates and progress-free survival rates were detected and counted between patients with or without HBV infection.The counts of MNC and CD34 positive cells in all patients were standard, and there was no significant difference between patients with or without HBV infection. HBV wasn't reactivated among the 8 patients with HBV infection. The 1, 3 and 5 years' overall survival rates and progress-free survival rates of patients with HBV infection were 100%, 85.7%, 57.1% and 100%, 80%, 53%, respectively and the 1,3 and 5 years' overall survival rates and progress-free survival rates of patients without HBV infection were 100%, 88.9%, 82.1% and 90%, 90%, 90%, respectively.HBV infection may have no effect on the collection of stem cells and hematopoietic reconstitution. Prophylactic use of nucleoside analogues can effectively prevent the hepatitis B virus reactivation, moreover had no effect on the collection and hematopoietic reconstitution.

To explore the autophagy of RPMI8226 cells induced by As(2)O(3) and its possible mechanisms.RPMI8226 was incubated with different concentration of As(2)O(3) for different time, and the inhibiting rate was calculated by MTT method. The autophagic rate of RPMI8226 cells incubated with different concentration of As(2)O(3) was determined by FACS. The change of cells ultrastructure was observed by transmission electron microsopy (TEM). After incubation with different concentration of As(2)O(3), the expression of Beclin-1 on RPMI8226 was detected by RT-PCR and Western blot.Different concentration of As(2)O(3) could significantly inhibit the proliferation of RPMI8226 cells (P0.05), and the inhibitory effect was in dose- and time-dependent way in a certain range. the autophagic rate increased with the increasing of drug concentration and prolonging of action time (P0.05). TEM results revealed a typical autophagosome in RPMI-8226 cell treated by As(2)O(3) for 48 hours. Beclin-1 was up-regulated in RPMI 8226 cells when treated with different concentration of As(2)O(3) for 48h (P0.05).As(2)O(3) can induce autophagy of RPMI8226 cells, and the mechanism may be associated with the upregulation of Beclin-1.

// Yu-Dong Zhang 1 , Jing Wang 2 , Chen-Jiang Wu 1 , Mei-Ling Bao 3 , Hai Li 3 , Xiao-Ning Wang 1 , Jun Tao 4 and Hai-Bin Shi 1 1 Department of Radiology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China 2 Center for Medical Device Evaluation, CFDA, Beijing, China 3 Department of Pathology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China 4 Department of Urology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China Correspondence to: Hai-Bin Shi, email: // Keywords : prostate cancer; biochemical recurrence; MRI; radical prostatectomy; support vector machine Received : April 27, 2016 Accepted : August 11, 2016 Published : August 15, 2016 Abstract Preoperatively predict the probability of Prostate cancer (PCa) biochemical recurrence (BCR) is of definite clinical relevance. The purpose of this study was to develop an imaging-based approach in the prediction of 3-years BCR through a novel support vector machine (SVM) classification. We collected clinicopathologic and MR imaging datasets in 205 patients pathologically confirmed PCa after radical prostatectomy. Univariable and multivariable analyses were used to assess the association between MR findings and 3-years BCR, and modeled the imaging variables and follow-up data to predict 3-year PCa BCR using SVM analysis. The performance of SVM was compared with conventional Logistic regression (LR) and D’Amico risk stratification scheme by area under the receiver operating characteristic curve (Az) analysis. We found that SVM had significantly higher Az (0.959 vs. 0.886; p = 0.007), sensitivity (93.3% vs. 83.3%; p = 0.025), specificity (91.7% vs. 77.2%; p = 0.009) and accuracy (92.2% vs. 79.0%; p = 0.006) than LR analysis. Performance of popularized D’Amico scheme was effectively improved by adding MRI-derived variables (Az: 0.970 vs. 0.859, p < 0.001; sensitivity: 91.7% vs. 86.7%, p = 0.031; specificity: 94.5% vs. 78.6%, p = 0.001; and accuracy: 93.7% vs. 81.0%, p = 0.007). Additionally, beside pathological Gleason score (hazard ratio [HR] = 1.560, p = 0.008), surgical-T3b (HR = 4.525, p < 0.001) and positive surgical margin (HR = 1.314, p = 0.007), apparent diffusion coefficient (HR = 0.149, p = 0.035) was the only independent imaging predictor of time to PSA failure. Therefore, We concluded that imaging-based approach using SVM was superior to LR analysis in predicting PCa outcome. Adding MR variables improved the performance of D’Amico scheme.

To assess a magnetic resonance imaging (MRI)-based nomogram in the prediction of prostate cancer (PCa) biochemical recurrence (BCR) within 3 years after prostatectomy.Between 2009 and 2013, 205 patients with biopsy-confirmed PCa had MRI before prostatectomy. BCR was defined as a PSA failure (0.2 ng/ml) after prostatectomy. MR features (cancer location, diameter, apparent diffusion coefficients [ADCs], PI-RADS v2 score, dynamic contrast-enhanced [DCE] type, and MR T-stage) were retrospectively evaluated for predicting 3-year BCR based on partial least square regression analysis. Second, imaging features were added to a popularized D'Amico and CAPRA scheme to determine imaging contribution to published nomograms. Lastly, a multivariable Cox regression analysis was employed to determine the independent risk factors of time to BCR.Three-year BCR rate (median follow-up of 44.9 mo) was 25.4% (52/205). The area under receiver operating characteristic (ROC) curve (Az) for MR nomogram (0.909, 95% confidence interval [CI]: 0.861-0.944) was higher than popularized D'Amico (0.793, 95% CI: 0.731-0.846, P = 0.001) and CAPRA (0.809, 95% CI: 0.748-0.860, P = 0.001). The performance of D'Amico (Az: 0.901, 95% CI: 0.852-0.938, P0.001) and CAPRA (Az: 0.894, 95% CI: 0.843-0.932, P = 0.004) was significantly improved by adding MR findings. Tumor ADCs (hazard ratio [HR] = 1.747; P = 0.011), PI-RADS score (HR = 4.123; P = 0.039), pathological Gleason score (HR = 3.701; P = 0.004), and surgical-T3b (HR = 6.341; P0.001) were independently associated with time to BCR.Multiparametric MRI, when converted into a prognostic nomogram, can predict the clinical outcome in patients with PCa after prostatectomy.3 J. Magn. Reson. Imaging 2017;45:586-596.