68Ga-RM2 PET-MRI versus MRI alone for evaluation of patients with biochemical recurrence of prostate cancer: a single-centre, single-arm, phase 2/3 imaging trial.

BACKGROUND: National Comprehensive Cancer Network guidelines include prostate-specific membrane antigen (PSMA)-targeted PET for detection of biochemical recurrence of prostate cancer. However, targeting a single tumour characteristic might not be sufficient to reflect the full extent of disease. Gastrin releasing peptide receptors (GRPR) have been shown to be overexpressed in prostate cancer. In this study, we aimed to evaluate the diagnostic performance of the GRPR-targeting radiopharmaceutical 68Ga-RM2 in patients with biochemical recurrence of prostate cancer. METHODS: This single-centre, single-arm, phase 2/3 trial was done at Stanford University (USA). Adult patients (aged ≥18 years) with biochemical recurrence of prostate cancer, a Karnofsky performance status of 50 or higher, increasing prostate-specific antigen concentration 0·2 ng/mL or more after prostatectomy or 2 ng/mL or more above nadir after radiotherapy, and non-contributory conventional imaging (negative CT or MRI, and bone scan) were eligible. All participants underwent 68Ga-RM2 PET-MRI. The primary outcome was the proportion of patients with PET-positive findings on 68Ga-RM2 PET-MRI compared with MRI alone after initial therapy, at a per-patient and per-lesion level. The primary outcome would be considered met if at least 30% of patients had one or more lesions detected by 68Ga-RM2 PET-MRI and the detection by 68Ga-RM2 PET-MRI was significantly greater than for MRI. Each PET scan was interpreted by three independent masked readers using a standardised evaluation criteria. This study is registered with ClinicalTrials.gov, NCT02624518, and is complete. FINDINGS: Between Dec 12, 2015, and July 27, 2021, 209 men were screened for eligibility, of whom 100 were included in analyses. Median follow-up was 49·3 months (IQR 36·7-59·2). The primary endpoint was met; 68Ga-RM2 PET-MRI was positive in 69 (69%) patients and MRI alone was positive in 40 (40%) patients (p<0·0001). In the per-lesion analysis 68Ga-RM2 PET-MRI showed significantly higher detection rates than MRI alone (143 vs 96 lesions; p<0·0001). No grade 1 or worse events were reported. INTERPRETATION: 68Ga-RM2 PET-MRI showed better diagnostic performance than MRI alone in patients with biochemical recurrence of prostate cancer. Further prospective comparative studies with PSMA-targeted PET are needed to gain a better understanding of GRPR and PSMA expression patterns in these patients. FUNDING: The US Department of Defense.

Rhizoma Atractylodis Macrocephalae-Assessing the influence of herbal processing methods and improved effects on functional dyspepsia.

Background: The unique pharmaceutical methods for the processing of botanical drugs according to the theory of traditional Chinese medicine (TCM) affect clinical syndrome differentiation and treatment. The objective of this study was to comprehensively elucidate the principles and mechanisms of an herbal processing method by investigating the alterations in the metabolites of Rhizoma Atractylodis Macrocephalae (AMR) processed by Aurantii Fructus Immaturus (AFI) decoction and to determine how these changes enhance the efficacy of aqueous extracts in treating functional dyspepsia (FD). Methods: A qualitative analysis of AMR before and after processing was conducted using UPLC-Q-TOF-MS/MS, and HPLC was employed for quantitative analysis. A predictive analysis was then conducted using a network analysis strategy to establish a botanical drug-metabolite-target-disease (BMTD) network and a protein-protein interaction (PPI) network, and the predictions were validated using an FD rat model. Results: A total of 127 metabolites were identified in the processed AMR (PAMR), and substantial changes were observed in 8 metabolites of PAMR after processing, as revealed by the quantitative analysis. The enhanced aqueous extracts of processed AMR (PAMR) demonstrate improved efficacy in treating FD, which indicates that this processing method enhances the anti-inflammatory properties and promotes gastric motility by modulating DRD2, SCF, and c-kit. However, this enhancement comes at the cost of attenuating the regulation of motilin (MTL), gastrin (GAS), acetylcholine (Ach), and acetylcholinesterase (AchE). Conclusion: Through this series of investigations, we aimed to unravel the factors influencing the efficacy of this herbal formulation in improving FD in clinical settings.

68Ga-PSMA-11 PET/MRI in Patients with Newly Diagnosed Intermediate- or High-Risk Prostate Adenocarcinoma: PET Findings Correlate with Outcomes After Definitive Treatment.

Prostate-specific membrane antigen (PSMA) PET offers an accuracy superior to other imaging modalities in initial staging of prostate cancer and is more likely to affect management. We examined the prognostic value of 68Ga-PSMA-11 uptake in the primary lesion and presence of metastatic disease on PET in newly diagnosed prostate cancer patients before initial therapy. Methods: In a prospective study from April 2016 to December 2020, 68Ga-PSMA-11 PET/MRI was performed in men with a new diagnosis of intermediate- or high-grade prostate cancer who were candidates for prostatectomy. Patients were followed up after initial therapy for up to 5 y. We examined the Kendall correlation between PET (intense uptake in the primary lesion and presence of metastatic disease) and clinical and pathologic findings (grade group, extraprostatic extension, nodal involvement) relevant for risk stratification, and examined the relationship between PET findings and outcome using Kaplan-Meier analysis. Results: Seventy-three men (age, 64.0 ± 6.3 y) were imaged. Seventy-two had focal uptake in the prostate, and in 20 (27%) PSMA-avid metastatic disease was identified. Uptake correlated with grade group and prostate-specific antigen (PSA). Presence of PSMA metastasis correlated with grade group and pathologic nodal stage. PSMA PET had higher per-patient positivity than nodal dissection in patients with only 5-15 nodes removed (8/41 vs. 3/41) but lower positivity if more than 15 nodes were removed (13/21 vs. 10/21). High uptake in the primary lesion (SUVmax > 12.5, P = 0.008) and presence of PSMA metastasis (P = 0.013) were associated with biochemical failure, and corresponding hazard ratios for recurrence within 2 y (4.93 and 3.95, respectively) were similar to or higher than other clinicopathologic prognostic factors. Conclusion: 68Ga-PSMA-11 PET can risk-stratify patients with intermediate- or high-grade prostate cancer before prostatectomy based on degree of uptake in the prostate and presence of metastatic disease.

Cytochrome P450 3A5 polymorphism affects the metabolism of sorafenib and its toxicity for hepatocellular carcinoma cells in vitro.

OBJECTIVE: Cytochrome P450 3A5 (CYP3A5) is a highly polymorphic gene and the encoded protein variants differ in catalytic activity, leading to inter-individual variation in metabolic ability. The aim of the current study was to investigate the effects of seven allelic variants on the ability of CYP3A5 to metabolize sorafenib in vitro and further explore the impacts of CYP3A5 polymorphism on the proliferation and apoptosis of hepatocellular carcinoma cell line (HepG2) induced by sorafenib. METHODS: Wild-type and variant CYP3A5 enzymes were expressed in Spodoptera frugiperda insect cells using a baculovirus dual-expression system, and protein expression was checked by western blot. The enzymes were incubated with sorafenib at 37°C for 30 min, and formation of the major metabolite sorafenib N-oxide was assayed using ultra-performance liquid chromatography and tandem mass spectrometry. Intrinsic clearance values (Vmax/Km) were calculated for each enzyme. Additionally, recombinant HepG2 cells transfecting with CYP3A5 variants were used to investigate the effects of sorafenib on the proliferation of HepG2 cells. RESULTS: Intrinsic clearance of the six variants CYP3A5*2, CYP3A5*3A, CYP3A5*3C, CYP3A5*4, CYP3A5*5, and CYP3A5*7 was 26.41-71.04% of the wild-type (CYP3A5*1) value. In contrast, the clearance value of the variant CYP3A5*6 was significantly higher (174.74%). Additionally, the decreased ATP levels and cell viability and the increased cell apoptosis in HepG2 cells transfected with CYP3A5*2, CYP3A5*3A, CYP3A5*3C, CYP3A5*4, CYP3A5*5, and CYP3A5*7 were observed, whereas, the increased ATP levels and cell viability and the reduced cell apoptosis in HepG2 cells transfected with CYP3A5*6 were also investigated when compared to CYP3A5*1. CONCLUSION: Our results suggest that CYP3A5 polymorphism influences sorafenib metabolism and pharmacotherapeutic effect in hepatic carcinomas. These data may help explain differential response to drug therapy for hepatocellular carcinoma, and they support the need for individualized treatment.

Two new dammarane-type triterpenoids from the green walnut husks of Juglans mandshurica Maxim.

Two new dammarane-type triterpenoids, dammar-3α,12(R),20(S)-triol-12,32(R);20,32-diepoxy-25-methy-25-en-tridecacyclic ether (1) and (23E)-12ß,20(R),25(S),26-tetrahydroxydammar-23-en-3-one (2) were isolated from the green walnut husks of Juglans mandshurica Maxim together with six known compounds. Their structures were elucidated through extensive spectroscopic analyses and by comparison with the literature, and the cytotoxic activities of these compounds were evaluated.

A systematic review and meta-analysis of clinical research on treating angina pectoris of coronary heart disease with traditional Chinese medicine to promote blood circulation and remove blood stasis.

BACKGROUND: Research has shown that traditional Chinese medicine (TCM) can achieve good results in the treatment of angina pectoris. In this study, we aimed to explore the therapeutic effect of TCM in the treatment of angina pectoris of coronary heart disease (CHD) through a literature search and meta-analysis. METHODS: The PubMed, Embase, CBM (China Biology Medicine) Web of Science databases were searched for studies on the treatment of angina pectoris of CHD with TCM. Inclusion and exclusion criteria were applied, and high-quality articles published from 2010.1 to 2021.8 were selected. The RevMan 5.3.5 software was used to evaluate the therapeutic effect indicators of TCM. RESULTS: Nine studies involving 824 patients were included in the meta-analysis, and the overall risk of literature bias was low. The results of meta-analysis showed that compared with conventional Western medicine, TCM + conventional Western medicine had a better efficacy indicators of angina pectoris using the fixed-effects model [odd rate (OR) =3.20, 95% confidence interval (CI): (2.09, 4.90), Z=5.35, P<0.00001]. The frequency of angina pectoris was measured by random-effects model, and the statistical results were [standard mean difference (SMD) =-1.85, 95% CI: (-2.29, -1.41), Z=8.22, P<0.00001]. The adverse events was measured by fixed-effects model, and the statistical results were [OR =0.48, 95% CI: (0.21, 1.08), Z=1.78, P=0.08]. DISCUSSION: The application of TCM in the treatment of angina pectoris of CHD can improve the therapeutic effect, reduce the frequency of angina pectoris, shorten the attack time, reduce serum total cholesterol, and improve the quality of life after treatment, but it has no obvious reducing effect on blood lipids.

Cytochrome P450 3A5 polymorphism affects the metabolism of sorafenib and its toxicity for hepatocellular carcinoma cells in vitro.

OBJECTIVE: Cytochrome P450 3A5 (CYP3A5) is a highly polymorphic gene and the encoded protein variants differ in catalytic activity, leading to inter-individual variation in metabolic ability. The aim of the current study was to investigate the effects of seven allelic variants on the ability of CYP3A5 to metabolize sorafenib in vitro and further explore the impacts of CYP3A5 polymorphism on the proliferation and apoptosis of hepatocellular carcinoma cell line (HepG2) induced by sorafenib. METHODS: Wild-type and variant CYP3A5 enzymes were expressed in Spodoptera frugiperda insect cells using a baculovirus dual-expression system, and protein expression was checked by western blot. The enzymes were incubated with sorafenib at 37°C for 30 min, and formation of the major metabolite sorafenib N-oxide was assayed using ultra-performance liquid chromatography and tandem mass spectrometry. Intrinsic clearance values (Vmax/Km) were calculated for each enzyme. Additionally, recombinant HepG2 cells transfecting with CYP3A5 variants were used to investigate the effects of sorafenib on the proliferation of HepG2 cells. RESULTS: Intrinsic clearance of the six variants CYP3A5*2, CYP3A5*3A, CYP3A5*3C, CYP3A5*4, CYP3A5*5, and CYP3A5*7 was 26.41-71.04% of the wild-type (CYP3A5*1) value. In contrast, the clearance value of the variant CYP3A5*6 was significantly higher (174.74%). Additionally, the decreased ATP levels and cell viability and the increased cell apoptosis in HepG2 cells transfected with CYP3A5*2, CYP3A5*3A, CYP3A5*3C, CYP3A5*4, CYP3A5*5, and CYP3A5*7 were observed, whereas, the increased ATP levels and cell viability and the reduced cell apoptosis in HepG2 cells transfected with CYP3A5*6 were also investigated when compared to CYP3A5*1. CONCLUSION: Our results suggest that CYP3A5 polymorphism influences sorafenib metabolism and pharmacotherapeutic effect in hepatic carcinomas. These data may help explain differential response to drug therapy for hepatocellular carcinoma, and they support the need for individualized treatment.

Components and Pharmacodynamical Mechanism of Yinfupian Based on Liquid Chromatography-Mass Spectrometry and Proteomics Analyses.

Objective: According to the treatment records of Yang deficiency syndrome (YDS) with characteristic decoction pieces of lateral root of Aconitum carmichaelii-Yinfupian (YF) in traditional Chinese medicine prepare school, known as "Jianchangbang". The aim of this study was to investigate differences in the composition and therapeutic mechanism of the unprocessed lateral root of Aconitum carmichaelii (ULRA) and its processed product (YF). Methods: Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and orthogonal partial least squares discriminant analysis method were used to determine and screen the main components of ULRA and YF. Changes in the histological structure and morphology of gonads in rats were observed using hematoxylin-eosin. Enzyme-linked immunosorbent assay was used to determine the contents of serum cyclic adenosine monophosphate and cyclic guanosine monophosphate in YDS rats treated with ULRA and YF. Tandem mass tag proteomics analysis was used to identify the differentially expressed proteins in YDS rats treated with ULRA and YF. Results: Both ULRA and YF exerted certain therapeutic effects on rats with YDS. They improved the gonadal morphology and increased the contents of serum cyclic adenosine monophosphate and cyclic guanosine monophosphate. After processing of ULRA into YF, the content of C19-diester-diterpenoid alkaloids decreased (converted into C19-monoester-diterpenoid alkaloids and C19-alkylol amine-diterpenoid alkaloids), whereas that of C20-diterpene alkaloids increased. Proteomics analysis showed that cytochrome P450 and aldehyde oxidase 3 (AOX3) were downregulated, whereas cathepsin G (CTSG) was upregulated in rats with YDS. Treatment with ULRA mainly downregulated the expression of α-actinin, fast skeletal troponin, creatine kinase, and myosin. Treatment with YF mainly upregulated the expression of mitochondrial ribosomal protein and mitochondrial inner membrane protein. Conclusion: ULRA and YF exerted good therapeutic effects on YDS; the main difference in components between these preparations was in C19-diterpenoid alkaloids. ULRA mainly acts on the muscle contraction-related proteins and is closely related to inflammation and myocardial injury. YF mainly acts on the mitochondrial proteins and is closely related to adenosine triphosphate energy metabolism.

Therapeutic effects and potential mechanism of dehydroevodiamine on N-methyl-N'-nitro-N-nitrosoguanidine-induced chronic atrophic gastritis.

BACKGROUNDS: Dehydroevodiamine (DHE) is a quinazoline alkaloid isolated from a Chinese herbal medicine, named Euodiae Fructus (Wu-Zhu-Yu in Chinese). This study aimed to investigate the therapeutic effects and potential mechanism of DHE on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced chronic atrophic gastritis (CAG) based on integrated approaches. METHODS: Therapeutic effects of DHE on serum biochemical indices and histopathology of gastric tissue in MNNG-induced CAG rats were analyzed. MNNG-induced GES-1 human gastric epithelial cell injury model was established. Cell viability and proliferation was quantified by a cell counting kit-8 assay. Cell morphology and mitochondrial membrane potential (MMP) were detected by a high content screening (HCS) assay. Cell migration and invasion were detected by a Transwell chamber. Moreover, UHPLC-Q-TOF/MS was performed to investigate the potential metabolites and signaling pathway affecting the protective effects of DHE on MNNG-induced cell migration and invasion of GES-1. Furthermore, in view of the key role of angiogenesis in the transformation of inflammation and cancer, this study explored relative mRNA and protein expression levels of HIF-1α-mediated VEGF pathway in vivo and in vitro by RT-PCR and Western Blotting, respectively. RESULTS: The results showed that the therapeutic effects of DHE on CAG rats were presented in down-regulation serum biochemical indices and alleviating histological damage of gastric tissue. Besides, DHE has an effect on increasing cell proliferation of GES-1 cells, ameliorating MNNG-induced gastric epithelial cell damage and mitochondrial dysfunction. In addition, DHE could inhibit MNNG induced migration and invasion of GES-1 cells. Cell metabolomics analyses showed that the protective effect of DHE on GES-1 cells is mainly associated with the regulation of inflammation metabolites and energy metabolism related pathways. It was found that DHE has a regulating effect on tumor angiogenesis and can inhibit the relative gene and protein expression of HIF-1α-mediated VEGF signaling pathway. CONCLUSIONS: The present work highlighted the role of DHE ameliorated gastric injury in MNNG-induced CAG rats in vivo and GES-1 cell migration in vitro by inhibiting HIF-1α/VEGF angiogenesis pathway. These results suggest that DHE may be the effective components of Euodiae Fructus, which provides a new agent for the treatment of CAG.

Relationship between Regular Green Tea Intake and Osteoporosis in Korean Postmenopausal Women: A Nationwide Study.

Mixed results have been reported regarding whether habitual tea intake affects bone health. This study investigated the relationship between green tea intake and bone mineral density (BMD) in postmenopausal Korean women. We used data from the Korean National Health and Nutrition Examination Surveys from 2008 to 2011 and divided the participants into three groups according to their frequency of green tea intake over the past 12 months. BMD of the lumbar spine, total femur, and femur neck was measured using dual-energy X-ray absorptiometry. The odds ratios (ORs) and 95% confidence intervals (CIs) of osteoporosis and osteopenia according to green tea consumption were analyzed. Participants who did not consume green tea or consumed less than one cup per day were more likely to have osteopenia of the lumbar spine or femur than those who consumed it once to three times a day (OR 1.81 and 1.85, 95% CI, 1.20-2.71; and 1.23-2.77). Moreover, ORs for osteoporosis were 1.91 (95% CI 1.13-3.23) and 1.82 (95% CI 1.09-3.05) in non-consumers and consumers who drank less than one cup per day, respectively, compared with the reference group. These results support that green tea consumption may have benefits on bone health.

Resorcylic Acid Lactones Produced by an Endophytic Penicillium ochrochloron Strain from Kadsura angustifolia.

Four new ß-resorcylic acid lactones, including penochrochlactone A (2: ), 4-O-desmethyl-aigialomycin B (4: ), and penochrochlactones C and D (5: and 6: ), two compounds isolated from a natural source for the first time, 5α, 6ß-acetonide-aigialomycin B (1: ) and penochrochlactone B (3: ), together with six known compounds, aigialomycin F (7: ), aigialomycins A, B, and D (8: -10: ), zeaenol (11: ), and oxozeaenol (12: ), were isolated from a mycelial solid culture of the endophytic fungus Penicillium ochrochloron SWUKD4.1850 from the medicinal plant Kadsura angustifolia by sequential purification over silica gel, Sephadex LH-20 column chromatography, and preparative HPLC. Their structures were elucidated by extensive spectroscopic analysis and chemical conversions. In addition, all the new compounds were evaluated for their cytotoxic and antibacterial activities in vitro. Penochrochlactone C (5: ) displayed moderate cytotoxicity against the HeLa tumor cell line with an IC50 value of 9.70 µM. In the antibacterial assays, compounds 4:  - 6: exhibited moderate activities against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa with MIC values between 9.7 and 32.0 µg/mL.

Network Pharmacology-Based Strategy for the Investigation of the Anti-Obesity Effects of an Ethanolic Extract of Zanthoxylum bungeanum Maxim.

Network pharmacology is considered as the next paradigm in drug discovery. In an era when obesity has become global epidemic, network pharmacology becomes an ideal tool to discover novel herbal-based therapeutics with effective anti-obesity effects. Zanthoxylum bungeanum Maxim (ZBM) is a medicinal herb. The mature pericarp of ZBM is used for disease treatments and as spice for cooking. Here, we used the network pharmacology approach to investigate whether ZBM possesses anti-obesity effects and reveal the underlying mechanism of action. We first built up drug-ingredient-gene symbol-disease network and protein-protein interaction network of the ZBM-related obesity targets, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. The results highlight apoptosis as a promising signaling pathway that mediates the anti-obesity effects of ZBM. Molecular docking also reveals quercetin, a compound in ZBM has the highest degree of connections in the compound-target network and has direct bindings with the apoptotic markers. Furthermore, the apoptotic effects of ZBM are further validated in 3T3-L1 adipocytes and in the high-fat diet-induced obesity mouse model. These findings not only suggest ZBM can be developed as potential anti-obesity therapeutics but also demonstrate the application of network pharmacology for the discovery of herbal-based therapeutics for disease treatments.

Effects of mung bean starch/guar gum-based edible emulsion coatings on the staling and safety of rice cakes.

Antimicrobial starch/gum-based edible emulsion coatings were developed to improve the storage stability of rice cakes by retarding starch retrogradation and inhibiting microbial growth. Rice cakes were coated with mung bean starch (MBS) and guar gum (GG) containing various concentrations of sunflower seed oil (SO). Among these, the (2 g MBS +0.75 g GG +1.5 g SO) / 100 g (optimum) decreased the hardness of rice cakes by 29 % and the crystallization rate (k) by 24 % compared with those of uncoated samples. The moisture loss in uncoated samples was markedly higher than that in the optimum blend-coated samples. Crystallinity analysis revealed the retarding effect of the developed coatings in starch retrogradation. Furthermore, adding 0.8 % (w/w) grapefruit seed extract to the optimum blend led to a distinct antimicrobial activity. Therefore, the newly developed edible coating was effective in maintaining the quality and safety of rice cakes.

Potential anti-diabetic isoprenoids and a long-chain δ-lactone from frangipani (Plumeria rubra).

A decoction of Plumeria rubra flowers has been used traditionally for the treatment of diabetes in China and Mexico. Chemical investigations on the bioactive constituents of these flowers led to the isolation of 30 compounds, including the four new compounds, one iridoiod (1), two triterpenoids (4, 5), and a long-chain δ-lactone (16). In addition, 26 known compounds (2, 3, 6-15, 17-30) are also reported. All of these compounds were identified on the basis of spectroscopic data interpretation and the absolute configurations of compound 4, 5, 16 were determined by Mosher's method. Compounds 1-4, 7, 8 and 16 showed moderate to significant inhibitory activities against α-glucosidase and protein tyrosine phosphatase 1B, with 4 having IC50 values of 19.45 µM and 0.21 µM, respectively.

α-Tetralone glycosides from the green walnut husks of Juglans mandshurica Maxim. and their cytotoxic activities.

Five new α-tetralone glycosides, juglanbiosides A-E (1-5), together with an α-tetralone derivative (15) and nine known 1,4-naphthoquinones (6-14) were isolated from the 95% EtOH extract of green walnut husks of Juglans mandshurica Maxim. Their structures were elucidated by comprehensive spectroscopic methods (1H, 13C NMR, DEPT, HSQC, HMBC, CD, HR-ESI-MS). In vitro cytotoxicities of all the isolated compounds were evaluated against BGC-823, HCT-15 and K562 cancer cell lines.[Formula: see text].

[Study on mechanism and method of membrane preparation and membrane process optimization based on molecular structure analysis of noneffective common macromolecules].

The molecular weight of the effective components of traditional Chinese medicine( TCM) is usually less than 1 000.However, " noneffective common macromolecules"( starch,pectin and other macromolecules commonly present in the water extract of TCM) generally have no physiological activity,which restricts the overall advantages of membrane technology to obtain small molecular pharmacodynamic substances,and such macromolecules are the main influence factor of membrane fouling. Therefore,in order to obtain the total pharmacological efficacy of TCM,based on the molecular structure analysis of noneffective common macromolecules,aimed at the key scientific problems in correlation between the molecular structure of noneffective common macromolecules and the pore structure of membrane material,and by referring to the material science theory and molecular simulation method,the correlations between noneffective common macromolecules' molecular structure-solution environment-membrane antagonism were investigated. Multidisciplinary approaches could be integrated to: ① optimize the spatial form of membrane surface and improve the membrane's antifouling ability; ② accurately control the pore structure and the size distribution of membranes,aimed at the innovative preparation technology of special membrane used for TCM; ③ adjust solution environment based on the analysis of molecular structure,and establish the pretreatment method based on the optimization of solution environment. Furthermore,the technical bottleneck on how to obtain the pharmacodynamic micromolecules effectively might be solved,and the theory and technology about TCM pharmaceutical engineering could be developed based on the concept of multivariate and integration.

A new triterpene from the green walnut husks of Juglans mandshurica Maxim.

A new triterpene named klodorol B (1), together with six known compounds, were isolated from the green walnut husks of Juglans mandshurica Maxim. Their structures were determined using spectroscopic methods on the basis of 1D and 2D NMR, and high-resolution electrospray ionization mass spectrometry. The isolated compounds were evaluated for their cytotoxic activities on human gastric carcinoma (BGC-823), human liver cancer (HepG-2) and human lung cancer (A549) cell lines. .

Cyclophosphamide for the treatment of acute lymphoblastic leukemia: A protocol for systematic review.

BACKGROUND: Previous clinical trials have reported that cyclophosphamide can be used for the treatment of acute lymphoblastic leukemia (ALL). However, its efficacy is still unclear. In this systematic review study, we aim to evaluate its efficacy and safety for ALL. METHODS: The following 9 databases will be searched from their inception to the present: Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), and four Chinese databases. The randomized controlled trials or case control studies of cyclophosphamide that assess the clinical efficacy and safety in patients with ALL are included. The methodological quality of all eligible included studies will be assessed by the Cochrane risk of bias tool.The primary outcome measurement will be all-cause mortality at the period of treatment and follow-up. The secondary outcome measurements will include the health-related quality of life (HRQL), postinduction complete remission (CR) rate, event-free survival (EFS), relapse rate, and adverse events. Two authors will independently select eligible studies, exact data, and assess the methodological quality of included studies. RevMan 5.3 software will be used to synthesize the data. Reporting bias will be evaluated by the funnel plots, Begg, and Egger tests. RESULTS: This systematic review will evaluate the clinical efficacy and safety of cyclophosphamide for ALL. DISSEMINATION AND ETHICS: The findings of this review will summarize the present evidence of cyclophosphamide for ALL, and may provide guidance for clinical practice of cyclophosphamide for ALL. Its results will be published through peer-reviewed journals. This study does not need ethic approval, because it will not involve the individual data. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018119333.

Efficiency of nitrogen and phosphorus removal by six macrophytes from eutrophic water.

Increased nitrogen and phosphorus pollution causes eutrophication in water bodies. Using aquatic plants to remove nutrients from water is an attractive phytoremediation. It is a cost-effective, environment-friendly, and efficient way that reduces water body eutrophication by the plant. It is important to choose suitable macrophytes to remove excess N and P under different nutrient conditions. In this study, six macrophyte species (Polygonum orientale, Juncus effuses, Iris pseudocorus, Phragmites australis, Iris sanguinea, Typha orientalis) were tested. Simulation experiment was conducted under five N and P levels. The removal rate, relative growth rate, and the dynamic nutrition concentration of cultivated solution were investigated. Of all the treatment, a 23-95% reduction in N removal and a 29-92% reduction in P removal were recorded. The results showed I. sanguinea is a promising species to treat various eutrophic waters and the other five species can be used specifically to treat certain types of water. The data provided a theoretical guidance to plant species selection for phytoremediation of polluted water bodies for the purpose of water quality improvement around the different reservoir in northern China.

Effectiveness and Safety of Clopidogrel Co-administered With Statins and Proton Pump Inhibitors: A Korean National Health Insurance Database Study.

Simultaneous competition for cytochrome P450 (CYP) 2C19 and CYP3A4 might diminish clopidogrel's antiplatelet effect by impacting its metabolic activation. This pharmacoepidemiologic study investigated whether proton pump inhibitors (PPIs) and CYP3A4-metabolized statins individually and jointly increase thrombotic events by attenuating clopidogrel's effectiveness. From Korean nationwide claims data (2007-2015), we selected 59,233 patients who initiated clopidogrel and statins after coronary stenting and compared thrombotic risks by PPI or CYP3A4-metabolized statin use or both. PPIs were associated with increased thrombotic risks (hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.12-1.45), unlike CYP3A4-metabolized statins (HR 1.03, 95% CI 0.98-1.07). PPIs with high CYP2C19-inhibitory potential were more relevant than those with low potential (HR 1.28, 95% CI 1.02-1.61). Joint effects of PPIs and CYP3A4-metabolized statins were nonsignificant (relative excess risk due to interaction -0.14, 95% CI -0.34 to 0.07). Concurrent PPIs were associated with increased thrombotic risks in patients receiving clopidogrel and statins; CYP3A4-metabolized statins did not exacerbate PPI-associated risks.