Phosphodiesterase 5 and Arginase Inhibitory Activities of the Extracts from Some Members of Nelumbonaceae and Nymphaeaceae Families.

The objectives of this study were (1) to investigate the effect of extracts from some plants in the families Nelumbonaceae and Nymphaeaceae on phosphodiesterase 5 (PDE5) and arginase, which have been used in erectile dysfunction treatment, and (2) to isolate and identify the compounds responsible for such activities. The characterization and quantitative analysis of flavonoid constituents in the active extracts were performed by HPLC. Thirty-seven ethanolic extracts from different parts of plants in the genus Nymphaea and Victoria of Nymphaeaceae and genus Nelumbo of Nelumbonaceae were screened for PDE5 and arginase inhibitory activities. The ethanolic extracts of the receptacles and pollens of Nelumbo nucifera Gaertn., petals of Nymphaea cyanea Roxb. ex G.Don, Nymphaea stellata Willd., and Victoria amazonica (Poepp.) Sowerby and the petals and receptacles of Nymphaea pubescens Willd. showed IC50 values on PDE5 of less than 25 µg/mL while none of the extracts showed effects on arginase. The most active extract, N. pubescens petal extract, was fractionated to isolate and identify the PDE5 inhibitors. The results showed that six flavonoid constituents including quercetin 3'-O-ß-xylopyranoside (1), quercetin 3-methyl ether 3'-O-ß-xylopyranoside (2), quercetin (3), 3-O-methylquercetin (4), kaempferol (5) and 3-O-methylkaempferol (6) inhibited PDE5 with IC50 values at the micromolar level.

Consensus on diagnostic criteria for deficiency syndrome in hypertension: a modified Delphi study.

OBJECTIVE: To reach consensus on the diagnostic criteria for deficiency syndrome in hypertension (YDSH) patients by a modified Delphi method. METHODS: Our study was consistent with T/CACM 1032-2017. The methodology of RAND/UCLA appr-opriateness was used to develop consensus guidance statements. A nationwide panel of experienced clinical experts from 19 provinces was constructed. These experts were all prominent in Traditional Chinese Medicine (TCM) of cardiovascular diseases. This con-sensus process consisted of two rounds of ques-tionnaires and a final round of consultation to analyze the weight score of each item. Moreover, the data extraction process is carried out independently by third-party researchers (LIANG Junya, SUN Yang, and DU Xiaona). When there is disagreement in all three rounds, the expert panel group (odd number) are invited to vote, and the one with more votes wins. In the questionnaires, participants were asked to rate the appropriateness of each syndrome item using a nine-point Likert scale. The consensus was defined as a panel median rating 1-3 or 7-9 without disagreement. And then the diagnostic criteria of YDSH were formed according to the weight score in the final round. RESULTS: Twenty-eight experts (84.8%) participated in the first round, and thirty-one (93.9%) finished the second round. After two rounds, the consensus of YDSH was reached on 11 items (25.6%), including symptoms, signs, and pulse condition. Twenty-one experts (63.6%) com-pleted the final round in which they used a grading system for each item. Red tongue with scanty fur had the highest weighting (22.8%), followed by heat in the palms and soles (20.1%). CONCLUSIONS: The consensus-based diagnostic criteria for YDSH, formed by a modified Delphi method, can be widely incorporated in TCM. A further clinical study will be conducted to analyze the diagnosis value and cut-off score of our YDSH criteria.

Analysis and interpretation of genetic testing results from 249 Chinese high to very-high risk non-metastatic prostate cancer patients / 中华泌尿外科杂志

Objective:To analyze germline genetic testing in Chinese high-to very-high-risk non-metastatic prostate cancer patients.Methods:This study included 249 Chinese patients with high- to very-high-risk non-metastatic prostate cancer for germline genetic testing, in Fudan University Shanghai Cancer Center, West China Hospital and Cancer Center of Sun Yat-sen University, from January 2018 to December 2022. High risk and very-high risk are termed according to National Comprehensive Cancer Network (NCCN) Prostate Cancer Guideline (2022 V1). The mean age of the patients was (66.7±9.2) years old and median PSA level was 28.50 (ranging 2.43 - 1481.11) ng/ml. Within these 249 patients, 84 (33.7%) were T 1-2, 98 (39.3%) were T 3-4, while 67 (26.9%) were unclear in T stage. Additionally, 51 patients (20.5%) were classified into International Society of Urological Pathology(ISUP) grade group 1-3 group and 198 patients (79.5%) were in ISUP 4-5 group. Focusing on 16 genetic susceptibility genes for prostate cancer, we interpret the germline genetic testing data in accordance with the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guideline, clarify the germline pathogenic mutation rate and elucidate the clinicopathological characteristics of germline pathogenic mutation carriers. Results:Among Chinese high-to very-high-risk non-metastatic prostate cancer patients, 7.2% (18/249) had germline pathogenic mutations. Patients with mutations had a significantly higher proportion of first-degree relatives with a history of malignancy than those without mutations (50% vs. 13%, P<0.001), but there was no difference in age of onset [(68.2±9.3)years vs. (66.6±9.2) years], PSA level (median: 40.68 ng/ml vs. 28.00 ng/ml), T stage [T 3-4: 38.9%(7/18)vs. 39.4%(91/231)] and ISUP grade [group 4-5: 88.9%(16/18) vs. 78.8%(182/231)]. Germline pathogenic mutations were observed in BRCA2 (7 patients, 38.9%), MSH2 (3 patients, 16.7%), PALB2 (2 patients, 11.1%), ATM (2 patients, 11.1%), RAD51C (1 patient, 5.6%), PMS2 (1 patient, 5.6%), MSH6 (1 patient, 5.6%) and HOXB13 (1 patient, 5.6%). By comparing with normal controls of East-Asian population, germline pathogenic mutations in BRCA2 ( OR=11.1, 95% CI 4.8-25.6, P<0.001) and MSH2 ( OR= 43.5, 95% CI 8.5-200.0, P<0.001) can significantly increase the risk of developing high- to very-high-risk prostate cancer in Chinese males. Conclusions:This study identified a germline pathogenic mutation rate of 7.2% in 249 Chinese patients with high- or very-high-risk non-metastatic prostate cancer. Carrying germline BRCA2 or MSH2 pathogenic mutations can significantly increase the risk of high- or very-high-risk prostate cancer in Chinese men.

Rules of Syndrome and Treatment of Unstable Angina Pectoris Guided by Vessel-collateral Theory and Mechanism Analysis Based on Network Pharmacology / 中国实验方剂学杂志

Objective:Guided by nutrient-defense stages in the vessel-collateral theory， the modern medical cases of unstable angina pectoris（UAP） were systematically collated and analyzed to explore the rules of syndrome and treatment of UAP and the molecular mechanism of core Chinese herbal combination in the treatment of UAP based on network pharmacology. Method:All medical cases with UAP treated by Chinese medicinal compounds were retrieved from PubMed，China National Knowledge Infrastructure （CNKI），Wanfang Data， VIP， and SinoMed published between database inception and November 2020. The syndromes of medical cases were determined based on the nutrient-defense stages of the vessel-collateral theory. Rules of syndrome and treatment of UAP were investigated by data mining methods， such as frequency statistics， cluster analysis， and enhanced FP-Growth algorithm. The molecular mechanism of core Chinese herbal combination in the treatment of UAP was analyzed by network pharmacology. Result:The first four syndromes of UAP with high frequencies were deficiency and stagnation of collateral Qi， blood stasis obstructing collaterals， depression and stagnation of collateral Qi， and turbid phlegm obstructing collaterals. The Chinese herbal medicines with high frequencies included Salviae Miltiorrhizae Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Chuanxiong Rhizoma， and Astragali Radix， which were effective in resolving stasis， dredging collaterals， replenishing Qi， consolidating defensive Qi， regulating Qi， relieving depression， and dispelling phlegm. The association analysis indicated that the core Chinese herbal combination in the treatment of UAP was Salviae Miltiorrhizae Radix Chuanxiong Rhizoma-Astragali Radix. Four Chinese herbal combinations were obtained by cluster analysis. As revealed by network pharmacology， the key components of Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma-Astragali Radix in the treatment of UAP included quercetin， luteolin， and tanshinone Ⅱ_A， and the key targets included serine/threonine-protein kinase 1 （Akt1）， mitogen-activated protein kinase 1 （MAPK1）， Jun， interleukin （IL）-6， and MAPK8. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis showed that phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt） signaling pathway might serve as the main pathway for its therapeutic efficacy. Conclusion:The basic pathogenesis of UAP is deficiency/depression and stagnation of collateral qi and turbid phlegm obstructing collaterals. The treatment should follow the principles of replenishing Qi， resolving stasis， and dredging collaterals， assisted with regulating Qi and resolving phlegm. The therapeutic efficacy of Salviae Miltiorrhizae Radix-Chuanxiong Rhizoma-Astragali Radix was achieved via multi-component， multi-target， and multi-pathway. This study is expected to inspire future UAP-related studies at the molecular level based on vessel-collateral theory.

Deconstruction Study of the Experience of Famous Old Traditional Chinese Medicine Doctors of Jiangsu, Zhejiang and Shanghai in Applying Medicinal Paste / 世界科学技术-中医药现代化

Objective: To study the experience of famous old Traditional Chinese Medicine doctors of Jiangsu, Zhejiangand Shanghai in applying medicinal paste according to the deconstruction analysis of the medical cases formed by miningthe linked data of original cases on the basis of TCM features. Methods: To apply a deconstruction analysis to thesedoctors. medical cases with the quantifiable trend data on the data processing platform of Medcase. Results: This studycollected 472 medical visits, 250 pathogenesis elements, 400 therapies and 529 kinds of herbs. Conclusion: The medicinal pastes are applied by these famous doctors to treat commonly seen consumptive diseases, namely to intervenesub-health status. The chief core indications are lassitude, poor sleep, lumbar soreness and poor appetite; the relatedtongue and pulse conditions are thin or white tongue coating, red or pale tongue proper, and a thready or wiry pulse; thechief pathogenesis elements are deficiency of the liver and kidney, and deficiency of the spleen and kidney; thefrequently used herbs are Radix Astragali seu Hedysari, Rhizoma Atractylodis Macrocephalae, Poria, Radix Angelicae Sinensis, Radix Paeoniae, Radix Glycyrrhizae, Radix Rehmanniae Preparata, etc. The prescriptions for medicinal pastesare made by modifying several basic formulas including Sijunzi Decoction, Siwu Decoction, Bazhen Decoction, DangguiBuxue Decoction, Liuwei Dihuang Pills, and Shengmai Decoction. The common excipients for pastes are Ejiao, rockcandy, Guibanjiao, Lujiaojio, etc. The guide for making the pastes are combined therapies, such as regulating both qi andblood, tonifying both yin and yang, and treating both deficiency and excess.

In vitro investigation on the magnetic thermochemotherapy mediated by magnetic nanoparticles combined with methotrexate for breast cancer treatment.

Cancer comprehensive treatment has been fully recognized as it can provide an effective multimodality approach for fighting cancers. In therapeutic oncology, hyperthermic adjuvant chemotherapy termed as thermochemotherapy plays an increasing role in multimodality cancer treatment. Currently, targeted nanothermotherapy is one of the effective hyperthermia approach based on magnetic nanoparticles (MNPs), which can be achieved by applying biocompatible nanoscaled metallic particles that convert electromagnetic energy into heat, for instance, magnetic fluid hyperthermia (MFH) mediated by superparamagnetic iron oxide nanoparticles (SPIONs). Upon exposure under alternative magnetic field (AMF), SPIONs can generate heat through oscillation of their magnetic moment. Nowadays, clinical trials at phase II are now under investigations for MFH on patients in Germany and Japan and demonstrate very inspiring for cancer therapy. In this work we explore the feasibility and effectiveness of magnetic thermochemotherapy mediated by magnetic nanoparticles combined with methotrexate, an anti-cancer drug, for breast cancer comprehensive treatment. Amino silane coated MNPs as agent of MFH were prepared by the chemical precipitation method. Physiochemical characterizations on MNPs have been systematically carried out by various instrumental analyses. Inductive heating property of the MNPs was evaluated by monitoring the temperature increase of the MNPs suspension under AMF. The in-vitro cytotoxicity results on human breast cancer cell MCF-7 by CCK-8 assay indicated the bi-modal cancer treatment approach for combined MFH and chemotherapy is more effective than mono-modal treatment, indicating a thermal enhancement effect of hyperthermia on drug cytocoxicity. The magnetic thermochemotherapy mediated by MNPs combined with methotrexate can realize cancer comprehensive treatment thus has great potential in clinical application.

Thermochemotherapy mediated by novel solar-planet structured magnetic nanocomposites for glioma treatment.

Cancer comprehensive treatment has been fully recognized as it can provide an effective multimodality approach for fighting cancers. This work evaluates the effects of a kind of novel solar-planet structured magnetic nanocomposites (MNCs) for magnetic thermochemotherapy. Amino silane coated magnetic nanoparticles (MNPs) as agent of magnetic mediated hyperthermia (MMH) for cancer treatment were prepared by the chemical precipitation method. Docetaxel (an anticancer drug) loaded polymeric nanoparticles (DNPs) composed of carboxylic-terminated poly (D,L-lactic-co-glycolic acid) (PLGA) with Vitamin E TPGS as emulsifier for sustained drug release were prepared by a modified solvent extraction/evaporation technique. Furthermore, the MNPs modified with amino groups could be covalently attached to the surface of carboxylic terminated DNPs to form the so-called solar-planet structured MNCs by 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) crosslinking. The prepared solar-planet structure has been confirmed by fluorescent observation. Inductive heating property of the nanocomposite was evaluation by monitoring the temperature increase of the MNCs suspension under alternative magnetic field (AMF). Drug encapsulation efficacy and drug release of the magnetic nanocomposite were conducted by high performance liquid chromatography (HPLC). In vitro evaluation of the novel nanocomposite as mediator for thermochemotherapy was conducted on the U251 human glioma cells and the synergistic effect between MMH and docetaxel chemotherapy was confirmed. All the observation supports that solar-planet structured MNC is a novel and effective mediator for magnetic thermochemotherapy. The MNCs can realize cancer comprehensive treatment thus has great potential in clinical application.

Characterization of two putative protein phosphatase genes and their involvement in phosphorus efficiency in Phaseolus vulgaris.

Protein dephosphorylation mediated by protein phosphatases plays a major role in signal transduction of plant responses to environmental stresses. In this study, two putative protein phosphatases, PvPS2:1 and PvPS2:2 were identified and characterized in bean (Phaseolus vulgaris). The two PvPS2 members were found to be localized to the plasma membrane and the nucleus by transient expression of PvPS2:GFP in onion epidermal cells. Transcripts of the two PvPS2 genes were significantly increased by phosphate (P(i) ) starvation in the two bean genotypes, G19833 (a P-efficient genotype) and DOR364 (a P-inefficient genotype). However, G19833 exhibited higher PvPS2:1 expression levels than DOR364 in both leaves and roots during P(i) starvation. Increased transcription of PvPS2:1 in response to P(i) starvation was further verified through histochemical analysis of PvPS2:1 promoter fusion ß-glucuronidase (GUS) in transgenic Arabidopsis plants. Analysis of PvPS2:1 overexpression lines in bean hairy roots and Arabidopsis showed that PvS2:1 was involved in root growth and P accumulation. Furthermore, expression levels of two P(i) starvation responsive genes were upregulated and the APase activities were enhanced in the overexpressing PvPS2:1 Arabidopsis lines. Taken together, our results strongly suggested that PvPS2:1 positively regulated plant responses to P(i) starvation, and could be further targeted as a candidate gene to improve crop P efficiency.

Novel sinomenine derivative 1032 improves immune suppression in experimental autoimmune encephalomyelitis.

Sinomenine (SIN) is an alkaloid isolated from the Chinese medicinal plant Sinomenium acutum. It is widely used as an immunosuppressive drug for treating autoimmune diseases. Due to its poor efficiency, the large-dose treatment presents some side effects and limits its further applications. In this study, we used chemical modification to improve the therapeutic effect of SIN in vitro and in vivo. A new derivative of sinomenine, named 1032, demonstrates significantly improved immunosuppressive activity over that of its parent natural compound (SIN). In an experimental autoimmune encephalomyelitis (EAE) model, 1032 significantly reduced encephalitogenic T cell responses and induced amelioration of EAE, which outcome was related to its selective inhibitory effect on the production of IL-17. By contrast, SIN treatment only led to a moderate alleviation of EAE severity and the expression level of IL-17 was not significantly reduced. Furthermore, 1032 exhibited suppression of Th17, but not Treg, cell differentiation, a result probably related to its inhibitory effect on IkappaB-alpha degradation as well as on IL-6 and TNF-alpha secretion in BMDCs. We speculate that 1032 as a novel anti-inflammatory agent may target DC to block IL-6 production, which in turn would terminate Th17 cell development. Thus, SIN derivative 1032 presents considerable potential in new drug development for treating autoimmune and inflammatory disease.

The study of electrical acupuncture stimulation therapy combined with pelvic floor muscle therapy for postprostatectomy incontinence / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the effectiveness and significance of whether electrical acupuncture stimulation combining with pelvic floor muscle therapy (PFMT) can improve the recovery of urinary continence.</p><p><b>METHODS</b>A total of 109 patients took part in the study of novel combination treatment for urinary continence from September 2008 to September 2009. Patients were divided into study group (n = 40) and control group (n = 69). The patients in study group received electrical acupuncture stimulation therapy combined with PFMT one week after removal the catheter. The patients in control group performed PFMT as the only treatment for post prostatectomy incontinence. The patients were followed up closely, with their clinical characteristics recorded, questionnaires of ICI-Q-SF filled up, and all the data for statistical analysis collected.</p><p><b>RESULTS</b>There was a significant difference between the study group and the control group in the urinary control curve (P = 0.029). The difference of continence probability between these two groups became greater from 4 weeks after surgery, and the difference reached the peak at 6 weeks (P = 0.023). Then the difference became smaller, and there was no difference at 16 weeks after surgery. ICI-Q-SF questionnaires showed the same results.</p><p><b>CONCLUSION</b>Electrical acupuncture stimulation therapy combining with PFMT can improve the recovery of patients' urinary continence after radical prostatectomy.</p>