Qualitative and quantitative evaluations of Chuanxiong dispensing granules by using chemical fingerprint in combination with chemometrics methods.

To better elucidate the chemical constituents and evaluate the quality consistency of Chuanxiong dispensing granules (CDG), qualitative and quantitative analyses were performed in this study. Firstly, a high-performance liquid chromatography-diode array detector (HPLC-DAD) based fingerprint was constructed by 12 batches of CDGs from different manufacturers, in which 16 common peaks were assigned. Then, two of them were directionally isolated for structural elucidation. According to the nuclear magnetic resonance (NMR) and mass spectrometry (MS) spectra, 5,6-dihydrophthalic acid was identified as novel compound, and 8-O-4/8-O-4-dehydrotriferulic acid was firstly discovered in plant belonging to the genus Ligusticum. Secondly, a total of 46 components were detected in CDG using high performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (HPLC-Q-TOF-MS), and 14 of them were unambiguously identified by comparing with reference standards. Additionally, a HPLC-DAD method was firstly established to quantify 10 characteristic peaks specified in the China National Standard of CDG, and the results revealed that ferulic acid (1.71 mg/g), chlorogenic acid (1.14 mg/g), 5,6-dihydrophthalic acid (1.13 mg/g), and senkyunolide I (1.13 mg/g) are the major components in CDGs. Chemometrics analyses suggested that phenolic acids are more important than phthalides in discrimination of CDGs from different manufacturers.

Over-expression of RRM2 predicts adverse prognosis correlated with immune infiltrates: A potential biomarker for hepatocellular carcinoma.

Background: Ribonucleotide reductase regulatory subunit M2 (RRM2) has been reported to be an oncogene in some malignant tumors, such as lung adenocarcinoma, oral squamous cell carcinoma, glioblastoma, and breast cancer. However, the clinical significance of RRM2 in hepatocellular carcinoma has been less studied. The aim of this study was to assess the importance of RRM2 in hepatocellular carcinoma (HCC) based on the Cancer Genome Atlas (TCGA) database. Methods: The RRM2 expression levels and clinical features were downloaded from the TCGA database. Immunohistochemistry results between tumor tissues and normal tissues were downloaded from the Proteinatlas database. Meanwhile, the expression levels of RRM2 in tumor and paraneoplastic tissues were further verified by qRT-PCR and Western Blotting. Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein-interactions (PPI) network were constructed to analyze RRM2-related downstream molecules. In addition, RRM2 expression-related pathways performed by gene set enrichment analysis (GSEA). Association analysis of RRM2 gene expression and immune infiltration was performed by single-sample GSEA (ssGSEA). Results: The RRM2 expression level in tumor tissues was higher than normal tissues (P <0.001). The elevated expression of RRM2 in HCC was significantly correlated with T stage (P <0.05), pathologic stage (P <0.05), tumor status (P <0.05), histologic grade (P<0.001), and AFP (P <0.001). HCC with higher RRM2 expression was positively associated with worse OS (overall survival), PFS (progression-free survival), and DSS (disease-specific survival). In the univariate analysis, the expression of RRM2, T stage, M stage, pathologic stage, and tumor status were negatively correlated with OS (P <0.05). Further analysis using multivariate Cox regression showed that tumor status (P<0.01) and RRM2 expression (P<0.05) were independent prognostic factors of OS in HCC. GO/KEGG analysis showed that the critical biological process (chromosome condensation and p53 signaling pathway) might be the possible function mechanism in promoting HCC. Moreover, GSEA showed that several pathways were enriched in RRM2 high-expression samples, including PD-1 signaling, cell cycle, P27 pathway, and T cell receptor signaling pathway. RRM2 was significantly correlated with the infiltration level of CD8 T cells, Cytotoxic cells, DCs, Neutrophils, NK cells, and T helper cells (P <0.05). Conclusion: Over-expression of RRM2 predict adverse prognosis and is correlated with immune infiltrates in HCC. RRM2 may be a significant molecular biomarker for HCC diagnosis and prognosis.

Senkyunolide I: A Review of Its Phytochemistry, Pharmacology, Pharmacokinetics, and Drug-Likeness.

Senkyunolide I (SI) is a natural phthalide that has drawn increasing interest for its potential as a cardio-cerebral vascular drug candidate. In this paper, the botanical sources, phytochemical characteristics, chemical and biological transformations, pharmacological and pharmacokinetic properties, and drug-likeness of SI are reviewed through a comprehensive literature survey, in order to provide support for its further research and applications. In general, SI is mainly distributed in Umbelliferae plants, and it is relatively stable to heat, acid, and oxygen, with good blood-brain barrier (BBB) permeability. Substantial studies have established reliable methods for the isolation, purification, and content determination of SI. Its pharmacological effects include analgesic, anti-inflammatory, antioxidant, anti-thrombotic, anti-tumor effects, alleviating ischemia-reperfusion injury, etc. Pharmacokinetic parameters indicate that its metabolic pathway is mainly phase Ⅱ metabolism, and it is rapidly absorbed in vivo and widely distributed in the kidneys, liver, and lungs.

Implications of Withaferin A for the metastatic potential and drug resistance in hepatocellular carcinoma cells via Nrf2-mediated EMT and ferroptosis.

Hepatocellular carcinoma (HCC) constitutes a major global health threat due to the high incidence and mortality. Sorafenib is known as the first-line medication for advanced HCC; however, it only extends the limited benefit for HCC patients as the development of acquired resistance. Withaferin A exerts broad pharmaceutical applications in several cancers. However, its effects on HCC cell metastatic potential and sorafenib resistance remain elusive. Here, we corroborated that Withaferin A greatly restrained cell viability, invasion, vasculogenic mimicry (VM) formation, and VE-cadherin levels in HepG2 and SNU449 cells. Moreover, Withaferin A sensitized sorafenib (SR)-resistant HCC cells to sorafenib. In striking contrast to the parental cells, lower ferroptosis was observed in SR-resistant cells as the lower ROS, MDA, and higher intracellular GSH levels in SR-resistant cells. Of interest, Withaferin A enhanced ferroptosis in SR-resistant cells, which was reversed by ferroptosis antagonist liproxstation-1. Notably, Withaferin A elevated Keap1 expression to mitigate Nrf2 signaling activation-mediated epithelial to mesenchymal transition (EMT) and ferroptosis-related protein xCT expression. Importantly, blockage of the Keap1/Nrf2 signaling overturned Withaferin A-evoked ferroptosis and facilitated sorafenib resistance. In addition, knockdown of Keap1 antagonized the inhibitory efficacy of Withaferin A on HCC cell viability, invasion, and VM formation. Consequently, Withaferin A may attenuate the metastatic potential and sorafenib resistance by regulating Keap1/Nrf2-associated EMT and ferroptosis. Thus, Withaferin A may serve as a promising agent for HCC therapy, especially for advanced HCC.

Phylogenetic analysis based on single-copy orthologous proteins in highly variable chloroplast genomes of Corydalis.

Corydalis is one of the few lineages that have been reported to have extensive large-scale chloroplast genome (cp-genome) rearrangements. In this study, novel cp-genome rearrangements of Corydalis pinnata, C. mucronate, and C. sheareri are described. C. pinnata is a narrow endemic species only distributed at Qingcheng Mountain in southwest China. Two independent relocations of the same four genes (trnM-CAU-rbcL) were found relocated from the typically posterior part of the large single-copy region to the front of it. A uniform inversion of an 11-14-kb segment (ndhB-trnR-ACG) was found in the inverted repeat region; and extensive losses of accD, clpP, and trnV-UAC genes were detected in all cp-genomes of all three species of Corydalis. In addition, a phylogenetic tree was reconstructed based on 31 single-copy orthologous proteins in 27 cp-genomes. This study provides insights into the evolution of cp-genomes throughout the genus Corydalis and also provides a reference for further studies on the taxonomy, identification, phylogeny, and genetic transformation of other lineages with extensive rearrangements in cp-genomes.

Identification of Hair Growth Promoting Components in the Kernels of Prunus mira Koehne and Their Mechanism of Action.

The application of the seed oil of Prunus mira Koehne (Tibetan name ཁམབུ།), a plant belonging to the Rosaceae family, for the treatment of alopecia has been recorded in Jingzhu Materia Medica (ཤེལ་གོང་ཤེལ་ཕྲེང་།) (the classic of Tibetan medicine) and Dictionary of Chinese Ethnic Medicine. This study aims to reveal the effective components and mechanism of hair growth promotion in the kernel of Prunus mira Koehne. Network pharmacology was used to predict the mechanism of action and effective components in the treatment of the kernel of Prunus mira Koehne. The contents of amygdalin in 12 batches of the kernel of Prunus mira Koehne were determined by HPLC. An animal model of the depilation of KM mice induced by sodium sulfide was created, and five effective components that promoted hair growth were initially screened. In the study of the effectiveness and mechanism of action, KM and C57BL/6 mice are selected as experimental objects, three screening tests for active components of the kernel of P. mira are performed, and three effective components are screened out from the eight components. HE staining was used to detect the number of hair follicles and the thickness of the dermis. RT-PCR and immunohistochemistry were used to evaluate the influence of the expression of indicators in the Wnt/ß-catenin signaling pathway in skin, including ß-catenin, GSK-3ß, and mRNA and protein expression levels of Cyclin D 1 and LEF 1. The network pharmacology study showed 12 signaling pathways involving 25 targets in the treatment of alopecia by the kernel of Prunus mira Koehne. vitamin E (3.125 mg/cm2/d), ß-sitosterol (0.061 mg/cm2/d), and linoleic acid (0.156 mg/cm2/d) in the kernel of Prunus mira Koehne can promote hair growth in mice, and the mechanism of action may be related to the Wnt/ß-catenin pathway.

Prunus mira Koehne in Sichuan, China: Recorded History as a Medicine and Food, Modern Applications, Distribution, and Ethnobotanical Investigations.

Prunus mira Koehne, a Prunus plant in the Rosaceae family, is named ཁམབུ། in Tibetan and "Guang he tao" in Chinese. It is mainly distributed in Tibet Autonomous Region, Yunnan Province, and Sichuan Province in China. It is also a rare "living fossil group" of peach genetic resources in the world. It is used in traditional Chinese medicine for the treatment of dysmenorrhea, injury, intestinal dryness, constipation, and other diseases, and is used in Tibetan medicine for the treatment of hair, eyebrows, and beard shedding. In this article, the botanical characteristics, medicinal history, modern applied research, and ethnobotanical investigation of P. mira were recorded and evaluated. P. mira was first recorded in Dumu Materia Medica. P. mira in Sichuan Province is mainly distributed in Ganzi Tibetan Autonomous Prefecture, and has certain economic and medicinal value. P. mira has high nutritional composition. It is made into high-quality edible oil, cosmetic base oil, fruit juice, fruit wine, fruit vinegar, "Liang guo", and other products. Oleic acid and linoleic acid are the main fat-soluble components of P. mira, which has an anti-inflammatory medicinal value and promotes hair growth. Its longevity and cold resistance can bring great genetic value and play an important role in maintaining peach genetic diversity. At present, there are few studies on the pharmacological effects of specific active components of P. mira and there are also few clinical studies. We can continue to study these aspects in the future. At the same time, products of P. mira have great market potential. All in all, P. mira is very worthy of further research and development.

Ultrafast identification of Pinelliae Rhizoma using colorimetric direct-VPCR.

With the increasing growth of the herbal market, a rapid and easy-to-use system is highly desirable in the high-throughput identification of massive herbal medicine samples. Here, an ultrafast and colorimetric detection system was devised based on simplifying template preparation and a newly developed amplification technique, named colorimetric direct-VPCR. The system was successfully applied to the identification of Pinelliae Rhizoma. Compared to the traditional method, the whole test can be finished within 30 min from the sample treatment to the testing results. The method was evaluated by correctly identifying 72 samples obtained from 9 different habitats, demonstrating its high reliability. In summary, we present an ultrafast (less than 30 min) and colorimetric detection platform (under ultraviolet lamp) based on direct-VPCR for the identification of Pinelliae Rhizoma. The high practicability (100% accuracy) of this pipeline enables it to be a promising method in the routine detection of other herbal materials. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-03035-9.

The Combination of Age, International Standardized Ratio, Albumin and γ-Glutamyl Transpeptidase (AIAG), Tumor Size and Alpha Fetoprotein (AFP) Stage as the Prognostic Model for Hepatitis B-Related Hepatocellular Carcinoma.

BACKGROUND: Advanced liver fibrosis can lead to cirrhosis, portal hypertension and liver failure. Besides, advanced liver fibrosis and cirrhosis are the major risk factors for hepatocellular carcinoma (HCC). Almost all patients with HCC also have liver cirrhosis. This study aims to predict the survival rate of hepatitis B-related hepatocellular carcinoma (HCC) by age, international standardized ratio, albumin and γ-glutamyl transpeptidase (AIAG), an indicator measuring the degree of cirrhosis. METHODS: A total of 501 hepatitis B-related HCC patients experiencing radical surgery were analyzed, retrospectively. General data about demographics and labs were collected at the date of diagnosis to calculate AIAG [age, international standardized ratio (INR), albumin and gamma-glutamyl transferase (GGT)]. The Kaplan-Meier curves and Cox analysis were used to evaluate overall survival (OS) and recurrence-free survival (RFS). The C-index was calculated in R software (version 4.0.3) to evaluate the accuracy of the prognostic model. RESULTS: During a median follow-up period of 30 months, 31.1% (156/501) of the patients died, and 34.3% (172/501) experienced the recurrence of HCC. Compared with patients with lower AIAG score, patients with higher AIAG score had higher Child-Pugh grade and were at higher Barcelona Clinic Liver Cancer (BCLC) stage (both P<0.05). Multivariate analysis suggested that GGT, alpha fetoprotein (AFP), tumor size, BCLC stage and AIAG grade were independent predictors of OS and RFS. Furthermore, the combined use of tumor size, AFP and AIAG stage could predict survival significantly better (C-index=0.710, 95% CI: 0.669-0.751) than BCLC stage. CONCLUSION: AIAG is significantly associated with survival of HCC patients, and provides additional prognostic information for patients with HCC. Our findings suggest that the combination of AIAG, tumor size and AFP stage has a better predictive value for the prognosis of patients with hepatitis B-related hepatocellular carcinoma. However, it is necessary for more external evidences to determine clinical utility.

Association of sleep quality before and after SARS-CoV-2 infection with clinical outcomes in hospitalized patients with COVID-19 in China.

Sleep is believed to benefit the host defense against pathogens. We aimed to investigate the association of sleep quality with clinical outcomes among hospitalized patients with COVID-19. We conducted a prospective cohort study in 205 adult hospitalized patients with diagnosed moderate COVID-19, with follow-up until hospital discharge or death. Pittsburgh Sleep Quality Index (PSQI) assessed sleep quality before and after infection. The primary outcome was the incidence of severe or critical pneumonia, and the secondary outcomes were duration of hospital stay and laboratory measurements during the follow up. Among the 205 included hospitalized patients, 185 (90.2 %) experienced poorer sleep quality after infection than before according to the PSQI score, and 25 (12.2 %) developed severe or critical pneumonia during follow-up. In Cox regression models, the adjusted hazard ratio of developing severe or critical pneumonia associated with each 1 score increment in the PSQI score before and after infection was 1.23 (95% CI: 1.09, 1.39) and 1.35 (95 % CI: 1.08, 1.67), respectively. Poorer sleep quality was also significantly associated with a prolonged hospital stay and more serious dysregulations in immune system indicated by several laboratory markers. Poorer sleep quality, either in the daily time or after infection with SARS-CoV-2, was associated with worse clinical outcomes. These findings highlight the importance of good sleep in confronting the emerging pandemic of COVID-19.

Ethnobotanical study on herbal market at the Dragon Boat Festival of Chuanqing people in China.

BACKGROUND: The Chuanqing people () are a linguistic group native to the Guizhou Province of China, with unique culture and rich knowledge of traditional medicinal plants. Herbal market at Dragon Boat Festival (DBF) plays an important role in the inheritance of traditional medicinal knowledge among the Chuanqing people. This study aims to record the profile of medicinal plants of the Chuanqing people, discuss the dilemmas faced by their inheritance, and propose some strategies for passing down information, which is critical for the inheritance and protection of the Chuanqing people's traditional medical knowledge. METHODS: Data were collected through key informants and semi-structured interviews and free listing. Collected voucher specimens were identified using by botanical taxonomy method and deposited in the herbarium. Data were analyzed through use-value (UV) and cultural importance index (CI) values. Medicinal plants were compared with the Information System of Chinese Rare and Endangered Plants of the Chinese Academy of Sciences. Results were compared with the Pharmacopoeia of the People's Republic of China (ChP), the Quality Standard of Traditional Chinese Medicine and National Medicine in Guizhou Province (QSG), and traditional medicines of Southeast Asian countries. RESULTS: A total of 102 species from 53 families and 92 genera were recorded, with Orchidaceae and Asparagaceae (six species each), and Berberidaceae and Asteraceae (five species each) as the predominant families. The whole plant (36%) was the most common medicinal part. Decoction (44%) was the most common preparation method. Seventy-one investigated human ailments were grouped into 12 categories. Diseases of the musculoskeletal system (34 mentions) were most frequently mentioned in this study. Moreover, the most frequently used taxon was Hedera sinensis (Tobler ) Hand.-Mazz. (UV and CI = 0.29). The Chuanqing people's medicine was highly similar to ChP and QSG. In comparison with Southeast Asian countries' traditional medicines, except for the same preparation methods, the similarities in terms of medicinal ingredients, plants, and disease treatment were very low. CONCLUSIONS: The herbal market at the DBF is an important platform for exchanging knowledge about the Chuanqing people's traditional medicinal plants. The Chuanqing people's traditional medicine is facing many challenges to its inheritance and development. To solve these problems, this study highlights the traditional medicinal knowledge of the Chuanqing people, providing basic data for further research and protection of minority medicine.

Morphology and Antibacterial Properties of Copper Precipitates in Ferrite Stainless Steel.

The size of copper precipitates is the main factor affecting the antibacterial performance of antibacterial stainless steel. To study the mechanism of copper precipitate growth in ferritic stainless steel, the shape coefficient η and average specific interfacial energy of copper precipitate σ ¯ were calculated. The growth process of copper precipitate was observed by atomic probe tomography and transmission electron microscope. The results show that the shape coefficient of copper precipitate was 3.053, and the average specific interfacial energy was σ ¯ = 0.4832 - 0.1652 × 10 - 3 T . The increase in the aging time resulted in an increase in the size of copper precipitates and a decrease in the number density. In addition, with the increase in the aspect ratio, the shape of the precipitated phase changed from an initial spherical shape to ellipsoid shape and finally to a rod shape. The increase in the annealing time enhanced the antibacterial activity of the tested steel until almost 100% of the bacteria were killed. Thus, the antibacterial performance is closely related to the size and total surface area per unit area of the precipitate.

Association between sleep structure and amnesic mild cognitive impairment in patients with insomnia disorder: a case-control study.

STUDY OBJECTIVES: To examine the association between sleep structure and amnesic mild cognitive impairment (aMCI) in patients with insomnia disorder. METHODS: A total of 256 patients with insomnia disorder were diagnosed by neurologists, 45 of whom were diagnosed with aMCI according to the Petersen criteria, and 45 participants with intact cognition were chosen as controls matched for age and education. A case-control study was conducted to compare sleep structure between aMCI and control patients with insomnia disorder. We evaluated self-reported sleep problems by the Insomnia Severity Index and objective sleep features by polysomnography. Logistic regression models were used to estimate the associations between sleep parameters and aMCI in patients with insomnia disorder. RESULTS: There was no significant difference in Insomnia Severity Index scores between the aMCI and control groups. In the logistic regression after adjustment for covariates, people with a longer sleep duration (adjusted odds ratio [aOR] = 0.56, 95% confidence interval [CI]: 0.36-0.89), greater sleep efficiency (aOR = 0.50, 95% CI: 0.32-0.77), and a higher percentage of total sleep time in stage 3 of non-rapid eye movement sleep (N3%) (aOR = 0.02, 95% CI: 0.01-0.15) have a lower relative probability of having aMCI. By contrast, higher N1% (aOR = 2.28, 95% CI: 1.36-3.82) and wake after sleep onset (aOR = 1.31, 95% CI: 1.11-1.55) may be risk factors for aMCI in patients with insomnia. CONCLUSIONS: In patients with insomnia disorder, sleep duration, sleep fragmentation, sleep efficiency, N1% and N3% were independently associated with the presence of aMCI. In the clinical setting, if patients with insomnia show much more serious abnormalities in these sleep indices, clinicians should pay attention to their cognitive function. In-depth research would also be worthwhile to elaborate the causality between sleep and cognitive decline.

Decompressive hemicraniectomy versus medical treatment of malignant middle cerebral artery infarction: a systematic review and meta-analysis.

OBJECTIVES: To estimate evidence for decompressive hemicraniectomy (DHC) versus medical treatment effects on survival rate and favorable functional recovery among patients of malignant middle cerebral artery infarction (MMCAI) in randomized controlled trials (RCTs). DESIGN: The present study is a systematic review and meta-analysis of RCTs. SETTING: The MEDLINE/PubMed, EMBASE, Springer, Cochrane Collaboration database, China National Knowledge Infrastructure (CNKI) database, and Wanfang database were comprehensively searched for RCTs regarding the effects of DHC versus medical treatment among patients of MMCAI in these English and Chinese electronic databases from inception to 1 June 2019. Two reviewers independently retrieved RCTs and extracted relevant information. The methodological quality of the included trials was estimated using the Cochrane risk of bias tool. Review Manager5.3.5 software was used for statistical analyses. The statistical power of meta-analysis was estimated by Power and Precision, version 4 software. PARTICIPANTS: Nine RCTs with a total of 425 patients with MMCAI, containing 210 cases in the DHC group and 215 cases in the medical treatment group, met the inclusion criteria were included. Primary outcomes were measured by survival rate, defined as modified Rankin scale (mRS) score 0-5 and favorable functional recovery as mRS score 0-3. The follow-up time of all studies was at 6-12months. RESULTS: First, compared with the medical treatment group, DHC was associated with a statistically significant increase survival rate (RR: 1.96, 95%CI 1.61-2.38, P < 0.00001) and favorable functional recovery (RR: 1.62, 95%CI 1.11-2.37, P = 0.01). Second, subgroup analysis: (1) Compared with the medical treatment group among patients age ≤60 years, DHC was associated with a statistically significant increase survival rate (RR = 2.20, 95%CI 1.60-3.04, P < 0.00001); (2) Compared with the medical treatment group among patients of age >60 years, DHC was also associated with a statistically significant increase survival rate (RR: 1.93, 95%CI 1.45-2.59, P < 0.00001); (3) Compared with the medical treatment group, the time of DHC was preformed within 48 h from the onset of stroke that could statistically significant increase survival rate (RR: 2.16, 95%CI 1.69-2.75, P < 0.00001). Third, sensitivity analyses that measured the results were consistent, indicating that the results were stable. Fourth, the results of statistical power analysis were ≥80%. Finally, the funnel plot of the survival rate included nine RCTs showed no remarkable publication bias. CONCLUSIONS: Our study results indicated that DHC could increase survival rate and favorable functional recovery among patients age ≤60 or >60 years. The optimal time for DHC might be no more than 48 h from the onset of symptoms. However, due to the limitations of this research, it is necessary to design high quality, large-scale RCTs to further evaluate these findings.

[Name standardization and variety arrangement of Chinese national "Qi medicinal herbs" based on VFP].

"Qi medicinal herbs" in China refers to a kind of regional national folk herbs related to the treatment of five labors and seven injuries,the last word of which is "Qi". Our study is to sort out and standardize the name and basic confused varieties through the establishment of " Qi medicinal herbs" VFP information database. " Qi medicinal herbs" variety sorting model of " literature research-variety survey-data mining-spatial distribution" was developed by means of literature analysis which the names and varieties of " Qi medicinal herbs" in the literature were summarized and sorted out. The relationship between the distribution of " Qi medicinal herbs" resources and the use of ethnic groups were visualized by Cytoscape 2. 8. 0 software. The information database of " Qi medicinal herbs" involved in 230 kinds of medicinal materials which including 211 species of plants( including varieties) from 66 families. Medicinal materials standard in China have 9 kinds of " Qi medicinal herbs". Among them,there are 31 kinds of " Qi medicinal herbs" with the confusion of " the different names of the same" and " the different substance of the same names". The most used ethnic groups are Tujia,Qiang and Miao. The main efficacy is clearing heat and detoxification,dispelling wind and removing dampness,etc.,and the main treatment is for injury,rheumatic arthralgia and so on. Names and varieties of " Qi medicinal herbs" among Chinese ethnic groups and folk are standardized and sorted out,which is served to promotethe " Qi medicinal herbs" reasonable protection and utilization of resources,and provide effective reference for exploring the information technology and geographical distribution of ethnic medicine and standardizing clinical medication.

In Vitro Effects on Thrombin of Paris Saponins and In Vivo Hemostatic Activity Evaluation of Paris fargesii var. brevipetala.

The resource shortage of Rhizoma Paridis has never been effectively addressed, and the industry continues to search for alternative resources. The in vitro effects on thrombin of Paris saponins and in vivo hemostatic activity of Paris fargesii var. brevipetala (PF) were evaluated in this study. PF is considered to be an alternative source of Rhizoma Paridis (RP). The in vitro incubation experiment was designed to investigate the effects on thrombin activity of Paris saponin H (PS H) and saponin extract in PF. The bleeding time of mouse tail snipping was used to evaluate the in vivo hemostatic effects of Paris saponins. Also, in vivo changes in four blood coagulation parameters in rats after oral administration of different groups of Paris saponins were compared. The effects of Paris saponins on liver function and blood lipid parameters were examined in order to avoid drug-induced liver injury. Activity studies of thrombin after ultra-filtration centrifugation showed that Paris saponins were able to enhance thrombin activity. Ultra performance liquid chromatography mass spectrometry (UPLC-MS) analysis results of the substrates led us to speculate that there is a specific binding between Paris saponins and thrombin. PS H and Paris saponins in PF significantly shortened the bleeding time in mice. One pathway by which Paris saponins enhance in vivo blood coagulation is by increasing fibrinogen (FIB), among the four blood coagulation parameters in rats. At the same time, the effects on liver and blood lipid parameters were insignificant. P. fargesii var. brevipetala can be developed as an alternative medicinal source of Rhizoma Paridis.

Hereditary protein S deficiency leads to ischemic stroke.

Hereditary protein S (PS) deficiency is an independent risk factor for venous thromboembolism. However, the correlation between PS and arterial thrombotic disease, such as cerebral thrombosis, is not clear. The present study focused on the molecular mechanisms underlying ischemic stroke caused by a PS gene mutation in one family. The activity of antithrombin, protein C and PS in the plasma of the proband was measured, and the genes encoding PS were amplified and sequenced. The cellular localization and expression of PS were analyzed in HEK­293 cells. The proband was a 50­year­old male. Plasma PS activity of the proband was 38.9%, which was significantly decreased compared with normal levels. Sequencing analysis revealed a PROS1 c.1486_1490delGATTA mutation on exon 12. This frameshift mutation converts Asp496 in the precursor PS into the termination codon. In addition, the PROS1 mutation was correlated with low PS activity in the family. Functional tests revealed that the mutant protein aggregated in the cytoplasm and its secretion and expression decreased. In conclusion, protein S mutation appeared to be the primary cause of thrombosis in the family of the present study. However, the correlation between PS deficiency and ischemic stroke requires further investigation.

Chemical characteristics of saponins from Paris fargesii var. brevipetala and cytotoxic activity of its main ingredient, paris saponin H.

More attention was paid to the anti-tumor activity of Rhizoma Paridis (RP) recently, of which the wild resource was decreased significantly. This study was aimed to elucidate the chemical characteristics of Paris fargesii var. brevipetala (PFB) that may be administrated as alternate resource of legal RP. A HPLC-ELSD method was established to characterize the steroid saponins in rhizomes of PFB and two legal Paris species [Paris polyphylla var. chinensis (PPC) and P. polyphylla var. yunnanensis (PPY)] in Chinese Pharmacopoeia (CP). Ten saponins (paris saponins I, II, V, VI, VII, H, gracillin and other three paris saponins) were involved as standards. The results indicated that PFB contained pennogenyl saponins as the main components with small amounts of diosgenin saponins. The total contents of the detected saponins in PFB ranged from 9.12mg/g to 85.33mg/g. Nine of the twelve PFB samples own a total content of paris saponins I, II, VI, and VII more than 6.0mg/g (meeting the standard of CP 2010 edition). Principal Component Analysis (PCA) and Partial Least Squares-Discriminate Analysis (PLS-DA) both confirmed the fact that saponin profiles of PFB, PPC and PPY were different from each other. In addition, paris saponin H (Ps H), the predominant saponin of PFB (>50%), was tested in vitro to evaluate its cytotoxic activities on HepG2, A549, RPE and L929 cells with a positive control of Cisplatin. Ps H showed a remarkable cytotoxic activity on A549 cells with an IC(50) value of 1.53±0.08µg/mL.

Increased placental growth factor in cerebrospinal fluid of patients with epilepsy.

Recent studies suggest that angiogenesis and vascular endothelial growth factor (VEGF) are involved in the pathophysiology of epilepsy. However, relatively little data are available linking placenta growth factor (PIGF) with epilepsy. In this study, we assessed concentrations of PIGF in cerebrospinal fluid (CSF) of 60 epileptic patients and 24 non-seizure subjects using sandwich enzyme-linked immunosorbent assays. Epileptic patients in general had higher concentration of CSF-PIGF than controls (7.95 ± 0.88 ng/l vs. 5.87 ± 0.79 ng/l, P < 0.01). CSF-PIGF level in secondary epileptic patients (8.59 ± 1.26 ng/l) was higher than that in idiopathic epileptic patients (7.62 ± 0.20 ng/l) (P < 0.05). In idiopathic epilepsy, CSF-PIGF level in patients with high seizure frequency was higher than those in patients with low seizure frequency and seizure-free in recent 3 years (7.78 ± 0.23 ng/l vs. 7.49 ± 0.09 ng/l and 7.59 ± 0.10 ng/l, P < 0.05). Concentration of CSF-PIGF in patients with a disease duration of > 5 years was higher than those in patients with durations of 1-5 years and <1 year (7.72 ± 0.20 ng/l vs. 7.52 ± 0.09 ng/l and 7.41 ± 0.07 ng/l, P < 0.05). These results indicate that preexisting brain damage, seizure frequency and disease duration are important factors contributing to elevated PIGF.