High-Quality Assembly and Analysis of the Complete Mitogenomes of German Chamomile (Matricaria recutita) and Roman Chamomile (Chamaemelum nobile).

German chamomile (Matricaria chamomilla L.) and Roman chamomile (Chamaemelum nobile) are the two well-known chamomile species from the Asteraceae family. Owing to their essential oils and higher medicinal value, these have been cultivated widely across Europe, Northwest Asia, North America, and Africa. Regarding medicinal applications, German chamomile is the most commonly utilized variety and is frequently recognized as the "star among medicinal species". The insufficient availability of genomic resources may negatively impact the progression of chamomile industrialization. Chamomile's mitochondrial genome is lacking in extensive empirical research. In this study, we achieved the successful sequencing and assembly of the complete mitochondrial genome of M. chamomilla and C. nobile for the first time. An analysis was conducted on codon usage, sequence repeats within the mitochondrial genome of M. chamomilla and C. nobile. The phylogenetic analysis revealed a consistent positioning of M. chamomilla and C. nobile branches within both mitochondrial and plastid-sequence-based phylogenetic trees. Furthermore, the phylogenetic analysis also showed a close relationship between M. chamomilla and C. nobile within the clade comprising species from the Asteraceae family. The results of our analyses provide valuable resources for evolutionary research and molecular barcoding in chamomile.

Characterization of antipsychotic utilization before clozapine initiation for individuals with schizophrenia: an innovative visualization of trajectories using French National Health Insurance data.

AIMS: Despite recommendations to initiate clozapine after two unsuccessful trials of antipsychotics, clozapine is underprescribed and initiated too late. The aim of this study was to describe different antipsychotic treatment sequences in the 36 months before the initiation of clozapine and to characterize clusters of treatment trajectories. METHODS: Using the French National Health Insurance database, a historical cohort study of the population in an area in western France was performed. The data from all new users of clozapine with a diagnosis of schizophrenia or schizoaffective disorder in the period of 2017-2018 were evaluated. All outpatient reimbursements for antipsychotics during the 36 months before clozapine initiation were analysed. Successive reimbursements for identical treatments were grouped into treatment trials (TTs), and different trajectories were clustered using a state sequence analysis. RESULTS: The results showed 1191 TTs for 287 individuals. The mean number of TTs per individual was 3.2. Risperidone, aripiprazole and haloperidol were the main treatments delivered. The frequencies of antipsychotics used differed between monotherapies and combination therapies. A three-cluster typology was identified: one cluster (n = 133) of 'less treated' younger individuals with fewer TTs and shorter TT durations; a second cluster (n = 53) of 'more treated' individuals with higher numbers of TTs and combinations of antipsychotics; and a third cluster (n = 103) of 'treatment-stable' older individuals with longer TT durations. CONCLUSIONS: The results indicate that the median number of TTs during the 36 months before clozapine prescription was higher than the two recommended. The different trajectories were associated with individual characteristics and treatment differences, suggesting that additional studies of clinical parameters are needed to understand barriers to clozapine prescription.

The iceberg of genomics: New perspectives in the use of genomics and epigenetics in oncology nursing clinical reasoning. A discursive paper.

BACKGROUND: Although, there is a wealth of information in the medical literature on the usefulness of genomic testing in assessing risk and its application in medical oncology decision making, there are no theoretical reflections in the nursing field. AIM: To understand the implications of molecular biology in nursing practice and highlight the role of Nursing Theory in guiding nurses' reasoning. MATERIALS AND METHODS: Searching literature published between 2000 and 2022 in Medline and Google Scholar. Scientific evidence was analysed by the authors expert in different fields. RESULTS: Based on the findings of the literature, concerns have been raised about the proper care of cancer patients who have a genomic risk profile determination. In particular, the absence of theoretical thinking and conceptual models that consider developments in molecular biology and their impact on nursing, in addition to the prevalence of heuristic thinking and the application of clinical patterns in nursing practice, could induce patient misjudgement with inadequate planning of preventive, curative, rehabilitative and educational nursing interventions. Nurses working in the field of oncology should be aware that the risk profile determined by genomics tests is merely the visible and stated portion of the cancer patient: the tip of iceberg. DISCUSSION: This study demonstrates how genomic testing takes into account a fraction of genes discovered in tumour tissue to establish a risk profile. This subset differs, for example, from the social genome, which can determine the risk of dementia, cancer and cardiovascular disease, but in response to social adversity. Nursing theory, which views the environment as a metaparadigm, must consider a conceptual model that can integrate the findings of genomic testing with recommendations from studies on the social genome of humans to make it easier to build nursing treatments that can better reduce these risks. CONCLUSION: A nursing theoretical discourse on genomics is a paramount requirement for developing effective nursing care.

Whole genome analysis of Streptomyces sp. RerS4, a Rehmannia glutinosa rhizosphere microbe producing a new lipopeptide.

Rehmannia glutinosa, a valuable medicinal plant, is threatened by ring rot, a condition that greatly affects its yield and quality. Interactions between plant and the rhizosphere soil microbiome in the context of pathogen invasion are generally more specific, with recruitment of specialized microbes potentially antagonistic to a certain pathogen. Isolation of microorganisms from rhizosphere soil of healthy and ring rot-infected R. glutinosa was carried out to screen antifungal microbes. A strain designated RerS4 isolated from ring rot-infected R. glutinosa rhizosphere soil with strong antifungal activities was selected for further study. RerS4 was taxonomically characterized as the genus Streptomyces according to its morphology and 16S rRNA sequences that were most closely related to Streptomyces racemochromogenes NRRL B-5430T (99.72%) and Streptomyces polychromogenes NBRC 13072T (99.72%). A new lipopeptide isolated from RerS4 showed restrained proliferation, but was devoid of significant antibacterial and antioxidant activity with minimum inhibitory concentration (MIC) values of 20.3 ± 2.5 and 70.8 ± 3.7 µg/mL and half-maximal inhibitory concentration (IC50) values of 23.3 ± 0.8 and 58.8 ± 2.9 µg/mL, respectively. In addition, we report the complete genome sequence of Streptomyces sp. RerS4, which consists of a 7,301,482 bp linear chromosome and a 242,139 bp plasmid. Genome analysis revealed that Streptomyces sp. RerS4 contained 25 biosynthetic gene clusters (BGCs) for secondary metabolites, among which 68% had low similarities with known BGCs, leading us to believe that Streptomyces sp. RerS4 could produce valuable bioactive compounds.

[Identification and biological characterization of pathogen causing black spot of Pseudostellaria heterophylla in Fujian province].

In Zherong county, Fujian province, the black spot of Pseudostellaria heterophylla often breaks out in the rainy season from April to June every year. As one of the main leaf diseases of P. heterophylla, black spot seriously affects the yield and quality of the medicinal material. To identify and characterize the pathogens causing black spot, we isolated the pathogens, identified them as a species of Alternaria according to Koch's postulates, and then tested their pathogenicity and biological characteristics. The results showed that the pathogens causing P. heterophylla black spot were A. gaisen, as evidenced by the similar colony morphology, spore characteristics, sporulation phenotype, and the same clade with A. gaisen on the phylogenetic tree(the maximum likelihood support rate of 100% and the Bayesian posterior probability of 1.00) built based on the tandem sequences of ITS, tef1, gapdh, endoPG, Alta1, OPA10-2, and KOG1077. The optimum conditions for mycelial growth of the pathogen were 25 ℃, pH 5-8, and 24 h dark culture. The lethal conditions for mycelia and spores were both treatment at 50 ℃ for 10 min. We reported for the first time the A. gaisen-caused black spot of P. heterophylla. The results could provide a theoretical basis for the diagnosis and control of P. heterophylla leaf spot diseases.

Childbearing Trajectories in a West African Setting: A Sequence Analysis Approach.

The lagging fertility transition in West Africa has important repercussions for global population growth but remains poorly understood. Inspired by Caldwell and colleagues' fertility transition framework, as well as by subsequent research, we examine diversity in women's holistic childbearing trajectories in Niakhar, Senegal, between the early 1960s and 2018 using a sequence analysis approach. We evaluate the prevalence of different trajectories, their contribution to overall fertility levels, and their association with women's socioeconomic and cultural characteristics. Four trajectories were observed: "high fertility," "delayed entry," "truncated," and "short." While the high fertility trajectory was most prevalent across cohorts, delayed entry grew in importance. The high fertility trajectory was more common among women born between 1960 and 1969 and was followed less often by divorced women and those from polygynous households. Women with primary education and those from higher status groups were more likely to experience delayed entry. The truncated trajectory was associated with lack of economic wealth, polygynous households, and caste membership. A short trajectory was related to lack of agropastoral wealth, divorce, and possibly secondary sterility. Our study advances knowledge on fertility transitions in Niakhar-and Sahelian West African contexts more generally-by showing the diversity of childbearing trajectories within high fertility regional contexts.

Deciphering anti-biofilm property of Arthrospira platensis-origin peptides against Staphylococcusaureus.

Arthrospira platensis is a valuable natural health supplement consisting of various types of vitamins, dietary minerals, and antioxidants. Although different studies have been conducted to explore the hidden benefits of this bacterium, its antimicrobial property has been poorly understood. To decipher this important feature, here, we extended our recently introduced optimization algorithm (Trader) for aligning amino acid sequences associated with the antimicrobial peptides (AMPs) of Staphylococcus aureus and A.platensis. As a result, similar amino acid sequences were identified, and several candidate peptides were generated accordingly. The obtained peptides were then filtered based on their potential biochemical and biophysical properties, and their 3D structures were simulated based on homology modeling techniques. Next, to investigate how the generated peptides can interact with S. aureus proteins (i.e., heptameric state of the hly and homodimeric form of the arsB), molecular docking approaches were used. The results indicated that four peptides included better molecular interactions relative to the other generated ones in terms of the number/average length of hydrogen bonds and hydrophobic interactions. Based on the outcomes, it can be concluded that the antimicrobial property of A.platensis might be associated with its capability in disturbing the membrane of pathogens and their functions.

Efficacy of electroacupunture at Zusanli (ST36) on jumping-injured muscle based on transcriptome sequencing and genes analysis.

OBJECTIVE: To reveal the efficacy and possible mechanism of electroacupuncture at Zusanli (ST36) on injured skeletal muscle induced by jumping load. METHODS: In the present study, female Sprague-Dawley rats were randomly divided into four groups with 6 of each, including normal control group (NC), jumping-induced muscle injury model group (JI), JI with electroacupuncture stimulation treatment group (EA), and JI with non-electroacupuncture stimulation group (NEA). Transmission electron microscopy, transcriptome sequencing and analysis, prediction of protein interaction networks, real-time polymerase chain reaction verification, and Western blotting were performed on the gastrocnemius muscle of ipsilateral lower limbs. RESULTS: The structural repair of injured gastrocnemius myofibers following jumping training in EA rats was better than that of NEA rats. A total of 136 genes were differentially expressed in EA rats relative to JI rats, with 55 genes upregulated and 81 genes downregulated. According to results of transcriptome analysis, and prediction of protein mutual interaction by the online STRING database, Heat shock protein beta-7 (Hspb7) and myozenin2 (Myoz2) genes were targeted. Expressions of Hspb7 and Myoz2 mRNAs were increased in EA rats relative to JI rats (0.05). The expression of Hspb7 protein was upregulated in EA rats relative to that in NC, JI, and NEA rats (0.01, 0.05, and0.05, respectively). The expression of Myoz2 protein was upregulated in EA rats relative to that in NC and JI rats (both 0.01respectively). CONCLUSIONS: The present results suggest that electroacupuncture stimulation at Zusanli (ST36) could improve muscle healing following jumping-induced muscle injury, owing to the upregulation of Hspb7 and Myoz2 proteins.

Cloning and expression analysis of HY5 transcription factor gene of safflower in response to light signal.

The flower of the safflower (Carthamus tinctorius L.) is a traditional Chinese medicine that can improve cerebral blood flow due to its enrichment in flavonoids. Light is one of the main environmental factors that affects safflower growth and flavonoid synthesis. Elongated hypocotyl 5 (HY5) plays an important role in plants' light signal transduction. However, no study of HY5 in safflower has been conducted. In this study, a 462-bp sequence of CtHY5 was successfully cloned. The expression pattern of CtHY5 in different safflower tissues and the expression patterns of CtHY5 and CtCHS1 in full-blooming flowers that were treated under different light intensities were studied. The subcellular localization and the overexpression of CtHY5 were carried out as well. CtHY5 has a DNA-binding region belonging to the basic leucine zipper transcription factor family. CtHY5 was specifically expressed in flowers. The expression level of CtHY5 first increased and then decreased with increasing light intensity, which was similar to the expression pattern of CtCHS1. The subcellular localization study was implemented in safflower protoplasts and the YFP fluorescence was observed in nucleus. The overexpression analysis initially verified the promotion effect of CtHY5 to the expression of CtCHS1 and the content of flavonoids.

Phylogenetic analysis of chloroplast genome of Tussilago farfara L / 药学学报

italic>Tussilago farfara L. is a perennial herb of Tussilago genus in the Compositae family. Its dried buds and leaves have good biological activities and have a long history of medicinal use in China and Europe. In this paper, we investigated the whole chloroplast genome characteristics, sequence duplication, structural variation and phylogeny of the Tussilago farfara L. After sequencing the Tussilago farfara L. chloroplast genome using Illumination technology, the complete Tussilago farfara L. chloroplast genome was further obtained by assembly and annotation, followed by a series of inverted repeat-large single copy/small single copy region contraction and expansion analysis, genome sequence variation, etc. The sequences of 13 homologous plants downloaded from NCBI were used to construct a neighbor-joining phylogenetic tree. The results showed that the total GC content of the chloroplast genome was 37.4% and the length was 150 300 bp; 125 genes were annotated, including 82 protein-coding genes, 35 tRNAs and 8 rRNAs; 148 (simple sequence repeats, SSR) loci were detected, and the relative synonymous codon usage showed that 31 codons out of 64 codons had a usage of >1. In the phylogenetic analysis, the chloroplast genomes of the seven species of Asteraceae, including the Yulin Tussilago farfara L., were highly conserved, and the sequence variation of the (large single-copy, LSC) and (small single-copy, SSC) regions was higher than that of the (inverted repeat, IR) region. This is in general agreement with the reported phylogeny of Yulin Tussilago farfara L. In this study, we obtained a high quality chloroplast genome and analyzed its genome characteristics, codon preference, SSR characteristics, SC/IR boundary, sequence variation and phylogeny, which can provide a basis for species identification, genetic diversity analysis and resource development of this medicinal plant.

Anti-inflammatory effect of green photobiomodulation in human adipose-derived mesenchymal stem cells.

Photo biomodulation (PBM) as a non-invasive and safe treatment has been demonstrated the anti-inflammatory potential in a variety of cell types, including stem cells. However, further investigations using different laser parameters combined with more accurate methods such as quantitative measurement of inflammatory gene expression at the mRNA level are still necessary. The aim of this study was to evaluate the effect of 532 nm green laser on cell proliferation as well as expression of inflammatory genes in human adipose-derived mesenchymal stem cells (hADMSCs) using RNA sequencing (RNA-seq) technique and confirmatory RT-PCR. hADMSCs were cultured in DMEM low glocuse medium with 10% fetal bovine serum until the fourth passage. Cultured cells were divided in two groups: control group (no laser irradiation) and laser group, irradiated with 532 nm laser at 44 m J/cm2 with an output power of 50 mW and a density of 6 mW/cm2, every other day, 7 s each time. The cell viability was assessed using MTT assay 24 h after each irradiation on days 3, 5, and 7 after cell seeding, followed by performing RNA-seq and RT-PCR. The MTT assay showed that PBM increased cell proliferation on day 5 after irradiation compared to day 3 and decreased on day 7 compared to day 5. In addition, gene expression analysis in hADMSCs using RNA-seq revealed down-regulation of inflammatory genes including CSF2, CXCL2, 3, 5, 6, 8, and CCL2, 7. These results indicate that 532 nm PBM with the parameters used in this study has a time-dependent effect on hADMSCs proliferation as well as anti-inflammatory potential.

Screening saikosaponin d (SSd)-producing endophytic fungi from Bupleurum scorzonerifolium Willd.

Saikosaponin d (SSd) is an important bioactive compound of traditional Chinese medicinal plant Bupleurum scorzonerifolium Willd. and exhibits many effects, such as anti-tumor, anti-inflammation and immunomodulatory. Since endophytic fungi possess the natural capacity to produce the similar secondary metabolite to that of their host plants, they are promising as alternative sources of plant bioactive natural products. In this study, in order to search for SSd-producing strains, endophytes were isolated from B. scorzonerifolium and were authenticated by the ITS sequence and the translation elongation factor-1alpha gene (TEF-1α) sequence analysis. The profile of metabolites present in the crude exacts was carried out by ultra performance liquid chromatography time-of-flight mass spectrometry (UPLC/Q-TOF-MS) analysis. The results showed that two strains, CHS2 and CHS3 from B. scorzonerifolium could produce SSd by UPLC/Q-TOF-MS analysis, and the amount of SSd produced by strain CHS2 and CHS3 were about 2.17 and 2.40 µg/mL, respectively. CHS2 and CHS3 showed a close phylogenetic relationship to Fusarium oxysporum and Fusarium acuminatum, respectively. According to our concern, no endophytic fungi capable of producing SSd from B. scorzonerifolium have been found before. Our clear intention was to isolate and identify these endophytic fungi that produce important active secondary metabolites, and then study the strains that produce this compound on a large scale through fermentation or even genetic study, to provide a feasible and more convenient way for the production of SSd.

[Identification of GeERF transcription factors in Gelsmium elegans and their expression under low temperature stress].

With prominent medicinal value, Gelsemium elegans has been overexploited, resulting in the reduction of the wild resource. As a result, artificial cultivation turns out to be a solution. However, this medicinal species is intolerant to low temperature, and thus genes responding to the low temperature are important for the cultivation of this species. Based on the transcriptome database of G. elegans at 4 ℃, 29 differentially expressed GeERF genes were identified. Bioinformatics analysis of 21 GeERF gene sequences with intact open reading frames showed that 12 and 9 of the GeERF proteins respectively clustered in DREB subgroup and ERF subgroup. GeDREB1 A-1-GeERF6 B-1, with molecular weight of 23.78-50.96 kDa and length of 212-459 aa, were all predicted to be hydrophilic and in nucleus. Furthermore, the full-length cDNA sequence of GeERF2B-1 was cloned from the leaves of G. elegans. Subcellular localization suggested that GeERF2B-1 was located in the nucleus. According to the quantitative reverse-transcription PCR(qRT-PCR), GeERF2B-1 showed constitutive expression in roots, stems, and leaves of G. elegans, and the expression was the highest in roots. In terms of the response to 4 ℃ treatment, the expression of GeERF2B-1 was significantly higher than that in the control and peaked at 12 h, suggesting a positive response to low temperature. This study lays a scientific basis for the functional study of GeERF transcription factors and provides gene resources for the improvement of stress resistance of G. elegans.

SAPPHIRE: A stacking-based ensemble learning framework for accurate prediction of thermophilic proteins.

Thermophilic proteins (TPPs) are important in the field of protein biochemistry and development of new enzymes. Thus, computational methods must be urgently developed to accurately and rapidly identify TPPs. To date, several computational methods have been developed for TPP identification; however, few limitations in terms of performance and utility remain. In this study, we present a novel computational method, SAPPHIRE, to achieve more accurate identification of TPPs using only sequence information without any need for structural information. We combined twelve different feature encodings representing different perspectives and six popular machine learning algorithms to train 72 baseline models and extract the key information of TPPs. Subsequently, the informative predicted probabilities from the baseline models were mined and selected using a genetic algorithm in conjunction with a self-assessment-report approach. Finally, the final meta-predictor, SAPPHIRE, was built and optimized by applying an optimal feature set. The performance of SAPPHIRE in the 10-fold cross-validation test showed that a superior predictive performance compared with several baseline models could be achieved. Moreover, SAPPHIRE yielded an accuracy of 0.942 and Matthew's coefficient correlation of 0.884, which were 7.68 and 5.12% higher than those of the current existing methods, respectively, as indicated by the independent test. The proposed computational approach is anticipated to facilitate large-scale identification of TPPs and accelerate their applications in the food industry. The codes and datasets are available at https://github.com/plenoi/SAPPHIRE.

Clinical efficacy of acupuncture for pain relief from renal colic: A meta-analysis and trial sequence analysis.

Background: This meta-analysis aimed at investigating the efficacy of acupuncture for relieving renal colic and reducing the risk of analgesic-related complications. Methods: Randomized controlled trials (RCTs) comparing the efficacy of acupuncture (acupuncture group) with conventional interventions (control group) were screened from MEDLINE, EMBASE, Cochrane library databases, China Knowledge Network (CNKI), and Airiti Library till July 15, 2022. The primary outcome was the rate of effective pain relief (response rate), while secondary outcomes included the time of onset of pain relief, visual analog scale (VAS) at 30-60 min and risk of side effects. Results: Thirteen eligible studies involving 1,212 participants published between 1992 and 2021 were analyzed. Compared with the control group, patients receiving acupuncture had a higher overall response rate [risk ratio (RR) = 1.12, 95% CI: 1.05-1.19, p = 0.0002, I 2 = 41%, 1,136 patients] (primary outcome) and a faster pain relief [MD = -10.74 min, 95% CI: -12.65 to -8.82, p < 0.00001, I 2 = 87%, 839 patients]. Patients receiving acupuncture had a lower pain score [MD = -0.65, 95% CI: -1.09 to -0.21, p = 0.21, I 2 = 55%, 327 patients] and risk of side effects (RR = 0.11, 95% CI: 0.04-0.26, p < 0.00001, I 2 = 0, 314 patients) compared to those receiving conventional interventions. Results from trial sequence analysis revealed sufficient evidence supporting the beneficial effects of acupuncture on response rate, time to pain relief, and pain score at 30-60 min. Conclusion: Compared with conventional analgesic-based interventions, acupuncture can more efficiently relieve renal colic with fewer adverse effects. The limited number and quality of included studies warrant more clinical RCTs to support our findings. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022346714.

Antimicrobial resistance among leprosy patients in Brazil: real-world data based on the National Surveillance plan

Brazil ranks second among countries for new cases and first for relapse cases of leprosy worldwide. The Mycobacterium leprae Resistance Surveillance Plan was established. We aimed to present the results of a 2-year follow-up of the National Surveillance Plan in Brazil. A cross-sectional study of leprosy cases was performed to investigate antimicrobial resistance (AMR) in Brazil from October 2018 to September 2020. Molecular screening targeting genes related to dapsone (folP1), rifampin (rpoB), and ofloxacin resistance (gyrA) was performed. During the referral period, 63,520 active leprosy patients were registered in Brazil, and 1,183 fulfilled the inclusion criteria for molecular AMR investigation. In total, only 16 (1.4%) patients had genetic polymorphisms associated with AMR. Of these, 8 (50%) had cases of leprosy relapse, 7 (43.8%) had cases of suspected therapeutic failure with standard treatment, and 1 (6.2%) was a case of new leprosy presentation. M. leprae strains with AMR-associated mutations were found for all three genes screened. Isolates from two patients showed simultaneous resistance to dapsone and rifampin, indicating multidrug resistance (MDR). No significant relation ship between clinical variables and the presence of AMR was identified. Our study revealed a low frequency of AMR in Brazil. Isolates were resistant mainly to dapsone, and a very low number of isolates were resistant to rifampin, the main bactericidal agent for leprosy, or presented MDR, reinforcing the importance of the standard World Health Organization multidrug therapy. The greater frequency of AMR among relapsed patients supports the need to constantly monitor this group

[Pharmacovigilance of traditional Chinese medicine: an exploration based on prescription sequence analysis and prescription sequence symmetry analysis].

Multiple methods should be incorporated into the research on pharmacovigilance of traditional Chinese medicine(TCM for a comprehensive and objective evaluation. The arrival of the era of medical big data allows it to be deeply integrated into medical research. The real world study(RWS) represented by hospital information system(HIS) provides a data basis for exploring the pharmacovigilance of TCM. Prescription sequence analysis(PSA) and prescription sequence symmetry analysis(PSSA) developed based on the former serve as a methodological basis for clinical safety evaluation of Chinese patent medicines after marketing. By collating the related studies of HIS, PSA and PSSA and employing the propensity score matching( PSM) method and nested case-control study(NCCS), this paper formed a HIS-, PSA-and PSSA-based technical system for clinical safety evaluation of Chinese patent medicines in the real world, in order to provide a methodological demonstration for the future research on the pharmacovigilance of TCM.

Pharmacovigilance of traditional Chinese medicine: an exploration based on prescription sequence analysis and prescription sequence symmetry analysis / 中国中药杂志

Multiple methods should be incorporated into the research on pharmacovigilance of traditional Chinese medicine(TCM for a comprehensive and objective evaluation. The arrival of the era of medical big data allows it to be deeply integrated into medical research. The real world study(RWS) represented by hospital information system(HIS) provides a data basis for exploring the pharmacovigilance of TCM. Prescription sequence analysis(PSA) and prescription sequence symmetry analysis(PSSA) developed based on the former serve as a methodological basis for clinical safety evaluation of Chinese patent medicines after marketing. By collating the related studies of HIS, PSA and PSSA and employing the propensity score matching( PSM) method and nested case-control study(NCCS), this paper formed a HIS-, PSA-and PSSA-based technical system for clinical safety evaluation of Chinese patent medicines in the real world, in order to provide a methodological demonstration for the future research on the pharmacovigilance of TCM.

Harnessing Single-Cell RNA Sequencing to Better Understand How Diseased Cells Behave the Way They Do in Cardiovascular Disease.

The transition of healthy arteries and cardiac valves into dense, cell-rich, calcified, and fibrotic tissues is driven by a complex interplay of both cellular and molecular mechanisms. Specific cell types in these cardiovascular tissues become activated following the exposure to systemic stimuli including circulating lipoproteins or inflammatory mediators. This activation induces multiple cascades of events where changes in cell phenotypes and activation of certain receptors may trigger multiple pathways and specific alterations to the transcriptome. Modifications to the transcriptome and proteome can give rise to pathological cell phenotypes and trigger mechanisms that exacerbate inflammation, proliferation, calcification, and recruitment of resident or distant cells. Accumulating evidence suggests that each cell type involved in vascular and valvular diseases is heterogeneous. Single-cell RNA sequencing is a transforming medical research tool that enables the profiling of the unique fingerprints at single-cell levels. Its applications have allowed the construction of cell atlases including the mammalian heart and tissue vasculature and the discovery of new cell types implicated in cardiovascular disease. Recent advances in single-cell RNA sequencing have facilitated the identification of novel resident cell populations that become activated during disease and has allowed tracing the transition of healthy cells into pathological phenotypes. Furthermore, single-cell RNA sequencing has permitted the characterization of heterogeneous cell subpopulations with unique genetic profiles in healthy and pathological cardiovascular tissues. In this review, we highlight the latest groundbreaking research that has improved our understanding of the pathological mechanisms of atherosclerosis and future directions for calcific aortic valve disease.

First report of 16SrI-B subgroup related phytoplasma associated with witches'-broom symptoms in Pericampylus glaucus in China.

Pericampylus glaucus is an important medicinal plant resource containing active components with potential antitumor activity in China (Zhao & Cui, 2009). During July through August 2020, plants displayed disease symptoms including "witches' broom", leaf chlorosis, leaflet and internode shortening that impacted their growth (Fig. 1). These plants were first found in Dingan county of Hainan province, China. Total DNA from 12 plants were extracted using 0.10 g fresh plant leaves based on CTAB method. After amplification using primers specific for phytoplasma 16S rRNA, tuf and secA gene targets, R16mF2R16mR1 (Lee et al, 1993), fTuf1/rTuf1 (Schneider et al., 1997) and secAfor1/secArev3 (Hodgetts et al., 2008), the target bands of the three gene fragments of phytoplasma were detected in the disease sample DNA from six disease plants, and not in the healthy sample DNA from six healthy plants. Nucleotide sequences of the three genes were obtained from the PCR products sequencing and analyzed by DNAMAN 5.0 software. The three gene fragments of the DNA extracted from the disease samples were identical, with length of 1334 bp 16S rRNA (GenBank accession: MT872515), 989 bp tuf (MT755960) and 750 bp secA (MT755961) gene fragments, putatively encoding 329 (tuf) and 249 (secA) amino acids sequence separately. The phytoplasma strain was named as Pericampylus glaucus witches'-broom (PgWB) phytoplasma, PgWB-hnda strain, belonging to 16SrI-B subgroup by iPhyClassifier analysis. Homology and phylogenetic analysis indicated that based on 16S rRNA gene fragments, PgWB-hnda, pepper yellow crinkle phytoplasma PYC-hnhk (MT760793), chinaberry witches'-broom phytoplasma CWB-hnsy1 (KP662119) and CWB-hn (EF990733), periwinkle virescence phytoplasma PeV-hnhk (KP662136), with 100.0 % identity value, arecanut yellow leaf phytoplasma AYL-hnwn (FJ998269) and AYL-hn (FJ694685), with 99.8 % identity value, were clustered into one clade. Based on the analysis of tuf gene sequence fragments, PgWB was closely related to PYC-hnhk (MT755960), CWB-hnsy1 (KP662155), PeV-hnhk (KP662172) with 99.9 % identity value. Based on the analysis of secA gene sequence fragments, PgWB was closely related to CWB-hnsy1 (KP662173) with 99.7 % identity value, PYC-hnhk (MT755961), PeV-hnhk (KP662190) with 99.4 % identity value. To our knowledge, this is the first time that Pericampylus glaucus witches'-broom disease caused by 16SrI-B subgroup phytoplasma strain was found in China. Multilocus sequence analysis showed that PgWB was closely related to the phytoplasma strains causing pepper yellow crinkle, chinaberry witches'-broom, periwinkle virescence and areca palm yellow leaf diseases, all occurred in Hainan Island of China.