Comprehensive Analysis of the Complete Mitochondrial Genome of Rehmannia chingii: An Autotrophic Species in the Orobanchaceae Family.

Rehmannia chingii is an important medicinal plant with immense value in scientific research. However, its mitochondrial genome (mitogenome) has not yet been characterized. Herein, based on whole-genome Illumina short reads and PacBio HiFi reads, we obtained the complete mitogenome of R. chingii through a de novo assembly strategy. We carried out comparative genomic analyses and found that, in comparison with the plastid genome (plastome) showing a high degree of structural conservation, the R. chingii mitogenome structure is relatively complex, showing an intricate ring structure with 16 connections, owing to five repetitive sequences. The R. chingii mitogenome was 783,161 bp with a GC content of 44.8% and contained 77 genes, comprising 47 protein-coding genes (CDS), 27 tRNA genes, and 3 rRNA genes. We counted 579 RNA editing events in 47 CDS and 12,828 codons in all CDSs of the R. chingii mitogenome. Furthermore, 24 unique sequence transfer fragments were found between the mitogenome and plastome, comprising 8 mitogenome CDS genes and 16 plastome CDS genes, corresponding to 2.39% of the R. chingii mitogenome. Mitogenomes had shorter but more collinear regions, evidenced by a comparison of the organelles of non-parasitic R. chingii, hemiparasitic Pedicularis chinensis, and holoparasitic Aeginetia indica in the Orobanchaceae family. Moreover, from non-parasitic to holoparasitic species, the genome size in the mitogenomes of Orobanchaceae species did not decrease gradually. Instead, the smallest mitogenome was found in the hemiparasitic species P. chinensis, with a size of 225,612 bp. The findings fill the gap in the mitogenome research of the medicinal plant R. chingii, promote the progress of the organelle genome research of the Orobanchaceae family, and provide clues for molecular breeding.

Species delimitation in Amana (Liliaceae): transcriptomes battle with evolutionary complexity.

Species delimitation has long been a subject of controversy, and there are many alternative concepts and approaches used to define species in plants. The genus Amana (Liliaceae), known as "East Asian tulips" has a number of cryptic species and a huge genome size (1C = 21.48-57.35 pg). It also is intriguing how such a spring ephemeral genus thrives in subtropical areas. However, phylogenetic relationships and species delimitation within Amana are challenging. Here we included all species and 84 populations of Amana, which are collected throughout its distribution range. A variety of methods were used to clarify its species relationships based on a combination of morphological, ecological, genetic, evolutionary and phylogenetic species concepts. This evidence supports the recognition of at least 12 species in Amana. Moreover, we explored the complex evolutionary history within the genus and detected several historical hybridization and introgression events based on phylogenetic trees (transcriptomic and plastid), phylonetworks, admixture and ABBA-BABA analyses. Morphological traits have undergone parallel evolution in the genus. This spring ephemeral genus might have originated from a temperate region, yet finally thrives in subtropical areas, and three hypotheses about its adaptive evolution are proposed for future testing. In addition, we propose a new species, Amana polymorpha, from eastern Zhejiang Province, China. This research also demonstrates that molecular evidence at the genome level (such as transcriptomes) has greatly improved the accuracy and reasonability of species delimitation and taxon classification.

Comparative analysis of Diospyros (Ebenaceae) plastomes: Insights into genomic features, mutational hotspots, and adaptive evolution.

Diospyros (Ebenaceae) is a widely distributed genus of trees and shrubs from pantropical to temperate regions, with numerous species valued for their fruits (persimmons), timber, and medicinal values. However, information regarding their plastomes and chloroplast evolution is scarce. The present study performed comparative genomic and evolutionary analyses on plastomes of 45 accepted Diospyros species, including three newly sequenced ones. Our study showed a highly conserved genomic structure across the Diospyros species, with 135-136 encoding genes, including 89 protein-coding genes, 1-2 pseudogenes (Ψycf1 for all, Ψrps19 for a few), 37 tRNA genes and 8 rRNA genes. Comparative analysis of Diospyros identified three intergenic regions (ccsA-ndhD, rps16-psbK and petA-psbJ) and five genes (rpl33, rpl22, petL, psaC and rps15) as the mutational hotspots in these species. Phylogenomic analysis identified the phylogenetic position of three newly sequenced ones and well supported a monophylogenetic (sub)temperate taxa and four clades in the pantropical taxa. The analysis codon usage identified 30 codons with relative synonymous codon usage (RSCU) values >1 and 29 codons ending with A and U bases. A total of three codons (UUA, GCU, and AGA) with highest RSCU values were identified as the optimal codons. Effective number of codons (ENC)-plot indicated the significant role of mutational pressure in shaping codon usage, while most protein-coding genes in Diospyros experienced relaxed purifying selection (d N/d S < 1). Additionally, the psbH gene showed positive selection (d N/d S > 1) in the (sub)temperate species. Thus, the results provide a meaningful foundation for further elaborating Diospyros's genetic architecture and taxonomy, enriching genetic diversity and conserving genetic resources.

An Analysis Regarding the Association Between the Nuclear Pore Complex (NPC) and Hepatocellular Carcinoma (HCC).

Background: The nuclear pore complex (NPC) is the main mediator of nuclear and cytoplasmic communication, and delaying or blocking nuclear RNA export and protein shuttling can inhibit cell proliferation and induce apoptosis. Although NPC is a research hotspot in structural biology, relevant studies in hepatocellular carcinoma are scarce, especially in terms of translation into clinical practice. Methods: This study used a bioinformatics approach combining validation experiments to investigate the biological mechanisms that may be related with NPC. A series of experiments performed to explore the function of the Targeting protein for Xenopus kinesin-like protein 2 (TPX2) in HCC. Results: Patients with HCC can be divided into two NPC clusters. Patients with high NPC levels (C1) had a shorter survival time than those with low NPC levels (C2) and are characterised by high levels of proliferative signals. We demonstrated that TPX2 regulates HCC growth and inhibits apoptosis in an NPC-dependent manner and contributes to the maintenance of HCC stemness. We developed the NPCScore to predict the prognosis and degree of differentiation in HCC patients. Conclusion: NPC plays an important role in the malignant proliferation of HCC. Assessing NPC expression patterns could help enhance our understanding of tumor cell proliferation and could guide more effective chemotherapeutic strategies.

Phylogenomics and integrative taxonomy reveal two new species of Amana (Liliaceae).

Until now the genus Amana (Liliaceae), known as 'East Asian tulips', has contained just seven species. In this study, a phylogenomic and integrative taxonomic approach was used to reveal two new species, Amana nanyueensis from Central China and A. tianmuensis from East China. A. nanyueensis resembles Amana edulis in possessing a densely villous-woolly bulb tunic and two opposite bracts, but differs in its leaves and anthers. Amana tianmuensis resembles Amana erythronioides in possessing three verticillate bracts and yellow anthers, but differs in aspects of its leaves and bulbs. These four species are clearly separated from each other in principal components analysis based on morphology. Phylogenomic analyses based on plastid CDS further support the species delimitation of A. nanyueensis and A. tianmuensis and suggests they are closely related to A. edulis. Cytological analysis shows that A. nanyueensis and A. tianmuensis are both diploid (2n = 2x = 24), different from A. edulis, which is either diploid (northern populations) or tetraploid (southern populations, 2n = 4x = 48). The pollen morphology of A. nanyueensis is similar to other Amana species (single-groove germination aperture), but A. tianmuensis is quite different because of the presence of a sulcus membrane, which creates the illusion of double grooves. Ecological niche modelling also revealed a niche differentiation between A. edulis, A. nanyueensis and A. tianmuensis.

Molecular phylogeography and species distribution modelling evidence of 'oceanic' adaptation for Actinidia eriantha with a refugium along the oceanic-continental gradient in a biodiversity hotspot.

BACKGROUND: Refugia is considered to be critical for maintaining biodiversity; while discerning the type and pattern of refugia is pivotal for our understanding of evolutionary processes in the context of conservation. Interglacial and glacial refugia have been studied throughout subtropical China. However, studies on refugia along the oceanic-continental gradient have largely been ignored. We used a liana Actinidia eriantha, which occurs across the eastern moist evergreen broad-leaved forests of subtropical China, as a case study to test hypotheses of refugia along the oceanic-continental gradient and 'oceanic' adaptation. RESULTS: The phylogeographic pattern of A. eriantha was explored using a combination of three cpDNA markers and 38 nuclear microsatellite loci, Species distribution modelling and dispersal corridors analysis. Our data showed intermediate levels of genetic diversity [haplotype diversity (hT) = 0.498; unbiased expected heterozygosity (UHE) = 0.510] both at the species and population level. Microsatellite loci revealed five clusters largely corresponding to geographic regions. Coalescent time of cpDNA lineages was dated to the middle Pliocene (ca. 4.03 Ma). Both geographic distance and climate difference have important roles for intraspecific divergence of the species. The Zhejiang-Fujian Hilly Region was demonstrated to be a refugium along the oceanic-continental gradient of the species and fit the 'refugia in refugia' pattern. Species distribution modelling analysis indicated that Precipitation of Coldest Quarter (importance of 44%), Temperature Seasonality (29%) and Mean Temperature of Wettest Quarter (25%) contributed the most to model development. By checking the isolines in the three climate layers, we found that A. eriantha prefer higher precipitation during the coldest quarter, lower seasonal temperature difference and lower mean temperature during the wettest quarter, which correspond to 'oceanic' adaptation. Actinidia eriantha expanded to its western distribution range along the dispersal corridor repeatedly during the glacial periods. CONCLUSIONS: Overall, our results provide integrated evidence demonstrating that the Zhejiang-Fujian Hilly Region is a refugium along the oceanic-continental gradient of Actinidia eriantha in subtropical China and that speciation is attributed to 'oceanic' adaptation. This study gives a deeper understanding of the refugia in subtropical China and will contribute to the conservation and utilization of kiwifruit wild resources in the context of climate change.

Elsholtziazhongyangii (Lamiaceae), a new species from Sichuan, China.

Elsholtziazhongyangii (Lamiaceae), a new species from Sichuan Province, China, is described and illustrated. The new species is morphologically similar to E.feddeif.feddei, but it can be easily distinguished from E.feddeif.feddei by smaller corolla (3.2-3.5 mm vs. 4.5-5.3 mm), bract indumentum (glabrous, except margin ciliate vs. villous, especially on veins abaxially, glabrous adaxially) and bract stalked (ca. 1.2 mm vs. sessile). Phylogenetic analyses, based on two nuclear ribosomal (ETS, ITS) and five plastid (rbcL, matK, trnL-F, ycf1, ycf1-rps15) regions, confirmed that the new species formed a monophyletic clade with robust support. The new species is currently known from western Sichuan.

Overexpression of NREP Promotes Migration and Invasion in Gastric Cancer Through Facilitating Epithelial-Mesenchymal Transition.

The identification of biomarkers and effective therapeutic targets for gastric cancer (GC), the most common cause of cancer-related deaths around the world, is currently a major focus area in research. Here, we examined the utility of Neuronal Regeneration Related Protein (NREP) as a prognostic biomarker and therapeutic target for GC. We assessed the clinical relevance, function, and molecular role of NREP in GC using bioinformatics analysis and experimental validation. Our results showed that in GC, NREP overexpression was significantly associated with a poor prognosis. Our findings also suggested that NREP may be involved in the activation of cancer-associated fibroblasts and the epithelial-mesenchymal transition (EMT), with transforming growth factor ß1 mediating both processes. In addition, NREP expression showed a positive correlation with the abundance of M2 macrophages, which are potent immunosuppressors. Together, these results indicate that NREP is overexpressed in GC and affects GC prognosis. Thus, NREP could be a prognostic biomarker and therapeutic target for GC.

FSTL3 is a Prognostic Biomarker in Gastric Cancer and is Correlated with M2 Macrophage Infiltration.

PURPOSE: Follistatin-related gene 3 (FSTL3), an established oncogene, can modulate target gene expression via members of the transforming growth factor ß (TGF-ß) superfamily. The present study was conducted to evaluate the expression of FSTL3 in gastric cancer (GC) and to determine its prognostic significance. We also evaluated the possible mechanisms involved in the oncogenic role of FSTL3 in gastric carcinogenesis and development. METHODS: We obtained data from the Human Protein Atlas, MethSurv, cBioPortal, UALCAN, TIMER, GEPIA, STRING, GeneMANIA, ONCOMINE, and MEXPRESS databases and examined it using R software. RNAi was used to establish stable FSTL3-knockdown (shFSTL3) and overexpression (OE) cell strains. Western blot; enzyme-linked immunosorbent (ELISA); and immunohistochemical (ICH), immunofluorescence, and phalloidin staining were used for examining protein expression. Cell invasion and migration were determined using transwell and scratch-wound assays. After tumor-associated macrophage (TAM) generation, co-culturing of cancer cells with TAMs was performed to confirm the relationship between FSTL3 and TAMs. RESULTS: In GC patients, FSTL3 mRNA and protein levels were upregulated. FSTL3 expression was significantly linked to cancer stage as well as to pathological tumor grade in GC. Moreover, a high expression of FSTL3 was associated with a dismal survival duration in patients with GC. Furthermore, functional enrichment analysis demonstrated that FSTL3 overexpression could activate epithelial-mesenchymal transition (EMT) by promoting F-actin expression and BMP/SMAD signaling. Finally, immunofluorescence staining confirmed that the overexpression of FSTL3 promoted the proliferation of M2 TAMs. CONCLUSION: Taken together, our findings suggest that FSTL3 may be involved in GC progression via the promotion of BMP/SMAD signaling-mediated EMT and M2 macrophage activation.

Bioinformatics-based analysis of the association between the A1-chimaerin (CHN1) gene and gastric cancer.

Gastric cancer (GC) is one of the most common causes of cancer-related deaths worldwide and the identification of additional therapeutic targets and biomarkers has become vital. The A1-chimaerin (CHN1) gene encodes a ras-related protein that can be activated or inactivated by binding to GTP or GDP. The present study aimed to assess the expression of CHN1 in GC tissue and cells, to explore its relationship with GC progression, and to discover the potential mechanisms underlying these associations. The ONCOMINE database and The Cancer Genome Atlas (TCGA) were used to determine the transcriptional levels of CHN1 in GC. Western blot and immunohistochemistry were used for detecting protein expression. Correlations between CHN1 levels and the clinical outcomes of GC patients were examined using Kaplan-Meier and Cox regression analyses. Moreover, the CIBERSORT algorithm was used to estimate immune cell infiltration. In GC patients, CHN1 transcription and CHN1 protein expression were upregulated, and a high expression of CHN1 was remarkably linked to poor survival in GC patients. CHN1 expression was associated with immune infiltrates and this gene showed potential involvement in multiple cancer-related pathways. Furthermore, the expression of CHN1 was correlated with the immunotherapeutic response. Finally, our results indicated that the pro-carcinogenic role of CHN1 may involve DNA methylation. To our knowledge, this is the first report characterizing CHN1 expression in GC. Our results show that high CHN1 levels could be used as a clinical biomarker for poor prognosis and that CHN1 inhibitors may have potential as anti-cancer drugs.

Expanded activated autologous lymphocyte infusions improve outcomes of low- and intermediate-risk childhood acute myeloid leukemia with low level of minimal residual disease.

The presence of minimal residual disease (MRD) is a risk factor for relapse among children with acute myeloid leukemia (AML), and eliminating MRD can usually improve survival rates. To investigate the effect of expanded activated autologous lymphocytes (EAALs) combined with chemotherapy on eliminating MRD and improving survival rates of children with AML, we retrospectively analyzed the results of 115 children with low- or intermediate-risk AML with MRD treated at the Pediatric Hematological Center, Peking University People's Hospital, between January 2010 and January 2016. The patients were assigned to the chemotherapy plus EAAL (combined therapy) group (n = 61) and chemotherapy group (n = 54). The MRD-negativity rates were 95.1% (58/61) in the combined therapy group and 63.0% (34/54) in the chemotherapy group (P < 0.0001) during consolidation treatment. The 5-year event-free survival rate was higher in the combined therapy group than in the chemotherapy group (86.3 ± 4.6% vs. 72.1 ± 6.1%, P = 0.025). No severe adverse event was observed after EAAL infusion. The present study showed that EAAL combined with chemotherapy could improve the MRD-negativity rate and event-free survival rate among children with AML with low level MRD-positive status.

Efficacy and Safety of Jiawei Suanzaoren Decoction Combined with Lorazepam for Chronic Insomnia: A Parallel-Group Randomized Controlled Trial.

BACKGROUND: Chronic insomnia is a major public health problem, but there are limited effective therapies. Jiawei Suanzaoren Decoction (JW-SZRD) has been used as an alternative option for treating insomnia. This study aimed to investigate the long-term efficacy and safety of JW-SZRD in combination with lorazepam for chronic insomnia. METHODS: A total of 207 participants were analyzed in this study. The treatment group (TG) received JW-SZRD and lorazepam orally, and the control group (CG) received lorazepam alone. The Insomnia Severity Index (ISI), the Self-Rating Depression Scale (SDS), the Self-Rating Anxiety Scale (SAS), and the Somatic Self-rating Scale (SSS) were evaluated at baseline, weeks 4, 8, and 12. The MOS 36-item Short Form Health Survey (SF-36) was assessed at baseline and week 12. Adverse effects (AEs) were evaluated by the Treatment Emergent Symptom Scale (TESS). RESULTS: Both TG and CG showed obvious improvements in the sleep onset latency (SOL) (P=0.001 and 0.005) and total sleep time (TST) (P=0.001 and 0.005) and total sleep time (TST) (P=0.001 and 0.005) and total sleep time (TST) (P=0.001 and 0.005) and total sleep time (TST) (P=0.001 and 0.005) and total sleep time (TST) (P=0.001 and 0.005) and total sleep time (TST) (d = 1.28). The ISI reduction rate in TG was higher than that in CG at weeks 4, 8, and 12 (P=0.001 and 0.005) and total sleep time (TST) (P=0.001 and 0.005) and total sleep time (TST) (P=0.001 and 0.005) and total sleep time (TST) (P=0.001 and 0.005) and total sleep time (TST) (P=0.001 and 0.005) and total sleep time (TST) (P=0.001 and 0.005) and total sleep time (TST) (. CONCLUSION: The combination of JW-SZRD with lorazepam can significantly improve sleep quality with fewer AEs. It is an effective treatment and superior to lorazepam alone for chronic insomnia.

Biological functions of Arabidopsis thaliana MBP-1-like protein encoded by ENO2 in the response to drought and salt stresses.

Arabidopsis thaliana ENO2 (AtENO2) plays an important role in plant growth and development. It encodes two proteins, a full-length AtENO2 and a truncated version, AtMBP-1, alternatively translated from the second start codon of the mRNA. The AtENO2 mutant (eno2- ) exhibited reduced leaf size, shortened siliques, a dwarf phenotype and higher sensitivity to abiotic stress. The objectives of this study were to analyze the regulatory network of the ENO2 gene in plant growth development and understand the function of AtENO2/AtMBP-1 to abiotic stresses. An eno2- /35S:AtENO2-GFP line and an eno2- /35S:AtMBP-1-GFP line of Arabidopsis were obtained. Results of sequencing by 454 GS FLX identified 578 upregulated and 720 downregulated differential expressed genes (DEGs) in a pairwise comparison (WT-VS-eno2- ). All the high-quality reads were annotated using the Gene Ontology (GO) terms. The DEGs with KEGG pathway annotations occurred in 110 pathways. The metabolic pathways and biosynthesis of secondary metabolites contained more DEGs. Moreover, the eno2- /35S:AtENO2-GFP line returned to the wild-type (WT) phenotype and was tolerant to drought and salt stresses. However, the eno2- /35S:AtMBP-1-GFP line was not able to recover the WT phenotype but it has a higher tolerance to drought and salt stresses. Results from this study demonstrate that AtENO2 is critical for the growth and development, and the AtMBP-1 coded by AtENO2 is important in tolerance of Arabidopsis to abiotic stresses.

Left atrial appendage orifice diameter measured with trans-esophageal echocardiography is independently related with peri-device leakage after Watchman device implantation.

Percutaneous left atrial appendage closure (LAAC) has emerged as an alternative of stroke prevention in non-valvular atrial fibrillation (NVAF) patients. Peri-device leakage after LAAC is common. This retrospective, case-control study aimed to identify risk factors related with peri-device leakage after LAAC with Watchman devices. Patients who underwent Watchman devices implantation received trans-esophageal echocardiography (TEE) before, during and 45 days after procedure. Peri-device leakage was defined as a residual flow of any size detected with TEE. Patients with residual flows were compared with sex and age matched controls without leakage after implantation. Basic clinical characteristics, as well as LAA imaging characteristics were collected and compared. From 2014 to 2016, 125 consecutive patients were implanted with Watchman devices in our center. TEE at 45 days after implantation identified 53 patients with peri-device leakages (2.62 ± 1.55 mm), who were compared with 43 sex and age matched controls who also received the Watchman devices implantation and had no peri-device residual flow. The basic clinical characteristics, as well as LAA morphology were comparable between the two groups, while patients with leakages had larger LAA orifice, longer LAA body and larger LAA volume. Multivariate logistic regression analysis showed that LAA orifice size measured with TEE was the only independent risk factor predicting post-procedural leakage. The AUC of the receiver operating characteristic (ROC) curve was 0.70. Using the TEE orifice size cutoff value of 18.7 mm yielded a sensitivity of 0.92 (specificity 0.52), while the cutoff value of 23.1 mm yielded a high specificity of 0.91 (sensitivity 0.24). Minor peri-device leakage ( < 5 mm) is common after LAAC with Watchman devices. LAA orifice diameter measured with TEE is the independent risk factor predicting peri-device leakage after the implantation.

[Research progress in the mechanism of translation initiation of eukaryotic mRNAs].

The translation of mRNA is a complicated multi-step process, including initiation, elongation and termination. Among them, the regulation of the initial stage plays the key role. There are many ways to initiate mRNA translation, and the most classical way is the m 7G cap-dependent scanning mechanism that was also the first mechanism identified. When cells encounter adversity and the classical mechanism is inhibited, other types of translation initiation mechanisms will be activated. In this review, we summarize the translation initiation mechanisms of eukaryotic mRNAs, especially some alternative mechanisms. It will provide a reference for further understanding of the expression and regulation of eukaryotic genes at the translation levels.

CSF miR-16 expression and its association with miR-16 and serotonin transporter in the raphe of a rat model of depression.

BACKGROUND: Depression is a common mental disorder with unknown mechanism. Emerging evidence shows that miRNAs play a critical role in the process of depression. Here we reported the cerebrospinal fluid (CSF) miR-16 expression and its association with miR-16 and serotonin transporter (SERT) in the raphe of a rat model of depression. METHODS: 20 rats were randomized to the control or CUMS (chronic unpredictable mild stress) group. The rats in the CUMS group underwent CUMS for 21 days, while those in the control group received no treatment. After anesthetization, CSF was collected for the measurement of miR-16. Then raphes from all rats were separated for determination of miR-16 and SERT protein. RESULTS: The expression levels of miR-16 in CSF and raphe of the CUMS group were significantly lower than those of the control group (P = 0.007 and 0.031). However, SERT protein in raphe of the CUMS group was obviously increased as compared that of the control group (P = 0.005). There was a positive correlation between CSF miR-16 and raphe miR-16 (r = 0.95, P = 0.000). Meanwhile, negative correlations between miR-16 and SERT protein in raphe (r = -0.70 P = 0.02), between CSF miR-16 and raphe SERT protein (r = -0.86, P = 0.002) were observed in the CUMS group. LIMITATIONS: We have not explored the reason why CSF miR-16 was decreased in the rat model of depression and only tested the association of miR-16 between CSF and raphe. CONCLUSIONS: CSF miR-16 was involved in the pathogenesis of depression via reflecting raphe miR-16 level, and thus affecting raphe SERT expression.

Finite element analysis of hollow out-of-plane HfO2 microneedles for transdermal drug delivery applications.

Transdermal drug delivery (TDD) based on microneedles is an excellent approach due to its advantages of both traditional transdermal patch and hypodermic syringes. In this paper, the fabrication method of hollow out-of-layer hafnium oxide (HfO2) microneedles mainly based on deep reactive ion etching of silicon and atomic layer deposition of HfO2 is described, and the finite element analysis of the microneedles based on ANSYS software is also presented. The fabrication process is simplified by using a single mask. The finite element analysis of a single microneedle shows that the flexibility of the microneedles can be easily adjusted for various applications. The finite element analysis of a 3 × 3 HfO2 microneedle array applied on the skin well explains the "bed of nail" effect, i.e., the skin is not liable to be pierced when the density of microneedles in array increases. The presented research work here provides useful information for design optimization of HfO2 microneedles used for TDD applications.

Modified Suanzaorentang Had the Treatment Effect for Generalized Anxiety Disorder for the First 4 Weeks of Paroxetine Medication: A Pragmatic Randomized Controlled Study.

Background. Paroxetine does not show satisfactory therapeutic effect for generalized anxiety disorder (GAD) patients for the first 2-4 weeks of medication. Diazepam is always concurrently used although it has some shortcomings such as physical dependence and withdrawal reactions. In this study, we aimed to identify whether modified Suanzaorentang (MSZRT), a combined Chinese formula including Suanzaorentang (SZRT) and Zhizichitang (ZZCT), could control the anxiety of GAD for the first 4 weeks of paroxetine medication. Methods. 156 GAD patients were randomized to the treatment of paroxetine, paroxetine-diazepam, or paroxetine-MSZRT for 4 weeks. Hamilton Anxiety Scale (HAMA) Test and Self-Rating Anxiety Scale (SAS) Test were determined each week as the evaluation of clinical efficacy. Adverse events (AEs) were also closely observed by performing the Treatment Emergent Symptom Scale (TESS) Test. Results. Both paroxetine-MSZRT and paroxetine-diazepam decreased more HAMA and SAS total scores than paroxetine from weeks 1 to 3. Paroxetine-MSZRT as well as paroxetine-diazepam had an obviously higher onset rate than paroxetine in each week. After 4 weeks' treatment, the overall effectiveness rate in the paroxetine-MSZRT group (90.00%) was obviously higher than those of the paroxetine group (74.42%) but did not significantly differ from the paroxetine-diazepam group (93.88%). Conclusion. MSZRT had the treatment effect for GAD when paroxetine was used for the first 4 weeks.

Efficacy and Safety of the WATCHMAN Left Atrial Appendage System for Stroke Prevention in Chinese Patients with Nonvalvular Atrial Fibrillation: A Single-center, Prospective, Observational Study.

BACKGROUND: In patients with nonvalvular atrial fibrillation (NVAF), embolic stroke is thought to be associated with left atrial appendage (LAA) thrombi. The WATCHMAN LAA Occlusion Device has been shown to be noninferior to conventional oral anticoagulation with warfarin for stroke prevention in patients with NVAF. This study aimed to evaluate the procedural feasibility, safety and 12-month outcomes of the WATCHMAN LAA Occlusion Device in NVAF patients with high risk for stroke in China. METHODS: The clinical data of 106 NVAF patients, who were consecutively underwent LAA closure with the WATCHMAN Device between April 2014 and May 2015, were collected. Patients were followed up at 1, 3, 6, and 12 months after discharge. A transesophageal echocardiograph was performed at 45 days after implantation and repeated in case of an unexpected event during the follow-up period. RESULTS: This study included 106 NVAF patients with a mean age of 64.2 ± 8.6 years (ranging from 50 to 88 years), and the mean CHA2DS2-VASc score of all patients was 3.6 ± 1.6 (ranging from 2 to 9). Among those 106 NVAF patients, 100 (94.3%) patients were implanted with the device successfully. The procedural success rate was 94.3% (100/106), and the occlusion rate was 100.0% (100/100). There were one tamponade, one ischemic stroke, and eight minor pericardial effusions during hospitalization. During 12-month follow-up period, two patients developed a thrombus layer on the device that resolved with additional anticoagulation: one with visible device-thrombus experienced transient ischemic stroke, and one had a hemorrhagic stroke. There were no deaths in this study. The overall survival rate was 100.0%, and nonmajor adverse event rate was 95.0% (95/100). In this study, the expected annual rate of ischemic stroke risk in these patients according to the CHA2DS2-VASc score was 4.0%, while the observed ischemic stroke rate was 2.0% per year. CONCLUSIONS: LAA closure with the WATCHMAN Device was feasible, efficient, and safe for NVAF to prevent the accidence of stroke in Chinese patients. During the 12-month follow-up period, the observed ischemic stroke rate (2.0% per year) in our study was lower than the predicted annual stroke risk (4.0%) using the CHA2DS2-VASc score.

Contributions of historical and contemporary geographic and environmental factors to phylogeographic structure in a Tertiary relict species, Emmenopterys henryi (Rubiaceae).

Examining how historical and contemporary geographic and environmental factors contribute to genetic divergence at different evolutionary scales is a central yet largely unexplored question in ecology and evolution. Here, we examine this key question by investigating how environmental and geographic factors across different epochs have driven genetic divergence at deeper (phylogeographic) and shallower (landscape genetic) evolutionary scales in the Chinese Tertiary relict tree Emmenopterys henryi. We found that geography played a predominant role at all levels - phylogeographic clades are broadly geographically structured, the deepest levels of divergence are associated with major geological or pre-Quaternary climatic events, and isolation by distance (IBD) primarily explained population genetic structure. However, environmental factors are clearly also important - climatic fluctuations since the Last Interglacial (LIG) have likely contributed to phylogeographic structure, and the population genetic structure (in our AFLP dataset) was partly explained by isolation by environment (IBE), which may have resulted from natural selection in environments with divergent climates. Thus, historical and contemporary geography and historical and contemporary environments have all shaped patterns of genetic structure in E. henryi, and, in fact, changes in the landscape through time have also been critical factors.