The molecular biology of NF2/Merlin on tumorigenesis and development.

The neurofibromatosis type 2 (NF2) gene, known for encoding the tumor suppressor protein Merlin, is central to the study of tumorigenesis and associated cellular processes. This review comprehensively examines the multifaceted role of NF2/Merlin, detailing its structural characteristics, functional diversity, and involvement in various signaling pathways such as Wnt/ß-catenin, Hippo, TGF-ß, RTKs, mTOR, Notch, and Hedgehog. These pathways are crucial for cellular growth, proliferation, and differentiation. NF2 mutations are specifically linked to the development of schwannomas, meningiomas, and ependymomas, although the precise mechanisms of tumor formation in these specific cell types remain unclear. Additionally, the review explores Merlin's role in embryogenesis, highlighting the severe developmental defects and embryonic lethality caused by NF2 deficiency. The potential therapeutic strategies targeting these genetic aberrations are also discussed, emphasizing inhibitors of mTOR, HDAC, and VEGF as promising avenues for treatment. This synthesis of current knowledge underscores the necessity for ongoing research to elucidate the detailed mechanisms of NF2/Merlin and develop effective therapeutic strategies, ultimately aiming to improve the prognosis and quality of life for individuals with NF2 mutations.

Potential therapeutic strategies for osteoarthritis via CRISPR/Cas9 mediated gene editing.

Osteoarthritis (OA) is an incapacitating and one of the most common physically degenerative conditions with an assorted etiology and a highly complicated molecular mechanism that to date lacks an efficient treatment. The capacity to design biological networks and accurately modify existing genomic sites holds an apt potential for applications across medical and biotechnological sciences. One of these highly specific genomes editing technologies is the CRISPR/Cas9 mechanism, referred to as the clustered regularly interspaced short palindromic repeats, which is a defense mechanism constituted by CRISPR associated protein 9 (Cas9) directed by small non-coding RNAs (sncRNA) that bind to target DNA through Watson-Crick base pairing rules where subsequent repair of the target DNA is initiated. Up-to-date research has established the effectiveness of the CRISPR/Cas9 mechanism in targeting the genetic and epigenetic alterations in OA by suppressing or deleting gene expressions and eventually distributing distinctive anti-arthritic properties in both in vitro and in vivo osteoarthritic models. This review aims to epitomize the role of this high-throughput and multiplexed gene editing method as an analogous therapeutic strategy that could greatly facilitate the clinical development of OA-related treatments since it's reportedly an easy, minimally invasive technique, and a comparatively less painful method for osteoarthritic patients.

Identification and characterization of waterlogging-responsive genes in the parental line of maize hybrid An'nong 876.

Waterlogging stress is an important abiotic stress that adversely affects maize growth and yield. The mechanism regulating the early stage of the maize response to waterlogging stress is largely unknown. In this study, CM37 and cmh15 seedlings were treated with waterlogging stress and then examined in terms of their physiological changes. The results indicated that inbred line cmh15 is more tolerant to waterlogging stress and less susceptible to peroxide-based damages than CM37. The RNA sequencing analysis identified 1,359 down-regulated genes and 830 up-regulated genes in the waterlogging-treated cmh15 plants (relative to the corresponding control levels). According to the Gene Ontology analysis for the differentially expressed genes (DEGs), some important terms were identified which may play important roles in the response to waterlogging stress. Moreover, enriched Kyoto Encyclopedia of Genes and Genomes pathways were also identified for the DEGs. Furthermore, the substantial changes in the expression of 36 key transcription factors may be closely related to the maize in response to waterlogging stress. This study offers important insights into the mechanism in regulating maize tolerance to waterlogging stress, with important foundations for future research.

Gene regulatory network from cranial neural crest cells to osteoblast differentiation and calvarial bone development.

Calvarial bone is one of the most complex sequences of developmental events in embryology, featuring a uniquely transient, pluripotent stem cell-like population known as the cranial neural crest (CNC). The skull is formed through intramembranous ossification with distinct tissue lineages (e.g. neural crest derived frontal bone and mesoderm derived parietal bone). Due to CNC's vast cell fate potential, in response to a series of inductive secreted cues including BMP/TGF-ß, Wnt, FGF, Notch, Hedgehog, Hippo and PDGF signaling, CNC enables generations of a diverse spectrum of differentiated cell types in vivo such as osteoblasts and chondrocytes at the craniofacial level. In recent years, since the studies from a genetic mouse model and single-cell sequencing, new discoveries are uncovered upon CNC patterning, differentiation, and the contribution to the development of cranial bones. In this review, we summarized the differences upon the potential gene regulatory network to regulate CNC derived osteogenic potential in mouse and human, and highlighted specific functions of genetic molecules from multiple signaling pathways and the crosstalk, transcription factors and epigenetic factors in orchestrating CNC commitment and differentiation into osteogenic mesenchyme and bone formation. Disorders in gene regulatory network in CNC patterning indicate highly close relevance to clinical birth defects and diseases, providing valuable transgenic mouse models for subsequent discoveries in delineating the underlying molecular mechanisms. We also emphasized the potential regenerative alternative through scientific discoveries from CNC patterning and genetic molecules in interfering with or alleviating clinical disorders or diseases, which will be beneficial for the molecular targets to be integrated for novel therapeutic strategies in the clinic.

Application of Musculoskeletal Ultrasound Guidance in Lumbar Transforaminal Endoscopic Surgery for Puncture and Catheterization.

BACKGROUND Foraminal puncture is a key step in foraminal endoscopic surgery, but the radiation dosage poses a clinical risk to patients. To reduce the radiation dosage, we investigated the feasibility and clinical effect of endoscopic transforaminal puncture through the use of the musculoskeletal ultrasound-guided lumbar percutaneous posterolateral approach. MATERIAL AND METHODS Retrospective data of 80 lumbar percutaneous posterolateral approach endoscopic surgery patients from March 2018 to June 2021 were analyzed. The clinical efficacy was assessed by visual analogue scale (VAS) and Oswestry disability index (ODI) during the follow-up. RESULTS Between the musculoskeletal ultrasound-guided group and the C-arm X-ray machine fluoroscopy group, the puncture time of the musculoskeletal ultrasound-guided group was significantly shorter than that of the C-arm X-ray machine fluoroscopy group (t=13.113, P=0.010). The radiation received in the ultrasound guidance group was significantly less than in the C-arm X-ray group. There was no difference in ODI values between the 2 groups before surgery (t=0.195, P=0.286), 3 months after surgery (t=0.235, P=0.092), and 1 year after surgery (t=0.168, P=0.173). There was no significant difference in VAS scores between the 2 groups before surgery (t=0.715, P=0.610), 3 months after surgery (t=0.367, P=0.192), and 1 year after surgery (t=0.496, P=0.390). CONCLUSIONS Our data demonstrate that musculoskeletal ultrasound can accurately guide the lumbar percutaneous posterolateral approach for endoscopic foraminal puncture, which can significantly reduce the puncture time and the amount of X-ray radiation.

Comparative Transcriptomics Reveals the Molecular Mechanism of the Parental Lines of Maize Hybrid An'nong876 in Response to Salt Stress.

Maize (Zeamays L.) is an essential food crop worldwide, but it is highly susceptible to salt stress, especially at the seedling stage. In this study, we conducted physiological and comparative transcriptome analyses of seedlings of maize inbred lines An'nong876 paternal (cmh15) and An'nong876 maternal (CM37) under salt stress. The cmh15 seedlings were more salt-tolerant and had higher relative water content, lower electrolyte leakage, and lower malondialdehyde levels in the leaves than CM37. We identified 2559 upregulated and 1770 downregulated genes between salt-treated CM37 and the controls, and 2757 upregulated and 2634 downregulated genes between salt-treated cmh15 and the controls by RNA sequencing analysis. Gene ontology functional enrichment analysis of the differentially expressed genes showed that photosynthesis-related and oxidation-reduction processes were deeply involved in the responses of cmh15 and CM37 to salt stress. We also found differences in the hormone signaling pathway transduction and regulation patterns of transcription factors encoded by the differentially expressed genes in both cmh15 and CM37 under salt stress. Together, our findings provide insights into the molecular networks that mediate salt stress tolerance of maize at the seedling stage.

Identification and Characterization of the Core Region of ZmDi19-5 Promoter Activity and Its Upstream Regulatory Proteins.

Drought-induced 19 (Di19) family genes play important roles in plant growth, development, and environmental stress responses. However, little is known about this family in maize. The upstream regulatory network of Di19 genes remains poorly understood in plant stress response, especially. In this study, seven ZmDi19 genes were identified, and sequence alignment, gene structure, and phylogenetic analysis was conducted. According to the phylogenetic analysis, the ZmDi19-5 promoter was cloned and multiple putative stress-responsive cis-acting elements (CAEs) were found in the promoter region. The transient transformation assay indicated that firefly luciferase (LUC)-expressed activity driven by the ZmDi19-5 promoter can be significantly induced by drought stress. A 450 bp core region of ZmDi19-5 promoter was identified, and 28 upstream regulatory proteins were screened using yeast one-hybird (Y1H) system. According to the functional annotation, some genes were related to photosynthesis, light response, and water transport, which may suggest the important roles of these genes in drought response. Particularly, five members that may be involved in drought response exhibited strong binding activity to the core region of the ZmDi19-5 promoter. This study laid an important foundation for further revealing the molecular mechanisms and regulatory network of Di19 genes in drought stress response.

Use of a Percutaneous Needle Release Technique for Trigger Thumb: A Retrospective Study of 11 Patients from a Single Center.

BACKGROUND Trigger finger is a very common disorder that occurs in both adults and children. Trigger finger presents mainly as pain and limited movement of the affected digit. This report describes a modified percutaneous needle release and an evaluation of its clinical efficacy to treat trigger thumb. MATERIAL AND METHODS Trigger thumb of 11 patients was released percutaneously using a specially designed needle (0.8×100 mm) with a planus tip. Complete release was ensured when no more grating sound was heard and the needle moved freely at the tip. Pain-related functional score was evaluated preoperatively and at 3 months postoperatively. Resolution of Notta's node, triggered or locked, Quinnell's criteria, and patient satisfaction were also assessed at 3 months after the operation. RESULTS After the percutaneous trigger thumb release, the overall visual analog scale (VAS) and pain-related functional scores declined significantly (P<0.01). There was no recurrence of thumb locking or triggering or Notta's node. Only the first patient had incomplete release of the first annular pulley, and all patients showed high satisfaction with the procedure at 3 months after their operation. During the study, patients did not experience any complications such as inflammation, edema, or digital nerve injury. CONCLUSIONS This study demonstrated that the percutaneous technique is effective, less time-consuming, and safe for treating trigger thumb. Our release technique using a specially designed percutaneous needle is a valuable treatment for trigger thumb.

Transcriptome Analysis of Tolerant and Susceptible Maize Genotypes Reveals Novel Insights about the Molecular Mechanisms Underlying Drought Responses in Leaves.

Maize (Zea mays L.) is the most essential food crop in the world. However, maize is highly susceptible to drought stress, especially at the seedling stage, and the molecular mechanisms underlying drought tolerance remain elusive. In this study, we conducted comparative transcriptome and physiological analyses of drought-tolerant (CML69) and susceptible (LX9801) inbred lines subjected to drought treatment at the seedling stage for three and five days. The tolerant line had significantly higher relative water content in the leaves, as well as lower electrolyte leakage and malondialdehyde levels, than the susceptible line. Using an RNA-seq-based approach, we identified 10,084 differentially expressed genes (DEGs) with 6906 and 3178 DEGs been annotated and unannotated, respectively. Two critical sets of drought-responsive DEGs, including 4687 genotype-specific and 2219 common drought-responsive genes, were mined out of the annotated DEGs. The tolerant-line DEGs were predominantly associated with the cytoskeleton, cell wall modification, glycolysis/gluconeogenesis, transport, osmotic regulation, drought avoidance, ROS scavengers, defense, and transcriptional factors. For the susceptible line, the DEGs were highly enriched in the photosynthesis, histone, and carbon fixation pathways. The unannotated DEGs were implicated in lncRNAs, including 428 previously reported and 22% putative TE-lncRNAs. There was consensus on both the physiological response and RNA-seq outcomes. Collectively, our findings will provide a comprehensive basis of the molecular networks mediating drought stress tolerance of maize at the seedling stage.

Maize WRKY114 gene negatively regulates salt-stress tolerance in transgenic rice.

KEY MESSAGE: Overexpression in rice of the isolated salt-responsive WRKY114 gene from maize resulted in decreases in both salt-stress tolerance and abscisic acid sensitivity by regulating stress- and abscisic acid-related gene expression. WRKYs are an important family of transcription factors that widely participate in plant development, defense regulation and stress responses. In this research, WRKY114 encoding a WRKY transcription factor was cloned from maize (Zea mays L.). ZmWRKY114 expression was down-regulated by salt stress but up-regulated by abscisic acid (ABA) treatments. ZmWRKY114 is a nuclear protein with no transcriptional activation ability in yeast. A yeast one-hybrid experiment confirmed that ZmWRKY114 possesses an ability to specifically bind to W-boxes. The heterologous overexpression of ZmWRKY114 in rice enhanced the salt-stress sensitivity as indicated by the transgenic plants having reduced heights, root lengths and survival rates under salt-stress conditions. In addition, transgenic plants also retained lower proline contents, but greater malondialdehyde contents and relative electrical leakage levels. Additionally, ZmWRKY114-overexpressing plants showed less sensitivity to ABA during the early seedling growth stage. Further analyses indicated that transgenic rice accumulated higher levels of ABA than wild-type plants under salt-stress conditions. Transcriptome and quantitative real-time PCR analyses indicated that a few regulatory genes, which play vital roles in controlling plant stress responses and/or the ABA signaling pathway, were affected by ZmWRKY114 overexpression when rice was treated with NaCl. Thus, ZmWRKY114 may function as a negative factor that participates in salt-stress responses through an ABA-mediated pathway.

Performance of Double-Arm Digital Subtraction Angiography (DSA)-Guided and C-Arm-Guided Percutaneous Kyphoplasty (PKP) to Treat Senile Osteoporotic Vertebral Compression Fractures.

BACKGROUND Osteoporotic vertebral compression fracture (OVCF) is a common fracture in the elderly. Conservative treatment requires prolonged bedding, which may lead to serious complications. To explore optimized use of percutaneous kyphoplasty (PKP) in the treatment of senile osteoporotic thoracolumbar vertebral compression fractures, in this study, we used C-arm-guided and double-arm digital subtraction angiography (DSA)-guided PKP to treat OVCF in elderly patients and analyzed the effective recovery. MATERIAL AND METHODS In all, 60 patients who presented with osteoporotic vertebral compression fractures at our hospital between July 2017 and February 2019 were analyzed. They were randomly divided into C-arm-guided group and the double-arm DSA-guided groups. Both groups were treated with percutaneous kyphoplasty. RESULTS A pain VAS score analysis revealed that there was no significant difference between the two groups before surgery (P>0.05). After surgery, the VAS scores showed a significant difference between the C-arm-guided group and the double-arm DSA-guided PKP treatment group (P<0.01). Moreover, with respect to the bone cement dosage, vertebral correction height, operation time, cumulative radiation dose, percolation rate, and volume of bone cement, the double-arm DSA-guided PKP treatment showed significantly better results than the C-arm-guided PKP treatment (P<0.01). CONCLUSIONS Our data revealed that double-arm DSA-guided PKP was more accurate in treatment of senile osteoporotic thoracolumbar vertebral compression fractures, producing excellent performance with more accurate intraoperative evaluation, shorter operative time, lower incidence of bone cement leakage, less intraoperative radiation dose, and higher safety, and thus, could be extensively applied to clinical surgery.

Regional difference in microRNA regulation in the skull vault.

BACKGROUND: The murine calvaria has several membrane bones with different tissue origins (e.g., neural crest-derived frontal bone vs. mesoderm-derived parietal bone). Neural crest-derived frontal bone exhibits superior osteogenic activities and bone regeneration. MicroRNA (miRNA) has been emerged as a crucial regulator during organogenesis and is involved in a range of developmental processes. However, the underlying roles of miRNA regulation in frontal bone and parietal bone is unknown. RESULTS: Total of 83 significantly expressed known miRNAs were identified in frontal bones versus parietal bones. The significantly enriched gene ontology and KEGG pathway that were predicted by the enrichment miRNAs were involved in several biological processes (cell differentiation, cell adhesion, and transcription), and multiple osteogenic pathways (e.g., focal adhesion, MAPK, VEGF, Wnt, and insulin signaling pathway. Focal adhesion and insulin signaling pathway were selected for target verification and functional analysis, and several genes were predicted to be targets genes by the differentially expressed miRNAs, and these targets genes were tested with significant expressions. CONCLUSIONS: Our results revealed a novel pattern of miRNAs in murine calvaria with dual tissue origins, and explorations of these miRNAs will be valuable for the translational studies to enhance osteogenic potential and bone regeneration in the clinic.

Genome-wide association study of maize plant architecture using F1 populations.

KEY MESSAGE: Genome-wide association study of maize plant architecture using F1 populations can better dissect various genetic effects that can provide precise guidance for genetic improvement in maize breeding. Maize grain yield has increased at least eightfold during the past decades. Plant architecture, including plant height, leaf angle, leaf length, and leaf width, has been changed significantly to adapt to higher planting density. Although the genetic architecture of these traits has been dissected using different populations, the genetic basis remains unclear in the F1 population. In this work, we perform a genome-wide association study of the four traits using 573 F1 hybrids with a mixed linear model approach and QTXNetwork mapping software. A total of 36 highly significant associated quantitative trait SNPs were identified for these traits, which explained 51.86-79.92% of the phenotypic variation and were contributed mainly by additive, dominance, and environment-specific effects. Heritability as a result of environmental interaction was more important for leaf angle and leaf length, while major effects (a, aa, and d) were more important for leaf width and plant height. The potential breeding values of the superior lines and superior hybrids were also predicted, and these values can be applied in maize breeding by direct selection of superior genotypes for the associated quantitative trait SNPs. A total of 108 candidate genes were identified for the four traits, and further analysis was performed to screen the potential genes involved in the development of maize plant architecture. Our results provide new insights into the genetic architecture of the four traits, and will be helpful in marker-assisted breeding for maize plant architecture.

Comparative transcriptome analysis reveals important roles of nonadditive genes in maize hybrid An'nong 591 under heat stress.

BACKGROUND: Heterosis is the superior performance of F1 hybrids relative to their parental lines for a wide range of traits. In this study, expression profiling and heterosis associated genes were analyzed by RNA sequencing (RNA-Seq) in seedlings of the maize hybrid An'nong 591 and its parental lines under control and heat stress conditions. RESULTS: Through performing nine pairwise comparisons, the maximum number of differentially expressed genes (DEGs) was detected between the two parental lines, and the minimum number was identified between the F1 hybrid and the paternal lines under both conditions, which suggested greater genetic contribution of the paternal line to heat stress tolerance. Gene Ontology (GO) enrichment analysis of the 4518 common DEGs indicated that GO terms associated with diverse stress responses and photosynthesis were highly overrepresented in the 76 significant terms of the biological process category. A total of 3970 and 7653 genes exhibited nonadditive expression under control and heat stress, respectively. Among these genes, 2253 (56.8%) genes overlapped, suggesting that nonadditive genes tend to be conserved in expression. In addition, 5400 nonadditive genes were found to be specific for heat stress condition, and further GO analysis indicated that terms associated with stress responses were significantly overrepresented, and 60 genes were assigned to the GO term response to heat. Pathway enrichment analysis indicated that 113 genes were involved in spliceosome metabolic pathways. Nineteen of the 33 overlapping genes assigned to the GO term response to heat showed significantly higher number of alternative splicing (AS) events under heat stress than under control conditions, suggesting that AS of these genes play an important role in response to heat stress. CONCLUSIONS: This study reveals the transcriptomic divergence of the maize F1 hybrid and its parental lines under control and heat stress conditions, and provides insight into the underlying molecular mechanisms of heterosis and the response to heat stress in maize.

A maize stress-responsive Di19 transcription factor, ZmDi19-1, confers enhanced tolerance to salt in transgenic Arabidopsis.

KEY MESSAGE: ZmDi19-1 can be induced by various abiotic stresses and enhance the salt tolerance of transgenic Arabidopsis thaliana. Drought-induced protein 19 (Di19) is an essential zinc finger family member that plays vital roles in regulating multiple stress responses. Here, the Di19 family gene in maize (Zea mays) ZmDi19-1 was characterized. We determined that ZmDi19-1 is constitutively expressed in root, stem, leaf and other maize tissues under normal conditions. In addition, ZmDi19-1 expression was induced by PEG and NaCl stresses. The subcellular localization revealed that ZmDi19-1 is a nuclear membrane protein. In yeast cells, ZmDi19-1 displayed transcriptional activity and could bind to the TACA(A/G)T sequence, which was corroborated using the dual luciferase reporter assay system. The overexpression of ZmDi19-1 in Arabidopsis thaliana enhanced the plants' tolerance to salt stress. Compared with wild-type, the Arabidopsis ZmDi19-1-overexpressing lines had higher relative water and proline contents, and lower malondialdehyde contents, in leaves under salt-stress conditions. The transcriptome analysis revealed 1414 upregulated and 776 downregulated genes, and an RNA-seq analysis identified some differentially expressed genes, which may be downstream of ZmDi19-1, involved in salt-stress responses. The data demonstrated that ZmDi19-1 responds to salt stress and may impact the expression of stress-related genes in Arabidopsis.

Global transcriptome and weighted gene co-expression network analyses reveal hybrid-specific modules and candidate genes related to plant height development in maize.

KEY MESSAGE: Weighted gene co-expression network analysis was explored to find key hub genes involved in plant height regulation. Plant height, an important trait for maize breeding because of its close relatedness to lodging resistance and yield, has been reported to be determined by multiple qualitative and quantitative genes. However, few genes related to plant height have been characterized in maize. Herein, three different maize hybrids, with extremely distinct plant height, which were further classified into low (L), middle (M) and high (H) group, were selected for RNA sequencing at three key developmental stages, namely, jointing stage (I), big flare period (II) and tasseling stage (III). Intriguingly, transcriptome profiles for hybrids ranging from low to high group exhibited significantly similarity in both jointing stage and big flare period. However, remarkably larger differentially expressed genes could be detected between hybrid from low to either middle or high group in tasseling stage. These results were repeatedly observed in both phenotyping and gene ontology enrichment analysis, indicating that transition from big flare period to tasseling stage plays a critical role in determination of plant height. Furthermore, weighted gene co-expression network analysis was explored to find key hub genes involved in plant height regulation. Hundreds of candidate genes, encoding various transcription factors, and regulators involved in internode cell regulation and cell wall synthesis were identified in our network. More importantly, great majority of candidates were correlated to either metabolism or signaling pathway of several plant phytohormones. Particularly, numerous functionally characterized genes in gibberellic acid as well as brassinosteroids signaling transduction pathways were also discovered, suggesting their critical roles in plant height regulation. The present study could provide a modestly comprehensive insight into networks for regulation of plant height in maize.

Factors Influencing the Outcomes of Artificial Hip Replacements.

Hip replacement is one of the most successful surgeries in the clinic for the removal of painful joints. Hip osteoarthritis and femoral head necrosis are the 2 main reasons for hip replacement. Several factors are associated with the outcomes of surgery. Nonsurgical factors include gender, age, body mass index, prosthetic material, and risk factors. Surgical factors are anesthesia, postoperative complications, and rehabilitation. Considering the increasing demand for hip arthroplasty and the rise in the number of revision operations, it is imperative to understand factor-related progress and how modifications of these factors promotes recovery following hip replacement. In this review, we first summarize recent findings regarding crucial factors that influence the outcomes of artificial hip replacement surgery. These findings not only show the time-specific effect for the treatment and recovery from hip arthroplasty in the clinic, but also provide suitable choices for different individuals for clinicians to consider. This, in turn, will help to develop the best possible postoperative program for specific patients.

[Medicinal laws and application examples of traditional Chinese medicine prescriptions for multiple aorto-arteritis].

To collect the literature on traditional Chinese medicine treatment for multiple aorto-arteritis from China National Knowledge Infrastructure(CNKI), establish prescriptions database after screening and normalizing the prescriptions reported in these literature, and analyze their medicinal rules by using traditional Chinese medicine inheritance support system. A total of 126 prescriptions for multiple aorto-arteritis were screened, containing 212 kinds of Chinese herbs. 26 core herb combinations were obtained by analysis of the commonly used herbs and their use frequencies. The treatment for multiple aorto-arteritis was manly of tonifying qi to nourish blood, promoting blood circulation to remove blood stasis, warming yang to dredge collaterals, and four new prescriptions were obtained. On this basis, two clinical cases were taken as the examples by analyzing the medicinal rules and the features of multiple aorto-arteritis. The first case showed that the herb combination of this study conformed to the basic core drug application mode and the core pathogenesis of multiple aorto-arteritis. The second case reflected the characteristics of the new prescriptions' herb combinations based on entropy hierarchical clustering. The practical analysis of the two clinical cases further indicated the reliability of the results. This study has certain guiding significance and reference value on new medicine research and development as well as clinical traditional Chinese medicine treatment for multiple aorto-arteritis.

Ganoderic acid a decreased Aß42-induced neurotoxicity in PC12 cells by reduced mitochondrial damage.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Accumulation of ß-amyloid (Aß) in the brain has been recognized as a key factor in the onset and progression of Alzheimer's disease (AD).The accumulation of Aß in the brain catalyzes the production of reactive oxygen species (ROS), which in turn triggers oxidative damage to cellular components such as DNA, lipids, and proteins. In the present study, we investigated the protective effect of Ganoderic acid A (GA.A) against Aß42-induced apoptosis in PC12 cells. Changes in mitochondrial membrane potential indicated that GA.A treats mitochondrial dysfunction by decreasing Aß42 deposition and inhibiting neural protofiber tangle formation. Changes in intracellular Ca2+ and caspase-3 indicated that GA.A reduced mitochondrial damage by Aß42 in PC12 cells, thereby decreasing ROS accumulation and reducing Aß protofiber-induced cytotoxicity. These features suggest that GA.A has great potential as an effective neuroprotective drug in the treatment of Alzheimer's disease.