[Meridian massage in the treatment of cervical spondylotic radiculopathy].

OBJECTIVE: To observe the clinical efficacy of meridian massage in the treatment of cervical spondylotic radiculopathy. METHODS: Sixty-four patients with cervical radiculopathy treated from March 2020 to June 2023 were divided into the observation group and the treatment group, with 32 cases in each group. The observation group received conventional treatment, including 14 males and 18 females with an average age of (41.34±7.23) years old ranging from 32 to 55 years old;the disease duration ranged from 9 to 17 months with an average of (14.23±3.56) months;C5 and C6 nerve root compression occurred in 12 cases, C7 nerve root compression occurred in 17 cases, C8 nerve root compression occurred in 3 cases. The treatment group received massage therapy on the basis of conventional treatment, including 17 males and 15 females with an average age of (40.86±6.97) years old ranging from 30 to 54 years old;the disease duration ranged from 8 to 18 months with an average of (15.43±3.48) months;C5 and C6 nerve root compression occurred in 14 cases, C7 nerve root compression occurred in 16 cases, C8 nerve root compression occurred in 2 cases. The clinical efficacy was evaluated by visual analogue scale(VAS), neck disability index(NDI) and clinical assessment scale for cervical spondylosis(CASCS) before and after 2-week treatment, and the range of motion of cervical spine was compared before and after treatment. RESULTS: After 2-week treatment, the VAS and NDI scores of the treatment group and the observation group decreased, while the CASCS scores increased(P<0.001). After 2-week treatment, the VAS and NDI scores were lower and the CASCS scores were higher in the treatment group than those of the observation group(P<0.001). Comparing with those before treatment, the range of motion of flexion, extension, left flexion, right flexion, left rotation and right rotation after 2-week treatment increased in two groups(P<0.05). Comparing with the observation group, the range of motion of flexion, extension, left flexion, right flexion, left rotation and right rotation increased more significantly in the treatment group(P<0.05). CONCLUSION: Meridian massage is effective in the treatment of cervical Spondylotic radiculopathy, which can effectively relieve neck pain, improve clinical symptoms and improve patient satisfaction.

Screening Strategy Identifies an Overlooked Deep-Ultraviolet Transparent Nonlinear Optical Crystal.

In the deep-ultraviolet (DUV) region, nonlinear optical (NLO) crystals must meet stringent requirements, including a large optical band gap and sufficient second harmonic generation (SHG) response. Typically, these criteria are fulfilled by borates, carbonates and nitrates containing π-conjugated groups. In contrast, sulfates and phosphates, with polarizabilities significantly smaller than those of π-conjugated groups, struggle to achieve similar performance. Here, we present the discovery of Mg2PO4Cl, a magnesium-based phosphate, identified from over 10,000 phosphates based on a polar-axial-symmetry screening strategy, which exhibits the highest SHG response (5.2 × KH2PO4 (KDP)) with phase-matching ability among non-π-conjugated DUV transparent NLO crystals. This compound belongs to the Pna21 space group, with [PO4] units consistently aligned along the 21 screw axis and glide planes throughout its crystal structure. Theoretical calculations attribute its remarkable SHG effect to the orderly arrangement of heteroanionic [MgO5Cl] and [MgO4Cl2] polyhedra alongside isolated [PO4] tetrahedra, supported by Berry phase analysis. Furthermore, a crystallographic structure analysis of phosphates and sulfates with significant SHG effects validates the effectiveness of our screening strategy. These findings offer valuable insights into the origins of NLO effects in non-π-conjugated compounds from both a material design and structural chemistry perspective, inspiring future efforts to revitalize DUV phosphates.

Analysis of chloroplast genome structure and phylogeny of the traditional medicinal of Ardisia crispa (Myrsinaceae).

Ardisia crispa(Myrsinaceae) is an ethnomedicine with horticultural and important medicinal values. Its morphology is complex, and its identification is difficult. We analyse the chloroplast genome characteristics and phylogenetic position of A. crispa to provide basic research data for the identification of A. crispa species and resource conservation. This study assemble and annotate the chloroplast genome of A. crispa and to compare it with the chloroplast genome within Ardisia. The A. crispa chloroplast genome is 156,785 bp in length, with a typical quadripartite structure containing 131 genes, including 86 protein-coding genes, 37 tRNA genes, and 8 rRNA genes; a total of 59 SSRs sites were identified, and the codon preference of this chloroplast genome is greater in A/U than in G/C, and leucine is the amino acid with the highest frequency of use. The chloroplast genomes of the nine Ardisia species are conserved in gene content and number, with more stable boundaries and less variation. In the phylogenetic tree, A. crispa is clustered on a branch with A. crispa var dielsii, and is closely related to A. mamillata and A. pedalis. In this study, we constructed and analyzed the chloroplast genome structure of A. crispa, and conducted phylogenetic analysis using the whole chloroplast genome sequence data of Ardisia plants, which is of great significance in understanding the genetic basis of A. crispa and adaptive evolution in Ardisia plants, and this will lay the foundation for the future research on A. crispa resource conservation and species identification.

Unlocking the Siderophore Biosynthesis Pathway and Its Biological Functions in the Fungal Insect Pathogen Beauveria bassiana.

Siderophores are small molecule iron chelators. The entomopathogenic fungus Beauveria bassiana produces a plethora of siderophores under iron-limiting conditions. In this study, a siderophore biosynthesis pathway, akin to the general pathway observed in filamentous fungi, was revealed in B. bassiana. Among the siderophore biosynthesis genes (SID), BbSidA was required for the production of most siderophores, and the SidC and SidD biosynthesis gene clusters were indispensable for the production of ferricrocin and fusarinine C, respectively. Biosynthesis genes play various roles in siderophore production, vegetative growth, stress resistance, development, and virulence, in which BbSidA plays the most important role. Accordingly, B. bassiana employs a cocktail of siderophores for iron metabolism, which is essential for fungal physiology and host interactions. This study provides the initial network for the genetic modification of siderophore biosynthesis, which not only aims to improve the efficacy of biocontrol agents but also ensures the efficient production of siderophores.

Significance and Possible Biological Mechanism for CLDN8 Downregulation in Kidney Renal Clear Cell Carcinoma Tissues.

Background: The clinical role of claudin 8 (CLDN8) in kidney renal clear cell carcinoma (KIRC) remains unclarified. Herein, the expression level and potential molecular mechanisms of CLDN8 underlying KIRC were determined. Methods: High-throughput datasets of KIRC were collected from GEO, ArrayExpress, SRA, and TCGA databases to determine the mRNA expression level of the CLDN8. In-house tissue microarrays and immunochemistry were performed to examine CLDN8 protein expression. A summary receiver operating characteristic curve (SROC) and standardized mean difference (SMD) forest plot were generated using Stata v16.0. Single-cell analysis was conducted to further prove the expression level of CLDN8. A clustered regularly interspaced short palindromic repeats knockout screen analysis was executed to assess the growth impact of CLDN8. Functional enrichment analysis was conducted using the Metascape database. Additionally, single-sample gene set enrichment analysis was implied to explore immune cell infiltration in KIRC. Results: A total of 17 mRNA datasets comprising 1,060 KIRC samples and 452 non-cancerous control samples were included in this study. Additionally, 105 KIRC and 16 non-KIRC tissues were analyzed using in-house immunohistochemistry. The combined SMD was -5.25 (95% confidence interval (CI): -6.13 to -4.37), and CLDN8 downregulation yielded an SROC area under the curve (AUC) close to 1.00 (95% CI: 0.99 - 1.00). CLDN8 downregulation was also confirmed at the single-cell level. Knocking out CLDN8 stimulated KIRC cell proliferation. Lower CLDN8 expression was correlated with worse overall survival of KIRC patients (hazard ratio of CLDN8 downregulation = 1.69, 95% CI: 1.2 - 2.4). Functional pathways associated with CLDN8 co-expressed genes were centered on carbon metabolism obstruction, with key hub genes ACADM, ACO2, NDUFS1, PDHB, SDHD, SUCLA2, SUCLG1, and SUCLG2. Conclusions: CLDN8 is downregulated in KIRC and is considered a potential tumor suppressor. CLDN8 deficiency may promote the initiation and progression of KIRC, potentially in conjunction with metabolic dysfunction.

Achieving Almost 100% Selectivity in Photocatalytic CO2 Reduction to Methane via In-Situ Atmosphere Regulation Strategy.

Artificial photosynthesis, harnessing solar energy to convert CO2 into hydrocarbons, presents a promising solution for climate change and energy scarcity. However, photocatalytic CO2 reduction often terminates at the CO stage due to limited electron transfer capacity, hindering the formation of higher-energy hydrocarbons such as CH4. This study introduces, for the first time, an in-situ atmosphere regulation strategy, refined from molecular imprinting methodologies, using dynamically reacting molecules to precisely engineer photocatalytic surface sites for selective *CO adsorption and hydrogenation in CO2-to-CH4 conversion. Specifically, the single-atom Cu catalyst (Cu-SA-CO) is prepared by anchoring single-atom Cu onto defective TiO2 substrates (Cu-SA-CO) under a CO reduction atmosphere. Under illumination, the catalyst exhibited outstanding CH4 selectivity (almost 100%) and productivity (58.5 µmol g-1 h-1). Mechanistic investigations reveal that the coordination environment of the Cu single atoms is significantly affected by dynamically reacting molecules (CO and *CHxO) during synthesis, leading to a Ti-Cu-O structure. The structure, with the synergistic interaction between Cu single atoms and oxygen defects, significantly enhances *CO adsorption and hydrogenation, thereby promoting the formation of methane. This work pioneers the use of dynamically reactive molecules as imprinted templates to tune photocatalytic CO2 reduction selectivity, providing a novel avenue for designing efficient photocatalysts.

A novel HLA-DRB4 allele, HLA-DRB4*01:179.

One nucleotide substitution in codon 30 of HLA-DRB4*01:03:01:01 results in a novel allele, HLA-DRB4*01:179.

Physicochemical stability of corn protein hydrolysate/tannic acid complex-based ß-carotene nanoemulsion delivery system.

Moderate non-covalent interaction of protein and polyphenols can improve the emulsifying property of protein itself. The corn protein hydrolysate (CPH) and tannic acid (TA) complex was successfully used to construct nanoemulsion for algal oil delivery. There has been no study on the feasibility of this nanoemulsion delivery system for other food functional components, for example, ß-carotene (ß-CE). CPH/TA complex-based nanoemulsion system for ß-CE delivery was studied, focusing on the effect of ß-CE content on the physicochemical stability of the nanoemulsions. The nanoemulsion delivery systems (dia. 150 nm) with low viscosity and good liquidity were easily fabricated by two-step emulsification. The nanoemulsions with high ß-CE content (>71.5 µg/mL) significantly increased (p < .05) the emulsion droplet size. However, there was no significant (p > .05) effect of ß-CE content on polydispersity index (PDI) and zeta potential of the nanoemulsions. The storage (30 days) experiment results demonstrated that the droplet size of the nanoemulsions with varying ß-CE content increased slightly during storage. However, the PDI values showed a slightly decreasing trend. Zeta potentials of the nanoemulsions showed no noticeable change during storage. Moreover, after storage of 30 days, the retention ratios of ß-CE were found to be up to 90%, which suggests an excellent protective effect for ß-CE by the nanoemulsion systems. The CPH/TA complex stabilized nanoemulsions could aggregate in gastric condition, but the ß-CE content did not have obvious effect on the digestive stability of the nanoemulsions. The CPH/TA complex could be employed as an emulsifier to construct a physicochemical stable nanoemulsion delivery system for lipophilic active components.

Diabetes Mellitus and Gynecological and Inflammation Disorders Increased the Risk of Pregnancy Loss in a Population Study.

(1) Background: Diabetes mellitus (DM) induces oxidative stress and inflammation with negative effect on pregnancy outcomes. This study aimed to determine whether DM increases the risk of pregnancy loss and to identify other potential risk factors; (2) Methods: We identified female patients diagnosed with DM from 2000-2015 in the Taiwanese National Health Insurance Research Database according to the International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9 CM) code 250. The event was pregnancy loss, defined as ICD-9 CM codes 630-639, which was tracked until 31 December 2015. The control group included 4-fold more non-DM female patients who were matched for age and disease severity. Multivariate Cox regression was employed to determine the risk factors associated with pregnancy loss; (3) Results: The hazard ratio (HR) for the risk of pregnancy loss due to DM was 1.407 (95% confidence interval: 1.099-1.801, p = 0.007), and the risk factors for older age, gynecological disorders and inflammation disorders were included. (4) Conclusions: The study concluded that women with DM have a greater risk of experiencing pregnancy loss. Healthcare providers should proactively manage and educate diabetic patients to reduce their risk of pregnancy loss. Understanding other probable risk factors can help in developing targeted interventions and support systems for women to improve pregnancy outcomes.

Comparative Transcriptomics of the Entomopathogenic Fungus Beauveria bassiana Grown on Aerial Surface and in Liquid Environment.

Beauveria bassiana, the causative agent of arthropod, proliferates in the host hemolymph (liquid environment) and shits to saprotrophic growth on the host cadaver (aerial surface). In this study, we used transcriptomic analysis to compare the gene expression modes between these two growth phases. Of 10,366 total predicted genes in B. bassiana, 10,026 and 9985 genes were expressed in aerial (AM) and submerged (SM) mycelia, respectively, with 9853 genes overlapped. Comparative analysis between two transcriptomes indicated that there were 1041 up-regulated genes in AM library when compared with SM library, and 1995 genes were down-regulated, in particular, there were 7085 genes without significant change in expression between two transcriptomes. Furthermore, of 25 amidase genes (AMD), BbAMD5 has high expression level in both transcriptomes, and its protein product was associated with cell wall in aerial and submerged mycelia. Disruption of BbAMD5 significantly reduced mycelial hydrophobicity, hydrophobin translocation, and conidiation on aerial plate. Functional analysis also indicated that BbAmd5 was involved in B. bassiana blastospore formation in broth, but dispensable for fungal virulence. This study revealed the high similarity in global expression mode between mycelia grown under two cultivation conditions.

The effect of the molecular weight of blackberry polysaccharides on gut microbiota modulation and hypoglycemic effect in vivo.

Blackberry polysaccharides with certain molecular weight distribution have good bioactivity. In this research, type 2 diabetes mice were used to investigate the hypoglycemic effect of blackberry polysaccharides with three different molecular weights, BBP (603.59 kDa), BBP-8 (408.13 kDa) and BBP-24 (247.62 kDa), through gut microbiota modulation. Blackberry polysaccharides exhibited stronger hypoglycemic activity after degradation, and the FBG of BBP, BBP-8 and BBP-24 was reduced to 20.21 ± 4.17 mmol L-1, 20.6 ± 7.23 mmol L-1 and 17.32 ± 6.59 mmol L-1 and OGTT-AUC was reduced by 14.76%, 19.80% and 25.04%, respectively, after 8-week intervention. Furthermore, 16S rRNA gene sequencing analysis indicated that BBP, BBP-8 and BBP-24 could reshape the diversity and composition of the gut microbiota. From 0 to 4 weeks, the F/B of BBP, BBP-8 and BBP-24 reduced by 56.44%, 47.19% and 62.04%, reaching 3.39, 6.54, and 3.11 in the 8th week, respectively, which suggested the faster utilization of BBP-24. Moreover, the intervention the three blackberry polysaccharides increased the relative abundance of the targeted beneficial bacteria Oscillospira and Bacteroidaceae Bacteroides and decreased the relative abundance of the pathogenic bacterium Allobaculum. In general, the result demonstrated that blackberry polysaccharides with a lower molecular weight are more easily fermented, making the theoretical basis for the development of blackberry polysaccharides as a probiotic food to rapidly regulate intestinal flora for type 2 diabetes.

Cla4A, a Novel Regulator of Gene Expression Networks Required for Asexual and Insect-Pathogenic Lifecycles of Beauveria bassiana.

Cla4, an orthologous p21-activated kinase crucial for non-entomopathogenic fungal lifestyles, has two paralogs (Cla4A/B) functionally unknown in hypocrealean entomopathogens. Here, we report a regulatory role of Cla4A in gene expression networks of Beauveria bassiana required for asexual and entomopathogenic lifecycles while Cla4B is functionally redundant. The deletion of cla4A resulted in severe growth defects, reduced stress tolerance, delayed conidiation, altered conidiation mode, impaired conidial quality, and abolished pathogenicity through cuticular penetration, contrasting with no phenotype affected by cla4B deletion. In ∆cla4A, 5288 dysregulated genes were associated with phenotypic defects, which were restored by targeted gene complementation. Among those, 3699 genes were downregulated, including more than 1300 abolished at the transcriptomic level. Hundreds of those downregulated genes were involved in the regulation of transcription, translation, and post-translational modifications and the organization and function of the nuclear chromosome, chromatin, and protein-DNA complex. DNA-binding elements in promoter regions of 130 dysregulated genes were predicted to be targeted by Cla4A domains. Samples of purified Cla4A extract were proven to bind promoter DNAs of 12 predicted genes involved in multiple stress-responsive pathways. Therefore, Cla4A acts as a novel regulator of genomic expression and stability and mediates gene expression networks required for insect-pathogenic fungal adaptations to the host and environment.

Recognition of the HLA-DRB3*03:65 allele in a Chinese individual.

We report a novel HLA-DRB3*03 allele, now named DRB3*03:65, identified by next-generation sequencing.

Photoreactivation Activities of Rad5, Rad16A and Rad16B Help Beauveria bassiana to Recover from Solar Ultraviolet Damage.

In budding yeast, Rad5 and Rad7-Rad16 play respective roles in the error-free post-replication repair and nucleotide excision repair of ultraviolet-induced DNA damage; however, their homologs have not yet been studied in non-yeast fungi. In the fungus Beauveria bassiana, a deficiency in the Rad7 homolog, Rad5 ortholog and two Rad16 paralogs (Rad16A/B) instituted an ability to help the insect-pathogenic fungus to recover from solar UVB damage through photoreactivation. The fungal lifecycle-related phenotypes were not altered in the absence of rad5, rad16A or rad16B, while severe defects in growth and conidiation were caused by the double deletion of rad16A and rad16B. Compared with the wild-type and complemented strains, the mutants showed differentially reduced activities regarding the resilience of UVB-impaired conidia at 25 °C through a 12-h incubation in a regime of visible light plus dark (L/D 3:9 h or 5:7 h for photoreactivation) or of full darkness (dark reactivation) mimicking a natural nighttime. The estimates of the median lethal UVB dose LD50 from the dark and L/D treatments revealed greater activities of Rad5 and Rad16B than of Rad16A and additive activities of Rad16A and Rad16B in either NER-dependent dark reactivation or photorepair-dependent photoreactivation. However, their dark reactivation activities were limited to recovering low UVB dose-impaired conidia but were unable to recover conidia impaired by sublethal and lethal UVB doses as did their photoreactivation activities at L/D 3:9 or 5:7, unless the night/dark time was doubled or further prolonged. Therefore, the anti-UV effects of Rad5, Rad16A and Rad16B in B. bassiana depend primarily on photoreactivation and are mechanistically distinct from those for their yeast homologs.

Mechanisms and fitness of ceftazidime/avibactam-resistant Klebsiella pneumoniae clinical strains in Taiwan.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection is a global public health issue, and ceftazidime/avibactam is recommended by international guidelines as the preferred treatment for KPC- and OXA-48-producing CRKP. Since its introduction in Taiwan in 2019, ceftazidime/avibactam-resistant strains have emerged. Our aim is to investigate the mechanisms of ceftazidime/avibactam resistance in CRKP in Taiwan and study their associated fitness costs. METHODS: Ceftazidime/avibactam-resistant CRKP strains with exposure to ceftazidime/avibactam isolated from clinical specimens were consecutively collected at Taipei Veterans General Hospital in 2020. The serial strains exhibiting ceftazidime/avibactam-susceptible and ceftazidime/avibactam-resistant phenotypes isolated from the same patient were characterized using whole-genome sequencing and tested for their growth rates and competitive abilities. RESULTS: A total of 35 ceftazidime/avibactam-resistant CRKP strains were identified, with 20 being metallo-ß-lactamase producers. Ten strains harboured KPC variants, exhibiting MIC for ceftazidime/avibactam ranging from 64 to ≥256 mg/L. The 10 strains demonstrating high-level ceftazidime/avibactam resistance possessed mutated KPC variants: KPC-33 (n = 3), KPC-31 (n = 1), KPC-39 (n = 1), KPC-44 (n = 1), KPC-58 (n = 1), KPC-90 (n = 1), and two novel KPC variants. Ceftazidime/avibactam-resistant strains with KPC-33 and KPC-39 showed a significant fitness cost and lower growth rate compared to their parental strains. In contrast, ceftazidime/avibactam-resistant strains with KPC-58 and KPC-58 plus D179Y showed similar growth rates and competitive abilities compared to their parental strains. CONCLUSIONS: Mutated KPC variants conferred high-level ceftazidime/avibactam resistance in Taiwan. Significant fitness costs were observed in both the ceftazidime/avibactam-resistant KPC-33 and KPC-39 strains. Despite conferring a similar level of ceftazidime/avibactam resistance, different KPC variants could entail varying degrees of fitness costs.

Two ferrous iron transporter-like proteins independently participate in asexual development under iron limitation and virulence in Beauveria bassiana.

Reductive assimilation pathway involves ferric reductase and ferrous iron transporter, which is integral for fungal iron acquisition. A family of ferric reductase-like proteins has been functionally characterized in the filamentous entomopathogenic fungus Beauveria bassiana. In this investigation, two ferrous iron transporter-like proteins (Ftr) were functionally annotated in B. bassiana. BbFtr1 and BbFtr2 displayed high similarity in structure and were associated with the plasma and nuclear membrane. Their losses had no negatively influence on fungal growth on various nutrients and development under the iron-replete condition. Single mutants of BbFTR1 and BbFTR2 displayed the iron-availability dependent developmental defects, and double mutant exhibited the significantly impaired developmental potential under the iron-limited conditions. In insect bioassay, the double mutant also showed the weaker virulence than either of two single disruption mutants. These results suggested that two ferrous iron transporter-like proteins function independently in fungal physiologies under the iron-deficient condition. Intriguingly, a bZIP transcription factor BbHapX was required for expression of BbFTR1 and BbFTR2 under iron-depleted conditions. This study enhances our understanding of the iron uptake system in the filamentous entomopathogenic fungi.

Lanternarene-Based Self-Sorting Double-Network Hydrogels for Flexible Strain Sensors.

Conductive flexible hydrogels have attracted immense attentions recently due to their wide applications in wearable sensors. However, the poor mechanical properties of most conductive polymer limit their utilizations. Herein, a double network hydrogel is fabricated via a self-sorting process with cationic polyacrylamide as the first flexible network and the lantern[33]arene-based hydrogen organic framework nanofibers as the second rigid network. This hydrogel is endowed with good conductivity (0.25 S m-1) and mechanical properties, such as large Young's modulus (31.9 MPa), fracture elongation (487%) and toughness (6.97 MJ m-3). The stretchability of this hydrogel is greatly improved after the kirigami cutting, which makes it can be used as flexible strain sensor for monitoring human motions, such as bending of fingers, wrist and elbows. This study not only provides a valuable strategy for the construction of double network hydrogels by lanternarene, but also expands the application of the macrocycle hydrogels to flexible electronics.

PCSK9 inhibitor added to high-intensity statin therapy to prevent cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention: a randomized, double- blind, placebo-controlled, multicenter SHAWN study.

BACKGROUND: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. METHODS: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1,212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at 1-year follow-up between 2 groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. CONCLUSION: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.

The upregulation and transcriptional regulatory mechanisms of Extra spindle pole bodies like 1 in bladder cancer: An immunohistochemistry and high-throughput screening Evaluation.

Background: This study aimed to explore the expression level and transcriptional regulation mechanism of Extra Spindle Pole Bodies Like 1 (ESPL1) in bladder cancer (BC). Methods: A multicentre database of samples (n = 1391) was assayed for ESPL1 mRNA expression in BC and validated at the protein level by immunohistochemical (IHC) staining of in-house samples (n = 202). Single-cell sequencing (scRNA-seq) analysis and enrichment analysis explored ESPL1 distribution and their accompanying molecular mechanisms. ATAC-seq, ChIP-seq and Hi-C data from multiple platforms were used to investigate ESPL1 upstream transcription factors (TFs) and potential epigenetic regulatory mechanisms. Immune-related analysis, drug sensitivity and molecular docking of ESPL1 were also calculated. Furthermore, upstream microRNAs and the binding sites of ESPL1 were predicted. The expression level and early screening efficacy of miR-299-5p in blood (n = 6625) and tissues (n = 537) were examined. Results: ESPL1 was significantly overexpressed at the mRNA level (p < 0.05, SMD = 0.75; 95 % CI = 0.09, 1.40), and IHC staining of in-house samples verified this finding (p < 0.0001). ESPL1 was predominantly distributed in BC epithelial cells. Coexpressed genes of ESPL1 were enriched in cell cycle-related signalling pathways, and ESPL1 might be involved in the communication between epithelial and residual cells in the Hippo, ErbB, PI3K-Akt and Ras signalling pathways. Three TFs (H2AZ, IRF5 and HIF1A) were detected upstream of ESPL1 and presence of promoter-super enhancer and promoter-typical enhancer loops. ESPL1 expression was correlated with various immune cell infiltration levels. ESPL1 expression might promote BC growth and affect the sensitivity and therapeutic efficacy of paclitaxel and gemcitabine in BC patients. As an upstream regulator of ESPL1, miR-299-5p expression was downregulated in both the blood and tissues, possessing great potential for early screening. Conclusions: ESPL1 expression was upregulated in BC and was mainly distributed in epithelial cells. Elevated ESPL1 expression was associated with TFs at the upstream transcription start site (TSS) and distant chromatin loops of regulatory elements. ESPL1 might be an immune-related predictive and diagnostic marker for BC, and the overexpression of ESPL1 played a cancer-promoting role and affected BC patients' sensitivity to drug therapy. miR-299-5p was downregulated in BC blood and tissues and was also expected to be a novel marker for early screening.

[Research progress on mechanism of traditional Chinese medicine intervention in angiogenesis in prevention and treatment of nontraumatic avascular necrosis of femoral head].

Nontraumatic avascular necrosis of the femoral head(NANFH) is a common and refractory femoral head disease that causes bone death due to interruption of blood supply. Early clinical symptoms are atypical, such as hip pain and limited joint function. In the late stage, severe pain, shortening of the affected limb, claudication, and other serious symptoms are common, which se-riously affects the quality of life of patients. Therefore, it is of great significance to actively improve the clinical symptoms of NANFH to enhance the quality of life of patients. The pathogenesis of NANFH is complex, such as traumatic vascular circulatory disorders, the use of hormones or other drugs, alcoholism, and diabetes mellitus. These factors directly or indirectly lead to femoral head vascular damage, thrombosis, and coagulation system disorders, which reduce the blood supply to the acetabulum and femoral head, thus causing ischaemic death of the femoral head or even femoral head collapse. NANFH is mainly categorized as "bone impotence" and "bone paralysis" in traditional Chinese medicine(TCM). The treatment of NANFH with TCM has the characteristics and advantages of a long history, stable and reliable therapeutic effect, fewer adverse reactions, good patient tolerance, and high acceptance. Previous studies have shown that the promotion of angiogenesis is a key initiative in the prevention and treatment of NANFH, and TCM can promote fe-moral head angiogenesis by interfering with the expression of angiogenesis-related factors, which in turn can help to restore the blood supply of the femoral head and thus improve clinical symptoms of NANFH and prevent and treat NANFH. This article described the roles of blood supply interruption and angiogenesis in NANFH and the accumulated knowledge and experience of TCM in NANFH and summarized the role of angiogenesis-related factors in NANFH and the research progress on TCM intervention, so as to provide an idea for the subsequent research and a new basis for the clinical application of TCM in the treatment of NANFH.