[Characteristics of soil moisture limitation and non-limitation in the response of sap flow to transpiration driving factors]. / æ ‘å¹²æ¶²æµå¯¹è’¸è ¾é©±åŠ¨å› å­å“åº”çš„åœŸå£¤æ°´åˆ†é™åˆ¶ä¸Žéžé™åˆ¶ç‰¹å¾.

Transpiration is a significant part of water cycle in forest ecosystems, influenced by meteorological factors and potentially constrained by soil moisture. We used Granier-type thermal dissipation probes to monitor xylem sap flow dynamics of three tree species (Quercus liaotungensis, Platycladus orientalis, and Robinia pseudoacacia) in a semi-arid loess hilly region, and to continuously monitor the key meteorological factors and soil water content (SWC). We established the SWC thresholds delineating soil moisture-limited and -unlimited sap flow responses to transpiration drivers. The results showed that mean sap flux density (Js) of Q. liaotungensis and R. pseudoacacia was significantly higher during period with higher soil moisture compared to lower soil moisture, while the difference in Js for P. orientalis between the two periods was not significant. We used an exponential saturation function to fit the relationship between the Js of each tree species and the integrated transpiration variable (VT) which reflected solar radiation and vapor pressure deficit. The difference in the fitting curve parameters indicated that there were distinct response patterns between Js and VT under different soil moisture conditions. There was a threshold in soil moisture limitation on sap flow for each species, which was identified as 0.129 m3·m-3 for Q. liaotungensis, 0.116 m3·m-3 for P. orientalis, and 0.108 m3·m-3 for R. pseudoacacia. Below the thresholds, Js was limited by soil moisture. Above these points, the normalized sensitivity index (NSI) for Q. liaotungensis and P. orientalis reached saturation, while that of R. pseudoacacia did not reach saturation but exhibited a significant reduction in moisture limitation. Among the three species, P. orientalis was the most capable of overcoming soil moisture constraints.

BDNF mimetics recover palmitic acid-induced injury in cardiomyocytes by ameliorating Akt-dependent mitochondrial impairments.

Cardiac lipotoxicity is a prevalent consequence of lipid metabolism disorders occurring in cardiomyocytes, which in turn precipitates the onset of heart failure. Mimetics of brain-derived neurotrophic factor (BDNF), such as 7,8-dihydroxyflavone (DHF) and 7,8,3'-trihydroxyflavone (THF), have demonstrated significant cardioprotective effects. However, it remains unclear whether these mimetics can protect cardiomyocytes against lipotoxicity. The aim of this study was to examine the impact of DHF and THF on the lipotoxic effects induced by palmitic acid (PA), as well as the concurrent mitochondrial dysfunction. H9c2 cells were subjected to treatment with PA alone or in conjunction with DHF or THF. Various factors such as cell viability, lactate dehydrogenase (LDH) release, death ratio, and mitochondrial function including mitochondrial membrane potential (MMP), mitochondrial-derived reactive oxygen species (mito-SOX) production, and mitochondrial respiration were assessed. PA dose-dependently reduced cell viability, which was restored by DHF or THF. Additionally, both DHF and THF decreased LDH content, death ratio, and mito-SOX production, while increasing MMP and regulating mitochondrial oxidative phosphorylation in cardiomyocytes. Moreover, DHF and THF specifically activated Akt signaling. The protective effects of DHF and THF were abolished when an Akt inhibitor was used. In conclusion, BDNF mimetics attenuate PA-induced injury in cardiomyocytes by alleviating mitochondrial impairments through the activation of Akt signaling.

Comparison of specificity and sensitivity of diagnostic methods for Enteromyxum leei and Enteromyxum fugu detected from cultured tiger puffer, Takifugu rubripes in Korea.

Enteromyxum leei and Enteromyxum fugu, which are myxosporean parasites, were first found in cultured tiger puffer Takifugu rubripes in Korea. We collected four tiger puffers that showed severe emaciation signs for our experiments. DNA sequencing was confirmed that the tiger puffers were coinfected with E. leei and E. fugu. Furthermore, similar amounts of E. leei and E. fugu were confirmed using real-time PCR in the intestine. To the best of our knowledge, there have been no reports of E. fugu infection in the olive flounder Paralichthys olivaceus. However, the diagnosis of inflowing water, discharged water and olive flounder samples using highly sensitive diagnostic methods confirmed the presence of E. fugu in water and fish samples from olive flounder farms near the tiger puffer farm. Therefore, the present study aimed to develop highly sensitive diagnostic methods such as real-time and two-step PCR for early diagnosis and follow-up of the emaciation disease and multiplex PCR for rapid diagnosis. The multiplex PCR method exhibited the same sensitivity as the one-step PCR method developed in this study, demonstrating its efficacy for rapid diagnosis. Therefore, the suggested methods can be utilized for the early diagnosis and rapid diagnosis of emaciation diseases and reduction of economic losses through rapid disease control.

Progress in quality management and control of donor organ procurement in foreign countries / 器官移植

Since the 20th century, organ transplantation has become a breakthrough technology to effectively save the lives of patients with end-stage organ failure, which has significantly enhanced the quality of life of patients. Organ donation is an important source of organ transplantation. Improving the quality of donor organ procurement is the key to promote the translation of donor organs and improve the prognosis of organ transplantation recipients. The United States, Spain and other countries have put forward a series of policies and standards in the quality management and control of donor organ procurement and achieved positive results. In this article, related concepts of medical quality management and control, advanced strategies and models of international donor organ procurement quality management, and quality control measures of Organ Procurement Organization, donors and donor organs were reviewed, aiming to provide reference for establishing a quality management and control system of donor organs with "Chinese characteristics" and advancing high-speed and high-quality development of donor organ procurement.

Distinct immunoreactions after a primary tumor microwave ablation using different heating parameters in a VX2 tumor model.

BACKGROUND: Thermal ablation of solid tumors in situ can activate the immune system and produce a specific immune response against the tumor. Microwave ablation (MWA) with different parameters can ablate tumors with similar sizes and cause different local inflammatory effects. Our aim was to determine the immunological effects induced by different energy modes of MWA for a primary tumor. METHODS: Seventy rabbits with VX2 tumors that were implanted subcutaneously underneath the right second nipple were treated with high-power MWA (40 W for 1 min), low-power MWA (20 W for 2 min), or surgical resection or were left without treatment (control). Survival time was evaluated by log-rank test. On day 14 after ablation, immunohistochemistry and flow cytometry were used to evaluate the T-cell immune responses. In addition, the cytokine patterns were identified by enzyme-linked immunosorbent assay. RESULTS: Tumor eradication was achieved completely in the MWA groups, as proven by nicotinamide adenine dinucleotide diaphorase staining. Compared with the three treatment groups, the control group had a significantly higher number of pulmonary metastases and worse survival; however, no significant difference was observed among the three treatment groups. More intra-tumoral and systemic CD4+ and CD8+ T-cells were induced in the MWA groups than in the control group. Compared with operation, MWA induced more systemic CD4+ T-cells. More intra-tumoral CD4+ and CD8+ T-cells and systemic CD4+ T-cells were induced by high-power MWA than by low-power MWA. Moreover, MWA increased the interleukin 2 (IL2) and IL12 levels and decreased the IL4, IL6, and IL10 levels. Importantly, the serum IL12 level was significantly higher after high-power MWA than after low-power MWA. CONCLUSION: High-power MWA enhanced the type 1 T helper immune response and may be selected for the treatment of solid tumors. Future studies are needed to confirm our results.

The role of intestinal microbes on intestinal barrier function and host immunity from a metabolite perspective.

The gut is colonized by many commensal microorganisms, and the diversity and metabolic patterns of microorganisms profoundly influence the intestinal health. These microbial imbalances can lead to disorders such as inflammatory bowel disease (IBD). Microorganisms produce byproducts that act as signaling molecules, triggering the immune system in the gut mucosa and controlling inflammation. For example, metabolites like short-chain fatty acids (SCFA) and secondary bile acids can release inflammatory-mediated signals by binding to specific receptors. These metabolites indirectly affect host health and intestinal immunity by interacting with the intestinal epithelial and mucosal immune cells. Moreover, Tryptophan-derived metabolites also play a role in governing the immune response by binding to aromatic hydrocarbon receptors (AHR) located on the intestinal mucosa, enhancing the intestinal epithelial barrier. Dietary-derived indoles, which are synthetic precursors of AHR ligands, work together with SCFA and secondary bile acids to reduce stress on the intestinal epithelium and regulate inflammation. This review highlights the interaction between gut microbial metabolites and the intestinal immune system, as well as the crosstalk of dietary fiber intake in improving the host microbial metabolism and its beneficial effects on the organism.

Gut macrobiotic and its metabolic pathways modulate cardiovascular disease.

Thousands of microorganisms reside in the human gut, and extensive research has demonstrated the crucial role of the gut microbiota in overall health and maintaining homeostasis. The disruption of microbial populations, known as dysbiosis, can impair the host's metabolism and contribute to the development of various diseases, including cardiovascular disease (CVD). Furthermore, a growing body of evidence indicates that metabolites produced by the gut microbiota play a significant role in the pathogenesis of cardiovascular disease. These bioactive metabolites, such as short-chain fatty acids (SCFAs), trimethylamine (TMA), trimethylamine N-oxide (TMAO), bile acids (BAs), and lipopolysaccharides (LPS), are implicated in conditions such as hypertension and atherosclerosis. These metabolites impact cardiovascular function through various pathways, such as altering the composition of the gut microbiota and activating specific signaling pathways. Targeting the gut microbiota and their metabolic pathways represents a promising approach for the prevention and treatment of cardiovascular diseases. Intervention strategies, such as probiotic drug delivery and fecal transplantation, can selectively modify the composition of the gut microbiota and enhance its beneficial metabolic functions, ultimately leading to improved cardiovascular outcomes. These interventions hold the potential to reshape the gut microbial community and restore its balance, thereby promoting cardiovascular health. Harnessing the potential of these microbial metabolites through targeted interventions offers a novel avenue for tackling cardiovascular health issues. This manuscript provides an in-depth review of the recent advances in gut microbiota research and its impact on cardiovascular health and offers a promising avenue for tackling cardiovascular health issues through gut microbiome-targeted therapies.

Prognosis analysis of multi-indicator combined with sequential organ failure assessment in patients with sepsis / 中华危重病急救医学

OBJECTIVE@#To explore the prognostic value of early multiple detection indicators in combination with sequential organ failure assessment (SOFA) in sepsis patients.@*METHODS@#A retrospective analysis was conducted. Patients with sepsis admitted to the department of critical care medicine of Huanggang Central Hospital of Yangtze University from May 2020 to May 2022 were selected as the research subjects. Coagulation indicators, inflammatory factors, blood routine, liver and kidney function, and blood gas analysis were collected at admission. Organ dysfunction was assessed based on the SOFA score within 24 hours after admission. Patients were divided into a survival group and a death group according to the outcome of 28 days in ICU. Differences in the above indicators between the two groups were compared. Multifactorial Logistic regression analysis was used to analyze prognostic factors of 28-day mortality in sepsis patients. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive performance of various indicators, the SOFA score, and the combine model for the 28-day outcome in patients with sepsis.@*RESULTS@#A total of 101 patients with sepsis were enrolled, 56 patients survived and 45 patients died. Compared to the survival group, patients in the death group were older, the proportion of patients with septic shock was larger, the SOFA score, and the proportion of pulmonary infection were higher, the prothrombin time (PT) and activated partial thromboplastin time (APTT) were significantly prolonged, the prothrombin activity (PTA) was significantly shortened, and antithrombin (AT) was significantly decreased, the levels of hypersensitivity C-reactive protein (hs-CRP), blood urea nitrogen (BUN), total bilirubin (TBil), and lactic acid (Lac) were significantly increased, while the platelet count (PLT) was significantly decreased. Multifactorial Logistic regression analysis showed that pulmonary infection [odds ratio (OR) = 0.010, 95% confidence interval (95%CI) was 0.001-0.164, P = 0.001], AT (OR = 0.944, 95%CI was 0.910-0.978, P = 0.002), hs-CRP (OR = 1.008, 95%CI was 1.001-1.015, P = 0.017), Lac (OR = 1.619, 95%CI was 1.195-2.193, P = 0.002), and SOFA score (OR = 1.363, 95%CI was 1.076-1.727, P = 0.010) were independent prognostic factors for 28-day mortality in patients. A combined model was constructed using pulmonary infection, AT, hs-CRP, Lac, and SOFA score. ROC curve analysis showed that the area under the ROC curve (AUC) for the combine model in predicting sepsis prognosis was 0.936 (95%CI was 0.869-0.975, P < 0.001), which was higher in value compared to single indicators (AUC of AT, hs-CRP, Lac, and SOFA score were 0.775, 0.666, 0.802, 0.796, respectively, all P < 0.05).@*CONCLUSIONS@#The predictive ability of the SOFA score for sepsis patient outcomes is limited. The combine model combining infection site, AT, hs-CRP, and Lac shows better predictive ability.

The Effect of a Multifaceted Intervention on Dietary Quality in Schoolchildren and the Mediating Effect of Dietary Quality between Intervention and Changes in Adiposity Indicators: A Cluster Randomized Controlled Trial.

Some studies have found associations between dietary quality and obesity and their concurrent changes were observed in a few interventions. The present study aimed to assess the effect of a multifaceted intervention for childhood obesity on dietary quality and examine the mediating effect of dietary quality between the intervention and changes in adiposity indicators. Based on the social ecological model, the cluster randomized controlled trial included five components (three targeted children and two targeted their environment). In total, 1176 children from three cities in China participated in a baseline (2018) and end-of-trial (2019) examination, including 605 children in the intervention group and 571 in the control group. Self-reported behavior and anthropometric measures were collected at both time points. The Diet Balance Index Revision (DBI-07) was calculated to assess dietary quality. Generalized linear mixed models were used to estimate the intervention effect on dietary quality and its mediating effects were examined. Compared to the controls, the proportion of sugar-sweetened beverage (SSB) intake (OR = 0.27, p < 0.001, corrected p < 0.001) decreased in the intervention group. Higher bound scores (HBS) of the DBI-07 indicating over-intake decreased in the intervention group compared to the controls (mean difference = −1.52, p = 0.005, corrected p = 0.015). Changes in the HBS partially mediated the associations between the intervention and changes in body mass index, waist circumference, and body fat percentage. Future intervention should promote knowledge, attitudes, and behaviors related to dietary quality.

Antibiotic Susceptibility of Bacterial Pathogens That Infect Olive Flounder (Paralichthys olivaceus) Cultivated in Korea.

Paralichthys olivaceus (olive flounder) is widely cultivated in Korea. However, data on the antibiotic susceptibility of bacterial pathogens that infect olive flounders in Korea are limited. The susceptibility of 84 strains of 3 pathogenic bacteria (Streptococcus spp., Vibrio spp., and Edwardsiella piscicida) to 18 antibiotics was tested using the minimum inhibitory concentration (MIC) panels, and the distribution of the MIC values for each species was confirmed. Among the panel antibiotics, nine commonly used antibiotics were selected, and the multiple antibiotic resistance (MAR) index and antibiotic resistance pattern were indicated using the disk diffusion method. It was confirmed that most of the isolates had a MAR index greater than 0.2, indicating a high-risk source. The distribution patterns of the MIC values and resistance pattern between gram-positive and gram-negative bacteria showed slightly different results. Ampicillin, erythromycin, and clindamycin were more effective against gram-positive bacteria than gram-negative bacteria. However, the MIC values of flumequine for gram-positive bacteria were higher than those of gram-negative bacteria. Through the distribution patterns of the MIC values and resistance patterns presented in this study, the need for monitoring the multidrug-resistant bacteria in aquaculture is emphasised.

Construction and Validation of a Novel Pyroptosis-Related Four-lncRNA Prognostic Signature Related to Gastric Cancer and Immune Infiltration.

Increasing evidence has demonstrated that pyroptosis, a type of inflammatory programmed cell death, plays an important role in the pathogenesis and progression of gastric cancer. However, it remains unclear whether pyroptosis-related long non-coding RNAs (lncRNAs) can be used to predict the diagnosis and prognosis of gastric adenocarcinoma. This study aimed to evaluate and test the role of the lncRNA signature associated with pyroptosis as a prognostic tool for stomach adenocarcinoma (STAD) and to ascertain their immune value. Relative RNA-sequencing data were extracted from The Cancer Genome Atlas database (TCGA), and data preprocessing was performed for STAD. Pearson correlation analysis was used to determine whether lncRNAs were significantly correlated with pyroptosis based on 23 genes related to pyroptosis. Univariate Cox regression and least absolute shrinkage and selection operator(LASSO) analyses were both adopted to select features and establish the pyroptosis-related lncRNA (PRL) prognostic signature. Kaplan-Meier(KM) survival analysis of the different risk groups was conducted according to the risk scores. We further examined the functional enrichment, tumor microenvironment, and landscape of mutation status among the different risk groups, and these analyses further explained the reasons for the differences in the prediction as well as survival value of the different risk groups. Four lncRNAs, including HAND2-AS1, LINC01354, RP11-276H19.1, and PGM5-AS1, were involved in the PRL signature and used to split STAD patients into two risk groups. Overall survival time(OS) was significantly higher in the low-risk group than in the high-risk group in both the training and validation groups. Functional enrichment analysis was further employed to analyze differentially expressed genes in high- and low-risk groups to identify potential molecular functions and pathways associated with pyroptosis in the gastric cancer microenvironment. Protein-protein interaction (PPI) and Friends analysis identified hub genes that may play a key role in differentially expressed genes in high- and low-risk groups. In addition, there were remarkable discrepancies between the different risk groups in the tumor stage (P < 0.01) and histologic grade (P < 0.05). Furthermore, drug-susceptibility testing indicated potential sensitive chemotherapeutic drugs for each risk group. This study is the first to establish and validate STAD-associated PRLs that can effectively guide the prognosis and the immune microenvironment in STAD patients and provide evidence for the development of molecularly targeted therapies related to pyroptosis.

FLAIR vessel hyperintensities predict functional outcomes in patients with acute ischemic stroke treated with medical therapy.

OBJECTIVES: The prognostic value of fluid-attenuated inversion recovery vessel hyperintensity (FVH) remains controversial in acute ischemic stroke (AIS). The objective was to investigate whether the presence of FVH could predict long-term functional outcomes in patients with AIS receiving medical therapy. METHODS: Consecutive AIS patients with anterior circulation large vessel stenosis (LVS) in multiple centers between January 2019 and December 2020 were studied. Presence of FVH was identified and evaluated as FVH (+). Quantification of FVH was performed using an FVH-Alberta Stroke Program Early CT Score (ASPECTS) system and divided into grades: FVH-ASPECTS of 0 = grade 0; 1-2 = grade 1; 3-7 = grade 2. Poor functional outcome was defined as modified Rankin scale > 2 at 3 months. RESULTS: Overall, 175 patients were analyzed (age, 64.31 ± 13.47 years; men, 65.1%), and 78.9% patients presented with FVH. Larger infarct volume (19.90 mL vs. 5.50 mL, p < 0.001), higher rates of FVH (+) (92.0% vs. 65.9%, p < 0.001), and higher FVH grades (grade 2, 34.5% vs. 10.2%, p < 0.001) were more prone to be observed in patients with poor functional outcomes. FVH (+) with infarct volume larger than 6.265 mL (adjusted odds ratio [aOR] 6.03, 95% confidence interval [CI] 1.82-19.98) and FVH grade (grade 1, aOR 3.07, 95% CI 1.12-8.43; grade 2, aOR 5.80, 95% CI 1.59-21.11) were independently associated with poor functional outcomes. CONCLUSION: FVH (+) combined with large infarct volume and high FVH grade can predict poor long-term functional outcomes in patients with LVS who receive medical therapy. KEY POINTS: • FVH is expected to be a contrast agent-independent alternative for assessing hemodynamic status in the acute stage of stroke. • FVH (+) and high FVH grade, quantified by FVH-ASPECTS rating system and grades, are associated with large infarct volume. • The combination of FVH and DWI-based infarct volume has independent predictive value for long-term functional outcomes in AIS patients with large artery stenosis treated with medical therapy.

Identification and Comprehensive Analysis of FREM2 Mutation as a Potential Prognostic Biomarker in Colorectal Cancer.

Gene mutations play an important role in tumor progression. This study aimed to identify genes that were mutated in colorectal cancer (CRC) and to explore their biological effects and prognostic value in CRC patients. We performed somatic mutation analysis using data sets from The Cancer Genome Atlas and International Cancer Genome Consortium, and identified that FREM2 had the highest mutation frequency in patients with colon adenocarcinoma (COAD). COAD patients were divided into FREM2-mutated type (n = 36) and FREM2-wild type (n = 278), and a Kaplan-Meier survival curve was generated to perform prognostic analysis. A FREM2-mutation prognosis model was constructed using random forest method, and the performance of the model was evaluated using receiver operating characteristic curve. Next, the random forest method and Cox regression analysis were used to construct a prognostic model based on the gene expression data of 36 FREM2-mutant COAD patients. The model showed a high prediction accuracy (83.9%), and 13 prognostic model characteristic genes related to overall survival were identified. Then, the results of tumor mutation burden (TMB) and microsatellite instability (MSI) analyses revealed significant differences in TMB and MSI among the risk scores of different prognostic models. Differentially expressed genes were identified and analyzed for functional enrichment and immune infiltration. Finally, 30 samples of CRC patients were collected for immunohistochemical staining to analyze the FREM2 expression levels, which showed that FREM2 was highly expressed in tumor tissues. In conclusion, CRC patients had a high level of FREM2 mutations associated with a worse prognosis, which indicated that FREM2 mutations may be potential prognostic markers in CRC.

[Series of group standards of Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions].

Drug instructions,the statutory and technical documents recording effectiveness and safety information,are an important basis for guiding doctors,pharmacists,and patients to use drugs rationally,and their scientificity,standardization,and accuracy directly affect the medication safety of the public. The sections of adverse drug events,contraindications,precautions,warnings,and application for specific populations in drug instructions directly express safety information and measures for rational use of drugs. In the drug life cycle,marketing authorization holders( MAHs) need to update safety information in the instructions promptly to ensure the safety and effectiveness of clinical drug medication. At present,revising instructions is an important measure to control drug risks. In the drug life cycle,in order to standardize the revision of safety information in the instructions by MAHs and eliminate inexact terms such as " unclear",the Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,have been established under the guidance of Standardization Department,China Association of Chinese Medicine. Therefore,on the basis of the existing rules and regulations,the standardized technical procedures for revising instructions came into being to help clinical safe and rational medication of drugs,and implement the strategy of " Healthy China".

[Interpretation of Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions].

Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,were proposed by Professor ZHANG Bing from Research Center for Pharmacovigilance and Rational Use of Traditional Chinese Medicine,and underwent centralized management by Chinese Association of Chinese Medicine. They were officially released on July 23 and implemented on July 31,2021. The series of group standards consist of six sections,including general principles,adverse drug events,contraindications,precautions,application for special populations,and warnings. The section of general principles is comprised of holistic and programmatic expressions,which explain the general technical requirements for revising the marketed Chinese patent medicine instructions. The other five sections focus on information collection,screening,transformation,and illustration of specific items,forming a standardized revision technical process. This series of standards is the result of multiple rounds of research and the suggestions of more than 200 experts in different professional fields of " medicine-pharmacy-management-law-enterprise" have been gathered therein to reach a consensus. With the purposes of establishing standardized technical specifications for the revision of safety information in the marketed Chinese patent medicine instructions,guiding marketing authorization holders in revising the instructions,filling the gaps in the research of Chinese patent medicine instructions,promoting the deve-lopment of pharmaceutical care and academic research,and encouraging the rational and safe medication of Chinese patent medicine,the series of group standards is of great significance.

Severity of Intracranial Large Artery Disease Correlates With Cerebral Small Vessel Disease.

BACKGROUND: Small vessel disease (SVD) shares common vascular risk factors with large artery disease (LAD). However, little is known about the relationship between intracranial artery stenosis and SVD burden. PURPOSE: To investigate whether SVD burden correlates with severity of intracranial LAD. STUDY TYPE: Retrospective. POPULATION: Five hundred and sixteen patients with LAD of arterial circulation were enrolled from one hospital, including 384 males (59 ± 11 years) and 132 females (60 ± 12 years). FIELD STRENGTH/SEQUENCE: 3 T. T1 -weighted fast spin echo (T1 W FSE), T2 W FSE, T2 fluid attenuated inversion recovery, diffusion-weighted imaging, susceptibility-weight imaging, and time-of-flight magnetic resonance angiography. ASSESSMENT: The LAD was divided into mild stenosis (<30%), moderate stenosis (30%-69%), and severe stenosis (≥70%). The Standard for Reporting Vascular Changes on Neuroimaging criteria was used to rate the SVD burden according to the level of white matter hyperintensity (WMH), perivascular space (PVS), cerebral microbleed (CMB), and lacunes. STATISTICAL TESTS: Lilliefors test, ANOVA, chi-squared test, Mann-Whitney U test, Wilcoxon signed rank test, Bonferroni test, Spearman's correlation, logistic regression, and Cohen's kappa test. RESULTS: The grade scores for centrum semiovale PVS (CS-PVS) were positively correlated with the degree of stenosis (R = 0.413), whereas the presence of severe basal ganglia PVS (BG-PVS) was associated with CMB (R = 0.508), lacunes (R = 0.365), and severe WMH (R = 0.478). In multivariate analysis, severe CS-PVS (adjusted odds ratio [aOR], 3.1; 95% confidence interval [CI], 1.9-4.8) and lacunes (aOR, 2.1; 95% CI, 1.3-3.4) were associated with severe stenosis of LAD. In addition, CS-PVS was related to severe stenosis in a dose-dependent manner: when CS-PVS score was 3 and 4, the aORs of severe stenosis were 1.9 and 7.7, respectively. DATA CONCLUSION: The severity of LAD in anterior circulation is associated with SVD burden, which suggests that different SVD burden may be used for risk stratification in LAD. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

New Prognostic Biomarkers and Drug Targets for Skin Cutaneous Melanoma via Comprehensive Bioinformatic Analysis and Validation.

Skin cutaneous melanoma (SKCM) is the most aggressive and fatal type of skin cancer. Its highly heterogeneous features make personalized treatments difficult, so there is an urgent need to identify markers for early diagnosis and therapy. Detailed profiles are useful for assessing malignancy potential and treatment in various cancers. In this study, we constructed a co-expression module using expression data for cutaneous melanoma. A weighted gene co-expression network analysis was used to discover a co-expression gene module for the pathogenesis of this disease, followed by a comprehensive bioinformatics analysis of selected hub genes. A connectivity map (CMap) was used to predict drugs for the treatment of SKCM based on hub genes, and immunohistochemical (IHC) staining was performed to validate the protein levels. After discovering a co-expression gene module for the pathogenesis of this disease, we combined GWAS validation and DEG analysis to identify 10 hub genes in the most relevant module. Survival curves indicated that eight hub genes were significantly and negatively associated with overall survival. A total of eight hub genes were positively correlated with SKCM tumor purity, and 10 hub genes were negatively correlated with the infiltration level of CD4+ T cells and B cells. Methylation levels of seven hub genes in stage 2 SKCM were significantly lower than those in stage 3. We also analyzed the isomer expression levels of 10 hub genes to explore the therapeutic target value of 10 hub genes in terms of alternative splicing (AS). All 10 hub genes had mutations in skin tissue. Furthermore, CMap analysis identified cefamandole, ursolic acid, podophyllotoxin, and Gly-His-Lys as four targeted therapy drugs that may be effective treatments for SKCM. Finally, IHC staining results showed that all 10 molecules were highly expressed in melanoma specimens compared to normal samples. These findings provide new insights into SKCM pathogenesis based on multi-omics profiles of key prognostic biomarkers and drug targets. GPR143 and SLC45A2 may serve as drug targets for immunotherapy and prognostic biomarkers for SKCM. This study identified four drugs with significant potential in treating SKCM patients.

The Landscape of the Tumor Microenvironment in Skin Cutaneous Melanoma Reveals a Prognostic and Immunotherapeutically Relevant Gene Signature.

The tumorigenesis of skin cutaneous melanoma (SKCM) remains unclear. The tumor microenvironment (TME) is well known to play a vital role in the onset and progression of SKCM. However, the dynamic mechanisms of immune regulation are insufficient. We conducted a comprehensive analysis of immune cell infiltration in the TME. Based on the differentially expressed genes (DEGs) in clusters grouped by immune infiltration status, a set of hub genes related to the clinical prognosis of SKCM and tumor immune infiltration was explored. Methods: We analyzed immune cell infiltration in two independent cohorts and assessed the relationship between the internal pattern of immune cell infiltration and SKCM characteristics, including clinicopathological features, potential biological pathways, and gene mutations. Genes related to the infiltration pattern of TME immune cells were determined. Furthermore, the unsupervised clustering method (k-means) was used to divide samples into three different categories according to TME, which were defined as TME cluster-A, -B, and -C. DEGs among three groups of samples were analyzed as signature genes. We further distinguished common DEGs between three groups of samples according to whether differences were significant and divided DEGs into the Signature gene-A group with significant differences and the Signature gene-B group with insignificant differences. The Signature gene-A gene set mainly had exon skipping in SKCM, while the Signature gene-B gene set had no obvious alternative splicing form. Subsequently, we analyzed genetic variations of the two signatures and constructed a competing endogenous RNA (ceRNA) regulatory network. LASSO Cox regression was used to determine the immune infiltration signature and risk score of SKCM. Finally, we obtained 13 hub genes and calculated the risk score based on the coefficient of each gene to explore the impact of the high- and low-risk scores on biologically related functions and prognosis of SKCM patients further. The correlation between the risk score and clinicopathological characteristics of SKCM patients indicated that a low-risk score was associated with TME cluster-A classification (p < 0.001) and metastatic SKCM (p < 0.001). Thirteen hub genes also showed different prognostic effects in pan-cancer. The results of univariate and multivariate Cox analyses revealed that risk score could be used as an independent risk factor for predicting the prognosis of SKCM patients. The nomogram that integrated clinicopathological characteristics and immune characteristics to predict survival probability was based on multivariate Cox regression. Finally, 13 hub genes that showed different prognostic effects in pan-cancers were obtained. According to immunohistochemistry staining results, Ube2L6, SRPX2, and IFIT2 were expressed at higher levels, while CLEC4E, END3, and KIR2DL4 were expressed at lower levels in 25 melanoma specimens. Conclusion: We performed a comprehensive assessment of the immune-associated TME. To elucidate the potential development of immune-genomic features in SKCM, we constructed an unprecedented set of immune characteristic genes (EDN3, CLEC4E, SRPX2, KIR2DL4, UBE2L6, and IFIT2) related to the immune landscape of TME. These genes are related to different prognoses and drug responses of SKCM. The immune gene signature constructed can be used as a robust prognostic biomarker of SKCM and a predictor of an immunotherapy effect.

[Technical specification for Instructions for Clinical Application of Chinese Patent Medicines in China Association of Chinese Medicine].

In order to solve the problems of confusion in clinical medication and imperfect instructions in Chinese patent medicines(CPMs), the Standardization Department of the China Association of Chinese Medicine and Center for Pharmacovigilance and Rational use of Chinese Medicine in Beijing University of Chinese Medicine jointly compiled the Instructions for Clinical Application of Chinese Patent Medicines(CPMs). As the interpretation and supplement of drug instruction information, it aims to guide clinical safety and rational use of CPMs. In addition, the technical specification for clinical application description of CPMs has been formulated, which covers the seven processes of "carding instructions, clinical investigation, data retrieval, data screening, evidence classification, path transformation and writing format". It will enable readers of Instructions for Clinical Application of Chinese Patent Medicines to understand the work behind the compilation.

[Progress in application of Bletilla striata polysaccharide in novel drug delivery systems and biomaterials].

As the main active ingredient of the orchidaceous herb Bletilla striata, B. striata polysaccharide(BSP) has pharmacological activities such as promoting coagulation, anti-inflammation, anti-oxidation, promoting wound healing, anti-tumor, and immunomodulation, and is biodegradable and non-toxic. Additionally, it has the material properties of suspension thickening, film-forming adhesion, coating and solubilizing, targeting and slow releasing, effect-enhancing and toxicity-reducing, etc., playing the role of unification of medicines and excipients. Therefore, BSP has a wide application prospect in the fields of drug delivery system and trauma repair. This paper reviews the research progress of BSP application in new drug delivery systems and biomaterials based on the related li-terature in recent years, with the aim of providing reference for the further research and application of BSP.