A Survey of Solid Form Landscape: Trends in Occurrence and Distribution of Various Solid Forms and Challenges in Solid Form Selection.

This survey provides a comprehensive analysis of solid form screens for 476 new chemical entities (NCEs) conducted at Pharmaron from 2016 to 2023. The findings from this survey reveal notable trends in polymorphism, salt formation, crystallization behavior and molecular weight (MW) distribution of the NCEs evaluated. Most solid form screens were conducted to select the preferred solid form for Investigational New Drug (IND) enabling projects, others were for candidate selection or late-stage development. Comparison to published historical data was made to show changes in occurrence of counterions/co-formers for salts/co-crystals, polymorphs, and the distribution of MWs over time. Increased complexity in the solid-form landscape and selection of the development form are discussed, including challenges in crystallization and selection of lead forms. The distribution of types of crystal forms and the observation of emerging and disappearing polymorphs are presented. These results highlight the evolving challenges and considerations in solid form screening and form selection and offer insights for future pharmaceutical development and crystallization strategies.

Assembly and comparative analysis of the first complete mitochondrial genome of Salix psammophila, a good windbreak and sand fixation shrub.

Salix psammophila, commonly known as the sandlive willow, is a vital shrub species within the Salicaceae family, particularly significant for its ecological role in regions susceptible to desertification and sandy soils. In this study, we assembled the complete S. psammophila mitochondrial genome using Pacbio HiFi third-generation sequencing data. The genome was found to be a typical single circular structure, with a total length of 715,555 bp and a GC content of 44.89%. We annotated 33 unique protein-coding genes (PCGs), which included 24 core mitochondrial genes and 9 variable genes, as well as 18 tRNA genes (5 of which were multicopy genes) and 3 rRNA genes. Comparative analysis of the PCGs from the mitochondrial genomes of S. psammophila, Populus deltoides, Populus simonii, Salix wilsonii, and Salix suchowensis revealed that these genes are relatively conserved within the Salicaceae family, with variability primarily occurring in the ribosomal protein genes. The absence of the rps14, which encodes a ribosomal protein, may have played a role in the evolution of stress tolerance in Salicaceae plants. Additionally, we identified 232 SSRs, 19 tandem repeat sequences, and 236 dispersed repeat sequences in the S. psammophila mitochondrial genome, with palindromic and forward repeats being the most abundant. The longest palindromic repeat measured 260 bp, while the longest forward repeat was 86,068 bp. Furthermore, 324 potential RNA editing sites were discovered, all involving C-to-U edits, with the nad4 having the highest number of edits. These findings provide valuable insights into the phylogenetic and genetic research of Salicaceae plants.

Tobacco Smoking Interacted with Alcohol Drinking Could Increase the Failure of PASI75 Achievement at Week 8 Among Patients with Psoriasis: Findings Based on a Psoriasis Cohort.

Purpose: Tobacco smoking and alcohol drinking are positively associated with psoriasis prevalence and disease severity. Researches focusing on the influence of smoking and drinking on the treatment efficacy of psoriasis are still limited, especially their interaction effect. This study aims to explore the interactive effects of smoking and drinking on the treatment efficacy in psoriasis patients. Patients and Methods: From 2021 to 2022, we recruited 560 patients with psoriasis from Shanghai Skin Diseases Hospital. Demographic and clinical features as well as treatment efficacy were collected through questionnaire interview and physical examination during patient's hospital visit at week 0, week 4 and week 8. Logistic regression model was used to explore the influence of smoking and drinking on the treatment efficacy in psoriasis patients, and multiplicative and additive interaction models were used to verify the interaction effect of smoking and drinking on the treatment efficacy. Results: The prevalence of smoking and drinking among psoriasis patients was respectively 43.8% and 25.4%, and 19.6% of them with both smoking and drinking. Logistic regression analysis showed that patients with smoking (OR=7.78, 95% CI: 5.26~11.49) and drinking (OR=5.21, 95% CI: 3.29~8.27) had higher risk of experiencing the failure to achieve PASI75 at week 8, even with the adjustment of confounders. Moreover, multiplicative as well as additive model showed that tobacco smoking interacted with alcohol drinking which influenced the treatment efficacy more severely (OR=12.74, 95% CI: 7.16~22.67). The proportion of PASI75 achievement in female patients (OR=19.54) and patients with methotrexate (OR=28.31) and biologics (OR=21.61) were more likely being affected by smoking and drinking. Conclusion: Tobacco smoking and alcohol drinking could increase the failure of PASI75 achievement in patients with psoriasis, individually and interactively. We recommend that dermatologists should educate patients to pay attention to the negative effects of smoking and drinking, encourage them to quit, and thus improve the treatment efficacy.

N-Doped Carbon Dots for Selective Detection of Fe3+ and Degradation of Fe3+/Basic Red 9 Complexes in Water Samples.

In this work, the eco-friendly N-doped carbon dots KF-CDs and A-CDs were derived from kiwifruit by a simple one-step hydrothermal strategy at 180 °C for 6 h. KF-CDs have a high fluorescence quantum yield (27.85%), it is obviously rapid quenched by Fe3+, and have a good linear relationship from 1 to 8.26 µM (the detection limit was 0.077 µM). Basic red 9 is extensively used in biological, environmental and industry. Although it makes a great contribution to the economy, its toxicity should be taken seriously, especially with harmful metal ions. Within 2 h, A-CDs could degrade basic red 9 with degradation efficiency 89.6%, even though there was a stable compound formed with Fe3+ that the degradation efficiency was up to 88.3%. The results complement the research blank of carbon dots in catalytic degradation of basic red 9.

Atlas of Metastatic Gastric Cancer Links Ferroptosis to Disease Progression and Immunotherapy Response.

BACKGROUND & AIMS: Metastases from gastric adenocarcinoma (GAC) lead to high morbidity and mortality. Developing innovative and effective therapies requires a comprehensive understanding of the tumor and immune biology of advanced GAC. Yet, collecting matched specimens from advanced, treatment-naïve patients with GAC poses a significant challenge, limiting the scope of current research, which has focused predominantly on localized tumors. This gap hinders deeper insight into the metastatic dynamics of GAC. METHODS: We performed in-depth single-cell transcriptome and immune profiling on 68 paired, treatment-naïve, primary metastatic tumors to delineate alterations in cancer cells and their tumor microenvironment during metastatic progression. To validate our observations, we conducted comprehensive functional studies both in vitro and in vivo, using cell lines and multiple patient-derived xenograft and novel mouse models of GAC. RESULTS: Liver and peritoneal metastases exhibited distinct properties in cancer cells and dynamics of tumor microenvironment phenotypes, supporting the notion that cancer cells and their local tumor microenvironments co-evolve at metastatic sites. Our study also revealed differential activation of cancer meta-programs across metastases. We observed evasion of cancer cell ferroptosis via GPX4 up-regulation during GAC progression. Conditional depletion of Gpx4 or pharmacologic inhibition of ferroptosis resistance significantly attenuated tumor growth and metastatic progression. In addition, ferroptosis-resensitizing treatments augmented the efficacy of chimeric antigen receptor T-cell therapy. CONCLUSIONS: This study represents the largest single-cell dataset of metastatic GACs to date. High-resolution mapping of the molecular and cellular dynamics of GAC metastasis has revealed a rationale for targeting ferroptosis defense in combination with chimeric antigen receptor T-cell therapy as a novel therapeutic strategy with potential immense clinical implications.

Shared decision-making implementation status among dermatologists engaging in medical esthetics: a cross-sectional study in China.

Objective: Shared decision-making (SDM) is a collaborative process in which patients and healthcare providers jointly make a medical decision. This cross-sectional study aimed to identify the implementation status of shared decision-making among dermatologists engaging in medical esthetics in China and to identify factors associated with the good practice of SDM among them. Methods: From January to June 2023, a total of 1,287 dermatologists engaging in medical esthetics in China were recruited and completed the online interviews about their implementation of SDM based on the Shared Decision-Making Questionnaire for Doctors (SDM-Q-Doc). Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) to explore factors associated with the higher SDM score achievement among dermatologists with medical esthetic practice. Results: The median value of the total SDM score was 39, and 48% (621/1278) of dermatologists with medical esthetic practice achieved at least 40 out of 45 scores. Logistic regression indicated that dermatologists aged 40-49 or ≥ 50 years and those engaging in medical esthetic practice for ≥5 years were more likely to achieve at least 40 out of 45 scores compared to dermatologists aged <30 years with less than 5 years of medical esthetic practice. The ORs were 1.82 (95% CI: 1.13-3.12), 1.94 (95% CI: 1.13-3.61), and 1.76 (95% CI: 1.34-2.31), respectively. Conclusion: The SDM implementation level among Chinese dermatologists engaging in medical esthetics is high, especially for those who are older age and have more years of practice. Hence, it is highly recommended to promote and enhance SDM practice among younger dermatologists engaging in medical esthetics with less working experience.

METI: deep profiling of tumor ecosystems by integrating cell morphology and spatial transcriptomics.

Recent advances in spatial transcriptomics (ST) techniques provide valuable insights into cellular interactions within the tumor microenvironment (TME). However, most analytical tools lack consideration of histological features and rely on matched single-cell RNA sequencing data, limiting their effectiveness in TME studies. To address this, we introduce the Morphology-Enhanced Spatial Transcriptome Analysis Integrator (METI), an end-to-end framework that maps cancer cells and TME components, stratifies cell types and states, and analyzes cell co-localization. By integrating spatial transcriptomics, cell morphology, and curated gene signatures, METI enhances our understanding of the molecular landscape and cellular interactions within the tissue. We evaluate the performance of METI on ST data generated from various tumor tissues, including gastric, lung, and bladder cancers, as well as premalignant tissues. We also conduct a quantitative comparison of METI with existing clustering and cell deconvolution tools, demonstrating METI's robust and consistent performance.

Enhancing Hydraulic Lime Mortar with Metakaolin: A Study on Improving Restoration Materials for Historic Buildings.

This study investigates the enhancement of hydraulic lime mortar (HLM) using varying contents of metakaolin (MK) to improve its application in the restoration of historic buildings. Samples from historic structures were analyzed, and the effects of different MK contents on the physical and mechanical properties of HLM were examined. The reaction mechanism and microstructural changes were evaluated using XRD and SEM analysis. The results indicated that increasing MK levels in HLM led to a decrease in fluidity, with fluidity reducing by 4.8% at 12% MK. The addition of MK increased water consumption for standard consistency by 5.4% and shortened the final setting time by 10.2%. MK consumption promoted secondary hydration, enhancing compressive strength by up to 98.1% and flexural strength by up to 55.1%, and increasing bonding strength by 26.9%. The density of HLM improved with MK addition, slightly reducing moisture content by 4.5% and water absorption by 4.6%, while the water vapor transmission properties decreased by 50.9%, indicating reduced porosity. The elastic modulus of the mortar increased significantly from 2.19 GPa to 7.88 GPa with the addition of MK, enhancing rigidity and crack resistance. The optimal blend for restoration materials was found to be 9.0% MK and 25.0% heavy calcium carbonate and was characterized by moderate mechanical strength, enhanced early strength, commendable permeability, minimal risk of cracking, and ease of application. This blend is highly suitable for the rehabilitation of historic structures.

Factors associated with a better treatment efficacy among psoriasis patients: a study based on decision tree model and logistic regression in Shanghai, China.

BACKGROUND: Many effective therapies for psoriasis are being applied in clinical practice in recent years, however, some patients still can't achieve satisfied effect even with biologics. Therefore, it is crucial to identify factors associated with the treatment efficacy among psoriasis patients. This study aims to explore factors influencing the treatment efficacy of psoriasis patients based on decision tree model and logistic regression. METHODS: We implemented an observational study and recruited 512 psoriasis patients in Shanghai Skin Diseases Hospital from 2021 to 2022. We used face-to-face questionnaire interview and physical examination to collect data. Influencing factors of treatment efficacy were analyzed by using logistic regression, and decision tree model based on the CART algorithm. The receiver operator curve (ROC) was plotted for model evaluation and the statistical significance was set at P < 0.05. RESULTS: The 512 patients were predominately males (72.1%), with a median age of 47.5 years. In this study, 245 patients achieved ≥ 75% improvement in psoriasis area and severity index (PASI) score in week 8 and was identified as treatment success (47.9%). Logistic regression analysis showed that patients with senior high school and above, without psoriasis family history, without tobacco smoking and alcohol drinking had higher percentage of treatment success in patients with psoriasis. The final decision tree model contained four layers with a total of seventeen nodes. Nine classification rules were extracted and five factors associated with treatment efficacy were screened, which indicated tobacco smoking was the most critical variable for treatment efficacy prediction. Model evaluation by ROC showed that the area under curve (AUC) was 0.79 (95%CI: 0.75 ~ 0.83) both for logistic regression model (0.80 sensitivity and 0.69 specificity) and decision tree model (0.77 sensitivity and 0.73 specificity). CONCLUSION: Psoriasis patients with higher education, without tobacco smoking, alcohol drinking and psoriasis family history had better treatment efficacy. Decision tree model had similar predicting effect with the logistic regression model, but with higher feasibility due to the nature of simple, intuitive, and easy to understand.

Retracing from Outcomes to Causes: NRF2-Driven GSTA4 Transcriptional Regulation Controls Chronic Inflammation and Oxidative Stress in Atopic Dermatitis Recurrence.

Atopic dermatitis (AD), a chronic and recurrent inflammatory skin disorder, presents a high incidence and imposes a substantial economic burden. Preventing its recurrence remains a significant challenge in dermatological therapy owing to poorly understood underlying mechanisms. In our study, we adopted a strategy of tracing the mechanisms of recurrence from clinical outcomes. We developed a mouse model of recurrent AD and applied clinically validated treatment regimens. Transcriptomic analyses revealed a pronounced enrichment in the glutathione metabolic pathway in the treated group. Through integrated bioinformatics and in vivo validation, we identified glutathione S-transferase alpha 4 (GSTA4) as a pivotal mediator in AD recurrence. Immunohistochemical analysis demonstrated decreased GSTA4 expression in lesions from patients with AD. Functionally, in vitro overexpression of GSTA4 significantly curtailed AD-like inflammatory responses and ROS production. Moreover, we discovered that NRF2 transcriptional activity regulates GSTA4 expression and function. Our treatment notably augmented NRF2-mediated GSTA4 transcription, yielding pronounced anti-inflammatory and ROS-neutralizing effects. Conclusively, our findings implicate GSTA4 as a critical factor in the recurrence of AD, particularly in the context of oxidative stress and chronic inflammation. Targeting the NRF2-GSTA4 axis emerges as a promising anti-inflammatory and antioxidative strategy for preventing AD recurrence.

Identification of angiogenesis-related genes and molecular subtypes for psoriasis based on random forest algorithm.

Psoriasis is a chronic immune-mediated recurrent skin disease causing systemic damage. Increased angiogenesis has been reported to participate in the progression of psoriasis. However, angiogenesis-related genes (ARGs) in psoriasis have not been systematically elucidated. Therefore, we aim to identify potential biomarkers and subtypes using two algorithmsr. Transcriptome sequencing data of patients with psoriasis were obtained, in which differentially expressed genes were assessed by principal component analysis. A diagnostic model was developed using random forest algorithm and validated by receiver operating characteristic (ROC) curves. Subsequently, we performed consensus clustering to calculate angiogenesis-associated molecular subtypes of psoriasis. Additionally, a correlation analysis was conducted between ARGs and immune cell infiltration. Finally, validation of potential ARG genes was performed by quantitative real-time PCR (qRT-PCR). We identified 29 differentially expressed ARGs, including 13 increased and 16 decreased. Ten ARGs, CXCL8, ANG, EGF, HTATIP2, ANGPTL4, TNFSF12, RHOB, PML, FOXO4, and EMCN were subsequently sifted by the diagnostic model based on a random forest algorithm. Analysis of the ROC curve (area under the curve [AUC] = 1.0) indicated high diagnostic performance in internal validation. The correlation analysis suggested that CXCL8 has a high positive correlation with neutrophil (R =0.8, P < 0.0001) and interleukins pathway (R = 0.79, P < 0.0001). Furthermore, two ARG-mediated subtypes were obtained, indicating potential heterogeneity. Finally, the qRT-PCR demonstrated that the mRNA expression levels of CXCL8 and ANGPTL4 were elevated in psoriasis patients, with a reduced expression of EMCN observed. The current paper indicated potential ARG-related biomarkers of psoriasis, including CXCL8, ANGPTL4, and EMCN, with two molecular subtypes.

Toxicokinetics of selenate in earthworm sub-tissues and potential bio-accessibility assessment of earthworm-derived selenium.

Selenium (Se) pollution is mainly caused by anthropogenic activities, and the resulting biosecurity concerns have garnered significant attention in recent years. Using one-compartmental toxicokinetic (TK) modelling, this study explored the kinetic absorption, sub-tissue distribution, and elimination processes of the main Se species (selenate, Se(VI)) in the cultivated aerobic soil of the earthworm Eisenia fetida. The bio-accessibility of earthworm-derived Se was assessed using an in vitro simulated gastrointestinal digestion test to evaluate its potential trophic risk. The results demonstrated that Se accumulated in the pre-clitellum (PC) and total tissues (TT) of earthworms in a time- and dose-dependent manner. The highest Se levels in the PC, post-clitellum (PoC), and TT were 70.54, 57.93, and 64.26 mg/kg during the uptake phase, respectively. The kinetic Se contents in the earthworms PC and TT were consistent with the TK model but not with PoC. The earthworm TT exhibited a faster uptake (Kus = 0.83-1.02 mg/kg/day) and elimination rate of Se (Kee = 0.044-0.049 mg/kg/day), as well as a shorter half-life time (LT1/2 = 15.88-14.22 days) than PC at low soil Se levels (≤5 mg/kg). Conversely, the opposite trend was observed with higher Se concentrations (10 and 20 mg/kg). These results are likely attributable to the tissue specificity and concentration of the toxicant. Earthworms PC and TT exhibited a higher kinetic Se accumulation factor (BAFk) than steady-state BAF (BAFss), with values ranging from 8 to 24 and 3-13, respectively. Furthermore, the bio-accessibility of earthworm-derived Se to poultry ranged from 66.25 % to 84.35 %. As earthworms are at the bottom of the terrestrial food chain, the high bio-accessibility of earthworm-derived Se poses a potential risk to predators. This study offers data support and a theoretical foundation for understanding the biological footprint of soil Se and its toxicological impacts and ecological hazards.

Barriers and Stimulus in Shared Decision Making Among Aesthetic Dermatologists in China: Findings from a Cross-Sectional Study.

Introduction: Shared decision making (SDM) is a collaborative process involving both healthcare providers and patients in making medical decisions, which gains increasing prominence in healthcare practice. But evidence on the level of SDM in medical practice and barriers as well as stimulus during the SDM implementation among aesthetic dermatologists is limited in China. Methods: From July to August 2023, 1938 dermatologists were recruited online in China. Data were collected through an electronic questionnaire covering: (1) demographic features; (2) SDM questionnaire physician version (SDM-Q-Doc); and (3) stimulus and barriers in SDM implementation. Logistic regression was applied to explore factors associated with SDM practice, barriers, and stimulus of SDM implementation, respectively. Results: The 1938 dermatologists included 1329 females (68.6%), with an average age of 35 years. The total SDM score ranged from 0 to 45, with a median value of 40 (IQR: 35-44), and the median stimulus score and barriers scores were 28 (IQR: 24-32) and 19 (IQR: 13-26), respectively. The prevalence of good SDM was 27.2%, logistic regression indicated that female dermatologists (odds ratio, OR=1.21, 95% confidence interval, CI: 0.96-1.51), and dermatologists with more years of aesthetic practice had a higher proportion of good SDM practice (OR was 1.44 for 5-9 years, 1.58 for 10-15 years and 1.77 for over 15 years). Moreover, female dermatologists and dermatologists with higher education level and serviced in private settings had lower barrier scores; female dermatologists and dermatologists with more years of aesthetic practice had higher stimulus scores. Conclusion: Chinese aesthetic dermatologists appear to implement SDM at an active level, with more stimulus and less barriers in SDM implementation. The integration of SDM into clinical practice among dermatologists is beneficial both for patients and dermatologists. Moreover, SDM practice should be strongly promoted and enhanced during medical aesthetics, especially among male dermatologists, dermatologists with less working experience, and those who work at public institutions.

Epidemiology of malignant tumors in patients with pemphigus: an analysis of trends from 1955 to 2021.

BACKGROUND: The incidence of malignant tumors has increased in patients with non-paraneoplastic pemphigus, although there has been no systematic analysis of global epidemiology. OBJECTIVE: To explore the epidemiology of various types of non-paraneoplastic pemphigus associated with malignant tumors. METHODS: Five databases from establishment through October 20, 2023, were searched. STATA SE 17 was used for the data analysis. Subgroup, meta-regression, and sensitivity analyses were used to evaluate the heterogeneity of pooled studies. RESULTS: A total of 6679 participants were included in our meta-analysis from 16 studies. The aggregated prevalence of tumors in patients diagnosed with pemphigus was 8%. The prevalence was 7% in patients with pemphigus vulgaris, 10% in those with pemphigus foliaceus, and 12% in individuals diagnosed with other types of pemphigus. The prevalence was 8% in Asia, 11% in Europe, and 8% in North America. From a country-specific perspective, patients with pemphigus from Israel, Greece, and Germany exhibited a higher prevalence of tumors at 11%. Furthermore, when categorized by the duration of the study period, the highest prevalence was observed in studies spanning 10 to 20 years, at 11%. CONCLUSION: These findings demonstrate the incidence and prevalence of malignant tumors in patients with non-paraneoplastic pemphigus, which may achieve early detection and intervention, and then reduce mortality rates.

Tobacco smoking negatively influences the achievement of greater than three-quarters reduction in psoriasis area and severity index after eight weeks of treatment among patients with psoriasis: Findings from a prospective study.

INTRODUCTION: Smoking is an independent and modifiable risk factor for the onset and development of psoriasis; however, evidence on the association between tobacco smoking and psoriasis treatment efficacy is limited. This study aimed to explore the influence of smoking on treatment efficacy in a cohort of patients with psoriasis in Shanghai, China. METHODS: Patients with psoriasis were recruited from the Shanghai Skin Disease Hospital between 2021 and 2022. The treatment for patients with psoriasis includes acitretin, methotrexate, narrow-band ultraviolet/benvitimod, and biologics. Data were collected using a structured questionnaire, physical examination, and disease severity estimation at baseline, week four, and week eight. The achievement of a ≥75% reduction in psoriasis area and severity index (PASI75) score from baseline to week 8 was set as the primary outcome for treatment efficacy estimation. Data were analyzed using SAS 9.4. RESULTS: A total of 560 patients with psoriasis were enrolled in this study, who were predominantly males (72.9%). The average age of patients was 48.4 years, and 38.8% of them were current smokers, 5.0% of them were former smokers. The median score of PASI among patients changed from 11.1 (interquartile range, IQR: 7.9-16.6) at baseline to 6.2 at week 4 and 3.1 at week 8, and 13.8% and 47.3% of patients with psoriasis achieved PASI75 at weeks 4 and 8, respectively. Logistic regression indicated that patients without tobacco smoking had a higher proportion of PASI75 achievement at week 8. The adjusted odds ratio (AOR) was 11.43 (95% CI: 6.91-18.89), 14.14 (95% CI: 8.27-24.20), and 3.05 (95% CI: 1.20-7.76) for non-smokers compared with smokers, current smokers, and former smokers, respectively. Moreover, former smokers had higher PASI75 achievement than current smokers (AOR=3.37), and patients with younger smoking initiation age, longer smoking duration, and higher smoking intensity had lower PASI75 achievement. CONCLUSIONS: Tobacco smoking was negatively associated with PASI75 achievement both in current and former smokers, and former smokers had higher PASI75 achievement than current smokers. The implementation of tobacco control measures is beneficial for improving treatment responses.

Real-world data of 5-aminolaevulinic acid-mediated photodynamic therapy for Bowen disease: a 10-year retrospective study in patients with darker-coloured skin (2011-2021).

BACKGROUND: Photodynamic therapy (PDT) has been strongly recommended as an excellent alternative treatment for Bowen disease (BD). However, reported data on 5-aminolaevulinic acid-mediated PDT (ALA-PDT) with red-light irradiation are limited and the long-term effectiveness remains to be determined, especially in dark-skinned populations. OBJECTIVES: We aimed to review routine clinical practice in the field of BD treatment with ALA-PDT over an extended study period (2011-2021), calculate the overall clearance rate, and explore and evaluate factors that might affect the effectiveness of therapy in a real-world setting. METHODS: The medical records of patients with BD who received ALA-PDT with red-light irradiation between February 2011 and June 2021 were reviewed and summarized. Univariate and multivariate analyses of clinically relevant variables that may affect treatment outcomes were conducted to identify risk predictors. RESULTS: The overall clearance rate of 122 BD lesions was 89.3% with a median follow-up time of 36 months. The correlation between the effectiveness and fluorescence intensity of pre-PDT or PDT sessions was statistically significant after eliminating the interference of confounding factors. All recurrences occurred in the first 2 years following ALA-PDT. CONCLUSIONS: ALA-PDT is an effective treatment for BD in patients with darker-coloured skin. Well-executed operations and effective pretreatment are the determinants of effectiveness. Fluorescence intensity of pre-PDT appeared to be a significant predictor of final effectiveness. In addition, 2 years of follow-up is necessary following ALA-PDT.

Formononetin attenuates psoriasiform inflammation by regulating interferon signaling pathway.

BACKGROUND: Psoriasis is a long-lasting, inflammatory, continuous illness caused through T cells and characterized mainly by abnormal growth and division of keratinocytes. Currently, corticosteroids are the preferred option. However, prolonged use of traditional topical medication can lead to adverse reactions and relapse, presenting a significant therapeutic obstacle. Improved alternative treatment options are urgently required. Formononetin (FMN) is a representative component of isoflavones in Huangqi (HQ) [Astragalus membranaceus (Fisch.) Bge.]. It possesses properties that reduce inflammation, combat oxidation, inhibit tumor growth, and mimic estrogen. Although FMN has been shown to ameliorate skin barrier devastation via regulating keratinocyte apoptosis and proliferation, there are no reports of its effectiveness in treating psoriasis. OBJECTIVE: Through transcriptomics clues and experimental investigation, we aimed to elucidate the fundamental mechanisms underlying FMN's action on psoriasis. MATERIALS AND METHODS: Cell viability was examined using CCK8 assay in this study. The results of analysis of differentially expressed genes (DEGs) between FMN-treated HaCaT cells and normal HaCaT cells using RNA-sequencing (RNA-seq) were presented on volcano plots and heatmap. Enrichment analysis was conducted on DEGs using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), and results were validated through RT-qPCR verification. After 12 days of FMN treatment in psoriasis mouse model, we gauged the PASI score and epidermis thickness. A variety of techniques were used to assess FMN's effectiveness on inhibiting inflammation and proliferation related to psoriasis, including RT-qPCR, HE staining, western blot, and immunohistochemistry (IHC). RESULTS: The findings indicated that FMN could suppress the growth of HaCaT cells using CCK8 assay (with IC50 = 40.64 uM) and 20 uM FMN could reduce the level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to the greatest extent. FMN-treated HaCaT cells exhibited 985 up-regulated and 855 down-regulated DEGs compared to normal HaCaT cells. GO analysis revealed that DEGs were linked to interferon (IFN) signaling pathway. Furthermore, FMN improved pathological features, which encompassed decreased erythema, scale, and thickness scores of skin lesions in psoriasis mouse model. In vivo experiments confirmed that FMN down-regulated expression of IFN-α, IFN-ß, IFN-γ, decreased secretion of TNF-α and IL-17 inflammatory factors, inhibited expression of IFN-related chemokines included Cxcl9, Cxcl10, Cxcl11 and Cxcr3 and reduced expression of transcription factors p-STAT1, p-STAT3 and IFN regulatory factor 1 (IRF1) in the imiquimod (IMQ) group. CONCLUSIONS: In summary, these results suggested that FMN played an anti-inflammatory and anti-proliferative role in alleviating psoriasis by inhibiting IFN signaling pathway, and FMN could be used as a potential therapeutic agent.

Efficacy and safety of Huzhang Granule, a compound Chinese herbal medicine, for acute gouty arthritis: A double-blind, randomized controlled trial.

BACKGROUND: Acute gouty arthritis (AGA) is an inflammatory joint disease with a high prevalence. Typical medical interventions, including nonsteroidal anti-inflammatory drugs, colchicine and glucocorticoids, can have serious adverse reactions. Huzhang Granule (HZG), a compound Chinese herbal medicine, has been used to treat AGA for more than 30 years with satisfactory effects and no significant adverse reactions. However, the efficacy and safety of HZG in AGA patients remains unknown. OBJECTIVE: The present investigation was designed to examine the efficacy and safety profile of HZG in managing AGA patients. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: The current study was conducted as a noninferiority, randomized controlled clinical trial on 180 eligible enrolled participants. Participants were randomly assigned into the HZG and etoricoxib groups. Treatments were administered for 5 d, during which the HZG group received HZG and placebo etoricoxib, while the etoricoxib group received etoricoxib and placebo HZG in the same ratio (1:1). MAIN OUTCOME MEASURES: The primary outcome was pain experienced by the patient in the gout-afflicted joint from days 2 to 5 of the treatment window. The pain level was measured via a visual analogue scale, ranging from 0 mm to 100 mm. The secondary outcomes comprised joint tenderness and swelling, reduction of inflammatory biomarkers, and the patient's and investigator's global evaluations of therapeutic response. RESULTS: The mean reduction in pain was -51.22 mm (95% confidence interval [CI], [-53.42, -49.03] mm) for the HZG and -52.00 mm (95% CI, [-54.06, -49.94] mm) for the etoricoxib groups. The mean difference between the two groups was 0.78 mm (95% CI, [-2.25, 3.81] mm). All additional efficacy endpoints, covering decreased inflammation and pain relief, yielded compelling proof of noninferiority. Patients in the HZG group exhibited a comparatively lower rate of adverse events compared to those in the etoricoxib group (4.44% vs 13.33%; P ≤ 0.05). CONCLUSION: HZG and etoricoxib groups demonstrated similar levels of analgesic effectiveness. The safety and efficacy of HZG indicates that it can be used as a potential therapeutic option for treating AGA. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2000036970). Please cite this article as: Wang H, Chen ST, Ding XJ, Kuai L, Hua L, Li X, Wang YF, Zhang M, Li B, Wang RP, Zhou M. Efficacy and safety of Huzhang Granule, a compound Chinese herbal medicine, for acute gouty arthritis: A double-blind, randomized controlled trial. J Integr Med. 2024; 22(3): 270-278.

Austin-Type Meroterpenoids from Fungi Reported in the Last Five Decades: A Review.

Austin was first isolated as a novel polyisoprenoid mycotoxin from Aspergillus ustus in 1976. Subsequently, some new austin-type meroterpenoids (ATMTs) have been continually found. This review attempts to give a comprehensive summary of progress on the isolation, chemical structural features, biological activities, and fungal biodiversity of 104 novel ATMTs from 5 genera of terrestrial- and marine-derived fungi reported from October 1976 to January 2023. The genera of Penicillium and Aspergillus are the two dominant producers, producing 63.5% and 30.8% of ATMTs, respectively. Moreover, about 26.9% of ATMTs display various pronounced bioactivities, including insecticidal, anti-inflammatory, cytotoxicity, antibacterial, and PTP1B inhibitory activities. The chemical diversity and potential activities of these novel fungal ATMTs are reviewed for a better understanding, and a relevant summary focusing on the source fungi and their taxonomy is provided to shed light on the future development and research of austin-type meroterpenoids.