Medical dilemma: Programmed death 1 blockade (sintilimab) therapy in patients suffering from tumours combined with psoriasis.

Tumour immunotherapy represented by immune checkpoint inhibitors (ICIs) has greatly improved the overall prognosis of patients with malignant tumours, and is regarded as an important breakthrough in the field of medicine in recent years. ICIs have gradually become the core of tumour therapy and are increasingly used in the clinic. In order to achieve early clinical prediction and management of immune-related adverse events (irAEs), it is still necessary to perform further research on the mechanisms, risk factors, and predictors of irAE occurrence in the future. Zhou et al describe the consultation of a patient with advanced gastric cancer combined with chronic plaque psoriasis. This case provides an important reference for the use of programmed cell death protein-1 (PD-1) inhibitors in patients of tumours combined with chronic plaque psoriasis. This case also highlights that screening of high-risk groups for irAEs is critical before applying PD-1 inhibitors to patients with chronic psoriasis combined with tumours. PD-1 inhibitors are new and potent antineoplastic agents that can cause serious immune-related adverse events such as toxic epidermal necrolysis release and psoriasis. Glucocorticosteroids are the first-line agents for irAEs. The incidence of rheumatic irAEs may be higher in reality, which will inevitably become a new challenge for rheumatologists and dermatologists.

Chinese herbal medicine for the treatment of intestinal cancer: preclinical studies and potential clinical applications.

Intestinal cancer (IC) poses a significant global health challenge that drives continuous efforts to explore effective treatment modalities. Conventional treatments for IC are effective, but are associated with several limitations and drawbacks. Chinese herbal medicine (CHM) plays an important role in the overall cancer prevention and therapeutic strategies. Recent years have seen a growing body of research focus on the potential of CHM in IC treatment, showing promising results in managing IC and mitigating the adverse effects of radiotherapy and chemotherapy. This review provides updated information from preclinical research and clinical observation on CHM's role in treatment of IC, offering insights into its comprehensive management and guiding future prevention strategies and clinical practice.

Fibrosis to carcinogenesis: unveiling the causal dynamics between pulmonary fibrosis and lung cancer.

Background: Previous clinical evidence has shown a correlation between pulmonary fibrosis (PF) and lung cancer (LC), but their causal relationship remains unknown. Methods: This study utilized a bidirectional two-sample Mendelian randomization (MR) approach to explore the causal relationship between PF and LC, including its subtypes. Genetic data were obtained from the IEU and FinnGen Genome-Wide Association Studies (GWAS). SNPs with genome-wide significance were selected, and analyses were conducted using Inverse-Variance Weighted (IVW), MR Egger, and Weighted Median methods. The IVW results for various subtypes of lung cancer and PF were used in a meta-analysis to investigate the overall causal effect between PF and lung cancer. Sensitivity analysis was used for both MR and meta-analysis to investigate the robustness of the results. Results: The bidirectional MR analysis showed no significant causal relationship between PF and overall, LC or its subtypes, except for SCLC, which had a significant positive association (OR = 1.29, 95% CI 1.07-1.57, p = 0.009). The meta-analysis results indicated no overall causal effect (OR = 1.067, 95% CI: 0.952-1.195, P = 0.265, I² = 57.3%). In the reverse MR analysis, NSCLC and LUSC showed significant associations with PF (OR = 1.12, 95% CI 1.01-1.23, p = 0.028 and OR = 1.04, 95% CI 1.01-1.08, p = 0.012, respectively), while the meta-analysis results indicated no significant causal effect (OR = 1.006, 95% CI: 0.973-1.040, P = 0.734, I² = 55.9%). Sensitivity analyses indicated no evidence of horizontal pleiotropy or significant heterogeneity. Conclusion: This study suggests a potential causal relationship between PF and SCLC, as well as between NSCLC and LUSC with PF. However, the overall causal relationship between PF and LC was not statistically significant, possibly due to individual variability and other influencing factors. Further research using data from diverse populations is needed to validate these findings.

20(S)-Ginsenoside Rh2 overcomes gemcitabine resistance in pancreatic cancer by inhibiting LAMC2-Modulated ABC transporters.

INTRODUCTION: Gemcitabine (GEM) is the first-line drug for pancreatic ductal adenocarcinoma (PDAC), but drug resistance severely restricts its chemotherapeutic efficacy. Laminin subunit γ2 (LAMC2) plays a crucial role in extracellular matrix formation in the development of GEM-resistance. However, the biological function of LAMC2 in GEM resistance and its molecular mechanisms are still unclear. 20(S)-Ginsenoside Rh2 (Rh2), one of the principal active components isolated from Ginseng Radix et Rhizoma, possesses strong anti-tumor effects. However, the effects of Rh2 on overcoming GEM resistance and its action mechanisms remain to be elucidated. OBJECTIVES: This study aimed to determine the efficacy of Rh2 on overcoming GEM resistance and to explore its underlying molecular mechanisms. METHODS: Clinical study, Western blotting, publicly available databasesand bioinformatic analyses were performed to investigate the protein expression of LAMC2 in the GEM-resistant PDAC patients and the acquired GEM-resistant PDAC cells. Then, the effects of Rh2 on overcoming the GEM resistance in PDAC were evaluated both in vitro and in vivo. Stable silencing or overexpression of LAMC2 in the GEM-resistant PDAC cells were established for validating the role of LAMC2 on Rh2 overcoming the GEM resistance in PDAC. RESULTS: The protein expression of LAMC2 was markedly increased in the GEM-resistant PDAC patient biopsies compared to the sensitive cases. The protein expression of LAMC2 was significantly higher in the acquired GEM-resistant PDAC cells than that in their parental cells. Rh2 enhanced the chemosensitivity of GEM in the GEM-resistant PDAC cells, and inhibited the tumor growth of Miapaca-2-GR cell-bearing mice and Krastm4TyjTrp53tm1BrnTg (Pdx1-cre/Esr1*) #Dam/J (KPC) mice. Rh2 effectively reversed the GEM resistance in Miapaca-2-GR and Capan-2-GR cells by inhibiting LAMC2 expression through regulating the ubiquitin-proteasome pathway. Knockdown of LAMC2 enhanced the chemosensitivity of GEM and the effects of Rh2 on overcoming the GEM resistance in PDAC cells and the orthotopic PDAC mouse model. Conversely, LAMC2 overexpression aggravated the chemoresistance of GEM and abolished the effects of Rh2 on overcoming GEM resistance via modulating ATP-binding cassette (ABC) transporters leading to the active GEM efflux. CONCLUSIONS: LAMC2 plays an important role in the GEM resistance in PDAC, and Rh2 is a potential adjuvant for overcoming the chemoresistance of GEM in PDAC.

A Hypoxia-Decidual Macrophage Regulatory Axis in Normal Pregnancy and Spontaneous Miscarriage.

The significance of hypoxia at the maternal-fetal interface is proven to be self-explanatory in the context of pregnancy. During the first trimester, low oxygen conditions play a crucial role in processes such as angiogenesis, trophoblast invasion and differentiation, and immune regulation. Recently, there has been increasing research on decidual macrophages, which contribute to the maintenance of immune tolerance, placental and fetal vascular development, and spiral artery remodeling, to investigate the effects of hypoxia on their biological behaviors. On these grounds, this review describes the dynamic changes in oxygen levels at the maternal-fetal interface throughout gestation, summarizing current knowledge on how the hypoxic environment sustains a successful pregnancy by regulating retention, differentiation and efferocytosis of decidual macrophages. Additionally, we explore the relationship between spontaneous miscarriages and an abnormal hypoxia-macrophage axis, shedding light on the underlying mechanisms. However, further studies are essential to elucidate these pathways in greater detail and to develop targeted interventions that could improve pregnancy outcomes.

Sulfated polysaccharide from Antrodia cinnamomea mycelium cultured with zinc sulfate stimulates M1 polarization of macrophages through AKT/mTOR pathways.

Antrodia cinnamomea-derived sulfated polysaccharides (Ac-SPSs) have health benefits, but their yield is low. This study explores a strategy to increase Ac-SPS yield and elucidates the biofunctions of Ac-SPS. For this, A. cinnamomea mycelia were treated with zinc sulfate (ZnSO4) administered at 1, 10, and 100 µM. Firstly, functional assay indicated that ZnSO4 increases the Ac-SPS yield by 20 %-30 % compared with the control treatment. ZnSO4 engenders a population of middle-molecular-weight (~200 kDa) Ac-SPSs. Ac-SPS (ASZ-10) from A. cinnamomea treated with 10 µM ZnSO4 exhibits the best anti-proliferation ability against lung cancer A549 cells. Co-treatment of ASZ-10 does not inhibit lipopolysaccharide-induced inflammation but does induce M1-related markers of macrophage RAW264.7 cells. Secondly, immunomodulatory properties showed that ASZ-10 increases the expression of CD80+ and CD86+ in M-CSF-stimulated bone-marrow-derived macrophages. ASZ-10 induces M1 polarization through up-regulation of the AKT/mTOR pathway as confirmed by AKT and mTOR inhibitors eliminating ASZ-10-induced M1-like markers of macrophages. Through systemic chemical and functional analysis, this study shows that trace amounts (10 µM) of ZnSO4 increase Ac-SPS yield and it reveals that ASZ-10 exhibits anti-cancer activity and acts as a stimulator for M1 macrophages by stimulation of AKT and mTOR.

Exploring the environmental contamination toxicity and potential carcinogenic pathways of perfluorinated and polyfluoroalkyl substances (PFAS): An integrated network toxicology and molecular docking strategy.

The objective of this study was to investigate the potential carcinogenic toxicity and mechanisms of PFAS in thyroid, renal, and testicular cancers base on network toxicology and molecular docking techniques. Structural modeling was performed to predict relevant toxicity information, and compounds and cancer-related targets were screened in multiple databases. The interaction of PFAS with three cancers and their key protein targets were explored by combining protein network analysis, enrichment analysis and molecular docking techniques. PFOA, PFOS, and PFHXS exhibited significant carcinogenic and cytotoxic effects. These compounds may induce cancer by mediating active oxygen metabolism and the transduction of phosphatidylinositol 3-kinase/protein kinase B signaling pathway through genes such as ALB, mTOR, MDM2, and ERBB2. Furthermore, the underlying toxic mechanisms may be linked to the pathways in cancer, chemical carcinogenesis through reactive oxygen species/receptor activation, and the FoxO signaling pathway. The results contribute to a comprehensive understanding of the effects of these environmental pollutants on genes, proteins, and metabolic pathways in living organisms. It revealed their toxicity mechanisms in inducing thyroid, renal, and testicular cancers, and provided a solid theoretical foundation for designing new environmental control strategies and drug screening initiatives. Additionally, the integrated application of network toxicology and molecular docking technology can enhance our understanding of the toxicity and mechanisms of unknown environmental pollutants, which is beneficial for protecting the environment and human health.

Cetylpyridinium chloride triggers paraptosis to suppress pancreatic tumor growth via the ERN1-MAP3K5-p38 pathway.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive solid malignancy with low 5-year survival and limited treatment options. We conducted an unbiased screening using FDA-approved drug and demonstrated that cetylpyridinium chloride (CPC), a component commonly found in mouthwash and known for its robust bactericidal and antifungal attributes, exhibits anticancer activity against human PDAC cells. CPC inhibited PDAC cell growth and proliferation by inducing paraptosis, rather than apoptosis. Mechanistically, CPC induced paraptosis through the initiation of endoplasmic reticulum stress, leading to the accumulation of misfolded proteins. Subsequently, the endoplasmic reticulum stress to nucleus signaling 1 (ERN1)-mitogen-activated protein kinase kinase kinase 5 (MAP3K5)-p38 mitogen-activated protein kinase (MAPK) signaling pathway was activated, ultimately culminating in the induction of paraptosis. In vivo experiments, including those involving patient-derived xenografts, orthotopic models, and genetically engineered mouse models of PDAC, provided further evidence of CPC's effectiveness in suppressing the growth of pancreatic tumors.

Regulating iron center by defective MoS2 for superior Fenton-like catalysis in water purification: The key role of surface interaction and superoxide radical in accelerating metal redox-cycling.

Transition metals exhibit high reactivity for Fenton-like catalysis in environmental remediation, but how to save consumption and reduce pollution is of great interest. In this study, rationally designed defect-engineered Fe@MoS2 (Fe@D-MoS2) was prepared by incorporating reactive iron onto structural defects generated from the chemical acid-etching, aiming to improve the energetic consumption of the catalyst in Fenton-like applications. Morphological and structural properties were elucidated in details, the Fenton-like reactivity was evaluated with five phenolic contaminants for oxidant activation, radical generation and environmental remediation. Compared to Fe@MoS2, Fe@D-MoS2 exhibited a 18.9-fold increase in phenol degradation (0.09 versus 1.79 min-1). Quenching experiments, electron paramagnetic resonance tests and electrochemical measurements revealed the dominant sulfate and superoxide radicals. Rendered by strong metal-substrate surface and electronic interactions from regulated chemical environment and coordination structure, the inert ≡ Fe(III) was reduced to the reactive ≡ Fe(II) accompanied by the ≡ Mo(IV) oxidation to ≡ Mo(V) in MoS2 lattice, with adjacent sulfur serving as the key electron transfer bridge. Therefore, this work shows that the incorporation of reactive centers is able to boost two-dimensional sulfide materials for environmental catalysis applications.

Serendipita indica Drives Sulfur-Related Microbiota in Enhancing Growth of Hyperaccumulator Sedum alfredii and Facilitating Soil Cadmium Remediation.

Endophytic fungus Serendipita indica can bolster plant growth and confer protection against various biotic and abiotic stresses. However, S. indica-reshaped rhizosphere microecology interactions and root-soil interface processes in situ at the submicrometer scale remain poorly understood. We combined amplicon sequencing and high-resolution nano X-ray fluorescence (nano-XRF) imaging of the root-soil interface to reveal cadmium (Cd) rhizosphere processes. S. indica can successfully colonize the roots of Sedum alfredii Hance, which induces a remarkable increase in shoot biomass by 211.32% and Cd accumulation by 235.72%. Nano-XRF images showed that S. indica colonization altered the Cd distribution in the rhizosphere and facilitated the proximity of more Cd and sulfur (S) to enter the roots and transport to the shoot. Furthermore, the rhizosphere-enriched microbiota demonstrated a more stable network structure after the S. indica inoculation. Keystone species were strongly associated with growth promotion and Cd absorption. For example, Comamonadaceae are closely related to the organic acid cycle and S bioavailability, which could facilitate Cd and S accumulation in plants. Meanwhile, Sphingomonadaceae could release auxin and boost plant biomass. In summary, we construct a mutualism system for beneficial fungi and hyperaccumulation plants, which facilitates high-efficient remediation of Cd-contaminated soils by restructuring the rhizosphere microbiota.

Toxicokinetics and Mussel Watch: Addressing Interspecies Differences for Coastal Cadmium Contamination Assessment.

Bivalves are often employed for biomonitoring contaminants in marine environments; however, in these large-scale programs, unavoidably, using multiple species presents a significant challenge. Interspecies differences in contaminant bioaccumulation can complicate data interpretation, and direct comparisons among species may result in misleading conclusions. Here, we propose a robust framework based on toxicokinetic measurements that accounts for interspecies differences in bioaccumulation. Specifically, via a recently developed double stable isotope tracer technique, we determined the toxicokinetics of cadmium (Cd)─a metal known for its high concentrations in bivalves and significant interspecies bioaccumulation variability─in six widespread bivalve species including mussels (Perna viridis, Mytilus unguiculatus, Mytilus galloprovincialis) and oysters (Magallana gigas, Magallana hongkongensis, Magallana angulata). Results show that oysters generally have higher Cd uptake rate constants (ku: 1.18-3.09 L g-1 d-1) and lower elimination rate constants (ke: 0.008-0.017 d-1) than mussels (ku: 0.21-0.64 L g-1 d-1; ke: 0.018-0.037 d-1). The interspecies differences in tissue Cd concentrations are predominantly due to Cd uptake rather than elimination. Utilizing toxicokinetic parameters to back-calculate Cd concentrations in seawater, we found that the ranking of Cd contamination levels at the six sites markedly differs from those based on tissue Cd concentrations. We propose that this approach will be useful for interpreting data from past and future biomonitoring programs.

Multiscale photocatalytic proximity labeling reveals cell surface neighbors on and between cells.

Proximity labeling proteomics (PLP) strategies are powerful approaches to yield snapshots of protein neighborhoods. Here, we describe a multiscale PLP method with adjustable resolution that uses a commercially available photocatalyst, Eosin Y, which upon visible light illumination activates different photo-probes with a range of labeling radii. We applied this platform to profile neighborhoods of the oncogenic epidermal growth factor receptor and orthogonally validated more than 20 neighbors using immunoassays and AlphaFold-Multimer prediction. We further profiled the protein neighborhoods of cell-cell synapses induced by bispecific T cell engagers and chimeric antigen receptor T cells. This integrated multiscale PLP platform maps local and distal protein networks on and between cell surfaces, which will aid in the systematic construction of the cell surface interactome, revealing horizontal signaling partners and reveal new immunotherapeutic opportunities.

Perioperative and oncologic outcomes of robot-assisted versus open surgery for pancreatic ductal adenocarcinoma: a systematic review and meta-analysis.

This systematic review and meta-analysis aimed to compare perioperative and oncologic outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) treated with robotic-assisted surgery versus open laparotomy. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials (RCTs) and cohort studies up to June 15, 2024, were identified using PubMed, EMBASE, and Google Scholar. Additionally, reference lists of included studies, relevant review articles, and clinical guidelines were manually searched. The primary outcomes evaluated were length of stay, 90-day mortality, postoperative pancreatic fistula (POPF), and Post-pancreatectomy haemorrhage (PPH). Secondary outcomes included estimated blood loss, reoperation rate, lymph node yield, and operative time. The final analysis included 10 retrospective cohort studies involving 23,272 patients (2,179 robotic-assisted and 21,093 open surgery). There were no significant differences between the two procedures in terms of postoperative pancreatic fistula, Post-pancreatectomy haemorrhage, lymph node yield, and operative time. However, patients undergoing robotic-assisted surgery had shorter lengths of stay, lower 90-day mortality, and less estimated blood loss compared to those undergoing open surgery. The reoperation rate was higher for the robotic-assisted group. Robotic-assisted surgery for pancreatic ductal adenocarcinoma is safe and feasible. Compared to open surgery, it offers better perioperative and short-term oncologic outcomes, but with a higher risk of reoperation.

Comparison of Volatile Compounds among Four Types of Teas Analyzed Using Gas Chromatography-Ion Mobility Spectrometry.

Gas chromatography-ion mobility spectrometry (GC-IMS) is a smart method that has been applied to determine the volatile compounds in Chinese teas, but its use in comparing the volatile compounds of different types of tea has not been mentioned. In this study, the volatile compounds found in four types of samples (green, yellow, white, and black teas) made with fresh leaves of Camellia sinensis (L.) Kuntze 'Zhongcha 111' were analyzed using GC-IMS. The results showed that 93 volatile compounds were identified from our tea samples and that the average volume of aldehydes was higher than that for other compounds, especially in white tea. The different samples were successfully categorized using multivariate statistical analysis. Using partial least squares discriminant analysis (PLS-DA), we found 15 key compounds, including four differential components: (E)-2-hexenal, 2-furanmethanethio, 2-hexanol, and 1-octene. There were 29 common components, and their total content reached 386.0 µg/g. Moreover, the 3-methyl-2-butenal and dimethyl disulfide detected in the four samples were also differential compounds, varying according to the manufacturing technology. Thus, this study demonstrates that different types of teas can be discriminated easily using GC-IMS and that this is helpful to shorten the time for improving tea quality and developing new products.

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

Brusatol alleviates pancreatic carcinogenesis via targeting NLRP3 in transgenic Krastm4Tyj Trp53tm1Brn Tg (Pdx1-cre/Esr1*) #Dam mice.

BACKGROUND: Pancreatic cancer (PanCa), ranked as the 4th leading cause of cancer-related death worldwide, exhibits an dismal 5-year survival rate of less than 5 %. Chronic pancreatitis (CP) is a known major risk factor for PanCa. Brusatol (BRT) possesses a wide range of biological functions, including the inhibition of PanCa proliferation. However, its efficacy in halting the progression from CP to pancreatic carcinogenesis remains unexplored. METHODS: We assess the effects of BRT against pancreatic carcinogenesis from CP using an experimentally induced CP model with cerulein, and further evaluate the therapeutic efficacy of BRT on PanCa by employing Krastm4TyjTrp53tm1BrnTg (Pdx1-cre/Esr1*) #Dam/J (KPC) mouse model. RESULTS: Our finding demonstrated that BRT mitigated the severity of cerulein-induced pancreatitis, reduced pancreatic fibrosis and decreased the expression of α-smooth muscle actin (α-SMA), which is a biomarker for pancreatic fibrosis. In addition, BRT exerted effects against cerulein-induced pancreatitis via inactivation of NLRP3 inflammasome. Moreover, BRT significantly inhibited tumor growth and impeded cancer progression. CONCLUSIONS: The observed effect of BRT on impeding pancreatic carcinogenesis through targeting NLRP3 inflammasome suggests its good potential as a potential agent for treatment of PanCa.

Improvement effects of a novel Chinese herbal formula in imiquimod and IL-23-stimulated mouse models of psoriasis.

BACKGROUND: Psoriasis is a long-term inflammatory skin disease. A novel herbal formula containing nine Chinese herbal medicines, named Inflammation Skin Disease Formula (ISDF), has been prescribed in clinics for decades. AIMS: To investigate the efficacy and action mechanisms of ISDF on psoriasis using imiquimod (IMQ) and Interleukin-23 (IL-23)-induced models in mice and reveal the pharmacokinetics profile of ISDF in rats. METHODS: Topical administration of IMQ and intradermal injection with IL-23 respectively induced skin lesions like psoriasis on the dorsal area of Balb/c and C57 mice. The mice's body weight, skin thickness, and psoriasis area and severity index (PASI) were assessed weekly. SD rats were used in the pharmacokinetics study and the contents of berberine and baicalin were determined. RESULTS: The PASI scores and epidermal thickness of mice were markedly decreased after ISDF treatment in both models. ISDF treatment significantly decreased the contents of IL-17A and IL-22 in the serum of IMQ- and IL-23-treated mice. Importantly, ISDF markedly downregulated IL-4, IL-6, IL-1ß, and tumor necrosis factor α (TNF-α) gene expression, and the phosphorylation of NF-κB p65, JNK, ERKs and MAPK p38 in IMQ-treated mice. The protein phosphorylation of Jak1, Jak2, Tyk2 and Stat3 was significantly mitigated in the ISDF-treated groups. The absorption of baicalin and berberine of ISDF through the gastrointestinal tract of rats was limited, and their distribution and metabolism in rats were also very slow, which suggested ISDF could be used in the long-term application. CONCLUSIONS: ISDF has a strong anti-psoriatic therapeutic effect on mouse models induced with psoriasis through IMQ and IL-23, which is achieved by inhibiting the activation of the Jak/Stat3-activated IL-23/Th17 axis and the downstream NF-κB signalling and MAPK signalling pathways. ISDF holds great potential to be a therapy for psoriasis and should be further developed for this purpose.

Prognostic implications of preoperative, postoperative, and dynamic changes of alpha-fetoprotein and des-gamma (γ)-carboxy prothrombin expression pattern for hepatocellular carcinoma after hepatic resection: a multicenter observational study.

Background: The utility of pre- and post-operative alpha-fetoprotein (AFP) and des-gamma (γ)-carboxy prothrombin (DCP) expression patterns and their dynamic changes as predictors of the outcome of hepatic resection for hepatocellular carcinoma (HCC) has yet to be well elucidated. Methods: From a multicenter database, AFP and DCP data during the week prior to surgery and the first post-discharge outpatient visit (within 1-2 months after surgery) were collected from patients with HCC who underwent hepatectomy. AFP-DCP expression patterns were categorized according to the number of positive tumor markers (AFP ≥ 20ng/mL, DCP ≥ 40mAU/mL), including double-negative, single-positive, and double-positive. Changes in the AFP-DCP expression patterns were delineated based on variations in the number of positive tumor markers when comparing pre- and post-operative patterns. Results: Preoperatively, 53 patients (8.3%), 337 patients (52.8%), and 248 patients (38.9%) exhibited double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Postoperatively, 463 patients (72.6%), 130 patients (20.4%), and 45 patients (7.0%) showed double-negative, single-positive, and double-positive AFP-DCP expression patterns, respectively. Survival analysis showed a progressive decrease in recurrence-free (RFS) and overall survival (OS) as the number of postoperative positive tumor markers increased (both P < 0.001). Multivariate analysis showed that postoperative AFP-DCP expression pattern, but not preoperative AFP-DCP expression pattern, was an independent risk factor for RFS and OS. Further analysis showed that for patients with positive preoperative markers, prognosis gradually improves as positive markers decrease postoperatively. In particular, when all postoperative markers turned negative, the prognosis was consistent with that of preoperative double-negative patients, regardless of the initial number of positive markers. Conclusions: AFP-DCP expression patterns, particularly postoperative patterns, serve as vital sources of information for prognostic evaluation following hepatectomy for HCC. Moreover, changes in AFP-DCP expression patterns from pre- to post-operation enable dynamic prognostic risk stratification postoperatively, aiding the development of individualized follow-up strategies.

[The Effecacy and Safety of Daratumumab Based Regimens in Relapsed/Refractory Multiple Myeloma: A Single-Center Real-World Data Analysis].

OBJECTIVE: To investigate the efficacy and safety of daratumumab based regimens in relapse and/or refractory multiple myeloma (RRMM) in the real world, as well as the impact of daratumumab on stem cell collection and engraftment. METHODS: The clinical data of patients with RRMM who received daratumumab in hematology department of the First Affiliated Hospital of Xiamen University from February 2019 to March 2023 and had evaluable efficacy were retrospective analysis. RESULTS: All 43 RRMM patients were treated with daratumumab-based combination regimens, including Dd, DVd, DRd, Dkd, DId, and Dara-DECP. With median follow-up time 10.1 (2.1-36.6) months, the best overall response rate (ORR) was 74.4% and a best complete response rate (CR) was 25.6%. 1-year overall survival rate (OS) was 84.5%. The most common severe hematologic adverse events (Grade>3) are 3/4 grade leukopenia（18.6%）, and the most common severe non-hematologic adverse events were infusion-related reactions (IRRs， 20.9%) and infections（7.0%）. Multivariate prognostic analysis showed that extramedullary infiltration was an independent adverse prognostic factor affecting OS （P =0.004）. The use of daratumumab has no effect on stem cell collection, or engraftment. CONCLUSION: Daratumumab is safe and effective in RRMM.